No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Association of Intensive Lifestyle Intervention, Fitness, and Body Mass Index With Risk of Heart Failure in Overweight or Obese Adults With Type 2 Diabetes Mellitus: An Analysis From the Look AHEAD Trial
Abstract
Background: Type 2 diabetes mellitus (T2DM) is associated with higher risk for heart failure (HF). The impact of a lifestyle intervention and changes in cardiorespiratory fitness (CRF), and body mass index (BMI) on risk for HF is not well-established.
Methods: Participants from the Look AHEAD (Action for Health in Diabetes) trial without prevalent HF were included. Time to event analyses were used to compare the risk of incident HF between the intensive lifestyle intervention (ILI) vs. diabetes support and education (DSE) groups. The associations of baseline measures of CRF estimated from a maximal treadmill test, BMI, and longitudinal changes in these parameters with risk of HF were evaluated using multivariable adjusted Cox models.
Results: Among the 5,109 trial participants, there was no significant difference in the risk of incident HF (n = 257) between the ILI vs. DSE groups [HR (95% CI) = 0.96 (0.75 to 1.23)] over a median follow-up of 12.4 years. In the most adjusted Cox models, the risk of HF was 39% and 62% lower among moderate fit [Tertile 2: HR (95% CI) = 0.61 (0.44 to 0.83)] and high fit [Tertile 3: HR (95% CI) = 0.38 (0.24 to 0.59)] groups, respectively (referent group: low fit, Tertile 1). Among HF subtypes, after adjustment for traditional CV risk factors and interval incidence of MI, baseline CRF was not significantly associated with risk of incident HFrEF. In contrast, the risk of incident HFpEF was 40% lower in moderate fit and 77% lower in the high fit groups. Baseline BMI was also not associated with risk of incident HF, HFpEF, or HFrEF after adjustment for CRF and traditional CV risk factors. Among participants with repeat CRF assessments (n = 3,902), improvements in CRF and weight loss over 4-year follow-up was significantly associated with lower risk of HF [HR (95% CI) per 10% increase in CRF = 0.90 (0.82 to 0.99), per 10% decrease in BMI = 0.80 (0.69 to 0.94)].
Conclusions: Among participants with T2DM in the Look AHEAD trial, the ILI did not appear to modify the risk of HF. Higher baseline CRF and sustained improvements in CRF and weight loss were associated with lower risk of HF.
Clinical Trial Registration: URL: https://www.clinicaltrials.gov Unique identifier: NCT00017953
... Epidemiological studies have consistently linked low levels of PA with increased HF risk. Observational studies have also shown that moderate-to-high levels of PA and/or CRF are associated with a lower risk of HF in a linear, graded fashion [112][113][114][115]. Furthermore, the associations between PA and CRF and HF risk are stronger and more dose-dependent for HF with preserved ejection fraction (HFpEF) than for HF with reduced ejection fraction (HFrEF) [114,116]. ...
... Epidemiological studies have consistently linked low levels of PA with increased HF risk. Observational studies have also shown that moderate-to-high levels of PA and/or CRF are associated with a lower risk of HF in a linear, graded fashion [112][113][114][115]. Furthermore, the associations between PA and CRF and HF risk are stronger and more dose-dependent for HF with preserved ejection fraction (HFpEF) than for HF with reduced ejection fraction (HFrEF) [114,116]. Observational studies have also shown that long-term increases in PA and CRF are associated with a reduced risk of HF [114,117]. However, exercise training and lifestyle PA interventions have failed to demonstrate a reduction in the risk of HF in limited RCTs. ...
... Observational studies have also shown that moderate-to-high levels of PA and/or CRF are associated with a lower risk of HF in a linear, graded fashion [112][113][114][115]. Furthermore, the associations between PA and CRF and HF risk are stronger and more dose-dependent for HF with preserved ejection fraction (HFpEF) than for HF with reduced ejection fraction (HFrEF) [114,116]. Observational studies have also shown that long-term increases in PA and CRF are associated with a reduced risk of HF [114,117]. However, exercise training and lifestyle PA interventions have failed to demonstrate a reduction in the risk of HF in limited RCTs. ...
The prescription of exercise for individuals with and without cardiovascular disease (CVD) should be scientifically-based yet adapted to the patient. This scientific statement reviews the clinical and physiologic basis for the prescription of exercise, with specific reference to the volume of physical activity (PA) and level of cardiorespiratory fitness (CRF) that confer significant and optimal cardioprotective benefits. Recommendations are provided regarding the appropriate intensity, frequency, and duration of training; the concept of MET-minutes per week; critical components of the exercise session (warm-up, conditioning phase, cool-down); methodologies for establishing the training intensity, including oxygen uptake reserve (V̇O2R), target heart rate derivation and rating perceived exertion; minimum and goal intensities for exercise training; and, types of training activities, including resistance training, adjunctive lifestyle PA, marathon/triathlon training, and high-intensity interval training. In addition, we discuss the rationale for and value of exercise training programs for patients with peripheral artery disease, diabetes mellitus, and heart failure.
... Epidemiological studies have consistently linked low levels of PA with increased HF risk. Observational studies have also shown that moderate-to-high levels of PA and/or CRF are associated with a lower risk of HF in a linear, graded fashion [112][113][114][115]. Furthermore, the associations between PA and CRF and HF risk are stronger and more dose-dependent for HF with preserved ejection fraction (HFpEF) than for HF with reduced ejection fraction (HFrEF) [114,116]. ...
... Epidemiological studies have consistently linked low levels of PA with increased HF risk. Observational studies have also shown that moderate-to-high levels of PA and/or CRF are associated with a lower risk of HF in a linear, graded fashion [112][113][114][115]. Furthermore, the associations between PA and CRF and HF risk are stronger and more dose-dependent for HF with preserved ejection fraction (HFpEF) than for HF with reduced ejection fraction (HFrEF) [114,116]. Observational studies have also shown that long-term increases in PA and CRF are associated with a reduced risk of HF [114,117]. However, exercise training and lifestyle PA interventions have failed to demonstrate a reduction in the risk of HF in limited RCTs. ...
... Observational studies have also shown that moderate-to-high levels of PA and/or CRF are associated with a lower risk of HF in a linear, graded fashion [112][113][114][115]. Furthermore, the associations between PA and CRF and HF risk are stronger and more dose-dependent for HF with preserved ejection fraction (HFpEF) than for HF with reduced ejection fraction (HFrEF) [114,116]. Observational studies have also shown that long-term increases in PA and CRF are associated with a reduced risk of HF [114,117]. However, exercise training and lifestyle PA interventions have failed to demonstrate a reduction in the risk of HF in limited RCTs. ...
Regular moderate-to-vigorous physical activity (PA) and increased levels of cardiorespiratory fitness (CRF) or aerobic capacity are widely promoted as cardioprotective measures in the primary and secondary prevention of atherosclerotic cardiovascular (CV) disease (CVD). Nevertheless, physical inactivity and sedentary behaviors remain a worldwide concern. The continuing coronavirus (COVID-19) pandemic has been especially devastating to patients with known or occult CVD since sitting time and recreational PA have been reported to increase and decrease by 28% and 33%, respectively. Herein, in this first of a 2-part series, we discuss foundational factors in exercise programming, with specific reference to energy metabolism, contemporary PA recommendations, the dose-response relationship of exercise as medicine, the benefits of regular exercise training, including the exercise preconditioning cardioprotective phenotype, as well as the CV risks of PA. Finally, we discuss the ‘extreme exercise hypothesis,’ specifically the potential maladaptations resulting from high-volume, high-intensity training programs, including accelerated coronary artery calcification and incident atrial fibrillation. The latter is commonly depicted by a reverse J-shaped or U-shaped curve. On the other hand, longevity data argue against this relationship, as elite endurance athletes live 3–6 years longer than the general population.
... У осіб із ХСН на тлі ЦД ризик госпіталізації на 50 % вищий, ніж у таких без діабету [11]. Крім того, пацієнти з ЦД та ХСН мають знач но гіршу якість життя, ніж пацієнти лише з ХСН [10,16]. У дослідженні I-PRESERVE (середній термін спостереження -4,1 року) смерть від ССЗ або госпіталізація з приводу ХСН відбулися у 34 % пацієнтів із ЦД та ХСН зі збереженою ФВ порівняно з 22 % у пацієнтів із ХСН зі збереженою ФВ, але без ЦД. ...
... На ризик серцево-судинної смерті та частоту госпіталізацій з приводу ХСН впливає глікемічний статус пацієнтів (нормоглікемія -НЬА1С < 6,0 %; предіабет -НЬА1С -5,5-6,4 %; недіагностований ЦД -НЬА1С > 6,5 %) [19]. Оскільки поєднання ХСН із ЦД значно погіршує якість і прогноз життя пацієнтів, успішне лікування діабету з норма лізацією рівня глікемії дозволяє суттєво зни зити ризик розвитку і прогресування ХСН [16]. ...
... У ба гатонаціональному випробуванні С VD-REAL2, де використовували аналогічний підхід, засто сування інгібіторів SGLT-2 було пов'язано зі зниженням ризику смерті від загальних при чин на 49 % та госпіталізації з приводу ХСН на 36 % [3,9]. За даними Американської ко легії кардіологів 2017 року, під час лікування різними інгібіторами SGLT-2 (53 % пацієнтів приймали канагліфлозин, 42 % -дапагліфло зин, 5 % -емпагліфлозин) кількість госпіталі зацій із приводу ХСН зменшувалась на 48 %, а смертність від будь-якої причинина 51 % порівняно з показником пацієнтів, котрі прий мали інші цукрознужуючі препарати [16,26]. Емпагліфлозин також сприяв покращанню функції лівого шлуночка при експерименталь но індукованій ХСН зі зниженою ФВ [30,31]. ...
The epidemiology of chronic heart failure in patients with diabetes mellitus type 2, their general pathophysiological mechanisms, the influence of diabetes mellitus type 2 on the course and prognosis of chronic heart failure are considered. The high prevalence of chronic heart failure of all phenotypes among patients with diabetes mellitus type 2 and the increased risk of developing diabetes mellitus type 2 in patients with chronic heart failure confirm the close relationship and the high degree of comorbidity between these pathological conditions. It is shown that the development and progression of chronic heart failure in patients with diabetes mellitus type 2 is the formation of diabetic cardiomyopathy, which is characterized by disorders of energy metabolism of cardiomyocytes, mitochondrial dysfunction with subsequent apoptosis and myocardial fibrosis. Important links in the pathogenesis of chronic heart failure in diabetes mellitus type 2 are also the accession of diabetic cardiovascular autonomic neuropathy, activation of the renin-angiotensin-aldosterone system, endothelial dysfunction, exposure to atherogenic factors, arterial hypertension, obesity. The features of treatment of chronic heart failure in patients with diabetes mellitus type 2, the results of randomized clinical studies, the choice of target glycemic levels, the effectiveness of different groups of antihyperglycemic agents, drugs for the treatment of chronic heart failure, as well as their impact on the course and prognosis of chronic heart failure. Keywords: chronic heart failure, diabetes mellitus type 2, course, prognosis, treatment.
... 36 Similarly, although the intensive lifestyle intervention did not lower the risk of heart failure (HF) compared with control, sustained, long-term improvements in weight loss and cardiorespiratory fitness were associated with lower risk of HF in the entire cohort. 41 Furthermore, intensive lifestyle intervention yielded improvements in other cardiovascular risk factors, 40,42 sleep apnea, 43 fitness, 44 renal disease, 45 peripheral neuropathy, 46 and depressive symptoms. 47 Thus, among patients with T2D with overweight or obese status, intensive lifestyle intervention results in moderate and sustained weight loss, control of cardiovascular risk factors, and substantial cardiovascular benefit for those with greater weight loss and fitness. ...
... 47 Thus, among patients with T2D with overweight or obese status, intensive lifestyle intervention results in moderate and sustained weight loss, control of cardiovascular risk factors, and substantial cardiovascular benefit for those with greater weight loss and fitness. 36,41,48 Physical Activity Physical activity is important in cardiovascular risk reduction among individuals with T2D (Table 1). Consistent with other prevention guidelines, 21 the American Diabetes Association (ADA) recommends ≥150 minutes of moderate-to-vigorous intensity aerobic activity per week, over at least 3 days, with no more than 2 consecutive days without activity for most adults with T2D. ...
Cardiovascular disease remains the leading cause of death in patients with diabetes. Cardiovascular disease in diabetes is multifactorial, and control of the cardiovascular risk factors leads to substantial reductions in cardiovascular events. The 2015 American Heart Association and American Diabetes Association scientific statement, "Update on Prevention of Cardiovascular Disease in Adults With Type 2 Diabetes Mellitus in Light of Recent Evidence," highlighted the importance of modifying various risk factors responsible for cardiovascular disease in diabetes. At the time, there was limited evidence to suggest that glucose-lowering medications reduce the risk of cardiovascular events. At present, several large randomized controlled trials with newer antihyperglycemic agents have been completed, demonstrating cardiovascular safety and reduction in cardiovascular outcomes, including cardiovascular death, myocardial infarction, stroke, and heart failure. This AHA scientific statement update focuses on (1) the evidence and clinical utility of newer antihyperglycemic agents in improving glycemic control and reducing cardiovascular events in diabetes; (2) the impact of blood pressure control on cardiovascular events in diabetes; and (3) the role of newer lipid-lowering therapies in comprehensive cardiovascular risk management in adults with diabetes. This scientific statement addresses the continued importance of lifestyle interventions, pharmacological therapy, and surgical interventions to curb the epidemic of obesity and metabolic syndrome, important precursors of prediabetes, diabetes, and comorbid cardiovascular disease. Last, this scientific statement explores the critical importance of the social determinants of health and health equity in the continuum of care in diabetes and cardiovascular disease.
... Recent studies have revealed that WC, as a measure of abdominal obesity, is an indicator of body composition, and a large WC may pose a higher cardiovascular disease (CVD) risk, even in individuals with a normal BMI (9). In addition, in the Look AHEAD trial, a reduction in BMI and WC during follow-up was associated with a lower risk of HF among participants with T2DM who were overweight or obese (7,10). Furthermore, bariatric surgery has been associated with a reduced risk of HF in over 5,000 patients with T2DM and obesity (11). ...
Background
To determine the association of unintentional changes in body mass index (BMI) and waist circumference (WC) with the risk of heart failure (HF) among adults with type 2 diabetes mellitus (T2DM).
Methods
This was a randomized controlled trial (the Action to Control Cardiovascular Risk in Diabetes [ACCORD] study), with a double 2×2 factorial design conducted at 77 clinical centers across the United States and Canada. In total, the study comprised 10,251 patients with T2DM and cardiovascular disease (CVD) or at a high risk of CVD. The outcome of interest in the present analysis was incident HF, defined as the first hospitalization event for HF or death due to HF. Hospitalization for HF was based on documented clinical and radiological evidence. Death due to HF was based on clinical, radiological, or postmortem evidence of HF, with an absence of an acute ischemic event according to clinical or postmortem evidence.
Results
Participants with class III obesity had the smallest BMI and WC changes, followed by those with normal weight, overweight, class I obesity, and class II obesity. Increasing BMI (hazard ratio [HR] per standard deviation increase, 1.24; 95% confidence interval [CI], 1.07–1.45) and WC (1.27; 1.10–1.47) were significantly associated with a higher risk of HF. The relationship between BMI and WC changes and HF formed a J-shaped curve, while stable BMI and WC were associated with lower risks of HF. Compared with participants in the first tertiles of BMI and WC change, those in the third tertiles had HRs of 1.41 (95% CI, 1.07–1.45) and 1.48 (1.12–1.95), respectively.
Conclusion
In conclusion, our findings suggest a noteworthy association between BMI and WC changes among adults with T2DM in HF. We observed a distinctive J-shaped curve in this relationship, indicating that participants with both low and high BMI and WC changes were more susceptible to developing HF.
Trial registration
http://www.clinicaltrials.gov. Unique identifier: NCT00000620
... Cardiorespiratory tness is signi cantly reduced in patients with T2D in the presence of an overall normal left ventricular ejection fraction [30] . A recent secondary analysis of the Look AHEAD (Action for Health in Diabetes) trial showed that cardiorespiratory tness was an independent predictor of incident HFpEF (but not HFrEF) in patients with T2D, after adjustment for traditional cardiovascular risk factors [31] . Many studies have reported that cardiorespiratory tness is signi cantly lower in adults with T2DM compared to healthy adults, even though they do not have signs or symptoms of or prevalent cardiovascular disease, and that a high CRF is associated with a 60 ~ 70% reduction in the risk of CVD. ...
Background
Regular exercise is a well-accepted strategy to improve cardiovascular system function in patients with type 2 diabetes mellitus. The results of trials assessing the impact of exercise training on cardiac function in T2DM have been inconsistent. Whether combined exercise training improve subclinical cardiac dysfunction in people with T2DM, however, is not known. Therefore, the purpose of this study was to investigate the effects of high-intensity interval training (HIIT) combined with resistance training (RT) and moderate-intensity continuous training (MICT) combined with RT on cardiac structure and function in patients with type 2 diabetes. The impact of HIIT + RT and MICT + RT on cardiorespiratory fitness and metabolic control was also investigated.
Methods
54 patients who met the inclusion criteria were randomly assigned to the HIIT + RT group, MICT + RT group, and control group (CG). With 18 participants in each group, for 12 weeks, three times per week exercise intervention. Patients underwent echocardiographic cardiac function and structure, metabolic and clinical evaluation at baseline and 3 months.
Results
(1) There was a significant difference between groups for changes on VO2peak. Greater increases on VO2peak were achieved for HIIT + RT in comparison to CG group, with significant difference between HIIT + RT and MICT + RT. VO2peak significantly increased for both HIIT + RT and MICT + RT (P༜0.01). (2) After 12 weeks of intervention, HIIT + RT significantly changed EF, LVPWT, LVEDD and LVESD and LVM (P༜0.01). MICT + RT only had significant effects on EF, LVPW (P༜0.01), and LVM (P༜0.05). Compared with CG, HIIT + RT significantly improve EF, LVEDD (P༜0.01), and LVM (P༜0.05) in T2DM patients. Compared with MICT + RT, HIIT + RT was more effective in improving LVEDD (P༜0.05).
Conclusions
(1) 12 weeks of HIIT + RT and MICT + RT significantly improved body weight and blood glucose control in T2DM patients, which would be beneficial to reduce the risk of cardiovascular disease in T2DM patients. (2) 12 weeks of HIIT + RT and MICT + RT significantly improved peak oxygen uptake and cardiac structure and function in T2DM patients; However, HIIT + RT was more effective in improving cardiopulmonary fitness and cardiac structure and function in T2DM patients.
... A U-shaped dose-dependent association was observed at the population level between BMI and adverse cardiovascular outcomes. 4,5 However, BMI dismisses the regional fat distribution and fails to differentiate fat mass from lean mass, thus making BMI-defined obesity a heterogeneous condition.. 6,7 Waist circumference, another easily acquired body measure parameter, is significantly correlated with the absolute fat amount in abdominal areas. 8 Recent research has highlighted the unique superiority of waist circumference over BMI in assessing cardiovascular complications related to obesity and predicting adverse outcomes. ...
We aim to investigate the influence of waist circumference and body mass index (BMI) on all‐cause death and cardiovascular‐specific death in patients with hypertension. This prospective cohort study, based on waist circumference and body mass index measurements in patients with hypertension, provided risk estimates of all‐cause mortality and cardiovascular events. The waist circumference‐to‐BMI ratio (WtBR) is an anthropometric measure integrating waist circumference and BMI. We utilized multivariable Cox regression analysis, restricted cubic spline model, Kaplan‐Meier plot, random forest analysis, and sensitivity analysis to assess the relationship of WtBR with all‐cause mortality. Subsequently, Fine‐Gray competing risk regression models were applied to precisely evaluate the probability of cardiovascular‐specific death attributed to high WtBR. The results indicate that thea deceased group showed significantly higher WtBR and lower BMI compared with the alive groups ( P < .05), while no significant difference was observed in waist circumference ( P = .373). When analyzed as continuous, the risk of all‐cause death elevated with increasing WtBR in the adjusted model with an HR of 2.42 (95% CI, 2.06‐2.85). The restricted cubic spline illustrated an elevated risk of all‐cause mortality as WtBR increased (J‐shaped curve). Nevertheless, WtBR showed no significant association with cardiovascular‐specific death and the prediction model exhibited a reliable performance in the testing set. This study supported that WtBR, an anthropometric measure, is independently associated with all‐cause death in hypertensive patients. It's advisable to routinely assess waist circumference in hypertensive patients regardless of BMI, in order to more effectively manage the risk of obesity‐related health.
... However, there is a growing randomized trial literature demonstrating the potential benefits in heart failure with preserved ejection fraction (HFpEF) in terms of improvement in health-related quality of life, exercise capacity, and mechanistic echocardiographic measures (see Supplementary material online, Table S1). However, whilst exercise capacity and health-related quality of life are strong prognostic predictors in HFpEF, 27,28 given the small number of recruited patients and relatively short follow-up of trials of exercise training interventions, there are insufficient data at this time to fully determine the impact of cardiac rehabilitation on clinical events, including mortality and hospital admission in HFpEF. 29 The 2022 American College of Cardiology/American Heart Association joint committee guidelines reflect this evidence gap and prioritize the need for appropriately powered randomized trials assessing the efficacy and safety of cardiac rehabilitation in HFpEF and heart failure with mildly reduced ejection fraction (HFmrEF) patients. ...
Cardiac rehabilitation remains the 'Cinderella' of treatments for heart failure. This state-of-the-art review provides a contemporary update on the evidence base, clinical guidance, and status of cardiac rehabilitation delivery for patients with heart failure. Given that cardiac rehabilitation participation results in important improvements in patient outcomes, including health-related quality of life, this review argues that an exercise-based rehabilitation is a key pillar of heart failure management alongside drug and medical device provision. To drive future improvements in access and uptake, health services should offer heart failure patients a choice of evidence-based modes of rehabilitation delivery, including home, supported by digital technology, alongside traditional centre-based programmes (or combinations of modes, 'hybrid') and according to stage of disease and patient preference.
... According to a recent meta-analysis of eight studies including 226,506 patients with chronic HF, weight loss >5% is associated with a 74% higher mortality risk as compared to stable weight [113]. Then again, weight loss has been shown to reduce the incidence of HF [114]. In addition, intentional weight loss for the obese may improve hemodynamics and cardiac structure, including reductions in circulating blood volume, left ventricular stroke volume, cardiac output, and left ventricular work [115,116]. ...
Background:
Obesity increases the risk of cardiovascular disease and heart failure (HF). However, in patients with established HF, many studies observed greater survival with increasing adiposity. This counterintuitive observation has been termed the "obesity paradox". In recent years, new HF therapies have emerged that improve prognosis in patients with HF. Some of these, such as sodium-glucose cotransporter 2 inhibitors (SGLT2i), cause weight loss and may therefore interfere with the obesity paradox.
Summary:
This article is a narrative review on the relationship between body weight and outcomes in patients with HF with special focus on new HF treatments. PubMed was searched for studies reporting the prognostic impact of obesity in HF from 2002 to February 22nd 2022. More than 400 records were examined, with 150 being included in the present review. Literature provides evidence for an obesity paradox in a broad range of HF patients, including acute and chronic HF across the spectrum of left ventricular ejection fraction. It has been verified in HF patients treated with SGLT2i but not in those using sacubitril/valsartan. Cardiorespiratory fitness and severity of HF seem to be important confounders of the obesity paradox in HF. While unintentional weight loss is associated with a poor prognosis in HF, weight loss associated with SGLT2i treatment appears safe.
Key messages:
Consensus has yet to emerge as to whether the obesity paradox is a true phenomenon in HF. As cardiorespiratory fitness is strongly associated with prognosis and significantly modifies the relationship between adiposity and survival in HF, regular physical activity is recommended irrespective from body weight. In HF patients with severe obesity, a modest weight reduction of 5-10% may be reasonable to improve HF symptoms and quality of life.
... La sensibilidad a la insulina aumentó significativamente en los participantes pertenecientes al grupo de intervención en comparación al grupo control. Pandey et al. (2020) 5,109 adultos con sobrepeso y obesos, de 45 a 76 años, con DT2. ...
El sobrepeso y la obesidad son los principales factores de riesgo de las enfermedades cardiometabólicas, entre ellas la diabetes mellitus tipo 2. En el año 2016 se reportó que en México el sobrepeso y obesidad afectaba al 72.5% de la población adulta, mientras que en el 2019 se estimó que 10% de la población tenía diabetes. Estas cifras tan alarmantes se deben, entre otros factores, al alto consumo de alimentos no saludables que prevalece en la población mexicana, el bajo nivel de actividad física y factores conductuales como el tabaquismo. Además, durante el último año, el encierro por la pandemia de COVID-19 se ha sumado entre los factores de riesgo de dichas condiciones. Debido a que el estilo de vida es uno de los determinantes de estas enfermedades, se deduce que la intervención en el estilo de vida debe ser una parte fundamental del tratamiento de las mismas. Por lo tanto, esta revisión tiene como objetivo evaluar el estado actual del conocimiento de los programas de intervención en el estilo de vida, así como los componentes claves que conforman dichos programas, que permitan disminuir el riesgo cardiometabólico de la población vulnerable. De acuerdo a los resultados analizados de la eficacia de algunas intervenciones del estilo de vida que han sido reportadas como casos de éxito para la adquisición de hábitos saludables, es clara la necesidad de incluir cada uno de los componentes para lograr el control, prevención o retraso del diagnóstico de enfermedades cardiometabólicas. Sin embargo, hace falta mayor análisis e investigación de programas realizados en condiciones específicas de salud y del grupo de población al que se aplicarían, para evaluar su eficacia en la situación actual que vive la población vulnerable.
... [36][37][38] Intentional weight loss, particularly targeting central adiposity, and prescription of SGLT2i are associated with lower risk of HF, but, currently, there are no validated risk scores recommended for HF risk stratification. 8,39,40 Both WATCH-DM and TRS-HF DM are HF risk prediction tools that incorporate routinely assessed clinical data and are now validated in multiple cohorts. In the present analyses, we demonstrated that novel risk scores could help target preventive HF therapies, such as intentional weight loss interventions and SGLT2i, to individuals who have the highest risk for developing HF and are therefore most likely to experience the greatest absolute risk reductions for incident HF. ...
Background
The WATCH‐DM (weight [body mass index], age, hypertension, creatinine, high‐density lipoprotein cholesterol, diabetes control [fasting plasma glucose], ECG QRS duration, myocardial infarction, and coronary artery bypass grafting) and TRS‐HF DM (Thrombolysis in Myocardial Infarction [TIMI] risk score for heart failure in diabetes) risk scores were developed to predict risk of heart failure (HF) among individuals with type 2 diabetes. WATCH‐DM was developed to predict incident HF, whereas TRS‐HF DM predicts HF hospitalization among patients with and without a prior HF history. We evaluated the model performance of both scores to predict incident HF events among patients with type 2 diabetes and no history of HF hospitalization across different cohorts and clinical settings with varying baseline risk.
Methods and Results
Incident HF risk was estimated by the integer‐based WATCH‐DM and TRS‐HF DM scores in participants with type 2 diabetes free of baseline HF from 2 randomized clinical trials (TECOS [Trial Evaluating Cardiovascular Outcomes With Sitagliptin], N=12 028; and Look AHEAD [Look Action for Health in Diabetes] trial, N=4867). The integer‐based WATCH‐DM score was also validated in electronic health record data from a single large health care system (N=7475). Model discrimination was assessed by the Harrell concordance index and calibration by the Greenwood‐Nam‐D’Agostino statistic. HF incidence rate was 7.5, 3.9, and 4.1 per 1000 person‐years in the TECOS, Look AHEAD trial, and electronic health record cohorts, respectively. Integer‐based WATCH‐DM and TRS‐HF DM scores had similar discrimination and calibration for predicting 5‐year HF risk in the Look AHEAD trial cohort (concordance indexes=0.70; Greenwood‐Nam‐D’Agostino P >0.30 for both). Both scores had lower discrimination and underpredicted HF risk in the TECOS cohort (concordance indexes=0.65 and 0.66, respectively; Greenwood‐Nam‐D’Agostino P <0.001 for both). In the electronic health record cohort, the integer‐based WATCH‐DM score demonstrated a concordance index of 0.73 with adequate calibration (Greenwood‐Nam‐D’Agostino P =0.96). TRS‐HF DM score could not be validated in the electronic health record because of unavailability of data on urine albumin/creatinine ratio in most patients in the contemporary clinical practice.
Conclusions
The WATCH‐DM and TRS‐HF DM risk scores can discriminate risk of HF among intermediate‐risk populations with type 2 diabetes.
... Regular physical activity facilitates improving blood glucose levels, reducing obesity (including visceral adiposity), maintaining control of CVD risk-factors, sustaining cardiorespiratory fitness, lowering risk of heart failure, and improving overall wellbeing. 7 The initial goal of weight-loss interventions, should be to achieve 5-10% weight-loss. ...
In the past decades, cardiovascular disease (CVD) has become a potential threat to sustainable and healthy living. In India, the
epidemiology has transitioned from predominantly infectious disease to noncommunicable disease (NCD). For preventing an epidemic
of NCDs, helmed by CVD at the forefront, there are important initiatives that need to be implemented, viz. boosting the health-care
system while regulating marketing and advertising to protect children and migrating/migrated poor from being unwittingly lured.
The gap between a patient realizing the disease and seeking medical help, and the patient yielding to the liabilities to avoid being
crippled, needs a major shift in mindset. Secondary prevention can bridge this care-gap by reducing health-care costs, increasing
economic productivity, and improving quality of life by laying strict guidelines to be followed for dietary modification, physical
activity, weight control, tobacco cessation, lipid management, BP reduction, diabetes control, goal- oriented pharmacotherapy, and
cardiac rehabilitation programs. Thus, primary health-care should be available to the patients with emphasis on the accessibility,
public participation, health promotion, building skills and competencies, technology, and intersectoral cooperation. This not only
limits an increase in disease burden later, but also ensures that the patient sustains better health outcomes early
... For instance, a large population-based cohort demonstrated that moderate weight loss (1-2-point BMI reduction) was associated with 28% lower odds for T2D, while an over 1 point increase in BMI was associated with 52% higher odds for T2D [86]. For patients with T2D and overweight or obesity, a post-hoc analysis of the Look AHEAD trial, a 10% decrease in BMI over 1 year and 4 years were independently associated with a 31% and 20% lower risk for incident HF, respectively [87]. ...
Heart failure (HF) is a complex clinical syndrome, associated with high rates of mortality, hospitalization, and impairment of quality of life. Obesity and type 2 diabetes are major cardiometabolic drivers, represented as distinct stages of adiposity- and dysglycemia-based chronic disease (ABCD, DBCD), respectively, and leading to cardiometabolic-based chronic disease (CMBCD). This review focuses on one aspect of the CMBCD model: how ABCD and DBCD influence genesis and progression of HF phenotypes. Specifically, the relationships of ABCD and DBCD stages with structural and functional heart disease, HF risk, and outcomes in overt HF are detailed. Also, evidence-based lifestyle, pharmacological, and procedural interventions that promote or reverse cardiac remodeling and outcomes in individuals at risk or with HF are discussed. In summary, driver-based chronic disease models for individuals at risk or with HF can expose prevention targets for more comprehensive interventions to improve clinical outcomes. Future randomized trials that investigate structured lifestyle, pharmacological, and procedural therapies specifically tailored for the CMBCD model are needed to develop personalized care plans to decrease HF susceptibility and improve outcomes.
... A J-or U-shaped curve was observed between waist circumference and mortality. 28,29 In a meta-analysis on 250,152 patients with coronary artery disease, patients with mildly elevated BMI (25-29.9 kg/m 2 ) showed the lowest risk for all-cause mortality (relative risk, .87; ...
This study aims to investigate the association between waist circumference and the development of hypertension based on a nationwide cohort Chinese population. A total of 5330 individuals free of hypertension at baseline were collected from the China Health and Retirement Longitudinal Study. The association between waist circumference and the development of hypertension was analyzed by an adjusted cox regression model and visualized by restricted cubic splines. Further, we applied the supervised machine learning methods to evaluate the importance of multiple variates for new‐onset hypertension. Additionally, the robustness of the association was assessed by a subgroup analysis. A total of 1490 individuals (28.0%) developed hypertension during a mean follow‐up of 3.32 years. The new‐onset hypertension was more observed in those with increased waist circumference (P for trend < .001). In the fully adjusted Cox regression, each 10 cm increase of waist circumference would result in an 18% elevated risk of hypertension. The random forest method and the Extreme Gradient Boosting method revealed waist circumference as an important feature to predict the development of hypertension. The sensitivity analysis indicated a consistent trend between waist circumference and new‐onset hypertension in all BMI categories. This study suggested high waist circumference as an independent risk factor for new‐onset hypertension based on a nationwide cohort of Chinese adults aged ≥45 years old. Our results supported that waist circumference should be routinely measured.
... Potential cases were grouped into definite or possible acute decompensated HF, chronic stable HF, HF unlikely, or unclassifiable. Incident HF referred to the first hospitalization for definite or possible acute HF exacerbation [21]. Further details about the ascertainment of HF events are provided in Additional file 1: Method S1. ...
Background
It remains unclear how the variability of adiposity indices relates to incident HF. This study evaluated the associations of the variability in several adiposity indices with incident heart failure (HF) in individuals with type 2 diabetes (T2DM).
Methods
We included 4073 participants from the Look AHEAD (Action for Health in Diabetes) study. We assessed variability of body mass index (BMI), waist circumference (WC), and body weight across four annual visits using three variability metrics, the variability independent of the mean (VIM), coefficient of variation (CV), and intraindividual standard deviation (SD). Multivariable Cox regression models were used to generate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for incident HF.
Results
Over a median of 6.7 years, 120 participants developed incident HF. After adjusting for relevant confounders including baseline adiposity levels, the aHR for the highest (Q4) versus lowest quartile (Q1) of VIM of BMI was 3.61 (95% CI 1.91–6.80). The corresponding aHRs for CV and SD of BMI were 2.48 (95% CI 1.36–4.53) and 2.88 (1.52–5.46), respectively. Regarding WC variability, the equivalent aHRs were 1.90 (95% CI 1.11–3.26), 1.79 (95% CI 1.07–3.01), and 1.73 (1.01–2.95) for Q4 versus Q1 of VIM, CV and SD of WC, respectively.
Conclusions
In a large sample of adults with T2DM, a greater variability of adiposity indices was associated with higher risks of incident HF, independently of traditional risk factors and baseline adiposity levels.
Registration-URL:https://clinicaltrials.gov/ct2/show/NCT00000620.
... A recent study suggested that exercise training in type 1 diabetes may also improve several important markers such as triglyceride level, LDL, waist circumference, and body mass (205). In adults with type 2 diabetes, higher levels of exercise intensity are associated with greater improvements in A1C and in cardiorespiratory fitness (206); sustained improvements in cardiorespiratory fitness and weight loss have also been associated with a lower risk of heart failure (207). Other benefits include slowing the decline in mobility among overweight patients with diabetes (208). ...
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc22-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
... • En pacientes de riesgo alto: c-LDL < 70 mg/dl, c-no-HDL < 100 mg/dl y Apo B < 80 mg/dl. En el paciente de alto riesgo, la obesidad constituye un claro agravante y, de igual manera, su control adecuado conlleva una disminución de su riesgo cardiovascular, incluyendo también una menor prevalencia de insuficiencia cardíaca y enfermedad renal crónica 12,13 . Es por ello que el control del peso y su reducción en caso de sobrepeso u obesidad debe ser una estrategia integrada en el manejo decidido de estos pacientes. ...
La mayoría de nuestros pacientes con diabetes tienen un riesgo cardiovascular (CV) elevado. Muchos de ellos, verdaderos pacientes invisibles, han visto empeorar su control en la pandemia de COVID-19. La pospandemia supone un reto en este sentido para devolver el óptimo control a nuestros pacientes con DM2. La correcta catalogación del riesgo cardiovascular real y su abordaje integral optimizado son clave en el correcto manejo de estos pacientes de alto riesgo. El presente artículo recoge las recomendaciones actuales y las claves para estructurar su atención en la pospandemia.
... 32 Similarly, higher BMI and intentional changes in body weight have been identified as important predictors of HF among patients with dia- betes in previous studies. 33,34 In the present study, we extend these observations by demonstrating the prognostic importance of different measures of obesity for the risk of HF in individuals with diabetes. Specifically, overall obesity, central obesity, and high FM contributed nearly 13%, 30%, and 14% risk of incident HF. ...
Background: Obesity and diabetes are associated with a higher risk of heart failure (HF). The inter-relationships between different measures of adiposity—overall obesity, central obesity, fat mass (FM)—and diabetes status for HF risk are not well-established.
Methods: Participant-level data from ARIC(visit-5) and CHS(visit-1) cohorts were obtained from the NHLBI BioLINCC, harmonized, and pooled for the present analysis, excluding individuals with prevalent HF. FM was estimated in all participants using established anthropometric prediction equations additionally validated using the bioelectrical impedance-based FM in the ARIC subgroup. Incident HF events on follow-up were captured across both cohorts using similar adjudication methods. Multivariable-adjusted Fine-Gray models were created to evaluate the associations of body mass index (BMI), waist circumference (WC), and FM with risk of HF in the overall cohort as well as among those with vs. without diabetes at baseline. The population attributable risk of overall obesity (BMI≥30 kg/m ² ), abdominal obesity (WC>88 and 102 cm in women and men, respectively), and high FM (above sex-specific median) for incident HF was evaluated among participants with and without diabetes.
Results: The study included 10,387 participants (52.9% ARIC; 25.1% diabetes; median age: 74 years). The correlation between predicted and bioelectrical impedance-based FM was high (R ² =0.90; n=5,038). Over a 5-year follow-up, 447 participants developed HF (4.3%). Higher levels of each adiposity measure were significantly associated with higher HF risk (HR [95% CI] per 1-SD higher BMI=1.19[1.09-1.31], WC=1.27[1.14-1.41]; FM=1.17[1.06-1.29]). A significant interaction was noted between diabetes status and measures of BMI (p-interaction=0.04) and WC (p-interaction=0.004) for the risk of HF. In stratified analysis, higher measures of each adiposity parameter were significantly associated with higher HF risk in individuals with diabetes (HR[95% CI] per 1-SD higher BMI=1.29[1.14-1.47], WC=1.48[1.29-1.70]; FM=1.25[1.09-1.43]) but not those without diabetes, including participants with prediabetes and euglycemia. The population attributable risk percentage of overall obesity, abdominal obesity, and high FM for incident HF was higher among participants with diabetes (12.8%, 29.9%, 13.7%, respectively) vs. those without diabetes (≤1% for each).
Conclusions: Higher BMI, WC, and FM are strongly associated with greater risk of HF among older adults, particularly among those with prevalent diabetes.
... At the same time, patients with T2DM and impaired functional capacity are at higher risk of developing HF. In a multicentre, randomised controlled trial that enrolled > 5000 obese subjects randomly assigned to lifestyle intervention or enhanced usual care to obtain weight loss, cardiorespiratory fitness at baseline emerged as an independent predictor of incident HFpEF (but not HFrEF) in patients with T2DM, after adjusting for common cardiovascular risk factors [32]. Furthermore, the presence of T2DM further reduces aerobic capacity in patients with a definite diagnosis of HF, regardless of LVEF [33]. ...
Type 2 diabetes mellitus (T2DM) represents a major health issue worldwide, as patients with T2DM show an excess risk of death for cardiovascular causes, twice as high as the general population. Among the many complications of T2DM, heart failure (HF) deserves special consideration as one of the leading causes of morbidity and reduced life expectancy. T2DM has been associated with different phenotypes of HF, including HF with reduced and preserved ejection fraction. Cardiopulmonary exercise testing (CPET) can evaluate the metabolic and ventilatory alterations related to myocardial dysfunction and/or peripheral impairment, representing a unique tool for the clinician to study the whole HF spectrum. While CPET allows for a thorough evaluation of functional capacity, it cannot directly differentiate central and peripheral determinants of effort intolerance. Combining CPET with imaging techniques could provide even higher accuracy and further insights into the progression of the disease since signs of left ventricular systolic and diastolic dysfunction can be detected during exercise, even in asymptomatic diabetic individuals. This review aims to dissect the alterations in cardiopulmonary function characterising patients with T2DM and HF to improve patient risk stratification.
Cardiovascular disease is an important cause of morbidity and mortality in Malaysia. Heart Failure (HF), the end stage of most diseases of the heart, is a common medical problem encountered in primary care and is an important cause of hospital admissions and readmissions with a significant impact on hospital expenditure. As the population ages, the prevalence of HF is expected to increase.
The 1st Clinical Practice Guidelines (CPG) in HF was published in 2000 with revisions in 2007, 2014 and 2019. Since then, there have been many new developments in this field. Thus, the publication of this 5th edition is timely. This CPG stresses on the early implementation and optimization of the “Foundational HF” medications. It also proposes a structured multidisciplinary strategy for the seamless care of patients with HF between hospital and primary care.
This CPG was drawn up by a committee appointed by the National Heart Association of Malaysia and Ministry of Health. It comprises cardiologists, nephrologists, family medicine and general physicians and pharmacists from the government, private sectors, and the public Universities.
Aim
Effort intolerance is frequent in patients with overweight/obesity and/or type 2 diabetes (T2D) free from cardiac and respiratory disease. We sought to quantify the independent effects of T2D and body mass index (BMI) on cardiopulmonary capacity and gain insights on the possible pathophysiology by case‐control and regression analyses.
Methods
Patients at high/moderate cardiovascular risk, with or without T2D, underwent spirometry and combined echocardiography‐cardiopulmonary exercise test as part of their clinical workup. Subjects with evidence of cardiopulmonary disease were excluded. The effects of T2D and obesity were estimated by multivariable models accounting for known/potential confounders and the major pathophysiological determinants of oxygen uptake at peak exercise (VO 2peak ) normalized for fat‐free mass (FFM).
Results
In total, 109 patients with T2D and 97 controls were included in the analysis. The two groups had similar demographic and anthropometric characteristics except for higher BMI in T2D (28.6 ± 4.6 vs. 26.3 ± 4.4 kg/m ² , p = .0003) but comparable FFM. Patients with T2D achieved lower VO 2peak than controls (18.5 ± 4.4 vs. 21.7 ± 8.3 ml/min/kg, p = .0006). Subclinical cardiovascular dysfunctions were observed in T2D: concentric left ventricular remodelling, autonomic dysfunction, systolic dysfunction and reduced systolic reserve. After accounting for confounders and major determinants of VO 2peakFFM , T2D still displayed reduced VO 2peak by 1.0 (−1.7/−0.3) ml/min/kg FFM , p = .0089, while the effect of BMI [−0.2 (−0.3/0.1) ml/min/kg FFM , p = .06 per unit increase], was largely explained by a combination of chronotropic incompetence, reduced peripheral oxygen extraction, impaired systolic reserve and ventilatory (in)efficiency.
Conclusions
T2D is an independent negative determinant of VO 2peak whose effect is additive to other pathophysiological determinants of oxygen uptake, including BMI.
Background: Exercise lowers blood glucose levels, improves insulin sensitivity, and helps prevent complications; therefore, it is highly effective for prevention and treatment of diabetes mellitus. However, many patients with diabetes do not meet the recommendations for the amount of exercise. In this study, we focus on the latest recommendations and discuss exercise therapies that are helpful for patients with diabetes.Current Concepts: Many studies have shown that exercise helps to improve blood glucose control, physical strength, and cardiorespiratory capacity in patients with type 1 or 2 diabetes. Patients with diabetes are advised to perform both aerobic and resistance exercises. Aerobic exercise is suitable for most patients and can rapidly lower blood glucose levels. Resistance exercise improves muscle strength and endurance and is useful for long-term stabilization of blood glucose levels. Combined aerobic and resistance exercise improves insulin resistance and additionally controls blood glucose levels. Patients with diabetes are recommended moderate intensity exercise for at least 150 min/week, at least thrice a week, without interruption in exercise for >2 consecutive days.Discussion and Conclusion: Exercise is an essential recommended lifestyle intervention for patients with diabetes, and regular exercise is important. Furthermore, patients with diabetes should avoid low-energy activities and minimize sitting time.
The burden of heart failure among people with type 2 diabetes is increasing globally. People with comorbid type 2 diabetes and heart failure often have worse outcomes than those with only one of these conditions-eg, higher hospitalisation and mortality rates. Therefore, it is essential to implement optimal heart failure prevention strategies for people with type 2 diabetes. A detailed understanding of the pathophysiology underlying the occurrence of heart failure in type 2 diabetes can aid clinicians in identifying relevant risk factors and lead to early interventions that can help prevent heart failure. In this Review, we discuss the pathophysiology and risk factors of heart failure in type 2 diabetes. We also review the risk assessment tools for predicting heart failure incidence in people with type 2 diabetes as well as the data from clinical trials that have assessed the efficacy of lifestyle and pharmacological interventions. Finally, we discuss the potential challenges in implementing new management approaches and offer pragmatic recommendations to help overcome these challenges.
Background:
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. Diabetes may identify an essential phenotype that significantly affects the prognosis of these patients. The WATCH-DM risk score has been validated for predicting the risk of heart failure in outpatients with type 2 diabetes mellitus (T2DM), but its ability to predict clinical outcomes in HFpEF patients with T2DM is unknown. We aimed to assess whether this risk score could predict the prognosis of diabetic phenotype patients with heart failure and preserved ejection fraction.
Methods:
We enrolled retrospectively 414 patients with HFpEF (70.03 ± 8.654 years, 58.70% female), including 203 (49.03%) type 2 diabetics. Diabetic HFpEF patients were stratified by baseline WATCH-DM risk score.
Results:
Diabetic HFpEF patients exhibited a trend toward more concentric remodeling/hypertrophy than nondiabetic HFpEF patients. When analyzed as a continuous variable, per 1-point increase in the WATCH-DM risk score was associated with increased risks of all-cause death (HR 1.181), cardiovascular death (HR 1.239), any hospitalization (HR 1.082), and HF hospitalization (HR 1.097). The AUC for the WATCH-DM risk score in predicting incident cardiovascular death (0.7061, 95% CI 0.6329-0.7792) was higher than that of all-cause death, any hospitalization, or HF hospitalization.
Conclusions:
As a high-risk phenotype for heart failure, diabetic HFpEF necessitates early risk stratification and specific treatment. To the best of our knowledge, the current study is the first to demonstrate that the WATCH-DM score predicts poor outcomes in diabetic HFpEF patients. Its convenience may allow for quick risk assessments in busy clinical settings.
Background:
In the CANVAS (Canagliflozin Cardiovascular Assessment Study) program, canagliflozin reduced the risk of heart failure (HF) hospitalization among individuals with type 2 diabetes mellitus (T2DM).
Objectives:
The purpose of this study was to evaluate heterogeneity in absolute and relative treatment effects of canagliflozin on HF hospitalization according to baseline HF risk as assessed by diabetes-specific HF risk scores (WATCH-DM [Weight (body mass index), Age, hyperTension, Creatinine, HDL-C, Diabetes control (fasting plasma glucose) and QRS Duration, MI and CABG] and TRS-HFDM [TIMI Risk Score for HF in Diabetes]).
Methods:
Participants in the CANVAS trial were categorized into low, medium, and high risk for HF using the WATCH-DM score (for participants without prevalent HF) and the TRS-HFDM score (for all participants). The outcome of interest was time to first HF hospitalization. The treatment effect of canagliflozin vs placebo for HF hospitalization was compared across risk strata.
Results:
Among 10,137 participants with available HF data, 1,446 (14.3%) had HF at baseline. Among participants without baseline HF, WATCH-DM risk category did not modify the treatment effect of canagliflozin (vs placebo) on HF hospitalization (P interaction = 0.56). However, the absolute and relative risk reduction with canagliflozin was numerically greater in the high-risk group (cumulative incidence, canagliflozin vs placebo: 8.1% vs 12.7%; HR: 0.62 [95% CI: 0.37-0.93]; P = 0.03; number needed to treat: 22) than in the low- and intermediate-risk groups. When overall study participants were categorized according to the TRS-HFDM score, a statistically significant difference in the treatment effect of canagliflozin across risk strata was observed (P interaction = 0.04). Canagliflozin significantly reduced the risk of HF hospitalization by 39% in the high-risk group (HR: 0.61 [95% CI: 0.48-0.78]; P < 0.001; number needed to treat: 20) but not in the intermediate- or low-risk groups.
Conclusions:
Among participants with T2DM, the WATCH-DM and TRS-HFDM can reliably identify those at high risk for HF hospitalization and most likely to benefit from canagliflozin.
Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes. In contrast, trials of exercise-based interventions have consistently demonstrated large, significant, clinically meaningful improvements in symptoms, objectively determined exercise capacity, and usually quality of life. This success may be attributed, at least in part, to the pleiotropic effects of exercise, which may favorably affect the full range of abnormalities-peripheral vascular, skeletal muscle, and cardiovascular-that contribute to exercise intolerance in HFpEF. Accordingly, this scientific statement critically examines the currently available literature on the effects of exercise-based therapies for chronic stable HFpEF, potential mechanisms for improvement of exercise capacity and symptoms, and how these data compare with exercise therapy for other cardiovascular conditions. Specifically, data reviewed herein demonstrate a comparable or larger magnitude of improvement in exercise capacity from supervised exercise training in patients with chronic HFpEF compared with those with heart failure with reduced ejection fraction, although Medicare reimbursement is available only for the latter group. Finally, critical gaps in implementation of exercise-based therapies for patients with HFpEF, including exercise setting, training modalities, combinations with other strategies such as diet and medications, long-term adherence, incorporation of innovative and more accessible delivery methods, and management of recently hospitalized patients are highlighted to provide guidance for future research.
Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure; its prevalence is increasing, and outcomes are worsening. Affected patients often experience severe exertional dyspnea and debilitating fatigue, as well as poor quality of life, frequent hospitalizations, and a high mortality rate. Until recently, most pharmacological intervention trials for HFpEF yielded neutral primary outcomes. In contrast, trials of exercise-based interventions have consistently demonstrated large, significant, clinically meaningful improvements in symptoms, objectively determined exercise capacity, and usually quality of life. This success may be attributed, at least in part, to the pleiotropic effects of exercise, which may favorably affect the full range of abnormalities-peripheral vascular, skeletal muscle, and cardiovascular-that contribute to exercise intolerance in HFpEF. Accordingly, this scientific statement critically examines the currently available literature on the effects of exercise-based therapies for chronic stable HFpEF, potential mechanisms for improvement of exercise capacity and symptoms, and how these data compare with exercise therapy for other cardiovascular conditions. Specifically, data reviewed herein demonstrate a comparable or larger magnitude of improvement in exercise capacity from supervised exercise training in patients with chronic HFpEF compared with those with heart failure with reduced ejection fraction, although Medicare reimbursement is available only for the latter group. Finally, critical gaps in implementation of exercise-based therapies for patients with HFpEF, including exercise setting, training modalities, combinations with other strategies such as diet and medications, long-term adherence, incorporation of innovative and more accessible delivery methods, and management of recently hospitalized patients are highlighted to provide guidance for future research.
The American Diabetes Association (ADA) “Standards of Care in Diabetes” includes the ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
Obesity is a chronic disease associated with serious complications and increased mortality. Weight loss through lifestyle changes results in modest weight loss long-term possibly due to compensatory biological adaptations (increased appetite and reduced energy expenditure) promoting weight gain. Bariatric surgery was until recently the only intervention that consistently resulted in ≥ 15% weight loss and maintenance. Our better understanding of the endocrine regulation of appetite has led to the development of new medications over the last decade for treatment of obesity with main target the reduction of appetite.
The efficacy of semaglutide 2.4 mg/week - the latest glucagon like peptide-1 (GLP-1) receptor analogue - on weight loss for people with obesity suggests that we are entering a new era in obesity pharmacotherapy where ≥15% weight loss is feasible. Moreover, the weight loss achieved with the dual agonist tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide) for people with type 2 diabetes and most recently also obesity, indicate that combining the GLP-1 with other gut hormones may lead to additional weight loss compared to GLP-1 receptor analogues alone and in the future, multi-agonist molecules may offer the potential to bridge further the efficacy gap between bariatric surgery and the currently available pharmacotherapies.
This article provides a review of the currently available interventions for weight loss and weight maintenance with a focus on pharmacological therapies for obesity approved over the last decade, as well as the emerging development of new obesity pharmacotherapies.
Aims:
To evaluate the contribution of baseline and longitudinal changes in cardiometabolic health (CMH) towards heart failure (HF) risk among adults with type 2 diabetes (T2D).
Methods and results:
Participants of the Look AHEAD trial with T2D and without prevalent HF were included. Adjusted Cox models were used to create a CMH score incorporating target levels of parameters weighted based on relative risk for HF. The associations of baseline and changes in the CMH score with risk of overall HF, HFpEF and HFrEF were assessed using Cox models. Among the 5,080 participants, 257 incident HF events occurred over 12.4-years follow-up. The CMH score included 2-points each for target levels of waist circumference, GFR, urine-albumin-to-creatinine-ratio, and 1-point each for BP and HbA1c at target. High baseline CMH score(6-8) was significantly associated with lower overall HF risk (aHR[ref=low score(0-3): 0.31[95% CI=0.21-0.47]) with similar associations observed for HFpEF and HFrEF. Improvement in CMH was significantly associated with lower risk of overall HF (aHR per 1-unit increase in score at 4-years: 0.80[95% CI=0.70-0.91]). In the ACCORD validation cohort, the baseline CMH score performed well for predicting HF risk with adequate discrimination (C-index=0.70), calibration (chi-square=5.53, p-value=0.70), and risk stratification (aHR[high(6-8) vs. low score(0-3): 0.35[95% CI=0.26-0.46]). In the LookAHEAD subgroup with available biomarker data, incorporating NT-proBNP to the baseline CMH score improved model discrimination (C-index=0.79) and risk stratification (aHR[high(8-10) vs. low score(0-4): 0.18[95% CI=0.09-0.35]).
Conclusions:
Achieving target levels of more CMH parameters at baseline and sustained improvements were associated with lower HF risk in T2D.
Background:
Whether lifestyle factors are similarly associated with risk of heart failure (HF) for individuals with different metabolic or genetic risk status remains unclear.
Methods:
We included 464 483 participants from UK Biobank who were free of major cardiovascular disease or HF during baseline recruitment. Healthy lifestyle factors included avoidance of smoking, no obesity, regular physical activity, and healthy diet. Lifestyle was categorized as favorable (3 or 4 healthy lifestyle factors), intermediate (2 healthy lifestyle factors), and unfavorable (0 or 1 healthy lifestyle factor) lifestyles. Metabolic status was defined by the presence of hypertension, high total cholesterol, or diabetes at baseline. A weighted genetic risk score was created based on 12 single-nucleotide polymorphisms associated with HF.
Results:
Compared with favorable lifestyle, the multivariable-adjusted hazard ratios of HF were 1.79 (95% CI, 1.68-1.90) and 2.90 (95% CI, 2.70-3.11) for intermediate lifestyle and unfavorable lifestyle, respectively (Ptrend <0.0001). This association was largely consistent regardless of the presence of any single metabolic risk factor or the number of metabolic risk factors (Pinteraction ≥0.21). The association was also similar across different genetic risk categories (Pinteraction=0.92). In a joint analysis, the hazard ratio of HF was 4.05 (95% CI, 3.43-4.77) comparing participants who had both higher genetic risk and an unfavorable lifestyle with those having lower genetic risk and a favorable lifestyle.
Conclusions:
Combined lifestyle was associated with incident HF regardless of metabolic or genetic risk status, supporting the recommendation of healthy lifestyles for HF prevention across the entire population.
Objective
The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers.
Methods
The American Association of Clinical Endocrinology (AACE) selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and informal consensus, according to established AACE protocol for guideline development.
Results
This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: 1) screening, diagnosis, glycemic targets, and glycemic monitoring; 2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; 3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; 4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes.
Conclusions
This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.
Background
Lower cardiorespiratory fitness (CRF) and higher body mass index (BMI) are associated with a higher risk of myocardial infarction and heart failure. However, the independent contribution of these lifestyle factors to the risk of atrial fibrillation (AF) is less well established.
Objective
Evaluate the association between midlife CRF, BMI, and risk of AF in older age.
Methods
The study included 18,493 participants without AF who underwent assessment of CRF (estimated using the maximal treadmill time) and BMI in middle age and had Medicare coverage after the age of 65 years. The association among midlife CRF, BMI, and risk of AF was assessed by fitting a proportional hazards intensity model to the failure time data with adjustment for potential confounders. The association between changes in CRF and BMI in middle age and the risk of AF was also assessed in the subset of participants with repeat CRF assessments.
Results
Among 18,493 participants (79% men), a higher midlife BMI was significantly associated with a higher risk of AF independent of CRF levels and other potential confounders (hazard ratio per 1-kg/m²: 1.05; 95% confidence interval: 1.03-1.06). Lower midlife CRF was also associated with higher risk of AF (hazard ratio per 1 metabolic equivalent higher CRF: 0.98; 95% confidence interval: 0.96-0.99). However, this association was attenuated and not significant after further adjustment for BMI. Change in CRF on follow-up was also not associated with the risk of AF after adjustment for other confounders.
Conclusion
The association between low fitness and AF was primarily driven by differences in BMI. In contrast, obesity was independently associated with excess AF risk.
Background:
Individuals with diabetes have a high frailty burden and increased risk of heart failure (HF). In this study, we evaluated the association of baseline and longitudinal changes in frailty with risk of HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF).
Methods:
Participants (age: 45-76 years) of the Look AHEAD trial without prevalent HF were included. The frailty index (FI) was used to assess frailty burden using a 35-variable deficit model. The association between baseline and longitudinal changes (1-year, 4-year follow-up) in FI with risk of overall HF, HFpEF (ejection fraction (EF)≥50%)], and HFrEF (EF<50%) independent of other risk factors and cardiorespiratory fitness was assessed using adjusted Cox models.
Results:
The study included 5,100 participants, of which 257 developed HF. In adjusted analysis, higher frailty burden was significantly associated with a greater risk of overall HF. Among HF subtypes, higher baseline FI was significantly associated with risk of HFpEF (HR[95% CI] per 1-SD higher FI: 1.37[1.15-1.63]) but not HFrEF (HR[95% CI]: 1.19[0.96-1.46]) after adjustment for potential confounders, including traditional HF risk factors. Among participants with repeat measures of FI at 1-year and 4-year follow-up, an increase in frailty burden was associated with a higher risk of HFpEF (HR[95%CI] per 1-SD increase in FI at 4-year: 1.78[1.35-2.34]) but not HFrEF after adjustment for other confounders.
Conclusions:
Among individuals with T2DM, higher baseline frailty and worsening frailty burden over time were independently associated with higher risk of HF, particularly HFpEF after adjustment for other confounders.
In this chapter, the authors present a broad view of the current background to the obesity pandemic and the importance of eating behavior. By examining differences in factors known to affect appetite regulation in individuals identified as “resistant” or “susceptible” to weight gain, they show how appetite processes mediate the relationship between differences in an individual's biology, physiology, and psychology and their eating behavior, and their response to (variations in) the environment. One approach to characterizing individual susceptibility is through the identification and characterization of phenotypes. Under controlled laboratory conditions, appetite sensations have been shown to be a valid and reliable method for measuring subjective motivation to eat and have been found to be associated with measured energy intake. However, not everyone reports a good relationship between their sensations of hunger and fullness and their eating behavior, and a weakened satiety response to food may contribute to impaired appetite control.
Purpose of review:
The burden of heart failure (HF) in the United States and worldwide is projected to rise. Prevention of HF can curb the burden of this chronic syndrome, but current approaches are limited. This review discusses team-based strategies aimed to prevent HF.
Recent findings:
Individuals at high risk for developing HF can be identified using HF risk scores, biomarkers, and cardiac imaging. Electronic medical records (EMR) can integrate clinical data to estimate HF risk and identify individuals who may benefit most from preventive therapies. Team-based interventions can lead to enhanced adherence to medications, optimization of medical management, and control of risk factors. Multifaceted interventions involve EMR-based strategies, pharmacist- and nurse-led initiatives, involvement of community personnel, polypills, and digital solutions.
Summary:
Team-based strategies aimed to prevent HF incorporate a broad group of personnel and tools. Despite implementation challenges, existing resources can be efficiently utilized to facilitate team-based approaches to potentially reduce the burden of HF.
Introduction:
We estimated the effects of cardiorespiratory fitness (CRF) and body mass index (BMI) at baseline on mortality and cardiovascular disease events in people with type 2 diabetes that participated in the Look AHEAD randomized clinical trial.
Methods:
Look AHEAD compared effects of an intensive lifestyle intervention with diabetes support and education on cardiovascular disease events in 5,145 adults aged 45-76 years with overweight/obesity and type 2 diabetes. In 4,773 participants, we performed a secondary analysis of the association of baseline CRF during maximal treadmill test (expressed as metabolic equivalents, METs) on mortality and cardiovascular disease events during mean follow-up of 9.2 years.
Results:
The mean (SD) CRF was 7.2 (2.0) METs. Adjusted for age, sex, race/ethnicity, body mass index, intervention group, and β-blocker use, all-cause mortality rate was 30% lower per SD greater METs (hazard ratio, HR = 0.70, 95% CI 0.60-0.81; rate difference, RD = -2.71 deaths/1000 person-years, 95% CI -3.79 to -1.63). Similarly, a SD greater METs predicted lower cardiovascular disease mortality (HR = 0.45, RD = -1.65 cases/1000 person-years) and a composite cardiovascular outcome (HR = 0.72; RD = -6.38). Effects of METs were homogeneous on the HR scale for most baseline variables and outcomes but heterogeneous for many on the RD scale, with greater RDs in subgroups at greater risk of the outcomes. For example, all-cause mortality was lower by 7.6 deaths/1000 person-years per SD greater METs in those with a history of cardiovascular disease at baseline but lower by only 1.6 in those without such history. BMI adjusted for CRF had little or no effect on these outcomes.
Conclusions:
Greater CRF is associated with reduced risks of mortality and cardiovascular disease events.
Background
Cardiometabolic disease, including cardiovascular disease (CVD) and type 2 diabetes (T2D), can result in serious late effects in patients with cancer. Preventing long-term complications in this population is an increasingly important priority in public health and clinical practice.
Objectives
The aim of this study was to investigate the role of a healthy lifestyle in the transition from a healthy status to the development of cancer and subsequent CVD and T2D.
Methods
The analysis was based on data from the UK Biobank and included 2 subsamples: a cancer-free cohort of 397,136 individuals in the general population and a cancer-prevalent cohort of 35,564 patients with cancer. All participants were 40 to 70 years of age and were free of CVD and T2D at recruitment. A healthy lifestyle that included no current smoking, regular physical activity, a healthy diet, and moderate alcohol consumption and sleep duration were included in a healthy lifestyle index (HLI).
Results
In the cancer-free cohort, during a maximum follow-up period of 15 years, 6.38% and 4.18% of patients with cancer developed CVD and T2D, respectively. A healthy lifestyle significantly mitigated the risk for transition from cancer to subsequent CVD and T2D, with HRs per 1-point increment in HLI of 0.90 (95% CI: 0.86-0.94) and 0.84 (95% CI: 0.79-0.89), respectively. In the cancer-prevalent cohort, each 1-point increment in HLI was similarly associated with lower risk for CVD (HR: 0.90; 95% CI: 0.87-0.93) and T2D (HR: 0.87; 95% CI: 0.83-0.91) in cancer survivors.
Conclusions
A healthy lifestyle is associated with a slower transition from cancer development to the subsequent development of CVD and T2D. Moreover, among patients with cancer, a healthy lifestyle is associated with lower risk for CVD and T2D. This study highlights the practical benefits of adherence to a healthy lifestyle.
Objective
This study aimed to examine the associations of waist circumference with hypertension and cardiometabolic dysregulation among normal-weight adults.
Methods
This cross-sectional study included 8795 normal-weight participants aged 20 to 79 years from the 2009–2018 US National Health and Nutrition Examination Survey. The demographic characteristics and cardiometabolic risk factors across waist circumference quartiles were summarized. We used adjusted multivariate logistic regression models, subgroup analysis, and restricted cubic spline to analyze the association between waist circumference and the prevalence of hypertension. Thereafter, we used the random forest supervised machine learning method, together with least absolute shrinkage and selection operator regression, to select hypertension-related features and created a predictive model based on regression analysis to identify hypertension in normal-weight individuals.
Results
Waist circumference was positively correlated with hypertension in the non-adjusted, minimally adjusted, and fully adjusted models, with odds ratios (95% confidence interval) of 2.28 (2.14–2.44), 1.27 (1.12–1.44), and 1.27 (1.12–1.44), respectively. In the fully adjusted model, participants in the highest waist circumference quartile had a higher risk of hypertension relative to those in the lowest quartile, with an odds ratio (95% confidence interval) of 3.87 (1.59–10.34). Sensitivity analysis demonstrated the robustness of the association. In the testing set, the predictive model exhibited good performance, with an area under the curve of 0.803, sensitivity of 0.72, specificity of 0.76, and negative predictive value of 0.84.
Conclusions
Measuring waist circumference may improve the evaluation of the risk of hypertension and help to manage cardiometabolic risk in normal-weight individuals.
Background
Lorcaserin, a selective serotonin 2C receptor agonist that modulates appetite, has proven efficacy for weight management in overweight or obese patients. The cardiovascular safety and efficacy of lorcaserin are undefined.
Methods
We randomly assigned 12,000 overweight or obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to receive either lorcaserin (10 mg twice daily) or placebo. The primary safety outcome of major cardiovascular events (a composite of cardiovascular death, myocardial infarction, or stroke) was assessed at an interim analysis to exclude a noninferiority boundary of 1.4. If noninferiority was met, the primary cardiovascular efficacy outcome (a composite of major cardiovascular events, heart failure, hospitalization for unstable angina, or coronary revascularization [extended major cardiovascular events]) was assessed for superiority at the end of the trial.
Results
At 1 year, weight loss of at least 5% had occurred in 1986 of 5135 patients (38.7%) in the lorcaserin group and in 883 of 5083 (17.4%) in the placebo group (odds ratio, 3.01; 95% confidence interval [CI], 2.74 to 3.30; P<0.001). Patients in the lorcaserin group had slightly better values with respect to cardiac risk factors (including blood pressure, heart rate, glycemic control, and lipids) than those in the placebo group. During a median follow-up of 3.3 years, the rate of the primary safety outcome was 2.0% per year in the lorcaserin group and 2.1% per year in the placebo group (hazard ratio, 0.99; 95% CI, 0.85 to 1.14; P<0.001 for noninferiority); the rate of extended major cardiovascular events was 4.1% per year and 4.2% per year, respectively (hazard ratio, 0.97; 95% CI, 0.87 to 1.07; P=0.55). Adverse events of special interest were uncommon, and the rates were generally similar in the two groups, except for a higher number of patients with serious hypoglycemia in the lorcaserin group (13 vs. 4, P=0.04).
Conclusions
In a high-risk population of overweight or obese patients, lorcaserin facilitated sustained weight loss without a higher rate of major cardiovascular events than that with placebo. (Funded by Eisai; CAMELLIA–TIMI 61 ClinicalTrials.gov number, NCT02019264.)
Background
Patients with diabetes are at higher risk for death and cardiovascular outcomes than the general population. We investigated whether the excess risk of death and cardiovascular events among patients with type 2 diabetes could be reduced or eliminated.
Methods
In a cohort study, we included 271,174 patients with type 2 diabetes who were registered in the Swedish National Diabetes Register and matched them with 1,355,870 controls on the basis of age, sex, and county. We assessed patients with diabetes according to age categories and according to the presence of five risk factors (elevated glycated hemoglobin level, elevated low-density lipoprotein cholesterol level, albuminuria, smoking, and elevated blood pressure). Cox regression was used to study the excess risk of outcomes (death, acute myocardial infarction, stroke, and hospitalization for heart failure) associated with smoking and the number of variables outside target ranges. We also examined the relationship between various risk factors and cardiovascular outcomes.
Results
The median follow-up among all the study participants was 5.7 years, during which 175,345 deaths occurred. Among patients with type 2 diabetes, the excess risk of outcomes decreased stepwise for each risk-factor variable within the target range. Among patients with diabetes who had all five variables within target ranges, the hazard ratio for death from any cause, as compared with controls, was 1.06 (95% confidence interval [CI], 1.00 to 1.12), the hazard ratio for acute myocardial infarction was 0.84 (95% CI, 0.75 to 0.93), and the hazard ratio for stroke was 0.95 (95% CI, 0.84 to 1.07). The risk of hospitalization for heart failure was consistently higher among patients with diabetes than among controls (hazard ratio, 1.45; 95% CI, 1.34 to 1.57). In patients with type 2 diabetes, a glycated hemoglobin level outside the target range was the strongest predictor of stroke and acute myocardial infarction; smoking was the strongest predictor of death.
Conclusions
Patients with type 2 diabetes who had five risk-factor variables within the target ranges appeared to have little or no excess risk of death, myocardial infarction, or stroke, as compared with the general population. (Funded by the Swedish Association of Local Authorities and Regions and others.)
Background:
Poor fitness in middle age is a risk factor for heart failure, particularly heart failure with a preserved ejection fraction. The development of heart failure with a preserved ejection fraction is likely mediated through increased left ventricular (LV) stiffness, a consequence of sedentary aging. In a prospective, parallel group, randomized controlled trial, we examined the effect of 2 years of supervised high-intensity exercise training on LV stiffness.
Methods:
Sixty-one (48% male) healthy, sedentary, middle-aged participants (53±5 years) were randomly assigned to either 2 years of exercise training (n=34) or attention control (control; n=27). Right heart catheterization and 3-dimensional echocardiography were performed with preload manipulations to define LV end-diastolic pressure-volume relationships and Frank-Starling curves. LV stiffness was calculated by curve fit of the diastolic pressure-volume curve. Maximal oxygen uptake (Vo2max) was measured to quantify changes in fitness.
Results:
Fifty-three participants completed the study. Adherence to prescribed exercise sessions was 88±11%. Vo2max increased by 18% (exercise training: pre 29.0±4.8 to post 34.4±6.4; control: pre 29.5±5.3 to post 28.7±5.4, group×time P<0.001) and LV stiffness was reduced (right/downward shift in the end-diastolic pressure-volume relationships; preexercise training stiffness constant 0.072±0.037 to postexercise training 0.051±0.0268, P=0.0018), whereas there was no change in controls (group×time P<0.001; pre stiffness constant 0.0635±0.026 to post 0.062±0.031, P=0.83). Exercise increased LV end-diastolic volume (group×time P<0.001), whereas pulmonary capillary wedge pressure was unchanged, providing greater stroke volume for any given filling pressure (loading×group×time P=0.007).
Conclusions:
In previously sedentary healthy middle-aged adults, 2 years of exercise training improved maximal oxygen uptake and decreased cardiac stiffness. Regular exercise training may provide protection against the future risk of heart failure with a preserved ejection fraction by preventing the increase in cardiac stiffness attributable to sedentary aging.
Clinical trial registration:
URL: https://www.clinicaltrials.gov. Unique identifier: NCT02039154.
Background:
Associations of obesity with incidence of heart failure have been observed, but the causality is uncertain. We hypothesized that gastric bypass surgery leads to a lower incidence of heart failure compared with intensive lifestyle modification in obese people.
Methods:
We included obese people without previous heart failure from a Swedish nationwide registry of people treated with a structured intensive lifestyle program and the Scandinavian Obesity Surgery Registry. All analyses used inverse probability weights based on baseline body mass index and a propensity score estimated from baseline variables. Treatment groups were well balanced in terms of weight, body mass index, and most potential confounders. Associations of treatment with heart failure incidence, as defined in the National Patient Register, were analyzed with Cox regression.
Results:
The 25 804 gastric bypass surgery patients had on average lost 18.8 kg more weight after 1 year and 22.6 kg more after 2 years than the 13 701 lifestyle modification patients. During a median of 4.1 years, surgery patients had lower heart failure incidence than lifestyle modification patients (hazard ratio, 0.54; 95% confidence interval, 0.36-0.82). A 10-kg achieved weight loss after 1 year was related to a hazard ratio for heart failure of 0.77 (95% confidence interval, 0.60-0.97) in both treatment groups combined. Results were robust in sensitivity analyses.
Conclusions:
Gastric bypass surgery was associated with approximately one half the incidence of heart failure compared with intensive lifestyle modification in this study of 2 large nationwide registries. We also observed a graded association between increasing weight loss and decreasing risk of heart failure.
Aims To investigate the association between cardiorespiratory fitness (CRF) and muscle strength in late adolescence and the long-term risk of heart failure (HF). Methods A cohort was created of Swedish men enrolled in compulsory military service between 1968 and 2005 with measurements for CRF and muscle strength ( n = 1,226,623; mean age 18.3 years). They were followed until 31 December 2014 for HF hospitalization as recorded in the Swedish national inpatient registry. Results During the follow-up period (median (interquartile range) 28.4 (22.0-37.0) years), 7656 cases of first HF hospitalization were observed (mean ± SD age at diagnosis 50.1 ± 7.9 years). CRF and muscle strength were estimated by maximum capacity cycle ergometer testing and strength exercises (knee extension, elbow flexion and hand grip). Inverse dose-response relationships were found between CRF and muscle strength with HF as a primary or contributory diagnosis with an adjusted hazards ratio (95% confidence interval) of 1.60 (1.44-1.77) for low CRF and 1.45 (1.32-1.58) for low muscle strength categories. The associations of incident HF with CRF and muscle strength persisted, regardless of adjustments for the other potential confounders. The highest risk was observed for HF associated with coronary heart disease, diabetes or hypertension. Conclusions In this longitudinal study of young men, we found inverse and mutually independent associations between CRF and muscle strength with risk of hospitalization for HF. If causal, these results may emphasize the importance of the promotion of CRF and muscle strength in younger populations.
Background
Findings from the Look AHEAD trial showed no significant reductions in the primary outcome of cardiovascular disease incidence in adults with type 2 diabetes randomly assigned to an intensive lifestyle intervention for weight loss compared with those randomly assigned to diabetes support and education (control). We examined whether the incidence of cardiovascular disease in Look AHEAD varied by changes in weight or fitness.
Methods
Look AHEAD was a randomised clinical trial done at 16 clinical sites in the USA, recruiting patients from Aug 22, 2001, to April 30, 2004. In the trial, 5145 overweight or obese adults aged 45–76 years with type 2 diabetes were assigned (1:1) to an intensive lifestyle intervention or diabetes support and education. In this observational, post-hoc analysis, we examined the association of magnitude of weight loss and fitness change over the first year with incidence of cardiovascular disease. The primary outcome of the trial and of this analysis was a composite of death from cardiovascular causes, non-fatal acute myocardial infarction, non-fatal stroke, or admission to hospital for angina. The secondary outcome included the same indices plus coronary artery bypass grafting, carotid endartectomy, percutaneous coronary intervention, hospitalisation for congestive heart failure, peripheral vascular disease, or total mortality. We adjusted analyses for baseline differences in weight or fitness, demographic characteristics, and risk factors for cardiovascular disease. The Look AHEAD trial is registered with ClinicalTrials.gov, number NCT00017953.
Findings
For the analyses related to weight change, we excluded 311 ineligible participants, leaving a population of 4834; for the analyses related to fitness change, we excluded 739 participants, leaving a population of 4406. In analyses of the full cohort (ie, combining both study groups), over a median 10·2 years of follow-up (IQR 9·5–10·7), individuals who lost at least 10% of their bodyweight in the first year of the study had a 21% lower risk of the primary outcome (adjusted hazard ratio [HR] 0·79, 95% CI 0·64–0·98; p=0·034) and a 24% reduced risk of the secondary outcome (adjusted HR 0·76, 95% CI 0·63–0·91; p=0·003) compared with individuals with stable weight or weight gain. Achieving an increase of at least 2 metabolic equivalents in fitness change was associated with a significant reduction in the secondary outcome (adjusted HR 0·77, 95% CI 0·61–0·96; p=0·023) but not the primary outcome (adjusted HR 0·78, 0·60–1·03; p=0·079). In analyses treating the control group as the reference group, participants in the intensive lifestyle intervention group who lost at least 10% of their bodyweight had a 20% lower risk of the primary outcome (adjusted HR 0·80, 95% CI 0·65–0·99; p=0·039), and a 21% lower risk of the secondary outcome (adjusted HR 0·79, 95% CI 0·66–0·95; p=0·011); however, change in fitness was not significantly associated with a change in the primary outcome.
Interpretation
The results of this post-hoc analysis of Look AHEAD suggest an association between the magnitude of weight loss and incidence of cardiovascular disease in people with type 2 diabetes. These findings suggest a need to continue to refine approaches to identify individuals who are most likely to benefit from lifestyle interventions and to develop strategies to improve the magnitude of sustained weight loss with lifestyle interventions.
Funding
US National Institute of Diabetes and Digestive and Kidney Diseases.
Importance
Whether sustained physical activity prevents cardiovascular disease (CVD) events in older adults is uncertain.
Objective
To test the hypothesis that cardiovascular morbidity and mortality would be reduced in participants in a long-term physical activity program.
Design, Setting, and Participants
The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, randomized trial. Participants were recruited at 8 centers in the United States. We randomized 1635 sedentary men and women aged 70 to 89 years with a Short Physical Performance Battery (SPPB) score of 9 or less but able to walk 400 m.
Interventions
The physcial activity (PA) intervention was a structured moderate-intensity program, predominantly walking 2 times per week on site for 2.6 years on average. The successful aging intervention consisted of weekly health education sessions for 6 months, then monthly.
Main Outcomes and Measures
Total CVD events, including fatal and nonfatal myocardial infarction, angina, stroke, transient ischemic attack, and peripheral artery disease, were adjudicated by committee, and silent myocardial infarction was assessed by serial electrocardiograms. A limited outcome of myocardial infarction, stroke, and CVD death was also studied. Outcome assessors and adjudicators were blinded to intervention assignment.
Results
The 1635 LIFE study participants were predominantly women (67%), with a mean (SD) age of 78.7 (5.2) years; 20% were African-American, 6% were Hispanic or other race or ethnic group, and 74% were non-Latino white. New CVD events occurred in 121 of 818 PA participants (14.8%) and 113 of 817 successful aging participants (13.8%) (HR, 1.10; 95% CI, 0.85-1.42). For the more focused combined outcome of myocardial infarction, stroke, or cardiovascular death, rates were 4.6% in PA and 4.5% in the successful aging group (HR, 1.05; 95% CI, 0.67-1.66). Among frailer participants with an SPPB score less than 8, total CVD rates were 14.2% in PA vs 17.7% in successful aging (HR, 0.76; 95% CI, 0.52-1.10), compared with 15.3% vs 10.5% among those with an SPPB score of 8 or 9 (HR, 1.59; 95% CI, 1.09-2.30) (P for interaction = .006). With the limited end point, the interaction was not significant (P = .59), with an HR of 0.94 (95% CI, 0.50-1.75) for an SPPB score less than 8 and an HR of 1.20 (95% CI, 0.62-2.34) for an SBBP score of 8 or 9.
Conclusions and Relevance
Among participants in the LIFE Study, an aerobically based, moderately intensive PA program was not associated with reduced cardiovascular events in spite of the intervention’s previously documented ability to prevent mobility disability.
Trial Registration
clinicaltrials.gov Identifier: NCT00116194.
Importance
In older adults reduced mobility is common and is an independent risk factor for morbidity, hospitalization, disability, and mortality. Limited evidence suggests that physical activity may help prevent mobility disability; however, there are no definitive clinical trials examining whether physical activity prevents or delays mobility disability.Objective
To test the hypothesis that a long-term structured physical activity program is more effective than a health education program (also referred to as a successful aging program) in reducing the risk of major mobility disability.Design, Setting, and Participants
The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, randomized trial that enrolled participants between February 2010 and December 2011, who participated for an average of 2.6 years. Follow-up ended in December 2013. Outcome assessors were blinded to the intervention assignment. Participants were recruited from urban, suburban, and rural communities at 8 centers throughout the United States. We randomized a volunteer sample of 1635 sedentary men and women aged 70 to 89 years who had physical limitations, defined as a score on the Short Physical Performance Battery of 9 or below, but were able to walk 400 m.Interventions
Participants were randomized to a structured, moderate-intensity physical activity program (n = 818) conducted in a center (twice/wk) and at home (3-4 times/wk) that included aerobic, resistance, and flexibility training activities or to a health education program (n = 817) consisting of workshops on topics relevant to older adults and upper extremity stretching exercises.Main Outcomes and Measures
The primary outcome was major mobility disability objectively defined by loss of ability to walk 400 m.Results
Incident major mobility disability occurred in 30.1% (246 participants) of the physical activity group and 35.5% (290 participants) of the health education group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98], P = .03).Persistent mobility disability was experienced by 120 participants (14.7%) in the physical activity group and 162 participants (19.8%) in the health education group (HR, 0.72 [95% CI, 0.57-0.91]; P = .006). Serious adverse events were reported by 404 participants (49.4%) in the physical activity group and 373 participants (45.7%) in the health education group (risk ratio, 1.08 [95% CI, 0.98-1.20]).Conclusions and Relevance
A structured, moderate-intensity physical activity program compared with a health education program reduced major mobility disability over 2.6 years among older adults at risk for disability. These findings suggest mobility benefit from such a program in vulnerable older adults.Trial Registration
clinicaltrials.gov Identifier: NCT01072500
The contemporary associations of type 2 diabetes with a wide range of incident cardiovascular diseases have not been compared. We aimed to study associations between type 2 diabetes and 12 initial manifestations of cardiovascular disease.
We used linked primary care, hospital admission, disease registry, and death certificate records from the CALIBER programme, which links data for people in England recorded in four electronic health data sources. We included people who were (or turned) 30 years or older between Jan 1, 1998, to March 25, 2010, who were free from cardiovascular disease at baseline. The primary endpoint was the first record of one of 12 cardiovascular presentations in any of the data sources. We compared cumulative incidence curves for the initial presentation of cardiovascular disease and used Cox models to estimate cause-specific hazard ratios (HRs). This study is registered at ClinicalTrials.gov (NCT01804439).
Our cohort consisted of 1 921 260 individuals, of whom 1 887 062 (98·2%) did not have diabetes and 34 198 (1·8%) had type 2 diabetes. We observed 113 638 first presentations of cardiovascular disease during a median follow-up of 5·5 years (IQR 2·1-10·1). Of people with type 2 diabetes, 6137 (17·9%) had a first cardiovascular presentation, the most common of which were peripheral arterial disease (reported in 992 [16·2%] of 6137 patients) and heart failure (866 [14·1%] of 6137 patients). Type 2 diabetes was positively associated with peripheral arterial disease (adjusted HR 2·98 [95% CI 2·76-3·22]), ischaemic stroke (1·72 [1·52-1·95]), stable angina (1·62 [1·49-1·77]), heart failure (1·56 [1·45-1·69]), and non-fatal myocardial infarction (1·54 [1·42-1·67]), but was inversely associated with abdominal aortic aneurysm (0·46 [0·35-0·59]) and subarachnoid haemorrhage (0·48 [0·26-0.89]), and not associated with arrhythmia or sudden cardiac death (0·95 [0·76-1·19]).
Heart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. The differences between relative risks of different cardiovascular diseases in patients with type 2 diabetes have implications for clinical risk assessment and trial design.
Wellcome Trust, National Institute for Health Research, and Medical Research Council.
Copyright © 2014 Shah et al. Open Access article distributed under the terms of CC BY. Published by .. All rights reserved.
Background:
Weight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether an intensive lifestyle intervention for weight loss would decrease cardiovascular morbidity and mortality among such patients.
Methods:
In 16 study centers in the United States, we randomly assigned 5145 overweight or obese patients with type 2 diabetes to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive diabetes support and education (control group). The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years.
Results:
The trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83 and 1.92 events per 100 person-years, respectively; hazard ratio in the intervention group, 0.95; 95% confidence interval, 0.83 to 1.09; P=0.51).
Conclusions:
An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes. (Funded by the National Institutes of Health and others; Look AHEAD ClinicalTrials.gov number, NCT00017953.).
AimsReduced physical activity is associated with increased risk of heart failure (HF) in middle-aged individuals. We hypothesized that physical inactivity is also associated with greater HF risk in older individuals, and examined if the association was consistent for HF with preserved ejection fraction (HFPEF) vs. HF with a reduced ejection fraction (HFREF).Methods and resultsWe evaluated 1142 elderly participants (mean age 76 years) from the Framingham Study without prior myocardial infarction and who attended a routine examination when daily physical activity was assessed systematically with a questionnaire. A composite score, the physical activity index (PAI), was calculated and modelled as tertiles, and related to incidence of HF, HFPEF, and HFREF on follow-up using proportional hazards regression models adjusting for age and sex, and then additionally for standard HF risk factors. Participants with HF and EF <45% vs. ≥45% were categorized as HFREF and HFPEF, respectively. On follow-up (mean 10 years), 250 participants developed HF (108 with HFPEF, 106 with HFREF, 36 with unavailable EF). In age- and sex-adjusted models, the middle and highest PAI tertiles were associated with a 15-56% lower risk of any HF, of HFREF, and of HFPEF, with a graded response across tertiles. In multivariable models, the association of higher PAI with lower risk of any HF and with HFPEF was maintained, whereas the association with HFREF was attenuated.Conclusions
Our study of an older community-based sample extends to the elderly and to HFPEF previous findings of a protective effect of physical activity on HF risk.
The primary aims of this paper were (1) to evaluate the influence of intensive lifestyle weight loss and exercise intervention (ILI) compared with diabetes support and education (DSE) upon Heart Rate Recovery (HRR) from graded exercise testing (GXT) and (2) to determine the independent and combined effects of weight loss and fitness changes upon HRR. In 4503 participants (45-76 years) who completed 1 year of intervention, HRR was measured after a submaximal GXT to compare the influence of (ILI) with (DSE) upon HRR. Participants assigned to ILI lost an average 8.6% of their initial weight versus 0.7% in DSE group (P < 0.001) while mean fitness increased in ILI by 20.9% versus 5.8% in DSE (P < 0.001). At Year 1, all exercise and HRR variables in ILI improved (P < 0.0001) versus DSE: heart rate (HR) at rest was lower (72.8 ± 11.4 versus 77.7 ± 11.7 b/min), HR range was greater (57.7 ± 12.1 versus 53.1 ± 12.4 b/min), HR at 2 minutes was lower (89.3 ± 21.8 versus 93.0 ± 12.1 b/min), and HRR was greater (41.25 ± 22.0 versus 37.8 ± 12.5 b/min). Weight loss and fitness gain produced significant separate and independent improvements in HRR.
Type 2 diabetes in normal-weight adults (body mass index [BMI] <25) is a representation of the metabolically obese normal-weight phenotype with unknown mortality consequences.
To test the association of weight status with mortality in adults with new-onset diabetes in order to minimize the influence of diabetes duration and voluntary weight loss on mortality.
Pooled analysis of 5 longitudinal cohort studies: Atherosclerosis Risk in Communities study, 1990-2006; Cardiovascular Health Study, 1992-2008; Coronary Artery Risk Development in Young Adults, 1987-2011; Framingham Offspring Study, 1979-2007; and Multi-Ethnic Study of Atherosclerosis, 2002-2011. A total of 2625 participants with incident diabetes contributed 27,125 person-years of follow-up. Included were men and women (age >40 years) who developed incident diabetes based on fasting glucose 126 mg/dL or greater or newly initiated diabetes medication and who had concurrent measurements of BMI. Participants were classified as normal weight if their BMI was 18.5 to 24.99 or overweight/obese if BMI was 25 or greater.
Total, cardiovascular, and noncardiovascular mortality.
The proportion of adults who were normal weight at the time of incident diabetes ranged from 9% to 21% (overall 12%). During follow-up, 449 participants died: 178 from cardiovascular causes and 253 from noncardiovascular causes (18 were not classified). The rates of total, cardiovascular, and noncardiovascular mortality were higher in normal-weight participants (284.8, 99.8, and 198.1 per 10,000 person-years, respectively) than in overweight/obese participants (152.1, 67.8, and 87.9 per 10,000 person-years, respectively). After adjustment for demographic characteristics and blood pressure, lipid levels, waist circumference, and smoking status, hazard ratios comparing normal-weight participants with overweight/obese participants for total, cardiovascular, and noncardiovascular mortality were 2.08 (95% CI, 1.52-2.85), 1.52 (95% CI, 0.89-2.58), and 2.32 (95% CI, 1.55-3.48), respectively.
Adults who were normal weight at the time of incident diabetes had higher mortality than adults who are overweight or obese.
To assess the association between BMI, fitness, and mortality in African American and Caucasian men with type 2 diabetes and to explore racial differences in this association.
We used prospective observational data from Veterans Affairs Medical Centers in Washington, DC, and Palo Alto, California. Our cohort (N = 4,156; mean age 60 ± 10.3 years) consisted of 2,013 African Americans (mean age, 59.5 ± 9.9 years), 2,000 Caucasians (mean age, 60.8 ± 10.5 years), and 143 of unknown race/ethnicity. BMI, cardiac risk factors, medications, and peak exercise capacity in metabolic equivalents (METs) were assessed during 1986 and 2010. All-cause mortality was assessed across BMI and fitness categories.
There were 1,074 deaths during a median follow-up period of 7.5 years. A paradoxic BMI-mortality association was observed, with significantly higher risk among those with a BMI between 18.5 and 24.9 kg/m(2) (hazard ratio [HR] 1.70 [95% CI 1.36-2.1]) compared with the obese category (BMI ≥ 35 kg/m(2)). This association was accentuated in African Americans (HR 1.95 [95% CI 1.44-2.63]) versus Caucasians (HR 1.53 [1.0-2.1]). The fitness-mortality risk association for the entire cohort and within BMI categories was inverse, independent, and graded. Mortality risks were 12% lower for each 1-MET increase in exercise capacity, and ~35-55% lower for those with an exercise capacity >5 METs compared with the least fit (≤ 5 METs). CONCLUSIONS A paradoxic BMI-mortality risk association was observed in African American and Caucasian patients with diabetes. The exercise capacity-mortality risk association was inverse, independent, and graded in all BMI categories but was more potent in those with a BMI ≥ 25 kg/m(2).
To examine the effect of an intensive lifestyle weight loss intervention (ILI) compared to diabetes support and education (DSE) on changes in fitness and physical activity in the Look AHEAD trial.
Randomized clinical trial to compare a lifestyle intervention for weight loss with a DSE condition in individuals with type 2 diabetes.
Data from 4376 overweight or obese adults with type 2 diabetes (age=58.7+/-6.8 years, body mass index (BMI)=35.8+/-5.8 kg/m(2)) who completed 1 year of the Look AHEAD trial and had available fitness data were analyzed.
Subjects were randomly assigned to DSE or ILI. DSE received standard care plus three education sessions over the 1-year period. ILI included individual and group contact throughout the year, restriction in energy intake and 175 min per week of prescribed physical activity.
Fitness was assessed using a submaximal graded exercise test. Physical activity was assessed by questionnaire in a subset of 2221 subjects.
Change in fitness was statistically greater in ILI vs DSE after adjustment for baseline fitness (20.9 vs 5.7%; P<0.0001). Multivariate analysis showed that change in fitness was greater in overweight vs obese Class II and III (P<0.05). Physical activity increased by 892+/-1694 kcal per week in ILI vs 108+/-1254 kcal per week in DSE (P<0.01). Changes in fitness (r=0.41) and physical activity (r=0.42) were significantly correlated with weight loss (P<0.0001).
The ILI was effective in increasing physical activity and improving cardiorespiratory fitness in overweight and obese individuals with type 2 diabetes. This effect may add to weight loss in improving metabolic control in patients in lifestyle intervention programs.
Extreme obesity is recognized to be a risk factor for heart failure. It is unclear whether overweight and lesser degrees of obesity also pose a risk.
We investigated the relation between the body-mass index (the weight in kilograms divided by the square of the height in meters) and the incidence of heart failure among 5881 participants in the Framingham Heart Study (mean age, 55 years; 54 percent women). With the use of Cox proportional-hazards models, the body-mass index was evaluated both as a continuous variable and as a categorical variable (normal, 18.5 to 24.9; overweight, 25.0 to 29.9; and obese, 30.0 or more).
During follow-up (mean, 14 years), heart failure developed in 496 subjects (258 women and 238 men). After adjustment for established risk factors, there was an increase in the risk of heart failure of 5 percent for men and 7 percent for women for each increment of 1 in body-mass index. As compared with subjects with a normal body-mass index, obese subjects had a doubling of the risk of heart failure. For women, the hazard ratio was 2.12 (95 percent confidence interval, 1.51 to 2.97); for men, the hazard ratio was 1.90 (95 percent confidence interval, 1.30 to 2.79). A graded increase in the risk of heart failure was observed across categories of body-mass index. The hazard ratios per increase in category were 1.46 in women (95 percent confidence interval, 1.23 to 1.72) and 1.37 in men (95 percent confidence interval, 1.13 to 1.67).
In our large, community-based sample, increased body-mass index was associated with an increased risk of heart failure. Given the high prevalence of obesity in the United States, strategies to promote optimal body weight may reduce the population burden of heart failure.
Patients with signs and symptoms of heart failure and a normal left ventricular ejection fraction are said to have diastolic heart failure. It has traditionally been thought that the pathophysiological cause of heart failure in these patients is an abnormality in the diastolic properties of the left ventricle; however, this hypothesis remains largely unproven.
We prospectively identified 47 patients who met the diagnostic criteria for definite diastolic heart failure; all the patients had signs and symptoms of heart failure, a normal ejection fraction, and an increased left ventricular end-diastolic pressure. Ten patients who had no evidence of cardiovascular disease served as controls. Left ventricular diastolic function was assessed by means of cardiac catheterization and echocardiography.
The patients with diastolic heart failure had abnormal left ventricular relaxation and increased left ventricular chamber stiffness. The mean (+/-SD) time constant for the isovolumic-pressure decline (tau) was longer in the group with diastolic heart failure than in the control group (59+/-14 msec vs. 35+/-10 msec, P=0.01). The diastolic pressure-volume relation was shifted up and to the left in the patients with diastolic heart failure as compared with the controls. The corrected left ventricular passive-stiffness constant was significantly higher in the group with diastolic heart failure than in the control group (0.03+/-0.01 vs. 0.01+/-0.01, P<0.001).
Patients with heart failure and a normal ejection fraction have significant abnormalities in active relaxation and passive stiffness. In these patients, the pathophysiological cause of elevated diastolic pressures and heart failure is abnormal diastolic function.
We examined associations of cardiovascular, metabolic, and body composition measures with exercise capacity using baseline data from 5,145 overweight and/or obese (BMI > or = 25.0 kg/m2) men and women with type 2 diabetes who were randomized participants for the Look AHEAD (Action for Health in Diabetes) clinical trial.
Peak exercise capacity expressed as METs and estimated from treadmill speed and grade was measured during a graded exercise test designed to elicit a maximal effort. Other measures included waist circumference, BMI, type 2 diabetes duration, types of medication used, A1C, history of cardiovascular disease, metabolic syndrome, beta-blocker use, and race/ethnicity.
Peak exercise capacity was higher for men (8.0 +/- 2.1 METs) than for women (6.7 +/- 1.7 METs) (P < 0.001). Exercise capacity also decreased across each decade of age (P < 0.001) and with increasing BMI and waist circumference levels in both sexes. Older age, increased waist circumference and BMI, a longer duration of diabetes, increased A1C, a history of cardiovascular disease, having metabolic syndrome, beta-blocker use, and being African American compared with being Caucasian were associated with a lower peak exercise capacity for both sexes. Hypertension and use of diabetes medications were associated with lower peak exercise capacity in women.
Individuals with diabetes who are overweight or obese have impaired exercise capacity, which is primarily related to age, female sex, and race, as well as poor metabolic control, BMI, and central obesity.
Diabetes causes cardiomyopathy and increases the risk of heart failure independent of hypertension and coronary heart disease. This condition called "Diabetic Cardiomyopathy" (DCM) is becoming a well- known clinical entity. Recently, there has been substantial research exploring its molecular mechanisms, structural and functional changes, and possible development of therapeutic approaches for the prevention and treatment of DCM. This review summarizes the recent advancements to better understand fundamental molecular abnormalities that promote this cardiomyopathy and novel therapies for future research. Additionally, different diagnostic modalities, up to date screening tests to guide clinicians with early diagnosis and available current treatment options has been outlined.
Objective
To investigate the associations of objectively measured cardiorespiratory fitness (CRF) and grip strength (GS) with incident heart failure (HF), a clinical syndrome that results in substantial social and economic burden, using UK Biobank data.
Patients and Methods
Of the 502,628 participants recruited into the UK Biobank between April 1, 2007, and December 31, 2010, a total of 374,493 were included in our GS analysis and 57,053 were included in CRF analysis. Associations between CRF and GS and incident HF were investigated using Cox proportional hazard models, with adjustment for known measured confounders.
Results
During a mean of 4.1 (range, 2.4-7.1) years, 631 HF events occurred in those with GS data, and 66 HF events occurred in those with CRF data. Higher CRF was associated with 18% lower risk for HF (hazard ratio [HR], 0.82; 95% CI, 0.76-0.88) per 1–metabolic equivalent increment increase and GS was associated with 19% lower incidence of HF risk (HR, 0.81; 95% CI, 0.77-0.86) per 5-kg increment increase. When CRF and GS were standardized, the HR for CRF was 0.50 per 1-SD increment (95% CI, 0.38-0.65), and for GS was 0.65 per 1-SD increment (95% CI, 0.58-0.72).
Conclusion
Our data indicate that objective measurements of physical function (GS and CRF) are strongly and independently associated with lower HF incidence. Future studies targeting improving CRF and muscle strength should include HF as an outcome to assess whether these results are causal.
Objective:
To investigate the associations of objectively measured cardiorespiratory fitness (CRF) and grip strength (GS) with incident heart failure (HF), a clinical syndrome that results in substantial social and economic burden, using UK Biobank data.
Patients and methods:
Of the 502,628 participants recruited into the UK Biobank between April 1, 2007, and December 31, 2010, a total of 374,493 were included in our GS analysis and 57,053 were included in CRF analysis. Associations between CRF and GS and incident HF were investigated using Cox proportional hazard models, with adjustment for known measured confounders.
Results:
During a mean of 4.1 (range, 2.4-7.1) years, 631 HF events occurred in those with GS data, and 66 HF events occurred in those with CRF data. Higher CRF was associated with 18% lower risk for HF (hazard ratio [HR], 0.82; 95% CI, 0.76-0.88) per 1-metabolic equivalent increment increase and GS was associated with 19% lower incidence of HF risk (HR, 0.81; 95% CI, 0.77-0.86) per 5-kg increment increase. When CRF and GS were standardized, the HR for CRF was 0.50 per 1-SD increment (95% CI, 0.38-0.65), and for GS was 0.65 per 1-SD increment (95% CI, 0.58-0.72).
Conclusion:
Our data indicate that objective measurements of physical function (GS and CRF) are strongly and independently associated with lower HF incidence. Future studies targeting improving CRF and muscle strength should include HF as an outcome to assess whether these results are causal.
Importance
Although metabolic surgery (defined as procedures that influence metabolism by inducing weight loss and altering gastrointestinal physiology) significantly improves cardiometabolic risk factors, the effect on cardiovascular outcomes has been less well characterized.
Objective
To investigate the relationship between metabolic surgery and incident major adverse cardiovascular events (MACE) in patients with type 2 diabetes and obesity.
Design, Setting, and Participants
Of 287 438 adult patients with diabetes in the Cleveland Clinic Health System in the United States between 1998 and 2017, 2287 patients underwent metabolic surgery. In this retrospective cohort study, these patients were matched 1:5 to nonsurgical patients with diabetes and obesity (body mass index [BMI] ≥30), resulting in 11 435 control patients, with follow-up through December 2018.
Exposures
Metabolic gastrointestinal surgical procedures vs usual care for type 2 diabetes and obesity.
Main Outcomes and Measures
The primary outcome was the incidence of extended MACE (composite of 6 outcomes), defined as first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation. Secondary end points included 3-component MACE (myocardial infarction, ischemic stroke, and mortality) and the 6 individual components of the primary end point.
Results
Among the 13 722 study participants, the distribution of baseline covariates was balanced between the surgical group and the nonsurgical group, including female sex (65.5% vs 64.2%), median age (52.5 vs 54.8 years), BMI (45.1 vs 42.6), and glycated hemoglobin level (7.1% vs 7.1%). The overall median follow-up duration was 3.9 years (interquartile range, 1.9-6.1 years). At the end of the study period, 385 patients in the surgical group and 3243 patients in the nonsurgical group experienced a primary end point (cumulative incidence at 8-years, 30.8% [95% CI, 27.6%-34.0%] in the surgical group and 47.7% [95% CI, 46.1%-49.2%] in the nonsurgical group [P < .001]; absolute 8-year risk difference [ARD], 16.9% [95% CI, 13.1%-20.4%]; adjusted hazard ratio [HR], 0.61 [95% CI, 0.55-0.69]). All 7 prespecified secondary outcomes showed statistically significant differences in favor of metabolic surgery, including mortality. All-cause mortality occurred in 112 patients in the metabolic surgery group and 1111 patients in the nonsurgical group (cumulative incidence at 8 years, 10.0% [95% CI, 7.8%-12.2%] and 17.8% [95% CI, 16.6%-19.0%]; ARD, 7.8% [95% CI, 5.1%-10.2%]; adjusted HR, 0.59 [95% CI, 0.48-0.72]).
Conclusions and Relevance
Among patients with type 2 diabetes and obesity, metabolic surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident MACE. The findings from this observational study must be confirmed in randomized clinical trials.
Trial Registration
ClinicalTrials.gov Identifier: NCT03955952
The prevalence of Type 2 diabetes mellitus (T2DM) has reached pandemic proportions. T2DM frequently causes macrovascular and/or microvascular pathologic changes and thereby increases the risks for the development of myocardial infarction, heart failure, stroke, renal failure, and reduced survival. This article describes the important interactions between T2DM, heart failure, and renal dysfunction, forming vicious circles. The interruption of these circles represents important therapeutic goals.
Objective:
Lifestyle intervention remains the cornerstone of management of type 2 diabetes mellitus (T2DM). However, adherence to physical activity (PA) recommendations and the impact of that adherence on cardiorespiratory fitness in this population have been poorly described. We sought to investigate adherence to PA recommendations and its association with cardiorespiratory fitness in a population of patients with T2DM.
Research design and methods:
A cross-sectional analysis of baseline data from a randomized clinical trial (NCT00424762) was performed. A total of 150 individuals with medically treated T2DM and atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD were recruited from outpatient clinics at a single academic medical center. All individuals underwent a graded maximal exercise treadmill test to exhaustion with breath-by-breath gas exchange analysis to determine VO2peak. PA was estimated using a structured 7-Day Physical Activity Recall interview.
Results:
Participants had a mean ± SD age of 54.9 ± 9.0 years; 41% were women, 40% were black, and 21% were Hispanic. The mean HbA1c was 7.7 ± 1.8% and the mean BMI, 34.5 ± 7.2 kg/m2. A total of 72% had hypertension, 73% had hyperlipidemia, and 35% had prevalent ASCVD. The mean ± SD reported daily PA was 34.3 ± 4 kcal/kg, only 7% above a sedentary state; 47% of the cohort failed to achieve the minimum recommended PA. Mean ± SD VO2peak was 27.4 ± 6.5 mL/kg fat-free mass/min (18.8 ± 5.0 mL/kg/min).
Conclusions:
On average, patients with T2DM who have or are at risk for ASCVD report low levels of PA and have low measured cardiopulmonary fitness. This underscores the importance of continued efforts to close this therapeutic gap.
Aims
Obesity is associated with increased risk of heart failure (HF). This risk may be modulated by improved cardiorespiratory fitness (CRF) as CRF is associated with favourable health outcomes. Thus, we assessed the interaction between body mass index (BMI), CRF and HF.
Methods and results
Cardiorespiratory fitness and BMI were assessed in 20 254 US male veterans (mean age 58.0 ± 11.3 years), who completed a maximal exercise treadmill test between 1987 and 2017. All had no evidence of ischaemia or HF prior to the exercise test. They were classified based on age‐stratified quartiles of peak metabolic equivalents (METs) achieved as: least‐fit (4.5 ± 1.3), low‐fit (6.7 ± 1.3), moderate‐fit (8.1 ± 1.1), and high‐fit (11.2 ± 2.4); and according to BMI as normal weight (18.5–24.9 kg/m²), overweight (25–29.9 kg/m²), and obese (≥ 30.0 kg/m²). During a median follow‐up of 13.4 years, there were 2979 HF events (10.8 events/1000 person‐years). HF risk was significantly higher in the obese category [hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.10–1.36; P < 0.001], but was no longer significant after further adjustment for METs. When compared to the least‐fit, HF risk declined progressively with increased CRF within all BMI categories. The risk was 63% (HR 0.37, 95% CI 0.30–0.47; P < 0.001), 66% (HR 0.37, 95% CI 0.28–0.40; P < 0.001), and 73% (HR 0.27, 95% CI 0.22–0.34; P < 0.001) lower for high‐fit individuals within normal weight, overweight and obese categories, respectively.
Conclusions
Increased CRF was associated with progressively lower HF risk regardless of BMI, suggesting that the elevated HF risk associated with obesity may be modulated by improved CRF.
Heart failure with preserved ejection fraction (HFpEF) is common, increasing in prevalence, and refractory to available pharmacotherapies. Our understanding of HFpEF has evolved from a disorder of diastolic dysfunction to a constellation of physiologic impairments that lead to elevated left ventricular filling pressures and exercise intolerance. Accordingly, the therapeutic and preventive focus has shifted to identifying lifestyle factors that may have more pleotropic effects on the pathophysiologic mechanisms that define HFpEF. Recent studies have demonstrated that physical inactivity, low fitness, and obesity are potential modifiable targets for prevention as well as management of HFpEF. In this review, we have discussed the emerging epidemiological, mechanistic, and clinical evidence that support the role of these lifestyle factors as key determinants of development and progression of HFpEF. We also summarize the available evidence and major knowledge gaps with regard to developing exercise training and weight loss as unique and effective therapeutic strategies for management of HFpEF. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Physical inactivity is one of the leading modifiable risk factors for global mortality, with an estimated 20% to 30% increased risk of death compared with those who are physically active. The “behavior” of physical activity (PA) is multifactorial, including social, environmental, psychological, and genetic factors. Abundant scientific evidence has demonstrated that physically active people of all age groups and ethnicities have higher levels of cardiorespiratory fitness, health, and wellness, and a lower risk for developing several chronic medical illnesses, including cardiovascular disease, compared with those who are physically inactive. Although more intense and longer durations of PA correlate directly with improved outcomes, even small amounts of PA provide protective health benefits. In this state-of-the-art review, the authors focus on “healthy PA” with the emphasis on the pathophysiological effects of physical inactivity and PA on the cardiovascular system, mechanistic/triggering factors, the role of preventive actions through personal, education/environment, and societal/authoritative factors, as well as factors to provide guidance for caregivers of health promotion regarding PA. Sustainable and comprehensive programs to increase PA among all individuals need to be developed and implemented at local, regional, national, and international levels to effect positive changes and improve global health, especially the reduction of cardiovascular disease.
Objectives:
This study prospectively examined physical activity levels and the incidence of heart failure (HF) in 137,303 women, ages 50 to 79 years, and examined a subset of 35,272 women who, it was determined, had HF with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF).
Background:
The role of physical activity in HF risk among older women is unclear, particularly for incidence of HFpEF or HFrEF.
Methods:
Women were free of HF and reported ability to walk at least 1 block without assistance at baseline. Recreational physical activity was self-reported. The study documented 2,523 cases of total HF, and 451 and 734 cases of HFrEF and HFpEF, respectively, during a mean 14-year follow-up.
Results:
After controlling for age, race, education, income, smoking, alcohol, hormone therapy, and hysterectomy status, compared with women who reported no physical activity (referent group), inverse associations were observed across incremental tertiles of total physical activity for overall HF (hazard ratio [HR]: Tertile 1 = 0.89, Tertile 2 = 0.74, Tertile 3 = 0.65; trend p < 0.001), HFpEF (HR: 0.93, 0.70, 0.68; p < 0.001), and HFrEF (HR: 0.81, 0.59, 0.68; p = 0.01). Additional controlling for potential mediating factors included attenuated time-varying coronary heart disease (CHD) (nonfatal myocardial infarction, coronary revascularization) diagnosis but did not eliminate the inverse associations. Walking, the most common form of physical activity in older women, was also inversely associated with HF risks (overall: 1.00, 0.98, 0.93, 0.72; p < 0.001; HFpEF: 1.00, 0.98, 0.87, 0.67; p < 0.001; HFrEF: 1.00, 0.75, 0.78, 0.67; p = 0.01). Associations between total physical activity and HF were consistent across subgroups, defined by age, body mass index, diabetes, hypertension, physical function, and CHD diagnosis. Analysis of physical activity as a time-varying exposure yielded findings comparable to those of baseline physical activity.
Conclusions:
Higher levels of recreational physical activity, including walking, are associated with significantly reduced HF risk in community-dwelling older women.
Background
-Community trends of acute decompensated heart failure (ADHF) in diverse populations may differ by race and sex.
Methods
-The Atherosclerosis Risk in Communities (ARIC) Study sampled heart failure related hospitalizations (age ≥55 years) in four US communities from 2005-2014 using ICD-9-CM codes. ADHF hospitalizations were validated by standardized physician review and computer algorithm, yielding 40,173 events after accounting for sampling design (unweighted n=8746).
Results
-Of the ADHF hospitalizations, 50% had reduced ejection fraction (HFrEF), 39% had preserved EF (HFpEF). HFrEF was more common in black men and white men, whereas HFpEF was most common in white women. Average age-adjusted rates of ADHF was highest in blacks (38.1 per 1000 black men, 30.5 per 1000 black women), with rates differing by HF type and sex. ADHF rates increased over the 10 years (average annual percent change, AAPC: black women +4.3%, black men +3.7%, white women +1.9%, white men +2.6%), mostly reflecting more acute HFpEF. Age-adjusted 28-day and 1-year case fatality proportions were approximately 10% and 30%, respectively, similar across race-sex groups and HF types. Only blacks showed decreased 1-year mortality over time (AAPC: black women -5.4%, black men -4.6%), with rates differing by HF type (AAPC: black women HFpEF -7.1%, black men HFrEF -4.7%).
Conclusions
-Between 2005-2014, trends in ADHF hospitalizations increased in four US communities, primarily driven acute HFpEF. Survival at one year was poor regardless of EF, but improved over time for black women and black men.
Objectives:
This study evaluated the contributions of obesity and changes in body mass index (BMI) in mid-life to long-term heart failure (HF) risk independent of cardiorespiratory fitness (CRF) levels.
Background:
Obesity and low CRF are well-established risk factors for HF. However, given the inverse association between CRF and obesity, the independent contributions of BMI toward HF risk are not fully understood.
Methods:
We included 19,485 participants from the Cooper Center Longitudinal Study who survived to receive Medicare coverage, from 1999 to 2009. CRF was estimated in metabolic equivalents (METS) according to Balke treadmill time. Associations of BMI and BMI change with HF hospitalization after age 65 were assessed by applying a proportional hazards recurrent events model to the failure time data.
Results:
After 127,110 person-years of follow-up, we observed 1,038 HF hospitalization events. Higher mid-life BMI was significantly associated with greater risk of HF hospitalization after adjusting for established HF risk factors (hazard ratio [HR]: 1.19; 95% confidence interval [CI]: 1.12 to 1.26) per 3 kg/m(2) higher BMI). This association was attenuated after adjusting for CRF (HR: 1.10; 95% CI: 1.03 to 1.17 per 3 kg/m(2) higher BMI). CRF accounted for 47% of the HF risk associated with BMI. BMI change was not significantly associated with risk of HF in older age after adjustment for CRF change.
Conclusions:
Higher BMI-associated risk of HF is explained largely by differences in CRF levels. Furthermore, BMI change is not significantly associated with HF risk after adjusting for CRF changes. These findings highlight the importance of CRF in mediating BMI-associated HF risk.
Objectives
This study sought to evaluate the association between early-life cardiorespiratory fitness (CRF) and measures of left ventricular (LV) structure and function in midlife.
Background
Low CRF in midlife is associated with a higher risk of heart failure. However, the unique contributions of early-life CRF toward measures of LV structure and function in middle age are not known.
Methods
CARDIA (Coronary Artery Risk Development in Young Adults) study participants with a baseline maximal treadmill test and an echocardiogram at year 25 were included. Associations among baseline CRF, CRF change, and echocardiographic LV parameters (global longitudinal strain [GLS] and global circumferential strain, E/e′) were assessed using multivariable linear regression.
Results
The study included 3,433 participants. After adjustment for baseline demographic and clinical characteristics, lower baseline CRF was significantly associated with higher LV strain (standardized parameter estimate [Std β] = −0.06; p = 0.03 for GLS) and ratio of early transmitral flow velocity to early peak diastolic mitral annular velocity (E/e′) (Std β = −0.10; p = 0.0001 for lateral E/e′), findings suggesting impaired contractility and elevated diastolic filling pressure in midlife. After additional adjustment for cumulative cardiovascular risk factor burden observed over the follow-up period, the association of CRF with LV strain attenuated substantially (p = 0.36), whereas the association with diastolic filling pressure remained significant (Std β = −0.05; p = 0.02 for lateral E/e′). In a subgroup of participants with repeat CRF tests at year 20, greater decline in CRF was significantly associated with increased abnormalities in GLS (Std β = −0.05; p = 0.02) and higher diastolic filling pressure (Std β = −0.06; p = 0.006 for lateral E/e′) in middle age.
Conclusions
CRF in young adulthood and CRF change were associated with measures of LV systolic function and diastolic filling pressure in middle age. Low CRF–associated abnormalities in systolic function were related to the associated higher cardiovascular risk factor burden. In contrast, the inverse association between CRF and LV diastolic filling pressure was independent of cardiovascular risk factor burden.
Background:
Lower leisure-time physical activity (LTPA) and higher body mass index (BMI) are independently associated with risk of heart failure (HF). However, it is unclear if this relationship is consistent for both heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).
Objectives:
This study sought to quantify dose-response associations between LTPA, BMI, and the risk of different HF subtypes.
Methods:
Individual-level data from 3 cohort studies (WHI [Women's Health Initiative], MESA [Multi-Ethnic Study of Atherosclerosis], and CHS [Cardiovascular Health Study]) were pooled and participants were stratified into guideline-recommended categories of LTPA and BMI. Associations between LTPA, BMI, and risk of overall HF, HFpEF (ejection fraction ≥45%), and HFrEF (ejection fraction <45%) were assessed by using multivariable adjusted Cox models and restricted cubic splines.
Results:
The study included 51,451 participants with 3,180 HF events (1,252 HFpEF, 914 HFrEF, and 1,014 unclassified HF). In the adjusted analysis, there was a dose-dependent association between higher LTPA levels, lower BMI, and overall HF risk. Among HF subtypes, LTPA in any dose range was not associated with HFrEF risk. In contrast, lower levels of LTPA (<500 MET-min/week) were not associated with HFpEF risk, and dose-dependent associations with lower HFpEF risk were observed at higher levels. Compared with no LTPA, higher than twice the guideline-recommended minimum LTPA levels (>1,000 MET-min/week) were associated with an 19% lower risk of HFpEF (hazard ratio: 0.81; 95% confidence interval: 0.68 to 0.97). The dose-response relationship for BMI with HFpEF risk was also more consistent than with HFrEF risk, such that increasing BMI above the normal range (≥25 kg/m(2)) was associated with a greater increase in risk of HFpEF than HFrEF.
Conclusions:
Our study findings show strong, dose-dependent associations between LTPA levels, BMI, and risk of overall HF. Among HF subtypes, higher LTPA levels and lower BMI were more consistently associated with lower risk of HFpEF compared with HFrEF.
Background:
Prior studies have demonstrated cardiorespiratory fitness (CRF) to be a strong marker of cardiovascular health. However, there are limited data investigating the association between CRF and risk of progression to heart failure (HF). The purpose of this study was to determine the relationship between CRF and incident HF.
Methods:
We included 66,329 patients (53.8% men, mean age 55 years) free of HF who underwent exercise treadmill stress testing at Henry Ford Health Systems between 1991 and 2009. Incident HF was determined using International Classification of Diseases, Ninth Revision codes from electronic medical records or administrative claim files. Cox proportional hazards models were performed to determine the association between CRF and incident HF.
Results:
A total of 4,652 patients developed HF after a median follow-up duration of 6.8 (±3) years. Patients with incident HF were older (63 vs 54 years, P<.001) and had higher prevalence of known coronary artery disease (42.3% vs 11%, P<.001). Peak metabolic equivalents (METs) of task were 6.3 (±2.9) and 9.1 (±3) in the HF and non-HF groups, respectively. After adjustment for potential confounders, patients able to achieve ≥12 METs had an 81% lower risk of incident HF compared with those achieving <6 METs (hazard ratio 0.19 [95% CI 0.14-0.29], P for trend < .001). Each 1 MET achieved was associated with a 16% lower risk (hazard ratio 0.84 [95% CI 0.82-0.86], P<.001) of incident HF.
Conclusions:
Our analysis demonstrates that higher level of fitness is associated with a lower incidence of HF independent of HF risk factors.
Background:
To examine the prognostic value of cardiorespiratory fitness (CRF) with risk of first major nonfatal myocardial infarction (MI), stroke, and heart failure (HF) events.
Methods:
Cardiorespiratory fitness, as measured by maximal oxygen uptake, was assessed at baseline in a prospective cohort of 2,089 men aged 42 to 61years.
Results:
During a mean (SD) follow-up of 19.1(8.4) years, 522 nonfatal acute MI events, 198 acute all-cause nonfatal stroke events, and 221 nonfatal HF events were recorded. The hazard ratio per 1-metabolic-equivalent increase in CRF was 0.93 (95% CI 0.88-0.97) for nonfatal MI, 0.94 (95% CI0.87-1.01) for nonfatal stroke, and 0.84 (95% CI 0.78-0.91) for nonfatal HF events after adjustment for cardiovascular risk factors (age, systolic blood pressure, body mass index, history of cardiovascular disease, diabetes, smoking, alcohol use, serum creatinine, low-density lipoprotein levels, physical activity, and socioeconomic status). Further adjustment for left ventricular hypertrophy and resting heart rate did not attenuate these associations. Addition of CRF to conventional cardiovascular disease risk factors significantly improved both discrimination (C index) and category free net reclassification index (cf-NRI) for nonfatal MI (change in C index, 0.015 [95% CI 0.010-0.020] and change in cf-NRI 0.27, P<.01) and HF (change in C index 0.040 [95% CI 0.010-0.060] and change in cf-NRI 0.88, P<.01).
Conclusion:
In this Finnish population, there is a strong, inverse, and independent association between CRF and acute nonfatal MI and HF risk.
Objective:
Diabetes is a common cause of shortened life expectancy. We aimed to assess the association between diabetes and cause-specific death.
Research design and methods:
We used the pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79 years old. Diabetes status was self-reported or defined as glycemia >125 mg/dL at baseline. Vital status and causes of death were ascertained by medical records review and linkage with the official death registry. The hazard ratios and cumulative mortality function were assessed with two approaches, with and without competing risks: proportional subdistribution hazard (PSH) and cause-specific hazard (CSH), respectively. Multivariate analyses were fitted for cardiovascular, cancer, and noncardiovascular noncancer deaths.
Results:
We included 55,292 individuals (15.6% with diabetes and overall mortality of 9.1%). The adjusted hazard ratios showed that diabetes increased mortality risk: 1) cardiovascular death, CSH = 2.03 (95% CI 1.63-2.52) and PSH = 1.99 (1.60-2.49) in men; and CSH = 2.28 (1.75-2.97) and PSH = 2.23 (1.70-2.91) in women; 2) cancer death, CSH = 1.37 (1.13-1.67) and PSH = 1.35 (1.10-1.65) in men; and CSH = 1.68 (1.29-2.20) and PSH = 1.66 (1.25-2.19) in women; and 3) noncardiovascular noncancer death, CSH = 1.53 (1.23-1.91) and PSH = 1.50 (1.20-1.89) in men; and CSH = 1.89 (1.43-2.48) and PSH = 1.84 (1.39-2.45) in women. In all instances, the cumulative mortality function was significantly higher in individuals with diabetes.
Conclusions:
Diabetes is associated with premature death from cardiovascular disease, cancer, and noncardiovascular noncancer causes. The use of CSH and PSH provides a comprehensive view of mortality dynamics in a population with diabetes.
Background
The excess risks of death from any cause and death from cardiovascular causes among persons with type 2 diabetes and various levels of glycemic control and renal complications are unknown. In this registry-based study, we assessed these risks according to glycemic control and renal complications among persons with type 2 diabetes.
Methods
We included patients with type 2 diabetes who were registered in the Swedish National Diabetes Register on or after January 1, 1998. For each patient, five controls were randomly selected from the general population and matched according to age, sex, and county. All the participants were followed until December 31, 2011, in the Swedish Registry for Cause-Specific Mortality.
Results
The mean follow-up was 4.6 years in the diabetes group and 4.8 years in the control group. Overall, 77,117 of 435,369 patients with diabetes (17.7%) died, as compared with 306,097 of 2,117,483 controls (14.5%) (adjusted hazard ratio, 1.15; 95% confidence interval [CI], 1.14 to 1.16). The rate of cardiovascular death was 7.9% among patients versus 6.1% among controls (adjusted hazard ratio, 1.14; 95% CI, 1.13 to 1.15). The excess risks of death from any cause and cardiovascular death increased with younger age, worse glycemic control, and greater severity of renal complications. As compared with controls, the hazard ratio for death from any cause among patients younger than 55 years of age who had a glycated hemoglobin level of 6.9% or less (≤52 mmol per mole of nonglycated hemoglobin) was 1.92 (95% CI, 1.75 to 2.11); the corresponding hazard ratio among patients 75 years of age or older was 0.95 (95% CI, 0.94 to 0.96). Among patients with normoalbuminuria, the hazard ratio for death among those younger than 55 years of age with a glycated hemoglobin level of 6.9% or less, as compared with controls, was 1.60 (95% CI, 1.40 to 1.82); the corresponding hazard ratio among patients 75 years of age or older was 0.76 (95% CI, 0.75 to 0.78), and patients 65 to 74 years of age also had a significantly lower risk of death (hazard ratio, 0.87; 95% CI, 0.84 to 0.91).
Conclusions
Mortality among persons with type 2 diabetes, as compared with that in the general population, varied greatly, from substantial excess risks in large patient groups to lower risks of death depending on age, glycemic control, and renal complications. (Funded by the Swedish government and others.)
Background:
-Prior studies have reported an inverse association between physical activity (PA) and risk of heart failure (HF). However, a comprehensive assessment of the quantitative dose-response association between PA and HF risk has not been reported previously.
Methods and results:
-Prospective cohort studies with participants >18 years of age that reported association of baseline PA levels and incident HF were included. Categorical dose response relationships between PA and HF risk were assessed using random effects models. Generalized least squares regression models were used to assess the quantitative relationship between PA (MET-min/week) and HF risk across studies reporting quantitative PA estimates. Twelve prospective cohort studies with 20,203 HF events among 370,460 participants (53.5% women; median follow-up: 13 years) were included. The highest levels of PA were associated with significantly reduced risk of HF [Pooled Hazard Ratio (HR)Highest vs. lowest PA: 0.70 (0.67-0.73)]. Compared with participants reporting no leisure time PA, those who engaged in guideline recommended minimum levels of PA (500 MET-min/week, 2008 US Federal Guidelines) had modest reductions in HF risk [RR: 0.90 (0.87 - 0.92)]. In contrast, a substantial risk reduction was observed among individuals who engaged in PA at twice [HR for 1000 MET-min/week: 0.81(0.77 - 0.86)] and four times [HR for 2000 MET-min/week: 0.65 (0.58 - 0.73)] the minimum guideline recommended levels.
Conclusions:
-There is an inverse, dose-response relationship between PA and HF risk. Doses of PA in excess of the guideline recommended minimum PA levels may be required for more substantial reductions in HF risk.
Overweight and obesity are major contributors to both type 2 diabetes and cardiovascular disease (CVD). Moreover, individuals with type 2 diabetes who are overweight or obese are at particularly high risk for CVD morbidity and mortality. Although short-term weight loss has been shown to ameliorate obesity-related metabolic abnormalities and CVD risk factors, the long-term consequences of intentional weight loss in overweight or obese individuals with type 2 diabetes have not been adequately examined. The primary objective of the Look AHEAD clinical trial is to assess the long-term effects (up to 11.5 years) of an intensive weight loss program delivered over 4 years in overweight and obese individuals with type 2 diabetes. Approximately 5000 male and female participants who have type 2 diabetes, are 45–74 years of age, and have a body mass index ⩾25 kg/m2 will be randomized to one of the two groups. The intensive lifestyle intervention is designed to achieve and maintain weight loss through decreased caloric intake and increased physical activity. This program is compared to a control condition given diabetes support and education. The primary study outcome is time to incidence of a major CVD event. The study is designed to provide a 0.90 probability of detecting an 18% difference in major CVD event rates between the two groups. Other outcomes include components of CVD risk, cost and cost-effectiveness, diabetes control and complications, hospitalizations, intervention processes, and quality of life.
Low midlife fitness is associated with higher risk for heart failure (HF). However, it is unclear to what extent this HF risk is modifiable and mediated by the burden of cardiac and non-cardiac co-morbidities. We studied the effect of cardiac and non-cardiac co-morbidities on the association of midlife fitness and fitness change with HF risk.Methods & ResultsLinking individual subject data from the Cooper Center Longitudinal Study (CCLS) with Medicare claims files, we studied 19,485 subjects (21.2% women) who survived to receive Medicare coverage from 1999 to 2009. Fitness estimated by Balke treadmill time at mean age of 49 years was analyzed as a continuous variable (in metabolic equivalents [METs]) and according to age- and sex-specific quintiles. Associations of midlife fitness and fitness change with HF hospitalization after age 65 were assessed by applying a proportional hazards recurrent events model to the failure time data with each co-morbidity entered as time-dependent covariates. After 127,110 person-years of Medicare follow up, we observed 1,038 HF hospitalizations. Higher midlife fitness was associated with a lower risk for HF hospitalization [HR 0.82 (0.76-0.87) per MET] after adjustment for traditional risk factors. This remained unchanged after further adjustment for the burden of Medicare-identified cardiac and non-cardiac co-morbidities [HR 0.83 (0.78-0.89)]. Each 1 MET improvement in midlife fitness was associated with a 17% lower risk for HF hospitalization in later life [HR 0.83 (0.74-0.93) per MET].Conclusions
Midlife fitness is an independent and modifiable risk factor for HF hospitalization at a later age.
Background:
Sedentary aging has deleterious effects on the cardiovascular system, including decreased left ventricular compliance and distensibility (LVCD). Conversely, Masters level athletes, who train intensively throughout adulthood, retain youthful LVCD.
Objectives:
The purpose of this study was to test the hypothesis that preservation of LVCD may be possible with moderate lifelong exercise training.
Methods:
Healthy seniors (n = 102) were recruited from predefined populations, screened for lifelong patterns of exercise training, and stratified into 4 groups: "sedentary" (<2 sessions/week); "casual" (2 to 3 sessions/week); "committed" (4 to 5 sessions/week); and "competitive" Masters level athletes (6 to 7 sessions/week). Right heart catheterization and echocardiography were performed while preload was manipulated using lower body negative pressure and rapid saline infusion to define LV pressure-volume relationships and Frank-Starling curves.
Results:
Peak oxygen uptake and LV mass increased with escalating doses of lifelong exercise, with little change in systolic function. At baseline, LV distensibility was greater in committed (21%) and competitive (36%) exercisers than in sedentary subjects. Group LV stiffness constants (sedentary: 0.062 ± 0.039; casual: 0.079 ± 0.052; committed: 0.055 ± 0.033; and competitive: 0.035 ± 0.033) revealed: 1) increased stiffness in sedentary subjects compared to competitive athletes, whereas lifelong casual exercise had no effect; and 2) greater compliance in committed exercisers than in sedentary or casual exercisers.
Conclusions:
Low doses of casual, lifelong exercise do not prevent the decreased compliance and distensibility observed with healthy, sedentary aging. In contrast, 4 to 5 exercise sessions/week throughout adulthood prevent most of these age-related changes. As LV stiffening has been implicated in the pathophysiology of many cardiovascular conditions affecting the elderly, this "dose" of exercise training may have important implications for prevention of cardiovascular disease.
Objectives
This study sought to compare the cross-sectional associations between fitness and echocardiographic measures of cardiac structure and function.
Background
Cardiorespiratory fitness is inversely associated with heart failure risk. However, the mechanism through which fitness lowers heart failure risk is not fully understood.
Methods
We included 1,678 men and 1,247 women from the Cooper Center Longitudinal Study who received an echocardiogram from 1999 to 2011. Fitness was estimated by Balke protocol (in metabolic equivalents) and also categorized into age-specific quartiles, with quartile 1 representing low fitness. Cross-sectional associations between fitness (in metabolic equivalents) and relative wall thickness, left ventricular end-diastolic diameter indexed to body surface area, left atrial volume indexed to body surface area, left ventricular systolic function, and E/e′ ratio were determined using multivariable linear regression analysis.
Results
Higher levels of mid-life fitness (metabolic equivalents) were associated with larger indexed left atrial volume (men: beta = 0.769, p < 0.0001; women: beta = 0.879, p value ≤0.0001) and indexed left ventricular end-diastolic diameter (men: beta = 0.231, p < 0.001; women: beta = 0.264, p < 0.0001). Similarly, a higher level of fitness was associated with a smaller relative wall thickness (men: beta = –0.002, p = 0.04; women: beta = –0.005, p < 0.0001) and E/e′ ratio (men: beta = –0.11, p = 0.003; women: beta = –0.13, p = 0.01). However, there was no association between low fitness and left ventricular systolic function (p = NS).
Conclusions
Low fitness is associated with a higher prevalence of concentric remodeling and diastolic dysfunction, suggesting that exercise may lower heart failure risk through its effect on favorable cardiac remodeling and improved diastolic function.
AimTo examine the relationship between cardiorespiratory fitness (CRF) and risk of incident heart failure (HF). Methods and resultsCardiorespiratory fitness, as measured by maximal oxygen uptake (VO2max), was assessed at baseline in a prospective cohort of 1873 men aged 42–61 years without HF or chronic respiratory disease. During a mean follow-up of 20.4 years, 152 incident HF events were recorded. Within-person variability was calculated using data from repeat measurements taken 11 years apart. The age-adjusted hazard ratio (HR) per unit increase (1 mL/kg/min of VO2max) in CRF was 0.89 [95% confidence interval (CI) 0.86–0.93], which was minimally attenuated to 0.94 (95% CI 0.90–0.98) after further adjustment for established HF risk factors (body mass index, systolic blood pressure, history of cardiovascular disease, diabetes, heart rate, and LV hypertrophy) and incident coronary events as a time-varying covariate. In a comparison of extreme quartiles of CRF levels (VO2max ≥35.4 vs. ≤25.7 mL/kg/min), the corresponding HRs were 0.27 (0.15–0.50) and 0.48 (0.25–0.92), respectively. Each 1 MET (metabolic equivalent of oxygen consumption) increment in CRF was associated with a 21% (7–33%) reduction in multivariable adjusted risk of HF. Addition of CRF to a HF risk prediction model containing established risk factors did not significantly improve risk discrimination (C-index change = 0.0164, P = 0.07). Conclusions
In this Finnish population, there is a strong, inverse, and independent association between long-term CRF and HF risk, consistent with a dose–response relationship. The protective effect of CRF on HF risk warrants further evaluation.
Background:
Multiple studies have demonstrated strong associations between cardiorespiratory fitness and lower cardiovascular disease mortality. In contrast, little is known about associations of fitness with nonfatal cardiovascular events.
Methods and results:
Linking individual participant data from the Cooper Center Longitudinal Study with Medicare claims files, we studied 20642 participants (21% women) with fitness measured at the mean age of 49 years and who survived to receive Medicare coverage from 1999 to 2009. Fitness was categorized into age- and sex-specific quintiles (Q) according to Balke protocol treadmill time with Q1 as low fitness. Fitness was also estimated in metabolic equivalents according to treadmill time. Associations between midlife fitness and hospitalizations for heart failure and acute myocardial infarction after the age of 65 years were assessed by applying a proportional hazards model to the multivariate failure time data. After 133514 person-years of Medicare follow-up, we observed 1051 hospitalizations for heart failure and 832 hospitalizations for acute myocardial infarction. Compared with high fitness (Q4-5), low fitness (Q1) was associated with a higher rate of heart failure hospitalization (14.3% versus 4.2%) and hospitalization for myocardial infarction (9.7% versus 4.5%). After multivariable adjustment for baseline age, blood pressure, diabetes mellitus, body mass index, smoking status, and total cholesterol, a 1 unit greater fitness level in metabolic equivalents achieved in midlife was associated with ≈20% lower risk for heart failure hospitalization after the age of 65 years (men: hazard ratio [95% confidence intervals], 0.79 [0.75-0.83]; P<0.001 and women: 0.81 [0.68-0.96]; P=0.01) but just a 10% lower risk for acute myocardial infarction in men (0.91 [0.87-0.95]; P<0.001) and no association in women (0.97 [0.83-1.13]; P=0.68).
Conclusions:
Fitness in healthy, middle-aged adults is more strongly associated with heart failure hospitalization than acute myocardial infarction outcomes decades later in older age.
Key points Healthy sedentary ageing leads to stiffening of the heart; however, when this process occurs during ageing has been unknown.
In this study, 70 healthy sedentary subjects were stratified into four groups: ‘young’– G 21−34 : 21–34 years; ‘early middle‐age’– G 35−49 : 35–49 years; ‘late middle‐age’– G 50−64 : 50–64 years; and ‘seniors’– G ≥65 : ≥65 years.
Invasive catheter measurements showed a substantially greater left ventricular (LV) compliance (more flexible/less stiff) in G 21−34 than G 50−64 and G ≥65 .
Although LV chamber compliance in G 50−64 and G ≥65 appeared identical, pressure–volume curves were shifted leftward, exhibiting a smaller volume for any given pressure with increasing age.
Our results suggest that LV stiffening with ageing occurs during the transition between youth and middle‐age and becomes manifest between the ages of 50–64; LV volume contraction and remodelling follow in the senior years. Early–late middle age thus may represent a ‘sweet spot’ when interventions to prevent stiff ageing hearts may be most effective.
Population-based research on heart failure (HF) is hindered by lack of consensus on diagnostic criteria. Framingham (FRM), National Health and Nutrition Examination Survey (NHANES), Modified Boston (MBS), Gothenburg (GTH), and International Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM) code criteria, do not differentiate acute decompensated heart failure (ADHF) from chronic stable HF. We developed a new classification protocol for identifying ADHF in the Atherosclerosis Risk in Communities (ARIC) Study and compared it with these other schemes.
A sample of 1180 hospitalizations with a patient address in 4 study communities and eligible discharge codes were selected. After assessing whether the chart contained evidence of possible HF signs, 705 were fully abstracted. Two independent reviewers classified each case as ADHF, chronic stable HF, or no HF, using ARIC classification guidelines. Fifty-nine percent of cases met ARIC criteria for ADHF and 13.9% and 27.1% were classified as chronic stable HF or no HF, respectively. Among events classified as HF by FRM criteria, 68.4% were validated as ADHF, 9.6% as chronic stable HF, and 21.9% as no HF. However, 92.5% of hospitalizations with a primary ICD-9-CM 428 "heart failure" code were validated as ADHF. Sensitivities of comparison criteria to classify ADHF ranged from 38-95%, positive predictive values from 62-92%, and specificities from 19-96%.
Although comparison criteria for classifying HF were moderately sensitive in identifying ADHF, specificity varied when applied to a randomly selected set of suspected HF hospitalizations in the community.
The extent to which diabetes mellitus or hyperglycemia is related to risk of death from cancer or other nonvascular conditions is uncertain.
We calculated hazard ratios for cause-specific death, according to baseline diabetes status or fasting glucose level, from individual-participant data on 123,205 deaths among 820,900 people in 97 prospective studies.
After adjustment for age, sex, smoking status, and body-mass index, hazard ratios among persons with diabetes as compared with persons without diabetes were as follows: 1.80 (95% confidence interval [CI], 1.71 to 1.90) for death from any cause, 1.25 (95% CI, 1.19 to 1.31) for death from cancer, 2.32 (95% CI, 2.11 to 2.56) for death from vascular causes, and 1.73 (95% CI, 1.62 to 1.85) for death from other causes. Diabetes (vs. no diabetes) was moderately associated with death from cancers of the liver, pancreas, ovary, colorectum, lung, bladder, and breast. Aside from cancer and vascular disease, diabetes (vs. no diabetes) was also associated with death from renal disease, liver disease, pneumonia and other infectious diseases, mental disorders, nonhepatic digestive diseases, external causes, intentional self-harm, nervous-system disorders, and chronic obstructive pulmonary disease. Hazard ratios were appreciably reduced after further adjustment for glycemia measures, but not after adjustment for systolic blood pressure, lipid levels, inflammation or renal markers. Fasting glucose levels exceeding 100 mg per deciliter (5.6 mmol per liter), but not levels of 70 to 100 mg per deciliter (3.9 to 5.6 mmol per liter), were associated with death. A 50-year-old with diabetes died, on average, 6 years earlier than a counterpart without diabetes, with about 40% of the difference in survival attributable to excess nonvascular deaths.
In addition to vascular disease, diabetes is associated with substantial premature death from several cancers, infectious diseases, external causes, intentional self-harm, and degenerative disorders, independent of several major risk factors. (Funded by the British Heart Foundation and others.).
Sedentary aging leads to increased cardiovascular stiffening, which can be ameliorated by sufficient amounts of lifelong exercise training. An even more extreme form of cardiovascular stiffening can be seen in heart failure with preserved ejection fraction (HFpEF), which comprises ~40~50% of elderly patients diagnosed with congestive heart failure. There are two major interrelated hypotheses proposed to explain heart failure in these patients: 1) increased left ventricular (LV) diastolic stiffness and 2) increased arterial stiffening. The beat-to-beat dynamic Starling mechanism, which is impaired with healthy human aging, reflects the interaction between ventricular and arterial stiffness and thus may provide a link between these two mechanisms underlying HFpEF. Spectral transfer function analysis was applied between beat-to-beat changes in LV end-diastolic pressure (LVEDP; estimated from pulmonary artery diastolic pressure with a right heart catheter) and stroke volume (SV) index. The dynamic Starling mechanism (transfer function gain between LVEDP and the SV index) was impaired in HFpEF patients (n = 10) compared with healthy age-matched controls (n = 12) (HFpEF: 0.23 ± 0.10 ml·m⁻²·mmHg⁻¹ and control: 0.37 ± 0.11 ml·m⁻²·mmHg⁻¹, means ± SD, P = 0.008). There was also a markedly increased (3-fold) fluctuation of LV filling pressures (power spectral density of LVEDP) in HFpEF patients, which may predispose to pulmonary edema due to intermittent exposure to higher pulmonary capillary pressure (HFpEF: 12.2 ± 10.4 mmHg² and control: 3.8 ± 2.9 mmHg², P = 0.014). An impaired dynamic Starling mechanism, even more extreme than that observed with healthy aging, is associated with marked breath-by-breath LVEDP variability and may reflect advanced ventricular and arterial stiffness in HFpEF, possibly contributing to reduced forward output and pulmonary congestion.
Congestive heart failure in the setting of a preserved left ventricular (LV) ejection fraction is increasing in prevalence among the senior population. The underlying pathophysiologic abnormalities in ventricular function and structure remain unclear for this disorder. We hypothesized that patients with heart failure with preserved ejection fraction (HFPEF) would have marked abnormalities in LV diastolic function with increased static diastolic stiffness and slowed myocardial relaxation compared with age-matched healthy controls.
Eleven highly screened patients (4 men, 7 women) aged 73±7 years with HFPEF were recruited to participate in this study. Thirteen sedentary healthy controls (7 men, 6 women) aged 70±4 years also were recruited. All subjects underwent pulmonary artery catheterization with measurement of cardiac output, end-diastolic volumes, and pulmonary capillary wedge pressures at baseline; cardiac unloading (lower-body negative pressure or upright tilt); and cardiac loading (rapid saline infusion). The data were used to define the Frank-Starling and LV end-diastolic pressure-volume relationships. Doppler echocardiographic data (tissue Doppler velocities, isovolumic relaxation time, propagation velocity of early mitral inflow , E/A-wave ratio) were obtained at each level of cardiac preload. Compared with healthy controls, patients with HFPEF had similar LV contractile function and static LV compliance but reduced LV chamber distensibility with elevated filling pressures and slower myocardial relaxation as assessed by tissue Doppler imaging.
In this small, highly screened patient population with hemodynamically confirmed HFPEF, increased end-diastolic static ventricular stiffness relative to age-matched controls was not a universal finding. Nevertheless, patients with HFPEF, even when well compensated, had elevated filling pressures, reduced distensibility, and increased diastolic wall stress compared with controls. In contrast, LV relaxation as assessed by tissue Doppler variables appeared consistently impaired in patients with HFPEF.
Invasive cardiopulmonary exercise testing was performed in 7 patients who presented with congestive heart failure, normal left ventricular ejection fraction and no significant coronary or valvular heart disease and in 10 age-matched normal subjects. Compared with the normal subjects, patients demonstrates severe exercise intolerance with a 48% reduction in peak oxygen consumption (11.6 +/- 4.0 versus 22.7 +/- 6.1 ml/kg per min; p less than 0.001), primarily due to a 41% reduction in peak cardiac index (4.2 +/- 1.4 versus 7.1 +/- 1.1 liters/min per m2; p less than 0.001). In patients compared with normal subjects, peak left ventricular stroke volume index (34 +/- 9 versus 46 +/- 7 ml/min per m2; p less than 0.01) and end-diastolic volume index (56 +/- 14 versus 68 +/- 12 ml/min per m2; p less than 0.08) were reduced, whereas peak ejection fraction and end-systolic volume index were not different. In patients, the change in end-diastolic volume index during exercise correlated strongly with the change in stroke volume index (r = 0.97; p less than 0.0001) and cardiac index (r = 0.80; p less than 0.03). Pulmonary wedge pressure was markedly increased at peak exercise in patients compared with normal subjects (25.7 +/- 9.1 versus 7.1 +/- 4.4 mm Hg; p less than 0.0001). Patients demonstrated a shift of the left ventricular end-diastolic pressure-volume relation upward and to the left at rest. Increases in left ventricular filling pressure during exercise were not accompanied by increases in end-diastolic volume, indicating a limitation to left ventricular filling.(ABSTRACT TRUNCATED AT 250 WORDS)
Type 2 diabetes and incidence of
- J Deanfield
- A Smeeth L Timmis
- H Hemingway