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Prevalence and predictors of cardiac hypertrophy and dysfunction in patients with Type 2 diabetes
Abstract
The aim of the present study was to determine the prevalence and predictors of an abnormal echocardiogram in patients with Type 2 diabetes. Cardiac function and structure were rigorously assessed by comprehensive transthoracic echocardiographic techniques in 229 patients with Type 2 diabetes. Cardiovascular risk factors and diabetic complications were assessed, and predictors of an abnormal echocardiogram were identified using multivariate logistic regression analysis. An abnormal echocardiogram was present in 166 patients (72%). LVH (left ventricular hypertrophy) occurred in 116 patients (51%), and cardiac dysfunction was found in 146 patients (64%), of whom 109 had diastolic dysfunction alone and 37 had systolic+/-diastolic dysfunction. Independent predictors of an abnormal echocardiogram were obesity, age, the number of antihypertensive drugs used (all P<0.001) and creatinine clearance (P<0.05). The risk of an abnormal echocardiogram increased by 9% for each year over 50 years of age {OR (odds ratio), 1.09 [95% CI (confidence interval), 1.04-1.15]}, 3-fold if obesity was present [BMI (body mass index) >30; OR, 4.2 (95% CI, 1.9-9.0)] and by 80% for each antihypertensive agent used [OR, 1.8 (95% CI, 1.3-2.4) per agent]. In conclusion, an abnormal cardiac echocardiogram is common in patients with Type 2 diabetes. Importantly, although cardiac abnormalities can be predicted by traditional risk factors, such as age, obesity and renal function, the absence of micro- or macro-vascular complications does not predict a normal echocardiogram. We suggest that an echocardiogram identifies those with Type 2 diabetes at increased cardiovascular risk due to occult LVH and diastolic dysfunction, and this information may lead to more aggressive management of known risk factors in the clinic.
... Like the current study, previous studies reported increases in BMI to be associated with LVDD [19,26,28,29]. Overweight and obesity are associated with increased plasma membrane content of fatty acids transporters such as plasma membrane-associated fatty acid-binding protein and fatty acid translocase which increases fatty acids uptake and utilization leading to cardiac steatosis [30] which induces overproduction of reactive oxygen species and ceramide causing myocardial damage [5,31]. ...
... Prior studies in Africa, Asia, and Europe similarly found advanced age was associated with LVDD [9,18,24,26,28]. This consistency could be explained by the physiological delay in relaxation of the left ventricle wall which occurs with increasing age hence abnormal diastolic function [22,23]. ...
... Unsurprisingly, hypertension was found to modify the association between BMI and LVDD in the current study. Several studies have reported hypertension as one of the major causes of left ventricular hypertrophy and diastolic dysfunction [28,[35][36][37]. Hypertension directly triggers the remodeling of cardiac walls through increases in the cardiac afterload and indirectly through the heightened activity of the renin-angiotensin system [38]. ...
Background
Left ventricular diastolic dysfunction (LVDD) is a recognized complication of diabetes mellitus that precedes and is a risk factor for heart failure. We aimed to determine the prevalence of LVDD and its association with body mass index in ambulatory adults with diabetes mellitus in rural Uganda.
Methods
We conducted a cross-sectional study, over 5 months, to enroll 195 ambulatory Ugandan adults living with diabetes mellitus for at least five years at Mbarara Regional Referral Hospital. We collected demographic, and clinical data and measured body mass index (BMI). Echocardiography was performed to determine LVDD by assessing the mitral inflow ventricular filling velocities (E/A and E/è ratios), tricuspid regurgitant jet peak velocity, and left atrium maximum volume index. We used logistic regression to estimate the odds ratio for the association of LVDD with BMI and evaluated the variation of associations by age and hypertension status.
Results
Of the 195 participants, 141 (72.31%) were female, the mean age was 62 [standard deviation, 11.50] years, and the median duration of diabetes diagnosis was 10 [interquartile range, 7, 15] years. Eighty-six percent (n = 168) had LVDD with the majority (n = 127, 65.1%) of participants in the grade 1 category of LVDD. In the adjusted model, the odds of LVDD for each 1 kg/m² increase in BMI was 1.11 [95% confidence interval 1.00, 1.25, p = 0.04]. The adjusted odds of LVDD among individuals aged ≥ 50 years with BMI ≥ 25 kg/m² was 13.82 times the odds of LVDD in individuals aged < 50 years with BMI < 25 kg/m².
Conclusion
LVDD is prevalent and positively associated with BMI among ambulatory Ugandan adults living with diabetes mellitus for at least five years. The association was higher for older overweight/obese than younger individuals with normal weight. Future studies should focus on the effect of weight loss on LVDD as a possible target for the prevention of heart failure.
... Patients with type 2 diabetes have associated hypertension [16], a high prevalence of previously unknown heart failure [17] and left ventricular dysfunction [17,18]. Left ventricular hypertrophy (LVH) is also highly prevalent in patients with type 2 diabetes [18] and hypertension [19] and is an established independent predictor of adverse cardiovascular outcomes, including stroke [20] and heart failure [21]. ...
... Patients with type 2 diabetes have associated hypertension [16], a high prevalence of previously unknown heart failure [17] and left ventricular dysfunction [17,18]. Left ventricular hypertrophy (LVH) is also highly prevalent in patients with type 2 diabetes [18] and hypertension [19] and is an established independent predictor of adverse cardiovascular outcomes, including stroke [20] and heart failure [21]. Patients with type 2 diabetes and co-morbid hypertension have increased left ventricular mass, more concentric left ventricular geometry, lower myocardial function, that is independent of age, sex, body size, arterial blood pressure and atherosclerosis, compared to hypertensive individuals without type 2 diabetes [16]. ...
... Higher left ventricular mass and concentric geometric changes have been demonstrated in approximately 35-40% of patients with type 2 diabetes [16,17]. Our data suggested more than 50% of participants will have LVH [18]. We calculated our sample size in order to include sufficient participant numbers for both the primary endpoint comparison (brain volume) and for the primary outcome measure (presence of cognitive impairment). ...
... The reported prevalence of LVH in patients with type 2 DM ranges from 19% to 56% in different studies [9][10][11]. In the present study, the prevalence of LVH was 59.1% in the patients with type 2 DM, which may have been due to the high prevalence of HTN (87.5%) in our study cohort with CKD. ...
... Most previous studies have reported a high rate of LV systolic dysfunction in patients with DM, ranging from 5% to 21.8% [9,10,21]. LV systolic function can be estimated using conventional methods such as LVEF or by methods independent of geometry such as mwFS. Both of these systolic parameters have been reported to be good predictors of cardiovascular events in patients with renal failure [22]. ...
... LV diastolic dysfunction has been reported to occur in 25% to 75% of patients with diabetes [9,10,[23][24][25]. We used the E/Ea ratio to define diastolic dysfunction according to tissue Doppler imaging. ...
Type 2 Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD) worldwide, and is associated with an increased risk of left ventricular (LV) hypertrophy, LV systolic and diastolic dysfunctions. The aim of this study was to investigate abnormal echocardiographic findings in patients with CKD with and without DM, and identify the factors associated with these abnormalities. We enrolled 356 pre-dialysis patients with CKD (stages 3-5), including 208 with DM and 148 without DM. The structure and systolic and diastolic functions of the left ventricle were assessed using echocardiography, and the clinical and echocardiographic parameters were analyzed. The patients with DM had higher rates of observed/ predicted left ventricular mass > 128% (69.5% vs. 56.7%, p = 0.015), midwall fractional shortening < 14% (22.6% vs. 8.8%, p = 0.001), and ratio of peak early transmitral filling wave velocity to early diastolic velocity of lateral mitral annulus > 12 (32.7% vs. 16.2%, p < 0.001) than those without DM. Multivariate analysis showed that male sex, a history of smoking, high systolic blood pressure, high body mass index, high levels of fasting glucose and total cholesterol, low levels of albumin and hemoglobin, and a low estimated glomerular filtration rate were associated with abnormal echocardiographic findings. The rates of inappropriate left ventricular mass, systolic and diastolic dysfunction were higher in our patients with CKD and DM than in those without DM.
... Patients with type 2 diabetes have associated hypertension [16], a high prevalence of previously unknown heart failure [17] and left ventricular dysfunction [17,18]. Left ventricular hypertrophy (LVH) is also highly prevalent in patients with type 2 diabetes [18] and hypertension [19] and is an established independent predictor of adverse cardiovascular outcomes, including stroke [20] and heart failure [21]. ...
... Patients with type 2 diabetes have associated hypertension [16], a high prevalence of previously unknown heart failure [17] and left ventricular dysfunction [17,18]. Left ventricular hypertrophy (LVH) is also highly prevalent in patients with type 2 diabetes [18] and hypertension [19] and is an established independent predictor of adverse cardiovascular outcomes, including stroke [20] and heart failure [21]. Patients with type 2 diabetes and co-morbid hypertension have increased left ventricular mass, more concentric left ventricular geometry, lower myocardial function, that is independent of age, sex, body size, arterial blood pressure and atherosclerosis, compared to hypertensive individuals without type 2 diabetes [16]. ...
... Higher left ventricular mass and concentric geometric changes have been demonstrated in approximately 35-40% of patients with type 2 diabetes [16,17]. Our data suggested more than 50% of participants will have LVH [18]. We calculated our sample size in order to include sufficient participant numbers for both the primary endpoint comparison (brain volume) and for the primary outcome measure (presence of cognitive impairment). ...
Background
Cognitive impairment is common in type 2 diabetes mellitus, and there is a strong association between type 2 diabetes and Alzheimer’s disease. However, we do not know which type 2 diabetes patients will dement or which biomarkers predict cognitive decline. Left ventricular hypertrophy (LVH) is potentially such a marker. LVH is highly prevalent in type 2 diabetes and is a strong, independent predictor of cardiovascular events. To date, no studies have investigated the association between LVH and cognitive decline in type 2 diabetes. The Diabetes and Dementia (D2) study is designed to establish whether patients with type 2 diabetes and LVH have increased rates of brain atrophy and cognitive decline. Methods
The D2 study is a single centre, observational, longitudinal case control study that will follow 168 adult patients aged >50 years with type 2 diabetes: 50% with LVH (case) and 50% without LVH (control). It will assess change in cardiovascular risk, brain imaging and neuropsychological testing between two time-points, baseline (0 months) and 24 months. The primary outcome is brain volume change at 24 months. The co-primary outcome is the presence of cognitive decline at 24 months. The secondary outcome is change in left ventricular mass associated with brain atrophy and cognitive decline at 24 months. DiscussionThe D2 study will test the hypothesis that patients with type 2 diabetes and LVH will exhibit greater brain atrophy than those without LVH. An understanding of whether LVH contributes to cognitive decline, and in which patients, will allow us to identify patients at particular risk. Trial registrationAustralian New Zealand Clinical Trials Registry (ACTRN12616000546459), date registered, 28/04/2016
... This means that the prevalence of diastolic dysfunction we reported of 55% among newly diagnosed diabetics may be an under estimate of a bigger problem. Omission of TDI may eliminate up to 25% of patients with pseudonormalization which may go unmasked 10 . This may call for longitudinal studies to evaluate this problem further using TDI. ...
... From a recent cohort in Australia among type 1 DM patients 10 , the prevalence of LVH alone was 9%, which is twice the prevalence in the general population; however, in our study, we found a higher prevalence up to 19.3%. This could be explained by the high prevalence of hypertension (62%), which was strongly associated with LVH in our study. ...
... The population he assessed had one or more CVD risk factors and used both rest echocardiography and myocardial scintigraphy which could have led to a higher prevalence compared to what we found. Piyush in a cohort among type 2 DM patients found LVH in 51% of all patients 10 . The difference between his and our findings may be due to a long duration of DM of 10 years in his study while our patient population was newly diagnosed. ...
Background:
The prevalence of Diabetes mellitus (DM) is on a rise in sub-Saharan Africa and will more than double by 2025. Cardiovascular disease (CVD) accounts for up to 2/3 of all deaths in the diabetic population. Of all the CVD deaths in DM, 3/4 occur in sub Saharan Africa (SSA). Non invasive identification of cardiac abnormalities, such as Left Ventricular Hypertrophy (LVH), diastolic and systolic dysfunction, is not part of diabetes complications surveillance programs in Uganda and there is limited data on this problem. This study sought to determine the prevalence, types and factors associated with echocardiographic abnormalities among newly diagnosed diabetic patients at Mulago National referral hospital in Uganda.
Methods:
In this cross sectional study conducted between June 2014 and December 2014, we recruited 202 newly diagnosed adult diabetic patients. Information on patients' socio-demographics, bio-physical profile, biochemical testing and echocardiographic findings was obtained for all the participants using a pre-tested questionnaire. An abnormal echocardiogram in this study was defined as the presence of LVH, diastolic and/or systolic dysfunction and wall motion abnormality. Bivariate and multivariate logistic regression analyses were used to investigate the association of several parameters with echocardiographic abnormalities.
Results:
Of the 202 patients recruited, males were 102(50.5%) and the mean age was 46±15 years. Majority of patients had type 2 DM, 156(77.2%) and type 1 DM, 41(20.3%) with mean HbA1C of 13.9±5.3%. Mean duration of diabetes was 2 months. The prevalence of an abnormal echocardiogram was 67.8 % (95% CI 60%-74%). Diastolic dysfunction, systolic dysfunction, LVH and wall motion abnormalities were present in 55.0%, 21.8%, 19.3% and 4.0% of all the participants respectively. In bivariate logistic regression analysis, the factors associated with an abnormal echocardiogram were age (OR 1.09 [95% CI 1.06-1.12], P <0.0001), type 2 DM (OR 5.8[95% CI 2.77-12.07], P<0.0001), hypertension (OR 2.64[95% CI 1.44-4.85], P=0.002), obesity (OR 3.51[955 CI 1.25-9.84], P=0.017 and increased waist circumference (OR 1.02[95% CI 1.00-1.04], P=0.024. On Multiple logistic regression analysis, age was the only factor associated with an abnormal echocardiogram (OR 1.09[95%CI 1.05-1.15], P<0.0001).
Conclusion:
Echocardiographic abnormalities were common among newly diagnosed adults with DM. Traditional CVD risk factors were associated with an abnormal echocardiogram in this patient population. Due to a high prevalence of echocardiographic abnormalities among newly diagnosed diabetics, we recommend screening for cardiac disease especially in patients who present with traditional CVD risk factors. This will facilitate early diagnosis, management and hence better patient outcomes.
... In man, CTGF gene expression is increased in ischaemic cardiac tissue [4] , and both CTGF gene and protein expression are upregulated in experimental models of cardiac injury and diabetes, and associated with ongoing cardiac fibrosis [5,78910 . Cardiac fibrosis increases the mechanical stiffness of the heart, which impairs myocardial contractility and contributes to left ventricular (LV) hypertrophy (LVH), and both diastolic and systolic dysfunction111213. Overexpression of CTGF is also thought to play a role in mediating glomerulosclerosis and tubulointerstitial fibrosis, key features of diabetic kidney disease, in both experimental models and in man14151617. ...
... Ethical approval was obtained from the Human Research Ethics Committee at Austin Health, Melbourne and participants provided consent. The study included 495 subjects with type 2 diabetes, prospectively recruited at attendance for transthoracic echocardiography as part of a complications surveillance program at Austin Health, Melbourne, Australia as previously described [13,23]. Subjects of non-European ancestry were excluded. ...
... Hypertension was defined as present if participants were on anti-hypertensive medication , had a history of hypertension and/or had evidence of hypertension (clinic blood pressure >130/80 mmHg) [24]. Urinary albumin excretion rate was estimated from a 24-hour urine collection and glycosylated hemoglobin (HbA 1c ) and fasting plasma glucose was measured as previously described [13]. The eGFR was calculated using the four component abbreviated MDRD equation [25]. ...
Connective tissue growth factor (CTGF) has been implicated in the cardiac and kidney complications of type 2 diabetes, and the CTGF -945 G/C polymorphism is associated with susceptibility to systemic sclerosis, a disease characterised by tissue fibrosis. This study investigated the association of the CTGF -945 G/C promoter variant with cardiac complications (left ventricular (LV) hypertrophy (LVH), diastolic and systolic dysfunction) and chronic kidney disease (CKD) in type 2 diabetes.
The CTGF -945 G/C polymorphism (rs6918698) was examined in 495 Caucasian subjects with type 2 diabetes. Cardiac structure and function were assessed by transthoracic echocardiography. Kidney function was assessed using estimated glomerular filtration rate (eGFR) and albuminuria, and CKD defined as the presence of kidney damage (decreased kidney function (eGFR <60 ml/min/1.73 m2) or albuminuria).
The mean age ± SD of the cohort was 62 ± 14 years, with a body mass index (BMI) of 31 ± 6 kg/m2 and median diabetes duration of 11 years [25th, 75th interquartile range; 5, 18]. An abnormal echocardiogram was present in 73% of subjects; of these, 8% had LVH alone, 74% had diastolic dysfunction and 18% had systolic ± diastolic dysfunction. CKD was present in 42% of subjects. There were no significant associations between the CTGF -945 G/C polymorphism and echocardiographic parameters of LV mass or cardiac function, or kidney function both before and after adjustment for covariates of age, gender, BMI, blood pressure and hypertension. CTGF -945 genotypes were not associated with the cardiac complications of LVH, diastolic or systolic dysfunction, nor with CKD.
In Caucasians with type 2 diabetes, genetic variation in the CTGF -945 G/C polymorphism is not associated with cardiac or kidney complications.
... Several studies defined DbCM as LVD consisting of both LV systolic dysfunction (LVSD) and LVDD, with or without LVH [8][9][10]44]. Existing results indicate that a common form of DbCM is LVDD, often characterized by a restrictive pattern, in the presence of preserved LVEF [4,8,9,16,45,46]. In previous studies of asymptomatic T2D populations with various comorbidities, such as HTN (66%-86% of patients) and CAD (19%-36% of patients), 25%-38% of patients had newly detected echocardiographic features of LVDD while only 3% of patients had LVSD [10,44]. ...
... DbCM is associated with an increased risk of progression to overt HF. It was previously shown that up to 24% of patients with DbCM/SBHF progress to SCHF or death within 1.5 years and 37% within 5 years [2,45]. In the study of Dandamudi et al. [8], 31% of patients with DbCM died or developed HF at 9 years. ...
Background
Diabetic cardiomyopathy (DbCM) is characterized by asymptomatic stage B heart failure (SBHF) caused by diabetes-related metabolic alterations. DbCM is associated with an increased risk of progression to overt heart failure (HF). The prevalence of DbCM in patients with type 2 diabetes (T2D) is not well established. This study aims to determine prevalence of DbCM in adult T2D patients in real-world clinical practice.
Methods
Retrospective multi-step review of electronic medical records of patients with the diagnosis of T2D who had echocardiogram at UC San Diego Medical Center (UCSD) within 2010–2019 was conducted to identify T2D patients with SBHF. We defined “pure” DbCM when SBHF is associated solely with T2D and “mixed” SBHF when other medical conditions can contribute to SBHF. “Pure” DbCM was diagnosed in T2D patients with echocardiographic demonstration of SBHF defined as left atrial (LA) enlargement (LAE), as evidenced by LA volume index ≥ 34 mL/m², in the presence of left ventricular ejection fraction (LVEF) ≥ 45%, while excluding overt HF and comorbidities that can contribute to SBHF.
Results
Of 778,314 UCSD patients in 2010–2019, 45,600 (5.9%) had T2D diagnosis. In this group, 15,182 T2D patients (33.3%) had echocardiogram and, among them, 13,680 (90.1%) had LVEF ≥ 45%. Out of 13,680 patients, 4,790 patients had LAE. Of them, 1,070 patients were excluded due to incomplete data and/or a lack of confirmed T2D according to the American Diabetes Association recommendations. Thus, 3,720 T2D patients with LVEF ≥ 45% and LAE were identified, regardless of HF symptoms. In this group, 1,604 patients (43.1%) had overt HF and were excluded. Thus, 2,116 T2D patients (56.9% of T2D patients with LVEF ≥ 45% and LAE) with asymptomatic SBHF were identified. Out of them, 1,773 patients (83.8%) were diagnosed with “mixed” SBHF due to comorbidities such as hypertension (58%), coronary artery disease (36%), and valvular heart disease (17%). Finally, 343 patients met the diagnostic criteria of “pure” DbCM, which represents 16.2% of T2D patients with SBHF, i.e., at least 2.9% of the entire T2D population in this study.
Conclusions
Our findings provide insights into prevalence of DbCM in real-world clinical practice and indicate that DbCM affects a significant portion of T2D patients.
... LVH is diagnosed by electrocardiography, echocardiography or cardiac magnetic resonance imaging. The prevalence of LVH in the general population is 10% [1] but rises to 40-70% in those with risk factors such as hypertension, aortic stenosis, diabetes and chronic kidney disease [2][3][4][5]. As LVH per se causes no symptoms (preclinical), it is often only diagnosed after patients present with symptoms such as heart failure [1]. ...
... Conventional risk factors do not explain all the variability in LVH [23], and a heritable component underlying LVH is recognized. We recently explored the genetic association of KLF15 single nucleotide polymorphisms (SNP) in patients with type 2 diabetes and an echocardiographic assessment of LV mass [2]. The intronic KLF15 SNP rs9838915 A allele was significantly associated with LV mass and the association was replicated in an independent cohort of >5000 type 2 diabetes patients ( Table 3). ...
Left ventricular hypertrophy (LVH) is an independent risk factor for adverse cardiovascular events and is often present in patients with hypertension. Treatment to reduce blood pressure and regress LVH is key to improving health outcomes, but currently available drugs have only modest cardioprotective effects. Improved understanding of the molecular mechanisms involved in the development of LVH may lead to new therapeutic targets in the future. There is now compelling evidence that the transcription factor Kruppel-like factor 15 (KLF15) is an important negative regulator of cardiac hypertrophy in both experimental models and in man. Studies have reported that loss or suppression of KLF15 contributes to LVH, through lack of inhibition of pro-hypertrophic transcription factors and stimulation of trophic and fibrotic signaling pathways. This review provides a summary of the experimental and human studies that have investigated the role of KLF15 in the development of cardiac hypertrophy. It also discusses our recent paper that described the contribution of genetic variants in KLF15 to the development of LVH and heart failure in high-risk patients.
... Diastolic dysfunction has been recognized to be more severe in diabetic patients than in those without diabetes [34], and it is also linked to a worse prognosis in these patients [35]. A prevalence rate of 25% to 75% of LV diastolic dysfunction has been reported in diabetic patients [36][37][38][39][40], compared to 5% to 21.8% for LV systolic dysfunction [36,40,41]. Therefore, LV diastolic function appears to be a more useful predictor of CV events than LV systolic function. ...
... Diastolic dysfunction has been recognized to be more severe in diabetic patients than in those without diabetes [34], and it is also linked to a worse prognosis in these patients [35]. A prevalence rate of 25% to 75% of LV diastolic dysfunction has been reported in diabetic patients [36][37][38][39][40], compared to 5% to 21.8% for LV systolic dysfunction [36,40,41]. Therefore, LV diastolic function appears to be a more useful predictor of CV events than LV systolic function. ...
The association between DM and left ventricular diastolic dysfunction, assessed using the ratio of peak early transmitral filling wave velocity (E) to early diastolic velocity of mitral annulus (Ea), with cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD) remains uncertain. This study included 356 CKD stage 3-5 patients underwent echocardiography. All patients were classified into four groups based on the presence of DM and E/Ea ≤ or > 9. CV events included CV death, hospitalization for heart failure, unstable angina or nonfatal myocardial infarction, sustained ventricular arrhythmia, transient ischemic attack, and stroke. There were 58 CV events during the mean observation period of 25.0 months. A combination of the presence of DM and E/Ea > 9 (vs. a combination of non-DM and E/Ea ≤ 9) was associated with CV events in unadjusted model (hazard ratio [HR], 6.990; 95% confidence interval [CI], 2.753-17.744; p < 0.001), and in a multivariate adjusted model (HR, 3.037; 95% CI, 2.088-7.177; p = 0.025). In the patients without DM, the E/Ea ratio (p = 0.033) improved the prediction of CV events, compared to the E/ Ea ratio (p = 0.018), left atrial diameter (p = 0.016) and left ventricular mass index (p = 0.001) in the patients with DM. The combination of DM and left ventricular diastolic dysfunction was associated with CV events in patients with CKD stage 3-5. Assessments of DM status and E/Ea ratio may facilitate identifying high-risk patient population of unfavorable CV outcomes.
... Cardiac function abnormalities on echography have been extensively described but hypertension and/or CAD have not been always excluded in the cohorts studied. Previous large studies have shown that left ventricle (LV) structure abnormalities including hypertrophy and/or concentric remodelling, diastolic filling, and relaxation alterations are often present in early stages of diabetes mellitus, before symptomatic heart failure [2][3][4][5][6]. However, these findings were not specific to diabetic cardiomyopathy as ischemic status was not always assessed in these studies. ...
... Recently, other studies using tissue Doppler or strain rate parameters have also shown early and subclinical systolic impairment [8][9][10][11] and systolic dysfunction may precede diastolic dysfunction [12]. In those latter papers [8][9][10][11], although myocardial ischemia was excluded, some patients had hypertension and the number of patients was much smaller than in former papers [2][3][4][5][6]. Cardiac echographic features may be associated with diabetes and most often with older age, male gender, higher body mass index (BMI), hypertension, renal dysfunction, or other metabolic parameters such as dyslipidemia [2,3,12,13]. ...
Aim. Our aim was to assess the prevalence of subclinical diabetic cardiomyopathy, occurring among diabetic patients without hypertension or coronary artery disease (CAD). Methods. 656 asymptomatic patients with type 2 diabetes for 14 ± 8 years (359 men, 59.7 ± 8.7 years old, HbA1c 8.7 ± 2.1%) and at least one cardiovascular risk factor had a cardiac echography at rest, a stress cardiac scintigraphy to screen for silent myocardial ischemia (SMI), and, in case of SMI, a coronary angiography to screen for silent CAD. Results. SMI was diagnosed in 206 patients, and 71 of them had CAD. In the 157 patients without hypertension or CAD, left ventricular hypertrophy (LVH: 24.1%) was the most frequent abnormality, followed by left ventricular dilation (8.6%), hypokinesia (5.3%), and systolic dysfunction (3.8%). SMI was independently associated with hypokinesia (odds ratio 14.7 [2.7-81.7], p < 0.01) and systolic dysfunction (OR 114.6 [1.7-7907], p < 0.01), while HbA1c (OR 1.9 [1.1-3.2], p < 0.05) and body mass index (OR 1.6 [1.1-2.4], p < 0.05) were associated with systolic dysfunction. LVH was more prevalent among hypertensive patients and hypokinesia in the patients with CAD. Conclusion. In asymptomatic type 2 diabetic patients, diabetic cardiomyopathy is highly prevalent and is predominantly characterized by LVH. SMI, obesity, and poor glycemic control contribute to structural and functional LV abnormalities.
... The extant literature suggests that LVH is widespread among individuals with T2D [40]. However, our study found that only 3.8% of T2D patients had LVH detected through ECG, notably lower than the previously reported estimates of LVH prevalence in T2D, ranging from 32 to 71% [40][41][42][43]. This discrepancy could be attributed to different diagnostic tools across studies, with most studies using echocardiography to detect LVH. ...
Background
Left ventricular hypertrophy (LVH) strongly predicts cardiovascular diseases (CVD) and death. One-fourth of Thai adults suffer from hypertension. Nevertheless, the information on LVH among Thai patients with hypertension is not well characterized. We aimed to identify the prevalence and factors associated with electrocardiographic LVH (ECG-LVH) among patients with hypertension in Thailand.
Methods
The present study obtained the dataset from the Thailand Diabetes Mellitus/Hypertension study, which included hypertension patients aged 20 years and older receiving continuous care at outpatient clinics in hospitals nationwide in 2011–2015 and 2018. Meanwhile, those without a record of 12-lead electrocardiography (ECG) were excluded from the analysis. ECG-LVH was defined as the LVH noted regarding ECG interpretation in the medical records. Multivariable logistic regression analysis was utilized for determining factors associated with ECG-LVH and presented as the adjusted odds ratio (AOR) and 95% confidence interval (CI).
Results
From 226,420 hypertensive patients in the Thailand Diabetes Mellitus/Hypertension study, 38,807 individuals (17.1%) with ECG data recorded were included in the analysis. The mean age was 64.8 ± 11.5 years, and 62.2% were women. Overall, 1,557 study participants had ECG-LVH, with an estimated prevalence of 4.0% (95% CI, 3.8–4.2%). Age-adjusted ECG-LVH prevalence among women and men was 3.4 and 5.1%, respectively ( P < 0.001). Multivariable analysis determined factors associated with ECG-LVH, including being men (AOR, 1.49; 95% CI, 1.31–1.69), individuals aged 70 to 79 years (AOR, 1.56; 95% CI, 1.20–2.02) and ≥ 80 years (AOR, 2.10; 95% CI, 1.58–2.78) compared to individuals aged less than 50 years, current smokers (AOR, 1.26; 95% CI, 1.09–1.46) compared to those who never smoked, systolic blood pressure ≥ 140 mmHg and diastolic blood pressure ≥ 90 mmHg (AOR, 1.58; 95% CI, 1.30–1.92) compared to systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg.
Conclusions
The current study illustrated the prevalence of ECG-LVH among Thai patients with hypertension who had ECG recorded and identified high-risk groups who tended to have ECG-LVH. The findings underscore the need for targeted interventions, particularly among high-risk groups such as older individuals, men, and current smokers, to address modifiable factors associated with ECG-LVH.
... Although HF with systolic dysfunction is commonly mentioned in clinical trials, HFpEF has raised increasing attention recently. Observation studies have demonstrated that diastolic dysfunction is prevalent in types 1 and 2 DM [16,17]. Left ventricular (LV) diastolic dysfunction is also common in patients with pre-DM [18]. ...
The coexistence of diabetes mellitus (DM) and heart failure (HF) is frequent and is associated with a higher risk of hospitalization for HF and all-cause and cardiovascular mortality. It has been estimated that millions of people are affected by HF and DM, and the prevalence of both conditions has increased over time. Concomitant HF and diabetes confer a worse prognosis than each alone; therefore, managing DM care is critical for preventing HF. This article reviews the prevalence of HF and diabetes and the correlated prognosis as well as provides a basic understanding of diabetic cardiomyopathy, including its pathophysiology, focusing on the relationship between DM and HF with a preserved ejection fraction and summarizes the potential aldosterone and the mineralocorticoid receptor antagonists approaches for managing heart failure and DM. Sodium–glucose cotransporter 2 inhibitors (SGLT2Is) are an emerging class of glucose-lowering drugs, and the role of SGLT2Is in DM patients with HF was reviewed to establish updated and comprehensive concepts for improving optimal medical care in clinical practice.
... Heart valve anatomy and function were assessed and these parameters together with those of chamber function were used to grade valvular lesions. echocardiographic abnormalities in patients on haemodialysis in Uganda LVH was defined as interventricular septum and/or left ventricular posterior wall diameter >11 mm [18]. Systolic dysfunction was defined by evidence of an EF <50% [19]. ...
Background: Cardiovascular disease is the most common cause of morbidity and premature mortality in patients on chronic haemodialysis. There are limited data on cardiac abnormalities among these patients in sub-Saharan Africa, including Uganda. We determined the prevalence and patterns of echocardiographic (echo) abnormalities among patients with end-stage renal disease (ESRD) on haemodialysis at Mulago National Referral Hospital, Kampala, Uganda. Methods: Eighty patients with ESRD on chronic haemodialysis were enrolled in the study over a period of five months from November 2017 to March 2018. We collected data on demographic and baseline clinical characteristics by reviewing charts and conducting patient interviews. Participants had blood pressure measurements performed and blood samples taken for laboratory investigations. We then conducted a cardiac evaluation using standard transthoracic echo protocols. Bivariable and multivariable analysis was performed to study associations with left ventricular hypertrophy and diastolic dysfunction. Results: Fifty-three of the 80 patients (66%) were male, mean age was 49 ± 16 years and the median duration on dialysis was 9.5 months (interquartile range 4–24 months). Twenty-eight (35%) had to travel >50 km to access dialysis. Seventy-four patients (93%) had at least one cardiac echo abnormality and 30% had at least three abnormalities. Left ventricular hypertrophy (68%) and diastolic dysfunction (64%) were the most common abnormalities. There was a high prevalence of factors that have previously been associated with left ventricular hypertrophy and diastolic dysfunction including anaemia (79%), poorly controlled hypertension (79%) and dyslipidaemia (56%) but none of these was statistically significantly associated in this study. Conclusions: Our study confirmed a high prevalence of cardiac abnormalities among a young population of African patients with ESRD on chronic dialysis. We recommend that echocardiography be part of the routine care to help plan early intervention for those at high risk of cardiovascular events.
... Diastolic dysfunction in vivo, as typically clinically indexed by elevated ratio of the left ventricular blood/tissue Doppler signals (E/e'), was apparent in both T1D and T2D rodent models (Figure 1e). The elevated E/e' levels recorded were commensurate with shifts considered clinically diagnostic of diastolic failure 33,34 . In T2D, no evidence of altered systolic function was detected, while small but significant reductions in ejection fraction and fractional shortening were observed in T1D animals where the diabetes phenotype was more progressed (Figure S2a-d). ...
Diabetic heart disease is highly prevalent and characterized by diastolic dysfunction. The mechanisms of diabetic heart disease are poorly understood and no targeted therapies are available. Here we show that the diabetic myocardium (type 1 and type 2) is characterized by marked glycogen elevation and ectopic cellular localization - a paradoxical metabolic pathology given suppressed cardiomyocyte glucose uptake in diabetes. We demonstrate involvement of a glycogen-selective autophagy pathway ('glycophagy') defect in mediating this pathology. Genetically manipulated deficiency of Gabarapl1, an Atg8 autophagy homologue, induces cardiac glycogen accumulation and diastolic dysfunction. Stbd1, the Gabarapl1 cognate autophagosome partner is identified as a unique component of the early glycoproteome response to hyperglycemia in cardiac, but not skeletal muscle. Cardiac-targeted in vivo Gabarapl1 gene delivery normalizes glycogen levels, diastolic function and cardiomyocyte mechanics. These findings reveal that cardiac glycophagy is a key metabolic homeostatic process perturbed in diabetes that can be remediated by Gabarapl1 intervention.
... When the glucose increases in the blood it can cause serious complications including: Cardiomyopathy, nephropathy, neuropathy, and retinopathy (5). Diabetes is a major risk factor for coronary artery disease and cardiovascular disease (6) is the most important cause of morbidity and mortality in patients with type 2 diabetes, accounting for approximately two-thirds of total mortality (7). Diastolic dysfunction has been described as an early sign of diabetic heart muscle disease preceding systolic damage (8) it is associated with future occurrence of heart failure, is a predictor of cardiovascular morbidity and mortality in the general population (9). ...
Background: Diabetes mellitus (DM) causes damaging effects on the cardiac function; these effects can be observed on the diastolic performance of the heart reflected on the change in transmitral blood velocity, the cardiac wall and septum thickness. Objectives: The present study was to assess the diastolic and systolic cardiac muscle performance for patients with type 2 diabetes mellitus compared with control individuals and to evaluate the index of myocardial performance. Patients and Methods: The study involved 97 patients (35 male and 62 female of average age of 56.2 ±10.755) of type 2 diabetes mellitus (DM), they were investigated for their left ventricle performance and compared with 51 normal individuals "the control group" (20 male and 31 female of average age of 41.4 ± 13.196). Measurements of isovolumetric contraction time IVCT, ejection time ET, ejection fraction EF%, isovolumetric relaxation time IVRT, the early and late peak velocities E and A of transmitral flow, left ventricle diameter in diastole and systole LVIDs, LVIDs, posterior wall thickness PWTd, and Interventricular septum thickness in diastole IVSTd were measured, and index of myocardial performance IMP was calculated. Results: Results reveal differences in these parameters for patients group relative to controls, in IVRT, ET, E, A, E/A, EF%, IMP, LVIDs, PWTd and IVSTd all are strongly significant with p value <0.001and for FS% p value = 0.0029 except for IVCT the change was 9.342% with p value 0.188 and the change in LVIDd-3.586%, p value 0.052 were not significant. Conclusion: Diabetes mellitus can cause a deleterious effect on the myocardium. The effect causes impairment in the cardiac diastolic performance and muscle contractility caused by the damage inflicted by hyperglycemia (high blood sugar). Also results show that IMP is increased in type 2 DM patients. This increase may be an early sign of diabetic cardiomyopathy in diabetic patients. Introduction:
... The study showed that one in five had a normal first cardiac echocardiogram, however, had developed an abnormal second echocardiogram with progressive changes such as a reduced peak septal mitral annular systolic velocity (S ), increased A wave velocity, increased deceleration time, and a reduced e' and E/e' ratio (Wai et al., 2014). In patients with T2D, age is the strongest predictor of declining cardiac function with the risk of an abnormal echocardiogram increasing by 9% for each year over 50 years of age (Srivastava et al., 2008). The potential mechanisms leading to this progressive decline in diastolic function remain to be determined. ...
The incidence of diabetes and its association with increased cardiovascular disease risk represents a major health issue worldwide. Diabetes-induced hyperglycemia is implicated as a central driver of responses in the diabetic heart such as cardiomyocyte hypertrophy, fibrosis, and oxidative stress, termed diabetic cardiomyopathy. The onset of these responses in the setting of diabetes has not been studied to date. This study aimed to determine the time course of development of diabetic cardiomyopathy in a model of type 1 diabetes (T1D) in vivo. Diabetes was induced in 6-week-old male FVB/N mice via streptozotocin (55 mg/kg i.p. for 5 days; controls received citrate vehicle). At 2, 4, 8, 12, and 16 weeks of untreated diabetes, left ventricular (LV) function was assessed by echocardiography before post-mortem quantification of markers of LV cardiomyocyte hypertrophy, collagen deposition, DNA fragmentation, and changes in components of the hexosamine biosynthesis pathway (HBP) were assessed. Blood glucose and HbA1c levels were elevated by 2 weeks of diabetes. LV and muscle (gastrocnemius) weights were reduced from 8 weeks, whereas liver and kidney weights were increased from 2 and 4 weeks of diabetes, respectively. LV diastolic function declined with diabetes progression, demonstrated by a reduction in E/A ratio from 4 weeks of diabetes, and an increase in peak A-wave amplitude, deceleration time, and isovolumic relaxation time (IVRT) from 4–8 weeks of diabetes. Systemic and local inflammation (TNFα, IL-1β, CD68) were increased with diabetes. The cardiomyocyte hypertrophic marker Nppa was increased from 8 weeks of diabetes while β-myosin heavy chain was increased earlier, from 2 weeks of diabetes. LV fibrosis (picrosirius red; Ctgf and Tgf-β gene expression) and DNA fragmentation (a marker of cardiomyocyte apoptosis) increased with diabetes progression. LV Nox2 and Cd36 expression were elevated after 16 weeks of diabetes. Markers of the LV HBP (Ogt, Oga, Gfat1/2 gene expression), and protein abundance of OGT and total O-GlcNAcylation, were increased by 16 weeks of diabetes. This is the first study to define the progression of cardiac markers contributing to the development of diabetic cardiomyopathy in a mouse model of T1D, confirming multiple pathways contribute to disease progression at various time points.
... In accordance with previous findings, several sociodemographic and clinical covariates of pathophysiological outcomes were found. Diabetes, a well-known risk factor for HF disease progression [39][40][41], was associated with increased inflammation and poor hematological function. Increasing age was associated with increased systemic inflammation and renal dysfunction. ...
Background
Self-care is assumed to benefit physiological function associated with prognosis in patients with chronic HF, but studies examining these relations are lacking. This study aims to prospectively examine the association of self-reported HF self-care with HF-associated pathophysiological markers, including renal, hematological, and immune function.
Method
Patients with chronic HF (n = 460, 66.2 ± 9.6 years, 75% men) completed questionnaires and provided blood samples at baseline and 12-month follow-up. Linear mixed models examined random intercept and fixed between- and within-subjects effects of global self-care and the individual self-care behaviors on log-transformed TNF-α, IL-6, and IL-10, the glomerular filtration rate of creatinine (GFRcreat), and hemoglobin (Hb), controlling for sociodemographic and clinical covariates.
Results
Self-care was independently associated with lower GFRcreat levels (β = − .14, P = .023) and improvement in self-care with a reduction in GFRcreat (β = − .03, P = .042). Individual self-care behaviors were differentially associated with renal, inflammatory, and hematological markers. Regular exercise was associated with level differences in IL-6 (P < .001), and improvement in exercise was associated with increasing GFRcreat (P = .002) and increasing Hb (P = .010). Fluid restriction was associated with lower overall GFRcreat (P = .006), and improvement in fluid restriction was associated with decreasing GFRcreat (P = .014). Low-sodium intake was associated with lower levels of Hb (P = .027), lower TNF-alpha (P = .011), and lower IL-10 (P = .029). Higher levels of medication adherence were associated with reduced pro-inflammatory activation (P < .007).
Conclusion
Our findings suggest that better global self-care was associated with poorer renal function. Performing self-care behaviors such as regular exercise and medication adherence was associated with improved physiological functioning, while restriction of fluid and sodium, and the associated daily weight monitoring were associated with adverse levels of pathophysiological biomarkers.
... Long-term haemodynamic changes in chronic anemia increase the workload and volume burden of the heart, cause remodeling of myocytes and vessels and hypertrophy is observed on the left ventricle (LV) [6,7]. Several published studies support the relationship between anemia and LV diastolic dysfunction in patients with cardiovascular disease, but the results are in conflict and the relationship between anemia and diastolic dysfunction is still unclear [8][9][10]. ...
There are few data on the effects of low hemoglobine levels on the left atrium (LA) in anemic patients. Our aim was to evaluate left atrial (LA) volume and functions in anemic patients using real time three-dimensional echocardiography (RT3DE) and also to investigate changes in variables of LA after the correction of anemia. In total, 55 iron-deficiency anemia patients without traditional cardiovascular (CV) risk factors and 30 age- and gender-matched controls were studied. Assessments included history, physical examination and echocardiography. Of the 55 patients with anemia enrolled, 50 (39 females and 11 males 40.3 years) were followed and underwent echocardiography after correction of the anemia. LA maximum volume (LAVmax), LA minimal volume (LAVmin), LAVmax index (LAVI), before atrial contraction volume (LAVpreA), LA total emptying fraction, LA active emptying volume were higher in anemic patients. LA passive emptying fraction was significantly lower in anemic patients. Following correction of anemia, LA volume and function parameters were observed to be significantly reduced. Moreover, significant increase was noted in LA passive emptying fraction. Correlation analysis was performed and a significant negative correlation was noted between the percentage change in hemoglobin level and percentage change in LAVI (r = − 0.382, p = 0.003). It was shown that volume and functions of LA are impaired in anemic patients. However impaired parameters were improved after correction of anemia. It may be thought that RT3DE LA parameters can be used as an important preclinical marker of disease pathogenesis before developing heart failure or atrial arrhythmia.
... Study characteristics and quality assessment of all the 28 included studies are shown in Table 1. Of all the included studies, the majority included participants derived from a hospital setting (n = 18), [13][14][15]20,21,[29][30][31][32][33][34][35][36][37][38][39][40][41] six studies recruited their participants from the population at large 18,[42][43][44][45][46] and four studies failed to report where they had selected their participants from. [47][48][49][50] Data on the prevalence of LVDD were available in 27 studies and data on HFpEF in two studies (Table 1). ...
Objective:
Type 2 diabetes is a risk factor for the development of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction. Our aim was to provide a summary estimate of the prevalence of left ventricular diastolic dysfunction and heart failure with preserved ejection fraction in type 2 diabetes patients and to investigate sex disparities.
Methods and results:
A systematic search of the databases Medline and Embase was conducted for studies reporting the prevalence of left ventricular diastolic dysfunction or heart failure with preserved ejection fraction among type 2 diabetes patients. Studies were only included if echocardiography was performed. Prevalence estimates were pooled using random-effects meta-analysis. A total of 28 studies were included. Data on the prevalence of left ventricular diastolic dysfunction were available in 27 studies. The pooled prevalence for left ventricular diastolic dysfunction in the hospital population (2959 type 2 diabetes participants) and in the general population (2813 type 2 diabetes participants) was 48% [95% confidence interval: 38%-59%] and 35% (95% confidence interval: 24%-46%), respectively. Heterogeneity was high in both populations, with estimates ranging from 19% to 81% in the hospital population and from 23% to 54% in the general population. For women and men, the pooled prevalence estimates of left ventricular diastolic dysfunction were 47% (95% confidence interval: 37%-58%) and 46% (95% confidence interval: 37%-55%), respectively. Only two studies presented the prevalence of heart failure with preserved ejection fraction; 8% (95% confidence interval: 5%-14%) in a hospital population and 25% (95% confidence interval: 21%-28%) in the general population [18% in men (mean age: 73.8; standard deviation: 8.6) and 28% in women (mean age: 74.9; standard deviation: 6.9)].
Conclusion:
The prevalence of left ventricular diastolic dysfunction among type 2 diabetes patients is similarly high in men and women, while heart failure with preserved ejection fraction seems to be more common in women than men, at least in community people with type 2 diabetes.
... The majority of these hospital setting studies were in the outpatient setting with only one including hospitalized patients. Four studies consisted of patients from the general population [2,[31][32][33]. All studies consisted of data regarding the prevalence of LVSD with only one study containing data on the prevalence of HFrEF in addition to LVSD (Table 1) [2]. ...
Background:
Type 2 diabetes mellitus (T2D) is associated with the development of left ventricular systolic dysfunction (LVSD) and heart failure with reduced ejection fraction (HFrEF). T2D patients with LVSD are at higher risk of mortality and morbidity than patients without LVSD, while progression of LVSD can be delayed or halted by the use of proven therapies. As estimates of the prevalence are scarce and vary considerably, the aim of this study was to retrieve summary estimates of the prevalence of LVSD/HFrEF in T2D and to see if there were any sex differences.
Methods:
A systematic search of Medline and Embase was performed to extract the prevalence of LVSD/HFrEF in T2D (17 studies, mean age 50.1 ± 6.3 to 71.5 ± 7.5), which were pooled using random-effects meta-analysis.
Results:
The pooled prevalence of LVSD was higher in hospital populations (13 studies, n = 5835, 18% [95% CI 17-19%]), than in the general population (4 studies, n = 1707, 2% [95% CI 2-3%]). Seven studies in total reported sex-stratified prevalence estimates (men: 7% [95% CI 5-8%] vs. women: 1.3% [95% CI 0.0.2.2%]). The prevalence of HFrEF was available in one general population study (5.8% [95% CI 3.7.6%], men: 6.8% vs. women: 3.0%).
Conclusions:
The summary prevalence of LVSD is higher among T2D patients from a hospital setting compared with from the general population, with a higher prevalence in men than in women in both settings. The prevalence of HFrEF among T2D in the population was only assessed in a single study and again was higher among men than women.
... The lower reported annual incidence of HF (0.2 per thousand) (7) and myocardial dysfunction (1 per 1,000) in type 1 DM (8) likely reflects the study of these in younger age groups. Nonetheless, subclinical evidence of diastolic dysfunction is observed in both types 1 and 2 diabetes, even in the absence of other comorbidities such as hypertension (9,10). ...
Heart failure is a complex clinical syndrome, the incidence and prevalence of which is increased in diabetes mellitus, pre-diabetes, and obesity. Although this may arise from underlying coronary artery disease, it often occurs in the absence of significant major epicardial coronary disease, and most commonly manifests as heart failure with preserved ejection fraction. Despite epidemiological evidence linking diabetes to heart failure incidence and outcome, the presence of a distinct primary "diabetic" cardiomyopathy has been difficult to prove, because the link between diabetes and heart failure is confounded by hypertension, microvascular dysfunction, and autonomic neuropathy. Nonetheless, several mechanistic associations at systemic, cardiac, and cellular/molecular levels explain different aspects of myocardial dysfunction, including impaired cardiac relaxation, compliance, and contractility. This review seeks to describe recent advances and limitations pertinent to integrating molecular mechanisms, clinical screening, and potential therapeutic avenues for this condition.
... 17 Left ventricular diastolic dysfunction was assessed noninvasively using echocardiography according to the ESC heart failure guidelines. 3 We started with 23 potential diagnostic predictors known from the literature of diagnostic studies evaluating those suspected of heart failure from primary care [11][12][13][14][18][19][20][21] and from the four primary care screening studies. The potential predictors were demographics (age, sex), medical history (ischaemic heart disease (IHD), atrial fibrillation, COPD or asthma, hypertension, peripheral vascular disease, diabetes mellitus), symptoms (dyspnoea leading at least to stop at a normal pace (Medical Respiratory Council (MRC) questionnaire (MRC 3)), orthopnoea, paroxysmal nocturnal dyspnoea), signs (systolic and diastolic blood pressure, heart rate, irregularity of pulse, body mass index (BMI), ankle oedema, pulmonary crepitations, raised jugular venous pressure, laterally displaced or broadened/sustained apex beat, hepatomegaly), NTproBNP and electrocardiogram (ECG). ...
Background
Prevalence of undetected heart failure in older individuals is high in the community, with patients being at increased risk of morbidity and mortality due to the chronic and progressive nature of this complex syndrome. An essential, yet currently unavailable, strategy to pre-select candidates eligible for echocardiography to confirm or exclude heart failure would identify patients earlier, enable targeted interventions and prevent disease progression. The aim of this study was therefore to develop and validate such a model that can be implemented clinically.
Methods and results
Individual patient data from four primary care screening studies were analysed. From 1941 participants >60 years old, 462 were diagnosed with heart failure, according to criteria of the European Society of Cardiology heart failure guidelines. Prediction models were developed in each cohort followed by cross-validation, omitting each of the four cohorts in turn. The model consisted of five independent predictors; age, history of ischaemic heart disease, exercise-related shortness of breath, body mass index and a laterally displaced/broadened apex beat, with no significant interaction with sex. The c-statistic ranged from 0.70 (95% confidence interval (CI) 0.64–0.76) to 0.82 (95% CI 0.78–0.87) at cross-validation and the calibration was reasonable with Observed/Expected ratios ranging from 0.86 to 1.15. The clinical model improved with the addition of N-terminal pro B-type natriuretic peptide with the c-statistic increasing from 0.76 (95% CI 0.70–0.81) to 0.89 (95% CI 0.86–0.92) at cross-validation.
Conclusion
Easily obtainable patient characteristics can select older men and women from the community who are candidates for echocardiography to confirm or refute heart failure.
... The Melbourne Diabetes Heart Cohort includes patients with type 2 diabetes and no known cardiac disease who were prospectively recruited at the time of transthoracic echocardiography, which was performed as part of the diabetes complications surveillance program at Austin Health, Melbourne (Srivastava et al., 2008;Patel et al., 2012a,b). Patients with a clinically indicated echocardiogram, a past history of heart failure or with moderate/severe valvular dysfunction on the echocardiographic study were excluded. ...
Left ventricular (LV) hypertrophy (LVH) is a heritable trait that is common in type 2 diabetes and is associated with the development of heart failure. The transcriptional factor Kruppel like factor 15 (KLF15) is expressed in the heart and acts as a repressor of cardiac hypertrophy in experimental models. This study investigated if KLF15 gene variants were associated with LVH in type 2 diabetes. In stage 1 of a 2-stage approach, patients with type 2 diabetes and no known cardiac disease were prospectively recruited for a transthoracic echocardiographic assessment (Melbourne Diabetes Heart Cohort) (n=318) and genotyping of two KLF15 single nucleotide polymorphisms (SNPs) (rs9838915, rs6796325). In stage 2, the association of KLF15 SNPs with LVH was investigated in the Genetics of Diabetes Audit and Research in Tayside Scotland (Go-DARTS) type 2 diabetes cohort (n=5631). The KLF15 SNP rs9838915 A allele was associated in a dominant manner with LV mass before (P=0.003) and after (P=0.001) adjustment for age, gender, body mass index (BMI) and hypertension, and with adjusted septal (P<0.0001) and posterior (P=0.004) wall thickness. LVH was present in 35% of patients. Over a median follow up of 5.6years, there were 22 (7%) first heart failure hospitalizations. The adjusted risk of heart failure hospitalization was 5.5-fold greater in those with LVH and the rs9838915 A allele compared to those without LVH and the GG genotype (hazard ratio (HR) 5.5 (1.6–18.6), P=0.006). The association of rs9838915 A allele with LVH was replicated in the Go-DARTS cohort. We have identified the KLF15 SNP rs9838915 A allele as a marker of LVH in patients with type 2 diabetes, and replicated these findings in a large independent cohort. Studies are needed to characterize the functional importance of these results, and to determine if the SNP rs9838915 A allele is associated with LVH in other high risk patient cohorts.
... Diabetes is a major risk factor for coronary artery disease and cardiovascular disease (Somaratne et al., 2011) is the most important cause of morbidity and mortality in patients with type-2 diabetes, accounting for approximately two-thirds of total mortality (Srivastava et al., 2008). Diastolic dysfunction has been described as an early sign of diabetic heart muscle disease preceding systolic damage (Raev, 1994) it is associated with future occurrence of heart failure, is a predictor of cardiovascular morbidity and mortality in the general population (Ike and Ikeh, 2006). ...
This study aimed to characterize and compare the heart wall disease in type-2 diabetic patient using echocardiography
ultrasound scan in order to assess these changes among both gender, Study population comprises a total of 113 adult’s diabetic patients
46 male 41.59% with mean age of 57.98 ±11.107 and 66 female 58.41%, with mean age of 56.03 ±10.270. Underwent ultrasound
examination after known diagnosis with diabetic disease using two-dimensional Real Time US machine with curvilinear transducer of
(3.5–6 MHz) at Ribat hospital, ventricular and atrial wall measurement was performed, Aortic annular diameter, Doppler trans aortic
flow was assessed by identifying the projection in which maximum peak flow velocity noted, after calibration, tracing the black-white
interface outlining the Doppler flow envelope. Heart rate was measured simultaneously. The result showed that Means of
Echocardiography parameters for Diabetes Type-2 patients between male and female was compared as the BMI having mean ± SD
(23.09967Kg/m2
±2.898752), (27.01367Kg/m2
±6.179767) the p-value 0.000101, Aortic root diameter (31.09 mm±3.425), (28.15
mm±3.553) the p-value 0.000026, left atrial diameter (36.87mm±4.241, (34.47mm±3.726) the p-value 0.001856, Left ventricular
diastolic diameter (46.87 mm±5.195), (44.47 mm±5.542) the p-value 0.02. And Left Ventricle systolic diameter (30.64mm ±5.306),
(28.64 mm± 5.110) the p-value 0.045766. For male and female respectively. Non–insulin-dependent DM has independent adverse
cardiac effects, including increased LV mass and wall thicknesses, reduced LV systolic chamber and myocardial function, and
increased arterial stiffness.
... 10,11 A significant and inverse association between glycated hemoglobin and TDI systolic parameters was also reported by a small study on asymptomatic type 2 diabetic patients, 12 while other studies did not observe such association. 13,14 So far, no large studies have focused their attention on a comprehensive evaluation of the relationship between s′ wave velocity and glycated hemoglobin in patients with diabetes. However, given the clinical relevance of this aspect, the main aim of this study was to evaluate the relationship between glycated hemoglobin and s′ wave velocity in a cohort of type 2 diabetic male outpatients with preserved left ventricular ejection fraction and without a previous history of ischemic heart disease. ...
Background:
Type 2 diabetes is strongly associated with the occurrence of cardiovascular diseases, especially heart failure. Some studies have suggested that subclinical systolic dysfunction as assessed by tissue Doppler imaging (TDI) is already present in uncomplicated diabetic patients with normal left ventricular ejection fraction (LVEF). Considering the importance of this aspect, the aim of this cross-sectional study was to examine the relationship between glycated hemoglobin and mean s' wave velocity (a reliable measure of early LV systolic dysfunction) in a cohort of type 2 diabetic outpatients with preserved LVEF and without ischemic heart disease.
Methods:
Forty-four male patients with newly diagnosed and 172 male patients with established type 2 diabetes were recruited for this cross-sectional study. All patients were evaluated with a transthoracic echocardiographic Doppler. The statistical analysis was conducted by a linear multivariate regression analysis, including several potential confounders.
Results:
The mean values of mean s' wave velocity were lower in patients with a worse glycemic control and progressively decreased across the quartiles of glycated hemoglobin. The multivariate linear regression analysis showed that mean s' wave velocity was inversely and independently associated with glycated hemoglobin (standardized beta coefficient -0.178; p = 0.043) after adjustment for age, duration of diabetes, body mass index, pulse pressure, estimated glomerular filtration rate, microvascular complication status, and indexed cardiac mass.
Conclusions:
These results suggest that s' wave velocity, as evaluated by TDI echocardiography, was an early marker of systolic dysfunction in type 2 diabetic patients with preserved LVEF and without prior ischemic heart disease. Moreover, early systolic dysfunction was independently associated with poor glycemic control in these patients. Future studies are needed to elucidate the pathogenic role of chronic hyperglycemia in the development of early LV systolic dysfunction.
... 4,6,7 In addition, because of advancing age and comorbidities, including hypertension and obesity, patients with type 2 diabetes are also prone to other cardiac pathologies affecting prognosis including but not limited to left ventricular hypertrophy, 8,9 reduced left and right ventricular ejection fraction, 10 dilated left atrium 11 or valve disorders. 12 However, previous reports on prevalence of echocardiographic findings were based on populations that were Abnormal echocardiography in patients with type 2 diabetes and relation to symptoms and clinical characteristics either small 6,7,13,14 from the primary care setting/general population 4,15,16 or included patients before the era of modern multifactorial treatment. 17 Even more, contemporary, intensive treatment of hypertension, hyperglycaemia, dyslipidemia and lifestyle factors 18 may have changed the risk profile for having echocardiographic abnormalities making it difficult to choose which patients to refer to echocardiography. ...
Objectives:
We aimed to determine the prevalence of echocardiographic abnormalities and their relation to clinical characteristics and cardiac symptoms in a large, contemporary cohort of patients with type 2 diabetes.
Results:
A total of 1030 patients with type 2 diabetes participated. Echocardiographic abnormalities were present in 513 (49.8%) patients, mainly driven by a high prevalence of diastolic dysfunction 178 (19.4%), left ventricular hypertrophy 213 (21.0%) and left atrial enlargement, 200 (19.6%). The prevalence increased markedly with age from 31.1% in the youngest group (<55 years) to 73.9% in the oldest group (>75 years) (p < 0.001) and was equally distributed among the sexes (p = 0.76). In univariate analyses, electrocardiographic abnormalities, age, body mass index, known coronary heart disease, hypertension, albuminuria, diabetes duration and creatinine were associated with abnormal echocardiography along with dyspnoea and characteristic chest pain (p < 0.05 for all). Neither of the cardiac symptoms nor clinical characteristics had sufficient sensitivity and specificity to accurately identify patients with abnormal echocardiography.
Conclusion:
Echocardiographic abnormalities are very common in outpatients with type 2 diabetes, but neither cardiac symptoms nor clinical characteristics are effective to identify patients with echocardiographic abnormalities.
... Le nombre de traitements antihypertenseurs (aucun, un traitement, deux traitements, plus de deux traitements) a été utilisé comme un marqueur de sévérité de l'hypertension. 90,91 Cette variable a été utilisée comme variable explicative de la vitesse de marche dans des modèles d'analyse de covariance avec les mêmes ajustements que ci-dessus. Un coefficient de régression a été calculé pour chacune des catégories de cette variable en prenant la catégorie « aucun traitement » comme groupe de référence ; un test de tendance linéaire a également été réalisé à l'aide de la méthode des contrastes. ...
Motor decline in the elderly is associated with an increased risk of morbidity and mortality, and represents a major issue for our ageing societies. Its etiology is usually multifactorial, and, in this work, we specifically addressed the contribution of vascular risk factors, based on crosssectional and longitudinal data from the Dijon center of the Three-City study. Motor function was assessed through measures of walking speed over 6 meters in participants aged 65 to 85 years old.We observed that baseline hypertension was associated with lower walking speed at baseline and greater motor decline over follow-up. Among participants with a baseline brain MRI, we observed a relationship between walking speed and the volume of brain subcortical gray matter structures, particularly the volume of the caudate nucleus. Slower walking speed at baseline was associated with an increased risk of all-cause death over 5 years of follow-up; this association was stronger for cardiovascular deaths.These results support the hypothesis of a contribution of vascular risk factors to motor decline in the elderly and contribute to improve our understanding of this process.
... Early diastolic impairment in the diabetic heart is intricately linked to cardiac histopathology. Cardiomyocyte hypertrophy and cardiac fibrosis are frequently observed in both experimental models and clinical settings of diabetes [32,39,40]. Consistent with our previous findings [32], Ntg diabetic mice exhibited enlarged cardiomyocytes in terms of width and area compared to nondiabetic controls. ...
Diabetes-induced cardiac complications include left ventricular (LV) dysfunction and heart failure. We previously demonstrated that LV phosphoinositide 3-kinase p110α (PI3K) protects the heart against diabetic cardiomyopathy, associated with reduced NADPH oxidase expression and activity. Conversely, in dominant negative PI3K(p110α) transgenic mice (dnPI3K), reduced cardiac PI3K signalling exaggerated diabetes-induced cardiomyopathy; associated with upregulated NADPH oxidase.
To examine whether chronic supplementation with the antioxidant coenzyme Q10 (CoQ10) could attenuate LV superoxide and diabetic cardiomyopathy in a setting of impaired PI3K signalling.
Diabetes was induced in 6-week-old non-transgenic and dnPI3K male mice via streptozotocin. After 4 weeks of diabetes, CoQ10 supplementation commenced (10mg/kg i.p., 3 times/week, 8 weeks). At study end (12 weeks of diabetes), markers of LV function, cardiomyocyte hypertrophy, collagen deposition, NADPH oxidase, oxidative stress (3-nitrotyrosine) and concentrations of CoQ9 and CoQ10 were determined.
LV NADPH oxidase (Nox2 gene expression and activity, on lucigenin-enhanced chemiluminescence), as well as oxidative stress, were increased by diabetes, exaggerated in diabetic dnPI3K mice, and attenuated by CoQ10. Diabetes-induced LV diastolic dysfunction (prolonged deceleration time, elevated end-diastolic pressure, impaired E/A ratio), cardiomyocyte hypertrophy and fibrosis, expression of atrial natriuretic peptide, connective tissue growth factor and β-myosin heavy chain, were all attenuated by CoQ10.
Chronic CoQ10 supplementation attenuates aspects of diabetic cardiomyopathy, even in a setting of reduced cardiac PI3K protective signalling. Given CoQ10 supplementation has been suggested to have positive outcomes in heart failure patients, chronic CoQ10 supplementation may be an attractive adjunct therapy for diabetic heart failure.
Copyright © 2015. Published by Elsevier Inc.
... Echocardiography in asymptomatic high CV risk type 2 diabetic patients may disclose heart abnormalities [5]. Selected echocardiographic abnormalities, including left ventricular (LV) systolic and diastolic dysfunction are related to CV risk factors and adverse CV events [5,6]. For example, the prevalence of LV hypertrophy was high (43%) in asymptomatic type 2 diabetic patients without CV disease and not taking antihypertensive medications [7], and LV diastolic dysfunction was present in almost 50% of asymptomatic subjects with newly diagnosed type 2 diabetes [4]. ...
Intensive multifactorial treatment aimed at prevention of cardiovascular (CV) disease may reduce left ventricular (LV) echocardiographic abnormalities in diabetic subjects. Plasma N-terminal (NT)-proBNP predicts CV mortality in diabetic patients but the association between P-NT-proBNP and the putative residual abnormalities in such patients are not well described. This study examined echocardiographic measurements of LV hypertrophy, atrial dilatation and LV dysfunction and their relation to P-NT-proBNP levels or subclinical coronary artery disease (CAD) in type 2 diabetic patients with microalbuminuria receiving intensive multifactorial treatment.
Echocardiography including tissue Doppler imaging and P-NT-proBNP measurements were performed in 200 patients without prior CAD. Patients with P-NT-proBNP > 45.2 ng/L and/or coronary calcium score ≥ 400 were stratified as high risk patients for CAD(n = 133) and examined for significant CAD by myocardial perfusion imaging and/or CT-angiography and/or coronary angiography.
LV mass index was 41.2 ± 10.9 g/m2.7 and 48 (24%) patients had LV hypertrophy. LA and RA dilatation were found in 54(27%) and 45(23%) patients, respectively, and LV diastolic dysfunction was found in 109(55%) patients. Patients with increased P-NT-proBNP levels did not have more major echocardiographic abnormalities. In 70(53%) of 133 high risk patients significant CAD was demonstrated and patients with LV hypertrophy had increased risk of significant CAD(adjusted odd ratio[CI] was 4.53[1.14-18.06]).
Among asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment, P-NT-proBNP levels is not associated with echocardiographic abnormalities. LV diastolic dysfunction was frequently observed, whereas LV hypertrophy was less frequent but associated with significant CAD.
Left ventricular diastolic dysfunction (LVDD) without symptoms, and heart failure (HF) with preserved ejection fraction (HFpEF) represent the most common phenotypes of HF in individuals with type 2 diabetes mellitus, and are more common than HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and left ventricular systolic dysfunction (LVSD) in these individuals. However, diagnostic criteria for HF have changed over the years, resulting in heterogeneity in the prevalence/incidence rates reported in different studies. We aimed to give an overview of the diagnosis and epidemiology of HF in type 2 diabetes, using both a narrative and systematic review approach; we focus narratively on diagnosing (using the 2021 European Society of Cardiology [ESC] guidelines) and screening for HF in type 2 diabetes. We performed an updated (2016–October 2022) systematic review and meta-analysis of studies reporting the prevalence and incidence of HF subtypes in adults ≥18 years with type 2 diabetes, using echocardiographic data. Embase and MEDLINE databases were searched and data were assessed using random-effects meta-analyses, with findings presented as forest plots. From the 5015 studies found, 209 were screened using the full-text article. In total, 57 studies were included, together with 29 studies that were identified in a prior meta-analysis; these studies reported on the prevalence of LVSD (n=25 studies, 24,460 individuals), LVDD (n=65 studies, 25,729 individuals), HFrEF (n=4 studies, 4090 individuals), HFmrEF (n=2 studies, 2442 individuals) and/or HFpEF (n=8 studies, 5292 individuals), and on HF incidence (n=7 studies, 17,935 individuals). Using Hoy et al’s risk-of-bias tool, we found that the studies included generally had a high risk of bias. They showed a prevalence of 43% (95% CI 37%, 50%) for LVDD, 17% (95% CI 7%, 35%) for HFpEF, 6% (95% CI 3%, 10%) for LVSD, 7% (95% CI 3%, 15%) for HFrEF, and 12% (95% CI 7%, 22%) for HFmrEF. For LVDD, grade I was found to be most prevalent. Additionally, we reported a higher incidence rate of HFpEF (7% [95% CI 4%, 11%]) than HFrEF 4% [95% CI 3%, 7%]). The evidence is limited by the heterogeneity of the diagnostic criteria over the years. The systematic section of this review provides new insights on the prevalence/incidence of HF in type 2 diabetes, unveiling a large pre-clinical target group with LVDD/HFpEF in which disease progression could be halted by early recognition and treatment.
Registration PROSPERO ID CRD42022368035.
Graphical Abstract
Left ventricular (LV) dysfunction is an early, clinically detectable sign of cardiomyopathy in type 2 diabetes mellitus (T2DM) that precedes the development of symptomatic heart failure. Pre-clinical models of diabetic cardiomyopathy are essential to develop therapies that may prevent or delay the progression of heart failure. This study examined the molecular, structural, and functional cardiac phenotype of two rat models of T2DM induced by a high-fat diet (HFD) with a moderate- or high-sucrose content (containing 88.9 or 346 g/Kg sucrose, respectively), plus administration of low-dose streptozotocin (STZ). At eight weeks of age, male Sprague-Dawley rats commenced a moderate- or high-sucrose HFD. Two weeks later, rats received low-dose STZ (35 mg/kg i.p. for two days) and remained on their respective diets. LV function was assessed by echocardiography one week prior to endpoint. At 22 weeks of age, blood and tissues were collected post-mortem. Relative to chow-fed sham rats, diabetic rats on a moderate- or high-sucrose HFD displayed cardiac reactive oxygen species dysregulation, perivascular fibrosis, and impaired LV diastolic function. The diabetes-induced impact on LV adverse remodeling and diastolic dysfunction was more apparent when a high-sucrose HFD was superimposed on STZ. In conclusion, a high-sucrose HFD in combination with low-dose STZ produced a cardiac phenotype that more closely resembled T2DM-induced cardiomyopathy than STZ diabetic rats subjected to a moderate-sucrose HFD.
Background: Left ventricular diastolic dysfunction (LVDD) is a recognized complication of diabetes mellitus which precedes and is a risk factor for heart failure. We aimed to determine the prevalence of LVDD and its association with body mass index (BMI) in ambulatory adults with diabetes mellitus.
Methods: We conducted a cross-sectional study of 195 ambulatory Ugandan adults living with diabetes mellitus for at least five years from the time of diagnosis at Mbarara Regional Referral Hospital (MRRH). We collected demographic, clinical data and measured body mass index. Laboratory tests included glycated hemoglobin (HbA1c), low-density lipoprotein (LDL), and urine microalbumin. Echocardiography was done to determine LVDD by assessing the mitral inflow E/A ratio, E/è ratio, TR jet peak velocity, and left atrium maximum volume index. Logistic regression was used to establish associations of body mass index and other covariates with LVDD.
Results: Overall, 195 participants were enrolled and 141(72.3%) were females. The mean age was 62 [standard deviation (SD), 11.5] years and median duration of diabetes diagnosis was 10 [Interquartile range (IQR), 7,15] years. LVDD was prevalent at 86% and majority, 127(65.13%) had grade-1 diastolic dysfunction. BMI ≥25kg/m² [adjusted Odds Ratio (aOR)=2.8, (95% confidence interval (CI)=1-7.6), p=0.038], age 50 year or more [aOR= 4.9, (95%CI=1.5-16.2), p=0.010], and history of hypertension [aOR= 3.0, (95% CI= 1.1-8.1), p=0.031] were associated with LVDD.
Conclusion: The prevalence of LVDD was high during the study period. We recommend early and periodic echocardiographic screening for diabetes patients with high body mass index.
Heart failure is an important manifestation of diabetic heart disease. Before the development of symptomatic heart failure, as much as 50% of patients with type 2 diabetes mellitus (T2DM) develop asymptomatic left ventricular dysfunction including left ventricular hypertrophy (LVH). Left ventricular hypertrophy (LVH) is highly prevalent in patients with T2DM and is a strong predictor of adverse cardiovascular outcomes including heart failure. Importantly regression of LVH with antihypertensive treatment especially renin angiotensin system blockers reduces cardiovascular morbidity and mortality. However, this approach is only partially effective since LVH persists in 20% of patients with hypertension who attain target blood pressure, implicating the role of other potential mechanisms in the development of LVH. Moreover, the pathophysiology of LVH in T2DM remains unclear and is not fully explained by the hyperglycemia-associated cellular alterations. There is a growing body of evidence that supports the role of inflammation, oxidative stress, AMP-activated kinase (AMPK) and insulin resistance in mediating the development of LVH. The recognition of asymptomatic LVH may offer an opportune target for intervention with cardio-protective therapy in these at-risk patients. In this article, we provide a review of some of the key clinical studies that evaluated the effects of allopurinol, SGLT2 inhibitor and metformin in regressing LVH in patients with and without T2DM.
Alternative splicing (AS) is dysregulated in Type 1 diabetic (T1D) hearts but mechanisms responsible are unclear. Here, we provide evidence that the RNA binding protein (RBP) PTBP1 is modulated in adult T1D hearts contributing to AS changes. We show that a spliced variant of PTBP1 that is highly expressed in normal newborn mouse hearts is aberrantly expressed in adult T1D mouse hearts. Comparing known PTBP1-target datasets to our T1D mouse transcriptome datasets, we discovered a group of genes with PTBP1 binding sites in their pre-mRNAs that are differentially spliced in T1D mouse hearts. We demonstrated that inducible expression of diabetes-induced PTBP1 spliced variant has less repressive splicing function. Notably, PTBP1 regulates AS of some of its targets antagonistically to RBFOX2. In sum, our results indicate that diabetic conditions disrupt developmental regulation of PTBP1 leading to differential AS of PTBP1 target genes. Identification of PTBP1 and PTBP1-regulated RNA networks can provide RNA-based therapies for the treatment of diabetes cardiac complications.
Due to the epidemic of Type 2 diabetes related to increased adiposity and sedentary lifestyles and the increasing incidence and improved prognosis of Type 1 diabetes, the primary care clinician (general practitioner) is likely to care for many people with diabetes during their career, the majority of whom will have Type 2 diabetes. The prevention, early diagnosis, and excellent management of diabetes are key to reducing the patient’s risk of diabetes complications. The chronic complications of diabetes relate to damage to the small and large vasculature and nerves, leading to diabetic retinopathy, nephropathy, and neuropathy; and accelerated atherosclerosis, leading to coronary artery disease (CAD), cerebrovascular disease, and peripheral vascular disease. People with diabetes who develop its microvascular complications are at particularly high risk of developing cardiovascular disease, which is the cause of death of over 60% of people with diabetes and is often silent. For the primary and secondary prevention of cardiovascular disease in people with diabetes (and the related microvascular complications), multiple risk factors need to be assessed and managed, including lifestyle (diet, exercise, and non-smoking), adiposity, glycemia and insulin resistance, blood pressure (BP), lipids, and vaccinations. Regular screening and treating vascular risk factors to proven targets are important. Clinical trials and meta-analyses provide evidence of the efficacy of many beneficial treatments for the primary and secondary prevention of diabetes-related vascular damage, yet often less than 10% of people with diabetes meet all recommended treatment targets. The primary care physician is ideally placed to manage diabetes, both directly and via assembling and coordinating a multidisciplinary team with the common goal of improving the quantity and quality of life of their patient with diabetes.
Regulation of cardiac fatty acid metabolism is central to the development of cardiac hypertrophy and heart failure. We investigated the effects of select fatty acids on the expression of genes involved in immediate early as well as inflammatory and hypertrophic responses in adult rat cardiomyocytes. Cardiac remodeling begins with upregulation of immediate early genes for c-fos and c-jun, followed by upregulation of inflammatory genes for nuclear factor kappa B (NF-κB) and nuclear factor of activated T-cells (NFAT). At later stages, genes involved in hypertrophic responses, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), are upregulated. Adult rat cardiomyocytes were treated with palmitic acid, a saturated fatty acid; oleic acid, a monounsaturated fatty acid; linoleic acid, a polyunsaturated fatty acid belonging to the n-6 class; and docosahexaenoic acid, a polyunsaturated fatty acid belonging to the n-3 class. Linoleic acid produced a greater increase in the mRNA expression of c-fos, c-jun, NF-κB, NFAT3, ANP, and BNP relative to palmitic acid and oleic acid. In contrast, docosahexaenoic acid caused a decrease in the expression of genes involved in cardiac hypertrophy. Our findings suggest that linoleic acid may be a potent inducer of genes involved in cardiac hypertrophy, whereas docosahexaenoic acid may be protective against the cardiomyocyte hypertrophic response.
Left ventricular mass index (LVMI) increase has been described in hypertension (HTN), but less is known about its association with type 2 diabetes (T2DM). As these conditions frequently co-exist, we investigated the association of T2DM, HTN and both with echocardiographic parameters, and hypothesized that patients with both had highest LVMI, followed by patients with only T2DM or HTN. Study population included 101 T2DM patients, 62 patients with HTN and no T2DM, and 76 patients with T2DM and HTN, excluded for ischemic heart disease. Demographic and clinical data, biochemical measurements, stress echocardiography, transthoracic 2D Doppler and tissue Doppler echocardiography were performed. Multivariable logistic regression was used to determine the independent association with T2DM. Linear regression models and Pearson's correlation were used to assess the correlations between LVMI and other parameters. Patients with only T2DM had significantly greater LVMI (84.9 ± 20.3 g/m2) compared to patients with T2DM and HTN (77.9 ± 16 g/m2) and only HTN (69.8 ± 12.4 g/m2). In multivariate logistic regression analysis, T2DM was associated with LVMI (OR 1.033, 95%CI 1.003-1.065, p = 0.029). A positive correlation of LVMI was found with fasting glucose (p < 0.001) and HbA1c (p = 0.0003). Increased LVMI could be a potential, pre-symptomatic marker of myocardial structural change in T2DM.
Background
Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin‐2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants.
Methods and Results
We used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure, a model of intrauterine growth restriction and Lcn2‐knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the YFS (Young Finns Study). In hypertrophic heart rats, cardiac and circulating Lcn2 was significantly overexpressed before, during, and after development of cardiac hypertrophy and heart failure. Lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction, whereas Lcn2‐knockout mice had smaller hearts. In cultured cardiomyocytes, Lcn2 activated molecular hypertrophic pathways and increased cell size, but reduced proliferation and cell numbers. Increased LCN2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. In the YFS,LCN2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. The single‐nucleotide polymorphism, rs13297295, located near LCN2 defined a significant cis‐eQTL for LCN2 expression.
Conclusions
Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failure.
Background/Aims: The effect of diabetes mellitus (DM) and gender on left ventricular (LV) structure is still controversial. The objective of this study was to evaluate the effect of gender and DM on LV structure in a sample of hypertensive patients in ErbilIraq. Methods: This cross sectional study was conducted in Rizgary hospital, Erbil Iraq, between April 2015 and April 2016. A convenience sample of 200 patients (100 males and 100 females), aged ≥18 years were enrolled. Half of the sample (Group I) had diabetes in addition to hypertension, while the other half (Group II) had hypertension only. The effects of age and DM on LV structure were evaluated in both groups. Results: In Group I, LV Diastolic dimensions and LV Systolic dimensions were significantly higher among male patients (P=0.023, 0.022 respectively) than female patients. In group II , the means of posterior wall (PW) , LV mass (LVM) , LVM index (LVMI) and relative wall thickness (RWT) were significantly higher among male patients (P=0.004, 0.016, 0.035 and 0.045 respectively) than female patients. The means of interventricular septum (IVS), PW and RWT (P=0.0013, 0.007 and 0.003 respectively), were significantly higher in diabetic females than nondiabetic females. No significant differences were found between diabetic and nondiabetic males. Conclusions: In the hypertensive nondiabetic group, the means of LVM, LVMI, PW, and RWT were significantly higher among male patients than females. The means of IVS, PW, and RWT were significantly higher in diabetic females than nondiabetic females.
Background:
The global prevalence of diabetes and its complications is increasing worldwide. Its role in coronary heart disease has been linked with the presence of left ventricular hypertrophy (LVH). The present study aims to determine the prevalence of electrocardiographic left ventricular hypertrophy (ECG-LVH) in adult diabetic subjects, its epidemiological and clinical correlates.
Methods:
A descriptive cross-sectional study involving 534 patients was conducted at the Edward Francis Small Teaching Hospital (formerly Royal Victoria Teaching Hospital), The Gambia. Four hundred and forty patients were included using a standard questionnaire. Anthropometry, laboratory investigations and electrocardiogram were carried out. We used the Lewis, Cornell, and Sokolow-Lyon Voltage criteria to define ECG-LVH. Minitab™ statistical software version 13.20 was used for analysis.
Results:
146 (35.2%) patients had ECG-LVH using all 3 criteria and this prevalence was higher among women being 116 (79.5%). A generally high prevalence of overweight (155/37.4%) and obesity (119/28.6%) was observed among study participants, and both clinic-day systolic and diastolic blood pressure (BP) were significantly higher in those with ECG-LVH. Poor diabetes control was observed in both groups.
Conclusion:
There was a high prevalence of ECG-LVH and it is especially so with combining multiple criteria, hence the need for screening. Clinic-day hypertension was associated with ECG-LVH hence the need for diagnosing and aggressive treatment of hypertension in patients with diabetes mellitus.
n several diseases involving the heart such as pressure overload, diabetic cardiomyopathy or myocardial infarction, fibrosis is a common disorder of myocardial extracellular matrix structure and function. The clinical significance of fibrosis is that accumulation of disorganized fibrillar collagen in the cardiac interstitium can inhibit diastolic and systolic function. Fibrosis is mediated by several different cellular and extracellular processes including disruptions of fibroblast differentiation, perturbations of post-translational processing and assembly of matrix molecules, and inappropriately organized matrix degradation by proteases and intracellular digestion. The enlargement of transformed fibroblast and myofibroblast populations in the diseased cardiac interstitium plays a critical role in the disorganized matrix remodeling that occurs after pressure overload or diabetes because these cells do not process and remodel interstitial collagen in a physiological fashion. New data that have examined the regulation of pro-collagen processing by molecules such as pro-collagen C-endopeptidase enhancer and modulation of collagen assembly by the secreted protein acidic and rich in cysteine, have suggested novel therapeutic targets for ameliorating cardiac fibrosis. Further, studies of transmembrane matrix metalloproteinases, such as MT-1, indicate the remarkable breadth of function and complexity of the matrix proteolytic family since MT-1 can break down the matrix and is also important in mediating collagen degradation by phagocytosis. Our growing recognition that the myocardial matrix is highly dynamic and comprises a wide range of matricellular and non-structural proteins and proteases in addition to well-defined structural proteins, suggests new approaches for myocardial fibrosis in a spectrum of cardiac diseases.
We read with interest the results of the Diabetes Mellitus and Diastolic Dysfunction (DADD) Follow-Up (DADD-FU) study by Venskutonyte et al. (1), which concluded that the prevalence of left ventricular diastolic dysfunction (LVDD) was low and that LVDD improved or remained stable over a 6-year period. We suggest these results may not be generalizable to all patients with diabetes, particularly as those studied were free of clinically detectable cardiovascular disease and 52% were on diet or no treatment for diabetes; among the exclusions were insulin use, blood pressure >160/95 mmHg, and renal impairment. The DADD-FU study comprised two separate groups—those with LVDD enrolled in the original DADD trial ( n = 41) and …
Diabetic kidney disease (DKD) occurs in 25%-40% of patients with diabetes. Given the dual problems of a significant risk of progression from DKD to end-stage renal disease (ESRD) and increased cardiovascular morbidity and mortality, it is important to identify patients at risk of DKD and ESRD and initiate protective renal and cardiovascular therapies. The importance of preventive therapy is emphasized further by worldwide increases in the incidence of diabetes. This review summarizes the evidence regarding the prognostic value and benefits of targeting established and novel risk markers for DKD development and progression. Family history of DKD, smoking history, and glycemic, blood pressure, and plasma lipid level control are established factors for identifying people at greatest risk of DKD development and progression. Absolute albumin excretion rate (AER) and glomerular filtration rate (GFR) measurements also are important, although AER categorization generally lacks the necessary specificity and sensitivity, and estimates of declining GFR are compromised by methodological limitations for GFRs in the normal-to-high range. Emerging risk markers for progressive loss of kidney function include markers of oxidation and inflammation, profibrotic cytokines, uric acid, advanced glycation end products, functional and structural markers of vascular dysfunction, kidney structural changes, and tubular biomarkers. Among these, the most promising are serum uric acid and soluble tumor necrosis factor receptor (type 1 and type 2) levels, especially in relation to GFR changes. At present, these can only be considered as risk markers because they only identify an individual at increased risk of progressive DKD and not necessarily related to the causal pathway promoting kidney damage. Further work is needed to establish whether modulating these factors improves the prognosis in DKD. Although change in urinary peptidome levels also is a promising marker, there currently is neither a clinical assay nor adequate studies defining its prognostic value. Until these or other novel markers become available for clinical use, predictive accuracy often may be increased with greater attention to established markers.
The aims of this observational study were to determine the prevalence and predictors of an abnormal echocardiogram in adults with type 1 diabetes, and to assess the evolution of changes in a subset of subjects.
Cardiac function and structure were prospectively investigated by comprehensive transthoracic echocardiographic techniques in asymptomatic adults with type 1 diabetes seen in the ambulatory care setting.
We recruited 136 subjects (mean age 39years, SD 14years) with a median diabetes duration of 21years [25(th), 75(th) interquartile range; 11, 29]. An abnormal echocardiogram was present in 29% of subjects; diastolic dysfunction in 69%, left ventricular hypertrophy in 38% and systolic dysfunction in 10%. The independent predictors of an abnormal echocardiogram were age, with a 9-fold increase in those ≥40years (OR 9.40 [95% CI 2.68-33.04], P <0.0001), and increased body mass index (BMI), with a 17% increase in risk (P=0.04). A second echocardiogram was available in 65 subjects (3.8±1.7years later). The results showed that one in five with a normal first study had developed an abnormal second study, mainly diastolic dysfunction, with age being the only independent predictor of progression (P=0.006).
Subclinical echocardiographic abnormalities are common in asymptomatic type 1 diabetes adults, and changes are progressive. The addition of an echocardiogram to complication surveillance programs in those with type 1 diabetes aged ≥40years may represent a cost-effective way to screen for, and aggressively treat, occult cardiac disease.
Background
Diabetes mellitus (DM) is associated with a substantially increased risk of developing heart failure. To verify the risk factors of preclinical left ventricular diastolic dysfunction (LVDD) in type 2 diabetic patients, we assessed the LVDD by tissue Doppler echocardiography and its relationship with various parameters in asymptomatic patients with type 2 DM.
Methods
We studied 100 asymptomatic patients with type 2 DM [age 61.6 ± 9.7 years, body mass index (BMI) 25.5 ± 4.8 kg/m2]. All patients underwent clinical evaluation, retinopathy, and laboratory assessment for BMI, fasting plasma glucose, C-peptide, lipids, Hemoglobin A1c (HbA1c), and urine albumin to creatinine ratio. Echocardiography including tissue Doppler imaging were performed to assess LVDD, which was defined with E/A < 0.75; or with 0.75 ≤ E/A and E/e’ ≥ 10. Normal diastolic function was defined with 0.75 ≤ E/A < 1.5 and E/e’ < 10. Patients with LV ejection fraction (LVEF) <50 % were excluded.
Results
Sixty-five patients were classified as having LVDD and 35 as having normal diastolic function. The logistic analysis revealed that age [odds ratio (OR) 1.14, 95 % confidence interval (CI) 1.06–1.22, P = 0.001), women (OR 7.63, 95 % CI 2.18–26.7, P = 0.002), left ventricular mass index (LVMI) (OR 1.04, 95 % CI 1.01–1.08, P = 0.004), and albuminuria (OR 7.95 95 % CI 1.74–21.6, P = 0.005) were associated with LVDD.
Conclusion
This study reveals a high incidence of LVDD in asymptomatic type 2 DM patients and, this finding was correlated with age, sex, LVMI and albuminuria. Screening for albuminuria and echocardiography may be useful for identifying individuals with a high cardiovascular risk and possible LVDD in type 2 DM patients.
We assessed left ventricular structural alterations associated with chronic kidney disease (CKD) in Congolese patients with type 2 diabetes.
This was a cross-sectional study of a case series. We obtained anthropometric, clinical, biological and echocardiographic measurements in 60 consecutive type 2 diabetes patients (37 females, 62% ) aged 20 years or older from the diabetes outpatient clinic, University of Kinshasa Hospital, DRC. We computed creatinine clearance rate according to the MDRD equation and categorised patients into mild (CrCl > 60 ml/min per 1.73 m(2)), moderate (CrCl 30-60 ml/min per 1.73 m(2)) and severe CKD (< 30 ml/min per 1.73 m(2)). Left ventricular hypertrophy (LVH) was indicated by a LV mass index (LVMI) > 51 g/m(2.7) and LV geometry was defined as normal, or with concentric remodelling, eccentric or concentric hypertrophy, using relative wall thickness (RWT) and LVMI.
Compared to patients with normal kidney function, CKD patients had higher uric acid levels (450 ± 166 vs 306 ± 107 µmol/l; p ≤ 0.001), a greater proportion of LVH (37 vs 14%; p ≤ 0.05) and longstanding diabetes (13 ± 8 vs 8 ± 6 years; p ≤ 0.001). Their left ventricular internal diameter, diastolic (LVIDD) was (47.00 ± 6.00 vs 43.00 ± 7.00 mm; p ≤ 0.001), LVMI was (47 ± 19 vs 36.00 ± 15 g/m2.7; p ≤ 0.05) and proportions of concentric (22 vs 11%; p ≤ 0.05) or eccentric (15 vs 3%; p ≤ 0.05) LVH were also greater. Severe CKD was associated with increased interventricular septum, diastolic (IVSD) (12.30 ± 3.08 vs 9.45 ± 1.94 mm; p ≤ 0.05), posterior wall thickness, diastolic (PWTD) (11.61 ± 2.78 vs 9.52 ± 1.77 mm; p ≤ 0.01), relative wall thickness (RWT) (0.52 ± 0.17 vs 0.40 ± 0.07; p ≤ 0.01) rate of LVH (50 vs 30%; p ≤ 0.05), and elevated proportions of concentric remodelling (25 vs 15%; p ≤ 0.05) and concentric LVH (42 vs 10%; p ≤ 0.05) in comparison with patients with moderate CKD. In multivariable adjusted analysis, hyperuricaemia emerged as the only predictor of the presence of LVH in patients with CKD (adjusted OR 9.10; 95% CI: 2.40-33.73).
In keeping with a higher rate of cardiovascular events usually reported in patients with impaired renal function, CKD patients exhibited LVH and abnormal LV geometry.
Cardiovascular disease is common in diabetes, and is associated with activation of the renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE)2 is a recently described member of the RAS, and this study investigated whether ACE2 polymorphisms are associated with hypertension, left ventricular (LV) mass, and cardiac function in type 2 diabetes.
Variants in ACE2 (rs1978124, rs2074192, rs4240157, rs4646156, rs4646188) were examined in 503 Caucasian subjects with type 2 diabetes. As ACE2 is located on the X chromosome, analyses were performed separately for men and women. Hypertension was defined by a history of hypertension, and/or antihypertensive medications or blood pressure (BP) >130/80 mm Hg. LV mass and systolic function (ejection fraction) were assessed by transthoracic echocardiography.
In men, hypertension was more prevalent with the ACE2 rs2074192 C allele (P = 0.023), rs4240157 G allele (P = 0.016) and rs4646188 T allele (P = 0.006). In men, the rs1978124 A allele was associated with a significantly lower ejection fraction compared to the G allele (62.3 ± 13.3 vs. 67.2 ± 10.9%, P = 0.002). This association remained significant after covariate adjustment for age, body mass index, hypertension, antihypertensive treatment, and BP. In women, the prevalence of hypertension was higher (P = 0.009) with the rs4240157 G allele, and the rs1978124 A allele was associated with significantly higher LV mass (P = 0.008).
In Caucasians with type 2 diabetes, genetic variation in ACE2 is associated with hypertension and reduced systolic function in men, and hypertension and increased LV mass in women.
Although several reports have described early changes of cardiac structure and function in diabetic patients, controversy persists regarding the existence of a clinically distinct diabetic cardiomyopathy. To this end, sex-specific linear regression analyses were used to examine the contribution of diabetes mellitus and glucose intolerance to age-adjusted echocardiographic parameters in 1,986 men (mean age 48 years) and 2,529 women (mean age 50 years) from the original Framingham Study cohort and the Framingham Offspring Study. Subjects with evidence of cardiovascular disease at the time of echocardiogram were excluded. Diabetics had higher heart rates than nondiabetics (67.9 vs 64.0 beats/min (p = 0.002) in men, and 73.1 vs 68.3 beats/min (p = 0.004) in women). Diabetic women had increased left ventricular (LV) wall thickness (18.7 vs 17.1 mm, p less than 0.001), relative wall thickness (0.403 vs 0.377, p = 0.008), LV end-diastolic dimension (46.9 vs 45.7 mm, p = 0.03) and LV mass corrected for height (100.4 vs 82.2 g/m, p less than 0.001). Women with glucose intolerance showed similar, less significant trends (p = 0.007 for wall thickness, p less than 0.01 for LV mass). In diabetic men, fractional shortening was slightly reduced (0.355 vs 0.360, p less than 0.05). In a multivariate model that included potentially confounding factors, diabetes remained an independent contributor to LV mass (p = 0.004) and wall thickness (p = 0.008) in women. In a separate linear regression model, which assessed the association of age with LV mass, the age-coefficient for diabetic women was much higher than that for nondiabetics (13.6 vs 6.6 g/m per 10-year increment in age).(ABSTRACT TRUNCATED AT 250 WORDS)
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.
The formation of advanced glycation end products (AGEs) on extracellular matrix components leads to accelerated increases in collagen cross linking that contributes to myocardial stiffness in diabetes. This study determined the effect of the crosslink breaker, ALT-711 on diabetes-induced cardiac disease. Streptozotocin diabetes was induced in Sprague-Dawley rats for 32 weeks. Treatment with ALT-711 (10 mg/kg) was initiated at week 16. Diabetic hearts were characterized by increased left ventricular (LV) mass and brain natriuretic peptide (BNP) expression, decreased LV collagen solubility, and increased collagen III gene and protein expression. Diabetic hearts had significant increases in AGEs and increased expression of the AGE receptors, RAGE and AGE-R3, in association with increases in gene and protein expression of connective tissue growth factor (CTGF). ALT-711 treatment restored LV collagen solubility and cardiac BNP in association with reduced cardiac AGE levels and abrogated the increase in RAGE, AGE-R3, CTGF, and collagen III expression. The present study suggests that AGEs play a central role in many of the alterations observed in the diabetic heart and that cleavage of preformed AGE crosslinks with ALT-711 leads to attenuation of diabetes-associated cardiac abnormalities in rats. This provides a potential new therapeutic approach for cardiovascular disease in human diabetes.
Tissue Doppler echocardiography (TDE) is used in the assessment of diastolic function, however, it is unclear whether the medial (E' med) or lateral (E' lat) annulus should be used. Our aim was to compare the diagnostic utility of E' med and E' lat. In 232 subjects left ventricular (LV) systolic and diastolic function was assessed via transthoracic echocardiography with TDE measurements obtained from both annuli. LV function was normal in 91 subjects (39%), with diastolic dysfunction found in 141 subjects (61%). TDE velocities decreased with age and progressive diastolic dysfunction for either annulus. E' med recorded significantly lower myocardial velocities than E' lat. Receiver operator curves showed improved area under the curve (AUC) for E' med than E' lat. Furthermore the AUC was significantly improved compared to E/A ratio and deceleration time. For diagnosing diastolic dysfunction, an E' med<11cm/s provided a sensitivity of 78%, specificity of 67% and positive predictive value of 70%. Whilst for diagnosing elevated filling pressures an E/E' medial ratio>8 provided values of 56%, 93% and 91%, respectively. In conclusion, although either annulus can be used, E' med provides better diagnostic utility.
• Background.—
This study was undertaken to identify whether diabetes mellitus (DM) accelerates the development of left ventricular hypertrophy (LVH) in hypertensive patients.Methods.— —
Cardiac structure, systolic function, and hemodynamics were evaluated by two-dimensional M-mode echocardiography in diabetic and nondiabetic patients with essential hypertension.Results. —
Patients with hypertension with and without DM had the same end-systolic and end-diastolic dimensions, cardiac output, total peripheral resistance, and ejection fraction. Diabetic hypertensive patients had greater interventricular septum (1.32±0.20 vs 1.07±0.20 cm) and posterior wall (1.20±0.20 vs 1.00 ± 0.10 cm) thickness than did nondiabetic hypertensive patients. Consequently, left ventricular mass index was greater in patients with hypertension and DM than in those without DM (158±45 vs 113±20 g/m2). With the use of Devereux criteria for recognition of LVH (left ventricular mass index above 134 g/m2 in men and above 110 g/m2 in women), 72% of the diabetic patients had LVH, whereas only 32% of the nondiabetic patients had LVH. Left ventricular contractility, as reflected by the ratio of end-systolic wall stress to end-systolic volume index, was decreased in diabetic compared with nondiabetic hypertensive patients.Conclusions.••
The data suggest that DM accelerates the development of LVH in patients with essential hypertension independent of arterial pressure and, therefore, may contribute to the increased cardiovascular morbidity and mortality in patients with hypertension.(Arch Intern Med. 1992;152:1001-1004)
Context:
Approximately half of patients with overt congestive heart failure (CHF) have diastolic dysfunction without reduced ejection fraction (EF). Yet, the prevalence of diastolic dysfunction and its relation to systolic dysfunction and CHF in the community remain undefined.
Objectives:
To determine the prevalence of CHF and preclinical diastolic dysfunction and systolic dysfunction in the community and determine if diastolic dysfunction is predictive of all-cause mortality.
Design, setting, participants:
Cross-sectional survey of 2042 randomly selected residents of Olmsted County, Minnesota, aged 45 years or older from June 1997 through September 2000.
Main outcome measures:
Doppler echocardiographic assessment of systolic and diastolic function. Presence of CHF diagnosis by review of medical records with designation as validated CHF if Framingham criteria are satisfied. Subjects without a CHF diagnosis but with diastolic or systolic dysfunction were considered as having either preclinical diastolic or preclinical systolic dysfunction.
Results:
The prevalence of validated CHF was 2.2% (95% confidence interval [CI], 1.6%-2.8%) with 44% having an EF higher than 50%. Overall, 20.8% (95% CI, 19.0%-22.7%) of the population had mild diastolic dysfunction, 6.6% (95% CI, 5.5%-7.8%) had moderate diastolic dysfunction, and 0.7% (95% CI, 0.3%-1.1%) had severe diastolic dysfunction with 5.6% (95% CI, 4.5%-6.7%) of the population having moderate or severe diastolic dysfunction with normal EF. The prevalence of any systolic dysfunction (EF < or =50%) was 6.0% (95% CI, 5.0%-7.1%) with moderate or severe systolic dysfunction (EF < or =40%) being present in 2.0% (95% CI, 1.4%-2.5%). CHF was much more common among those with systolic or diastolic dysfunction than in those with normal ventricular function. However, even among those with moderate or severe diastolic or systolic dysfunction, less than half had recognized CHF. In multivariate analysis, controlling for age, sex, and EF, mild diastolic dysfunction (hazard ratio, 8.31 [95% CI, 3.00-23.1], P<.001) and moderate or severe diastolic dysfunction (hazard ratio, 10.17 [95% CI, 3.28-31.0], P<.001) were predictive of all-cause mortality.
Conclusions:
In the community, systolic dysfunction is frequently present in individuals without recognized CHF. Furthermore, diastolic dysfunction as rigorously defined by comprehensive Doppler techniques is common, often not accompanied by recognized CHF, and associated with marked increases in all-cause mortality.
Background:
Blood pressure is an important determinant of the risks of macrovascular and microvascular complications of type 2 diabetes, and guidelines recommend intensive lowering of blood pressure for diabetic patients with hypertension. We assessed the effects of the routine administration of an angiotensin converting enzyme (ACE) inhibitor-diuretic combination on serious vascular events in patients with diabetes, irrespective of initial blood pressure levels or the use of other blood pressure lowering drugs.
Methods:
The trial was done by 215 collaborating centres in 20 countries. After a 6-week active run-in period, 11 140 patients with type 2 diabetes were randomised to treatment with a fixed combination of perindopril and indapamide or matching placebo, in addition to current therapy. The primary endpoints were composites of major macrovascular and microvascular events, defined as death from cardiovascular disease, non-fatal stroke or non-fatal myocardial infarction, and new or worsening renal or diabetic eye disease, and analysis was by intention-to-treat. The macrovascular and microvascular composites were analysed jointly and separately. This trial is registered with ClinicalTrials.gov, number NCT00145925.
Findings:
After a mean of 4.3 years of follow-up, 73% of those assigned active treatment and 74% of those assigned control remained on randomised treatment. Compared with patients assigned placebo, those assigned active therapy had a mean reduction in systolic blood pressure of 5.6 mm Hg and diastolic blood pressure of 2.2 mm Hg. The relative risk of a major macrovascular or microvascular event was reduced by 9% (861 [15.5%] active vs 938 [16.8%] placebo; hazard ratio 0.91, 95% CI 0.83-1.00, p=0.04). The separate reductions in macrovascular and microvascular events were similar but were not independently significant (macrovascular 0.92; 0.81-1.04, p=0.16; microvascular 0.91; 0.80-1.04, p=0.16). The relative risk of death from cardiovascular disease was reduced by 18% (211 [3.8%] active vs 257 [4.6%] placebo; 0.82, 0.68-0.98, p=0.03) and death from any cause was reduced by 14% (408 [7.3%] active vs 471 [8.5%] placebo; 0.86, 0.75-0.98, p=0.03). There was no evidence that the effects of the study treatment differed by initial blood pressure level or concomitant use of other treatments at baseline.
Interpretation:
Routine administration of a fixed combination of perindopril and indapamide to patients with type 2 diabetes was well tolerated and reduced the risks of major vascular events, including death. Although the confidence limits were wide, the results suggest that over 5 years, one death due to any cause would be averted among every 79 patients assigned active therapy.
LR: 20061115; JID: 7501160; 0 (Antilipemic Agents); 0 (Cholesterol, HDL); 0 (Cholesterol, LDL); 57-88-5 (Cholesterol); CIN: JAMA. 2001 Nov 21;286(19):2401; author reply 2401-2. PMID: 11712930; CIN: JAMA. 2001 Nov 21;286(19):2400-1; author reply 2401-2. PMID: 11712929; CIN: JAMA. 2001 Nov 21;286(19):2400; author reply 2401-2. PMID: 11712928; CIN: JAMA. 2001 Nov 21;286(19):2400; author reply 2401-2. PMID: 11712927; CIN: JAMA. 2001 May 16;285(19):2508-9. PMID: 11368705; CIN: JAMA. 2003 Apr 16;289(15):1928; author reply 1929. PMID: 12697793; CIN: JAMA. 2001 Aug 1;286(5):533-5. PMID: 11476650; CIN: JAMA. 2001 Nov 21;286(19):2401-2. PMID: 11712931; ppublish
This study was undertaken to identify whether diabetes mellitus (DM) accelerates the development of left ventricular hypertrophy (LVH) in hypertensive patients.
Cardiac structure, systolic function, and hemodynamics were evaluated by two-dimensional M-mode echocardiography in diabetic and nondiabetic patients with essential hypertension.
Patients with hypertension with and without DM had the same end-systolic and end-diastolic dimensions, cardiac output, total peripheral resistance, and ejection fraction. Diabetic hypertensive patients had greater interventricular septum (1.32 +/- 0.20 vs 1.07 +/- 0.20 cm) and posterior wall (1.20 +/- 0.20 vs 1.00 +/- 0.10 cm) thickness than did nondiabetic hypertensive patients. Consequently, left ventricular mass index was greater in patients with hypertension and DM than in those without DM (158 +/- 45 vs 113 +/- 20 g/m2). With the use of Devereux criteria for recognition of LVH (left ventricular mass index above 134 g/m2 in men and above 110 g/m2 in women), 72% of the diabetic patients had LVH, whereas only 32% of the nondiabetic patients had LVH. Left ventricular contractility, as reflected by the ratio of end-systolic wall stress to end-systolic volume index, was decreased in diabetic compared with nondiabetic hypertensive patients.
The data suggest that DM accelerates the development of LVH in patients with essential hypertension independent of arterial pressure and, therefore, may contribute to the increased cardiovascular morbidity and mortality in patients with hypertension.
The quantitation of two-dimensional echocardiographic images has been frustrated by the lack of concrete recommendations. The recent statement by the American Society of Echocardiography has rectified that deficiency. This discussion reviews the recommendations of the Society, focusing on the general and technical considerations for quantitation, computational equipment, cavity volume measurements, and the quantitation of left ventricular mass. The author's recent experience with directing a quantitative laboratory is discussed. In particular, the advantage of on-line bedside quantitation and mass storage of images and measured parameters is presented. An example of a digitized study is given along with measuring methodology.
The postmortem findings and clinical records of 27 patients with proved diabetic glomerulosclerosis were examined and reviewed for evidence of primary myocardial disease. Twenty-three cases were excluded because of complicating conditions such as hypertension, significant obstruction of the major coronary arteries or valvular disease. Four patients demonstrated cardiomegaly and congestive heart failure of no known cause.The autopsy findings consisted of left ventricular hypertrophy and, in 1 case, right ventricular hypertrophy as well, in the absence of major coronary artery disease. Histopathologic study revealed diffuse fibrotic strands extending between bundles of muscle fibers and myofibrillar hypertrophy. In 1 case, the small intramural coronary arterioles demonstrated thickening of the wall and narrowing of the lumen due primarily to the deposition of acid mucopolysaccharide material in the subendothelial layers and subsequent subintimal thickening and medial hypertrophy.It is postulated that the myocardial disease seen in these cases is probably secondary to diabetic mjcroangiopathy although the direct effects of the abnormal myocardial metabolism in diabetes could not be excluded.
To assess predictors of CVD mortality among men with and without diabetes and to assess the independent effect of diabetes on the risk of CVD death.
Participants in this cohort study were screened from 1973 to 1975; vital status has been ascertained over an average of 12 yr of follow-up (range 11-13 yr). Participants were 347,978 men aged 35-57 yr, screened in 20 centers for MRFIT. The outcome measure was CVD mortality.
Among 5163 men who reported taking medication for diabetes, 1092 deaths (603 CVD deaths) occurred in an average of 12 yr of follow-up. Among 342,815 men not taking medication for diabetes, 20,867 deaths were identified, 8965 ascribed to CVD. Absolute risk of CVD death was much higher for diabetic than nondiabetic men of every age stratum, ethnic background, and risk factor level--overall three times higher, with adjustment for age, race, income, serum cholesterol level, sBP, and reported number of cigarettes/day (P < 0.0001). For men both with and without diabetes, serum cholesterol level, sBP, and cigarette smoking were significant predictors of CVD mortality. For diabetic men with higher values for each risk factor and their combinations, absolute risk of CVD death increased more steeply than for nondiabetic men, so that absolute excess risk for diabetic men was progressively greater than for nondiabetic men with higher risk factor levels.
These findings emphasize the importance of rigorous sustained intervention in people with diabetes to control blood pressure, lower serum cholesterol, and abolish cigarette smoking, and the importance of considering nutritional-hygienic approaches on a mass scale to prevent diabetes.
Standard Doppler indexes of transmitral filling vary in response to alterations in left ventricular (LV) relaxation or preload. To determine whether color M-mode Doppler flow propagation velocity (vp), a new index of LV relaxation, is affected by preload, we obtained LV volumes, standard Doppler filling indexes, and vp in 20 patients at baseline, during Trendelenburg's position, inverse Trendelenburg's position, and after inhalation of amyl nitrite. LV end-diastolic volume decreased from 111 +/- 41 mL at baseline and 116 +/- 43 mL during Trendelenburg's position, to 104 +/- 40 during inverse Trendelenburg's maneuver and 92 +/- 33 mL after inhalation of amyl nitrite (P <.0001). Peak early filling velocity decreased from 79 +/- 19 cm/s and 90 +/- 20 cm/s to 73 +/- 22 cm/s and 64 +/- 20 cm/s, respectively (P < 0.0001). In contrast, no significant changes were found in vp (48 +/- 24 and 50 +/- 26 cm/s vs 48 +/- 25 and 48 +/- 25 cm/s). We conclude that vp is not affected significantly by preload. Thus vp may provide a more reliable and independent assessment of LV relaxation.
The renin-angiotensin system is upregulated with diabetes, and this may contribute to the development of a dilated myopathy. Angiotensin II (Ang II) locally may lead to oxidative damage, activating cardiac cell death. Moreover, diabetes and hypertension could synergistically impair myocardial structure and function. Therefore, apoptosis and necrosis were measured in ventricular myocardial biopsies obtained from diabetic and diabetic-hypertensive patients. Accumulation of a marker of oxidative stress, nitrotyrosine, and Ang II labeling were evaluated quantitatively. The diabetic heart showed cardiac hypertrophy, cavitary dilation, and depressed ventricular performance. These alterations were more severe with diabetes and hypertension. Diabetes was characterized by an 85-fold, 61-fold, and 26-fold increase in apoptosis of myocytes, endothelial cells, and fibroblasts, respectively. Apoptosis in cardiac cells did not increase additionally with diabetes and hypertension. Diabetes increased necrosis by 4-fold in myocytes, 9-fold in endothelial cells, and 6-fold in fibroblasts. However, diabetes and hypertension increased necrosis by 7-fold in myocytes and 18-fold in endothelial cells. Similarly, Ang II labeling in myocytes and endothelial cells increased more with diabetes and hypertension than with diabetes alone. Nitrotyrosine localization in cardiac cells followed a comparable pattern. In spite of the difference in the number of nitrotyrosine-positive cells with diabetes and with diabetes and hypertension, apoptosis and necrosis of myocytes, endothelial cells, and fibroblasts were detected only in cells containing this modified amino acid. In conclusion, local increases in Ang II with diabetes and with diabetes and hypertension may enhance oxidative damage, activating cardiac cell apoptosis and necrosis.
s described in Part I of this 2-part article, 1 diastolic heart failure is common and causes significant alterations in prognosis. In Part II, experimental studies that have provided insight into the mechanisms that cause diastolic heart failure will be described.2-19 In addition, current treatment strategies and the design of future clinical trials of diastolic heart failure will be discussed. The development of truly effective therapy for diastolic heart failure depends on gaining a clear under- standing of the basic mechanisms that alter diastolic function and the ability to efficiently target these mechanisms to correct these abnormalities in diastolic function.
The most suitable antihypertensive drug to reduce the risk of cardiovascular disease in patients with hypertension and diabetes is unclear. In prespecified analyses, we compared the effects of losartan and atenolol on cardiovascular morbidity and mortality in diabetic patients.
As part of the LIFE study, in a double-masked, randomised, parallel-group trial, we assigned a group of 1195 patients with diabetes, hypertension, and signs of left-ventricular hypertrophy (LVH) on electrocardiograms losartan-based or atenolol-based treatment. Mean age of patients was 67 years (SD 7) and mean blood pressure 177/96 mm Hg (14/10) after placebo run-in. We followed up patients for at least 4 years (mean 4.7 years [1.1]). We used Cox regression analysis with baseline Framingham risk score and electrocardiogram-LVH as covariates to compare the effects of the drugs on the primary composite endpoint of cardiovascular morbidity and mortality (cardiovascular death, stroke, or myocardial infarction).
Mean blood pressure fell to 146/79 mm Hg (17/11) in losartan patients and 148/79 mm Hg (19/11) in atenolol patients. The primary endpoint occurred in 103 patients assigned losartan (n=586) and 139 assigned atenolol (n=609); relative risk 0.76 (95% CI 0.58-.98), p=0.031. 38 and 61 patients in the losartan and atenolol groups, respectively, died from cardiovascular disease; 0.63 (0.42-0.95), p=0.028. Mortality from all causes was 63 and 104 in losartan and atenolol groups, respectively; 0.61 (0.45-0.84), p=0.002.
Losartan was more effective than atenolol in reducing cardiovascular morbidity and mortality as well as mortality from all causes in patients with hypertension, diabetes, and LVH. Losartan seems to have benefits beyond blood pressure reduction.
2risk of cardiovascular disease was doubled in men with diabetes and tripled in women with the disease, even after adjustment for other risk factors such as hypertension, smoking, and dyslipidaemia. To improve this statistic, researchers need first to characterise the precise type of cardiac abnormalities associated with diabetes. To this end, the term diabetic cardiomyopathy was coined 30 years ago. 3 Since then, the definition of diabetic cardiomyopathy has been greatly redefined, and there is now general agreement on the type of heart disease associated with diabetes. There are three main interlinked characteristics of diabetic heart disease. 4 First, patients with diabetes develop more severe coronary artery disease at a younger age, and have more multivessel disease and microangiopathy than do individuals without diabetes. 5
We sought to investigate whether pseudonormal (PN) filling was associated with death or hospital admission in patients with congestive heart failure (CHF).
The high mortality rate associated with CHF is related to many clinical and echocardiographic variables. In particular, a short mitral deceleration time and restrictive diastolic filling predict death and/or hospital admission. We hypothesized that differentiating patients with nonrestrictive filling might identify an intermediate PN group that may be associated with intermediate risk.
A total of 115 patients admitted to the hospital for exacerbation of CHF symptoms underwent pre-discharge Doppler echocardiography to determine mitral inflow (before and after preload reduction) and pulmonary venous return. Patients were followed up for one year, and all-cause mortality and re-admission data were analyzed.
The classification of filling patterns was: abnormal relaxation (AR) in 46 (40%) patients, pseudonormal (PN) filling in 42 (36.5%) patients and restrictive filling pattern (RFP) in 27 (23.4%) patients. When comparing the RFP group with the AR group, all-cause mortality was higher (38.4% vs. 17.4%, p = 0.033), hospital admission was higher (70.3% vs. 54.3%, p = 0.073), death/hospital admission was higher (77.8% vs. 56.5%, p = 0.02), CHF hospital admission was higher (40.7% vs. 15.2%, p = 0.01) and death/CHF hospital admission was higher (62.9% vs. 26.1%, p = 0.0005). Mortality in the PN group was not significantly different from that in the two other groups, but re-admissions were higher than the AR group (76.2% vs. 54.3%, p = 0.006), as was death/re-admission (78.6% vs. 56.5%, p = 0.004) and death/CHF re-admission (47.6% vs. 26.1%, p = 0.03). Re-admissions in the PN and RFP groups were comparable.
In a general hospital population of older patients with CHF, PN filling was associated with hospital admission rates similar to those seen with restrictive filling. The combined end point of death/CHF hospital admission was similar for restrictive filling and AR. Measurement of these variables is easy to add to routine clinical echocardiography and may provide important prognostic information in a wide range of patients with CHF.
Approximately half of patients with overt congestive heart failure (CHF) have diastolic dysfunction without reduced ejection fraction (EF). Yet, the prevalence of diastolic dysfunction and its relation to systolic dysfunction and CHF in the community remain undefined.
To determine the prevalence of CHF and preclinical diastolic dysfunction and systolic dysfunction in the community and determine if diastolic dysfunction is predictive of all-cause mortality.
Cross-sectional survey of 2042 randomly selected residents of Olmsted County, Minnesota, aged 45 years or older from June 1997 through September 2000.
Doppler echocardiographic assessment of systolic and diastolic function. Presence of CHF diagnosis by review of medical records with designation as validated CHF if Framingham criteria are satisfied. Subjects without a CHF diagnosis but with diastolic or systolic dysfunction were considered as having either preclinical diastolic or preclinical systolic dysfunction.
The prevalence of validated CHF was 2.2% (95% confidence interval [CI], 1.6%-2.8%) with 44% having an EF higher than 50%. Overall, 20.8% (95% CI, 19.0%-22.7%) of the population had mild diastolic dysfunction, 6.6% (95% CI, 5.5%-7.8%) had moderate diastolic dysfunction, and 0.7% (95% CI, 0.3%-1.1%) had severe diastolic dysfunction with 5.6% (95% CI, 4.5%-6.7%) of the population having moderate or severe diastolic dysfunction with normal EF. The prevalence of any systolic dysfunction (EF < or =50%) was 6.0% (95% CI, 5.0%-7.1%) with moderate or severe systolic dysfunction (EF < or =40%) being present in 2.0% (95% CI, 1.4%-2.5%). CHF was much more common among those with systolic or diastolic dysfunction than in those with normal ventricular function. However, even among those with moderate or severe diastolic or systolic dysfunction, less than half had recognized CHF. In multivariate analysis, controlling for age, sex, and EF, mild diastolic dysfunction (hazard ratio, 8.31 [95% CI, 3.00-23.1], P<.001) and moderate or severe diastolic dysfunction (hazard ratio, 10.17 [95% CI, 3.28-31.0], P<.001) were predictive of all-cause mortality.
In the community, systolic dysfunction is frequently present in individuals without recognized CHF. Furthermore, diastolic dysfunction as rigorously defined by comprehensive Doppler techniques is common, often not accompanied by recognized CHF, and associated with marked increases in all-cause mortality.
The prevalence of left ventricular diastolic abnormalities in the general population is largely unclear. Thus, the aim of this study was, firstly, to identify abnormal diastolic function by echocardiography in an age-stratified population-based European sample (MONICA Augsburg, n=1274, 25 to 75 years, mean 51+/-14) and, secondly, to analyse clinical and anthropometric parameters associated with diastolic abnormalities.
The overall prevalence of diastolic abnormalities, as defined by the European Study Group on Diastolic Heart Failure (i.e. age dependent isovolumic relaxation time (92-105 ms) and early (E-wave) and late (A-wave) left ventricular filling (E/A-ratio, 1-0.5)) was 11.1%. When only subjects treated with diuretics or with left atrial enlargement were considered (suggesting diastolic dysfunction) the prevalence was 3.1%. The prevalence of diastolic abnormalities varied according to age: from 2.8% in individuals aged 25-35 years to 15.8% among those older than 65 years (P<0.01). Significantly higher rates of diastolic abnormalities were observed in men as compared to women (13.8% vs 8.6%, P<0.01). Independent predictors of diastolic abnormalities were arterial hypertension, evidence of left ventricular (LV) hypertrophy, and coronary artery disease. Interestingly, in the absence of these predisposing conditions, diastolic abnormalities (4.3%) or diastolic dysfunction (1.1%) were rare, even in subjects older than 50 years of age (4.6%) and (1.2%), respectively. In addition to these factors, diastolic dysfunction was related to high body mass index, high body fat mass, and diabetes mellitus.
The prevalences of diastolic abnormalities and diastolic dysfunction are higher than that of systolic dysfunction and are increased (despite age-dependent diagnostic criteria) in the elderly. However, in the absence of risk factors for diastolic abnormalities or diastolic dysfunction, namely LV hypertrophy, arterial hypertension, coronary artery disease, obesity and diabetes the condition is rare even in elderly subjects. These data allow speculation on whether diastolic heart failure may be prevented by improved implementation of measures directed against predisposing conditions.
We sought to compare systolic and diastolic function in American Indians with diabetes mellitus (DM) based on albuminuria status.
Albuminuria has been shown to predict cardiovascular disease (CVD) in populations with DM. However, the mechanism of the association of albuminuria and CVD is unclear.
We compared echo-derived indices of left ventricular (LV) systolic and diastolic function in three groups of American Indians with DM based on albuminuria status: I = no albuminuria (<30 mg albumin/g creatinine); II = microalbuminuria (30 to 300 mg/g); and III = macroalbuminuria (>300 mg/g).
Group II and III were slightly older than Group I with no significant gender difference between groups. Systolic blood pressure increased and body mass index decreased from Group I to Group III. Left ventricular systolic function was lower in the groups with albuminuria with step-wise decreases in ejection fraction and stress-corrected midwall shortening (MWS) from Group I to Group III. Similar findings were noted in diastolic LV filling with lower mitral E/A ratios and longer deceleration times in groups with albuminuria. The proportion of participants with abnormal MWS and abnormal LV diastolic relaxation showed step-wise increases from no albuminuria to macroalbuminuria. In multivariate analysis, albuminuria status remained independently associated with both systolic and diastolic dysfunction after adjusting for age, gender, body mass index, systolic blood pressure, duration of diabetes, coronary artery disease, and LV mass.
Albuminuria is independently associated with LV systolic and diastolic dysfunction in type 2 DM; this may explain in part the relationship of albuminuria to increased cardiovascular (CV) events in the DM population. Screening for albuminuria identifies individuals with high CV risk and possible cardiac dysfunction.
Guidelines aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic procedure. They should be helpful in everyday clinical decision-making. A great number of guidelines have been issued in recent years by different organisations--European Society of Cardiology (ESC), American Heart Association (AHA), American College of Cardiology (ACC), and other related societies. By means of links to web sites of National Societies several hundred guidelines are available. This profusion can put at stake the authority and validity of guidelines, which can only be guaranteed if they have been developed by an unquestionable decision-making process. This is one of the reasons why the ESC and others have issued recommendations for formulating and issuing guidelines. In spite of the fact that standards for issuing good quality guidelines are well defined, recent surveys of guidelines published in peer-reviewed journals between 1985 and 1998 have shown that methodological standards were not complied with in the vast majority of cases. It is therefore of great importance that guidelines and recommendations are presented in formats that are easily interpreted. Subsequently, their implementation programmes must also be well conducted. Attempts have been made to determine whether guidelines improve the quality of clinical practice and the utilisation of health resources. In addition, the legal implications of medical guidelines have been discussed and examined, resulting in position documents, which have been published by a specific task force. The ESC Committee for practice guidelines (CPG) supervises and coordinates the preparation of new guidelines and expert consensus documents produced by task forces, expert groups or consensus panels. The Committee is also responsible for the endorsement of these guidelines or statements.
Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with diabetes mellitus (DM). The pathophysiology of CVD in diabetes involves traditional and novel cardiac risk factors, including hypertension, dyslipidemia, smoking, genetic factors, hyperglycemia, insulin resistance/hyperinsulinemia, metabolic abnormalities, oxidative/glycoxidative stress, inflammation, endothelial dysfunction, a procoagulant state and myocardial fibrosis. Specific vascular, myopathic and neuropathic alterations have been suggested to be responsible for the excessive cardiovascular morbidity and mortality in diabetes. These alterations manifest themselves clinically as coronary heart disease, congestive heart failure and/or sudden cardiac death. In order to contain the emerging epidemic of CVD in DM, diabetic patients should ideally have excellent glycemic control, a low normal blood pressure and low levels of low-density lipoprotein cholesterol, and be taking an angiotensin-converting enzyme inhibitor and aspirin, which may go some way to containing the emerging epidemic of CVD in DM.
A number of recent community-based epidemiologic studies suggest that 40% to 50% of the cases of heart failure have preserved left ventricular systolic function. Although diastolic heart failure is often not well clinically recognized, it is associated with marked increases in morbidity and all-cause mortality. Doppler echocardiography has emerged as the principal clinical tool for the assessment of left ventricular diastolic function. Doppler mitral inflow velocity-derived variables remain the cornerstone of the evaluation of diastolic function. Pulmonary venous Doppler flow indices and mitral inflow measurements with Valsalva's maneuver are important adjuncts for differentiating normal and pseudonormal mitral inflow patterns. Unfortunately, these Doppler flow variables are significantly influenced by loading conditions and, therefore, the results from these standard techniques can be inconclusive. Recently, color M-mode and Doppler tissue imaging have emerged as new modalities that are less affected by preload and, thus, provide a strong complementary role in the assessment of diastolic function. This review will discuss the diastolic properties of the left ventricle, Doppler echocardiographic evaluation, and grading of diastolic dysfunction.
Patients with diabetes mellitus have a high incidence of coronary heart disease and congestive heart failure (CHF). Thiazolidinediones (TZD) are a new class of pharmacological agents for the treatment of Type 2 diabetes mellitus, which have many beneficial cardiovascular effects. Peripheral oedema and weight gain have been reported in 4.8% of subjects on TZDs alone, with a higher incidence noted in those receiving combination insulin therapy (up to 15%), but there is limited data on the occurrence of CHF.
In this paper, we report on six cases of TZD-induced fluid retention with symptoms and signs of peripheral oedema and/or CHF that occurred in subjects attending our diabetic clinic. The predominant finding in all cases was of diastolic dysfunction. All subjects were obese and hypertensive, with 5/6 having the additional risk factor of LVH, 5/6 subjects had microvascular complications, whilst 3/6 were also on insulin therapy.
We suggest that obese, hypertensive diabetics may benefit from echocardiographic screening prior to commencement of TZDs, as these agents may exacerbate underlying undiagnosed left ventricular diastolic dysfunction.
Because diabetes mellitus substantially increases the risk of development of heart failure, we sought to establish early alterations in left ventricular systolic and diastolic function in patients with diabetes mellitus with and without coexisting systemic hypertension. We studied 134 subjects using echocardiography comprising standard 2-dimensional and conventional Doppler as well as tissue Doppler imaging. Our study demonstrated the early appearance of both left ventricular systolic and diastolic dysfunction in diabetic patients at rest and the contributory effects of diabetes to myocardial impairment produced by hypertension, as well as the high usefulness of tissue Doppler imaging in detection and quantitation of myocardial dysfunction in diabetics. This method was superior to other echocardiographic techniques and plasma brain natriuretic peptide evaluation.
The aims of this study were to update previous estimates of the congestive heart failure (CHF) incidence rate in patients with type 2 diabetes, compare it with an age- and sex-matched nondiabetic group, and describe risk factors for developing CHF in diabetic patients over 6 years of follow-up.
We performed a retrospective cohort study of 8,231 patients with type 2 diabetes and 8,845 nondiabetic patients of similar age and sex who did not have CHF as of 1 January 1997, following them for up to 72 months to estimate the CHF incidence rate. In the diabetic cohort, we constructed a Cox regression model to identify risk factors for CHF development.
Patients with diabetes were much more likely to develop CHF than patients without diabetes (incidence rate 30.9 vs. 12.4 cases per 1,000 person-years, rate ratio 2.5, 95% CI 2.3-2.7). The difference in CHF development rates between persons with and without diabetes was much greater in younger age-groups. In addition to age and ischemic heart disease, poorer glycemic control (hazard ratio 1.32 per percentage point of HbA(1c)) and greater BMI (1.12 per 2.5 units of BMI) were important predictors of CHF development.
The CHF incidence rate in type 2 diabetes may be much greater than previously believed. Our multivariate results emphasize the importance of controlling modifiable risk factors for CHF, namely hyperglycemia, elevated blood pressure, and obesity. Younger patients may benefit most from risk factor modification.
Tissue Doppler imaging is being increasingly used for assessing global ventricular function in systole and diastole, and for quantifying regional wall motion abnormalities both in systolic heart failure with mechanical dyssynchrony and ischemic heart disease. Its use as a predictive tool is recent and the authors review publications relating to this aspect.
Peak early diastolic mitral annular velocity is a powerful predictor of outcome in a variety of cardiovascular conditions and adds incremental value to clinical parameters and standard mitral Doppler inflow velocities. Tissue Doppler imaging can also predict the development of hypertrophic cardiomyopathy in asymptomatic individuals carrying the genetic mutation even before the onset of overt left ventricular hypertrophy. In addition, the standard deviation of the time to peak systolic velocity is a good marker of mechanical asynchrony and can predict reverse remodeling. It may also be useful in identifying individuals with ischemic heart disease and regional wall motion abnormalities who have an adverse outcome.
Tissue Doppler imaging is a powerful new echocardiographic tool that is now becoming the standard for assessing ventricular function in a variety of situations and diseases.
We sought to determine the prognostic value of left ventricular (LV) mitral annular velocities measured by tissue Doppler imaging (TDI) in hypertensive patients with echocardiographic evidence of LV hypertrophy.
Echo LV hypertrophy and LV geometry provide additional predictive value of all-cause mortality beyond traditional cardiovascular risk factors. Limited data exist regarding the predictive value of TDI velocities for cardiovascular risk stratification in treated hypertensive patients.
Two-dimensional and Doppler echocardiograms were obtained in 252 consecutive subjects, including 174 subjects with systemic hypertension and 78 age-matched normal subjects. The end point was cardiac death in subsequent median follow-up of 19 months.
Nineteen patients (7.54%) died of cardiac causes. The TDI mitral annulus systolic velocity and the early diastolic mitral annular velocity (Em) were significantly lower in the non-survivors (all P < 0.001). The pseudonormal (PN) or restrictive filling pattern (RFP) was associated with cardiac mortality. The other parameters associated with cardiac mortality were LV ejection fraction, LV mass index, inter-ventricular septal wall thickness in diastole and the ratio of early mitral inflow to early myocardial velocity. In multivariate analysis, Em, inter-ventricular septal wall thickness in diastole and either PN or RFP were the strongest predictors. The addition of Em < 3.5 cm/s significantly improved the outcome of a model that contained clinical risk factors, inter-ventricular septal wall thickness in diastole > 1.4 cm and either PN or RFP (P = 0.043).
Early diastolic mitral annulus velocity measured by TDI provides prognostic information, incremental to clinical data and standard echocardiographic variables, for risk stratification of hypertensive patients under treatment.
Anaemia is common in patients with diabetes and associated with an increased risk of diabetic complications. Although the role of anaemia in heart failure is established, we hypothesize that anaemia also contributes to an increased risk of cardiac dysfunction in patients with Type II diabetes. In the present study, 228 consecutive adults with diabetes were investigated using transthoracic echocardiography. Echocardiographic parameters were correlated with the Hb (haemoglobin) level and adjusted for other risk factors for cardiac dysfunction using multivariate analysis. More than one in five patients (23%) had anaemia, which was an independent risk factor for cardiac dysfunction on echocardiography. Over one-third of all patients with evidence of abnormal cardiac function (diastolic and/or systolic dysfunction) on echocardiography had anaemia compared with <5% of patients with normal echocardiographic findings. Most patients with anaemia had cardiac dysfunction (94%), with the major abnormality being diastolic dysfunction associated with an increased left ventricular mass and impaired relaxation indices. A continuous association between diastolic function and Hb was also observed in patients without anaemia. In patients with a history of cardiovascular disease, systolic dysfunction was twice as common in patients with anaemia. Anaemia was also correlated with plasma markers of cardiac risk, including BNP (brain natriuretic peptide), CRP (C-reactive protein) and AVP (arginine vasopressin). Notably, the predictive utility of these markers was eliminated after adjusting for Hb. Consequently, the inexpensive measurement of Hb may be a useful tool to identify diabetic patients at increased risk of cardiac dysfunction.
Aims Under-reporting of diabetes on death certificates contributes to the unreliable estimates of mortality as a result of diabetes. The influence of obesity on mortality in Type 2 diabetes is not well documented. We aimed to study mortality from diabetes and the influence of obesity on mortality in Type 2 diabetes in a large cohort selected from the General Practice Research Database (GPRD).
Methods A cohort of 44 230 patients aged 35–89 years in 1992 with Type 2 diabetes was identified. A comparison group matched by year of birth and sex with no record of diabetes at any time was identified (219 797). Hazards ratios (HRs) for all-cause mortality during the period January 1992 to October 1999 were calculated using the Cox Proportional Hazards Model. The effects of body mass index (BMI), smoking and duration of diabetes on all-cause mortality amongst people with diabetes was assessed (n = 28 725).
Results The HR for all-cause mortality in Type 2 diabetes compared with no diabetes was 1.93 (95% CI 1.89–1.97), in men 1.77 (1.72–1.83) and in women 2.13 (2.06–2.20). The HR decreased with increasing age. In the multivariate analysis in diabetes only, the HR for all-cause mortality amongst smokers was 1.50 (1.41–1.61). Using BMI 20–24 kg/m2 as the reference range, for those with a BMI 35–54 kg/m2 the HR was 1.43 (1.28–1.59) and for those with a BMI 15–19 kg/m2 the HR was 1.38 (1.18–1.61).
Conclusions Patients with Type 2 diabetes have almost double the mortality rate compared with those without. The relative risk decreases with age. In people with Type 2 diabetes, obesity and smoking both contribute to the risk of all-cause mortality, supporting doctrines to stop smoking and lose weight.
Marked reductions in cardiovascular disease (CVD) morbidity and mortality have occurred in the United States over the last 50 years. We tested the hypothesis that the relative burden of CVD attributable to diabetes mellitus (DM) has increased over the past 5 decades.
Participants aged 45 to 64 years from the Framingham Heart Study, who attended examinations in an "early" time period (1952 to 1974), were compared with those who attended examinations in a later time period (1975 to 1998). The risk of CVD events (n=133 among those with and 1093 among those without DM) attributable to DM in the 2 time periods was assessed with Cox proportional hazards models; population attributable risk of DM as a CVD risk factor was calculated for each time period. The age- and sex-adjusted hazard ratio for DM as a CVD risk factor was 3.0 (95% CI, 2.3 to 3.9) in the earlier time period and 2.5 (95% CI, 1.9 to 3.2) in the later time period. The population attributable risk for DM as a CVD risk factor increased from 5.4% (95% CI, 3.8% to 6.9%) in the earlier time period to 8.7% (95% CI, 5.9% to 11.4%) in the later time period (P for attributable risk ratio=0.04), although multivariable adjustment resulted in attenuation of these findings (P=0.12); most of these observations were found among men.
The proportion of CVD attributable to DM has increased over the past 50 years in Framingham. These findings emphasize the need for increased efforts to prevent DM and to aggressively treat and control CVD risk factors among those with DM.
Diastolic dysfunction might represent an important pathophysiological intermediate between hypertension and heart failure. Our aim was to determine whether inhibitors of the renin-angiotensin-aldosterone system, which can reduce ventricular hypertrophy and myocardial fibrosis, can improve diastolic function to a greater extent than can other antihypertensive agents.
Patients with hypertension and evidence of diastolic dysfunction were randomly assigned to receive either the angiotensin receptor blocker valsartan (titrated to 320 mg once daily) or matched placebo. Patients in both groups also received concomitant antihypertensive agents that did not inhibit the renin-angiotensin system to reach targets of under 135 mm Hg systolic blood pressure and under 80 mm Hg diastolic blood pressure. The primary endpoint was change in diastolic relaxation velocity between baseline and 38 weeks as determined by tissue doppler imaging. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00170924.
186 patients were randomly assigned to receive valsartan; 198 were randomly assigned to receive placebo. 43 patients were lost to follow-up or discontinued the assigned intervention. Over 38 weeks, there was a 12.8 (SD 17.2)/7.1 (9.9) mm Hg reduction in blood pressure in the valsartan group and a 9.7 (17.0)/5.5 (10.2) mm Hg reduction in the placebo group. The difference in blood pressure reduction between the two groups was not significant. Diastolic relaxation velocity increased by 0.60 (SD 1.4) cm/s from baseline in the valsartan group (p<0.0001) and 0.44 (1.4) cm/s from baseline in the placebo group (p<0.0001) by week 38. However, there was no significant difference in the change in diastolic relaxation velocity between the groups (p=0.29).
Lowering blood pressure improves diastolic function irrespective of the type of antihypertensive agent used.
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The incidence of congestive heart failure in type 2 diabetes: an update
- Nichols