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Metabolic syndrome, C-reactive protein, and prognosis in patients with established coronary artery disease
Abstract
The prognosis associated with metabolic syndrome and high-sensitivity C-reactive protein (hs-CRP) in patients with stable coronary artery disease has not been well established.
The WIZARD study was to determine the effects of 12 weeks of antibiotic therapy on coronary heart disease events in patients with stable coronary artery disease and known Chlamydia pneumoniae exposure. Baseline metabolic risk factors were available for 3319 patients enrolled from 1997 to 1998. The primary outcome was the first occurrence of death, recurrent myocardial infarction, coronary revascularization procedure, or hospitalization for angina.
Of the 3319 subjects, 825 patients experienced the primary outcome during the mean follow-up of 37 months. For the composite outcome, there was an increased hazard ratio (HR) for metabolic syndrome (HR 1.40, 95% CI 1.22-1.61) (unadjusted) and for hs-CRP (HR 1.60, 95% CI 1.38-1.85) (unadjusted). Both the metabolic syndrome and hs-CRP indicated, in a multivariable model including age and sex, an increased HR for the primary outcome (metabolic syndrome: HR 1.33, 95% CI 1.15-1.53; hs-CRP: HR 1.52, 95% CI 1.30-1.76).
Although related, the presence of the metabolic syndrome and increased levels of hs-CRP were associated with increased risk of adverse cardiovascular outcomes.
... 7 Studies have suggested higher prevalence of ACS in age 60 years or older and predominantly in males which is in agreement to the result obtained in present study. 8 The skewed gender distribution bias was also a feature in Interheart study and its South Asian cohort. 9 Hypertension, a conventional risk factor is implicated in CAD. ...
... The prevalence of hypertension is comparable to that in Create registry (37.7%), and higher than that reported in south Asian cohort of INTERHEART study (17.8%). 8,9 Tobacco smoking is a known modifiable risk factor for CAD. 8 The prevalence of tobacco smoking was low in present study (25.3%). Overall, the mean age of smokers presenting with CAD was younger as compared to non smokers with CAD. ...
... 8,9 Tobacco smoking is a known modifiable risk factor for CAD. 8 The prevalence of tobacco smoking was low in present study (25.3%). Overall, the mean age of smokers presenting with CAD was younger as compared to non smokers with CAD. ...
Background: India has shown a rising trend in the prevalence of coronary artery disease (CAD) in urban as well as in rural population. Acute coronary syndrome (ACS) is the main reason for the mortality in India. Study of risk factors and biomarkers is important to catch the diagnosis early in order to decrease the mortality. Objective was to study risk factors and brain natriuretic peptide (BNP), troponine I, and CKMB and their effect on outcome in ACS patients in tertiary hospital.Methods: One hundred and fifty ACS patients were studied in Emergency Department of Medicine, Nehru Hospital, BRD Medical College, Gorakhpur from January 2017 to December 2017. Data on age sex socioeconomic status, medical history, baseline clinical characteristics, time to reach hospital and treatment in hospital, along with biomarkers including BNP, Troponin Iand CKMB was estimated. Baseline ECG was obtained at admission and repeated at 12 -24 hours and every 24 hours thereafter. A 2D Echocardiogram was performed within initial 48-72 hours for analysis of LVEF and wall motion abnormalities.Results: Male (58.7%) preponderance was observed with mean age of 60.12±10.58 years. Most of the patients were from rural areas (87.3%) and had hypertension (44.7%). Chest pain was most common symptom (56%). Most of them had duration of symptoms for 6-12 hours (56%). NSTEMI, STEMI and unstable angina were equally distributed between the genders (p>0.05). Out of 150 patients, 15 (10%) were thrombolysed, 78.52% had RWMA. In-hospital mortality was higher; among the patients of age >75 years (38.5%) (p=0.008), male patient (12.5%) (p>0.05), rural patient (10.7%) (p>0.05), hypertensive patient (17.3%) (p>0.05), patients of Killip class IV (48.3%)(p=0.0001) and patients having severe LVD (33.3%) (p=0.0001). In-hospital mortality was 1.2% and 1.1% among those in whom beta blocker and ACE inhibitors was present (p>0.0001). BNP and CKMB was significantly higher among expired patients (1762.62±1444.89 vs 840.76±1294.82; p=0.001) similarly troponin I was significantly higher among expired patients (67.29±45.63 vs 43.99±41.73; p=0.006) than alive.Conclusions: ACS was more prevalent in male, living in fifth to sixth decade of life, had hypertension. STEMI was more common. Patients on ACE inhibitors and beta-blocker had better outcome. Mortality was higher in patients with Killip’s class IV, higher value of troponin I, age more than 75 years and had hypertension and dyslipidemia.
... The adventitia contains collagen fibrils and a cellular population such as fibroblasts and mast cells. Vasa vasorum and nerve endings localize in this outermost layer of the arterial wall [12][13][14][15] . ...
... high-sensitivity C-reactive protein (CRP)], indices of fibrinolytic function [e.g. tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1)] [10,14,25] . ...
... Another factor important for the rupture is the propagating pulse wave during the cardiac cycle that causes changes in lumen size and shape with deformation and bending of plaques, and particularly of eccentric plaques [12][13][14][15] . ...
Coronary heart disease is the single most common cause of illness and death in the developed world. Coronary atherosclerosis is by far the most frequent cause of ischemic heart disease, and plaque disruption with superimposed thrombosis is the main cause of the acute coronary syndromes of unstable angina, myocardial infarction, and sudden death. Atherosclerosis is the result of a complex interaction between blood elements, disturbed flow, and vessel wall abnormality, involving several pathological processes: inflammation, with increased endothelial permeability, endothelial activation, and monocyte recruitment; growth, with smooth muscle cell proliferation, migration, and matrix synthesis; degeneration, with lipid accumulation; necrosis, possibly related to the cytotoxic effect of oxidized lipid; calcification/ossification, which may represent an active rather than a dystrophic process; and thrombosis, with platelet recruitment and fibrin formation. In this review we discuss these processes and the possible pathological effects of Chlamydia infection and the ensuing phlogosis.
... Moreover, elevated hs-CRP levels were associated with reduced abilities in clearance of oxidative stressors and inflammatory mediators, thus increase the incidence of cardiovascular events 23 . It has been reported that elevated hs-CRP levels were associated with increased risk of adverse cardiovascular outcomes in patients with different CAD phenotypes [24][25][26] . Aguilar et al. focused on stable CAD and enrolled 3319 patients and followed up for 37 months, they found that increased levels of hs-CRP were associated with higher risk of adverse cardiac events 24 . ...
... It has been reported that elevated hs-CRP levels were associated with increased risk of adverse cardiovascular outcomes in patients with different CAD phenotypes [24][25][26] . Aguilar et al. focused on stable CAD and enrolled 3319 patients and followed up for 37 months, they found that increased levels of hs-CRP were associated with higher risk of adverse cardiac events 24 . The FRISC study included 917 patients with unstable coronary artery disease and the investigators found that elevated CRP levels were strongly associated with the long-term risk of death from heart disease 25 . ...
The study aimed to determine whether high sensitivity C-reactive protein to prealbumin (hs-CRP/PAB) ratio could be used to predict in-hospital major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS). A total of 659 patients with ACS were included in the study. Patients were divided into two groups: high hs-CRP/PAB ratio group (hs-CRP/PAB ≥0.010) and low hs-CRP/PAB ratio group (hs-CRP/PAB <0.010). MACE was defined as death, cardiogenic shock, re-infarction and acute heart failure. Logistic regression was performed and the receiver operating characteristic curve (ROC) was generated to evaluate the correlation of hs-CRP/PAB ratio and MACE in patients with ACS. The occurrence rate of MACE was significantly higher in high hs-CRP/PAB ratio group when compared with that in low hs-CRP/PAB ratio group (P < 0.001). Multivariable analysis determined that hs-CRP/PAB ratio was an independent predictor of MACE (adjusted odds ratio: 1.276, 95% confidence interval: 1.106–1.471, P = 0.001). Moreover, the area under the curve value of hs-CRP/PAB ratio for predicting MACE was higher than hs-CRP and equal to PAB. High hs-CRP/PAB ratio was considered as a prognostic parameter of MACE in ACS patients, with the predictive power equal to PAB but greater than hs-CRP.
... Each of the components of the metabolic syndrome has been independently associated with vascular dysfunction (4)(5)(6)(7)(8). In addition to insulin resistance, release of proinflammatory cytokines (e.g., interleukin-6, tumor necrosis factora) by visceral adipose tissue or other as yet undefined factors may also contribute to vascular dysfunction (9) or adverse clinical outcomes (10,11) in patients with the metabolic syndrome. However, they do not together fully explain the 2.6-fold increased risk of coronary death among those with the metabolic syndrome (12), suggesting that other mechanisms may contribute to the association between the metabolic syndrome and the increased risk of CAD. ...
... The effect of the metabolic syndrome on cardiovascular events was independent of its association with diabetes, and the risks associated with diabetes and the metabolic syndrome were incremental to each other. Similar findings have been reported in the WIZARD study (11). Our findings suggest that the increased risk associated with the metabolic syndrome in high-risk individuals may be related to the effect of insulin resistance on atherosclerosis burden (32) rather than coronary microvascular function (33). ...
The metabolic syndrome affects 25% of the U.S. population and greatly increases the risk of diabetes and coronary artery disease (CAD). We tested the hypothesis that the metabolic syndrome is associated with impaired coronary vasodilator function, a marker of atherosclerotic disease activity.
Four hundred sixty-two patients at risk for CAD, as defined by a low-density lipoprotein cholesterol ≥ 160 mg/dL with fewer than 2 coronary risk factors, a low-density lipoprotein cholesterol ≥ 130 mg/dL with 2 or more coronary risk factors, or with documented CAD were included. A subset of 234 individuals underwent repeated PET at 1 y. Myocardial blood flow (MBF) and vasodilator reserve were assessed by PET. Modified criteria of the National Cholesterol Education Program, Adult Treatment Panel III were used to characterize the metabolic syndrome.
Adenosine- and cold-stimulated MBF were similar in patients with and without metabolic syndrome, whereas baseline MBF showed a stepwise increase with increasing features of the syndrome. Consequently, patients with metabolic syndrome showed a lower coronary flow reserve (CFR) (2.5 ± 1.0) than those without metabolic syndrome (3.0 ± 0.9, P = 0.004). Differences in CFR were no longer present after correcting rest flows for the rate-pressure product. Change in MBF and CFR at 1 y were not different across groups of patients with increasing features of the metabolic syndrome.
Patients with metabolic syndrome demonstrate impaired CFR, which is related to the augmentation in resting coronary blood flow caused by hypertension. In high-risk individuals, peak adenosine- and cold-stimulated blood flows are impaired even in the absence of the metabolic syndrome.
... Similarly, 2 other groups have independently reported that, at least in women, baseline high-sensitivity CRP (hsCRP) rose significantly with culmination of components of the metabolic syndrome [3,10]. This phenomenon has been mirrored in moderately hypercholesterolemic men [2] and in patients with histories of myocardial infarction [11], with both sets of investigators concluding that hsCRP added prognostic CVD and diabetes risk information beyond that provided by the presence of the metabolic syndrome. ...
... Participants were classified as having the metabolic syndrome (619 of 1082) if they fulfilled the criteria established by the NCEP Adult Treatment Panel III (ATP-III) [13], whereas target organ damage was defined by the presence of cardiac hypertrophy, thickening of the carotid arterial wall, and renal impairment. Upon correlating these factors to fasting hsCRP levels, the authors confirmed previous reports of a positive association between hsCRP concentrations and increased metabolic disorders [2,3,[9][10][11]. Furthermore, it was evident that elevated hsCRP and metabolic syndrome comorbidity is solidly indicative of target organ damage. ...
... In this study, a remarkably worse short-term prognosis was observed in patients with serum hs-CRP levels > 4 mg/L, CRP > 5.25 mg/L. which are compatible with previous findings [28] [29]. It is most likely that CRP has a role in all phases of atherosclerosis by directly influencing processes such as endothelial damage, complement activation, apoptosis, vascular cell activation, and thrombosis [30]. ...
Background: Acute coronary syndrome (ACS) is the leading cardiovascular
(CV) cause of mortality. C reactive protein (CRP) has linked with long-term
risk of recurrent cardiovascular events or death. Albumin, in contrast to CRP
known as a negative acute-phase protein. Thus a newly introduced marker
assessed relation of CRP to albumin ratio (CAR), which may provide better
results than the use of either marker alone. The aim of the study is to assess
the association of C-reactive protein to albumin ratio (CAR) with in-hospital
short-term major adverse cardiac events (MACEs) in acute coronary syndrome
(ACS) patients. Patients & Methods: A multi-centers prospective cohort
study was conducted at coronary intensive care units (CICU) in Baghdad
during the period from March to October 2021 that included a total of 132
patients who were diagnosed as a case of ACS. They were assessed for major
adverse cardiac events (MACEs) like cardiogenic shock, arrhythmias, post-MI
angina, and acute heart failure while inside the ward, in addition to need for
early interventional therapeutic approach in relation to (CAR) immediately at
time of admission to hospital. Results: High values of CAR, whether using
hs-CRP or CRP, were identified as an independent predictor for in-hospital
MACEs (P value < 0.001 and 0.002 respectively. A cut-off value of CAR (using
hs-CRP) is 3.18 mg/L in context of discrimination between medically treated
ACS patients and death outcome in term of high CAR. A cut-off value of CAR
(using CRP) as 9.13 mg/L suggests the usefulness in discrimination of outcome in relation to medically managed patients, at presentation. CAR had a
positive significant correlation with hospital stay (r = 0.210, P = 0.036). Conclusion: The CAR was independently correlated with in-hospital short-term
MACEs and can be used for risk stratification in patients with ACS.
... In this study, a remarkably worse short-term prognosis was observed in patients with serum hs-CRP levels > 4 mg/l, CRP > 5.25 mg/l. These results of the present study are compatible with previous ndings [29,30] . It is most likely that CRP has a role in all phases of atherosclerosis by directly in uencing processes such as endothelial damage, complement activation, apoptosis, vascular cell activation, and thrombosis [31] It is suggested that decreased albumin plasma concentrations may be attributed development and progression of atherosclerosis [32,33] . ...
Background:
Acute coronary syndrome (ACS) is the leading cardiovascular (CV) cause of mortality . C reactive protein (CRP) has linked with long-term risk of recurrent cardiovascular events or death. Albumin, in contrast to CRP known as negative acute-phase proteins. Thus a newly introduced marker assessed relation of CRP to albumin ratio (CAR), which may provide better results than the use of either marker alone.
Aim: - to assess the association of C-reactive protein to albumin ratio (CAR) with in hospital short-term major adverse cardiac events (MACEs) in acute coronary syndrome (ACS) patients.
Patients & methods: A multi-centers prospective cohort study conducted at coronary intensive care units (CICU) in Baghdad during the period from March to October 2021 that included a total of 132 patients who were diagnosed as a case of ACS. They were assessed for major adverse cardiac events (MACEs) like cardiogenic shock, arrhythmias, post-MI angina, and acute heart failure while inside the ward, in addition to need for early interventional therapeutic approach in relation to (CAR) immediately at time of admission to hospital.
Results: High values of CAR, whether using hs-CRP or CRP, were identified as an independent predictor for in-hospital MACEs (P value < 0.001 and 0.002 respectively. A cut off value of CAR (using hs-CRP) in is 3.18 mg/L in context of discrimination between medically treated ACS patients and death outcome in term of high CAR . A cut off value of CAR (using CRP) as 9.13mg/L suggests the usefulness in discrimination of outcome in relation to medically managed patients , at presentation . CAR had a positive significant correlation with hospital stay (r= 0.210, P =0.036) .
Conclusion: The CAR was independently correlated with in-hospital short-term MACEs and can be used for risk stratification in patients with ACS.
... [42] Of the 3319 patients with stable CAD, per unit log-transformed hs-CRP was associated with 52% higher risk of MACEs. [43] These findings further supported the predictive value of CRP in stable CAD patients. ...
Background:
Conflicting results have been reported on the association of C-reactive protein (CRP) level with adverse outcomes in patients with stable coronary artery disease (CAD). The objective of this meta-analysis was to evaluate the predictive value of baseline CRP level in stable CAD patients.
Methods:
Two reviewers independently searched PubMed and Embase databases from their inception to November 28, 2021 to identify studies assessing the value of baseline CRP level in predicting adverse outcomes in stable CAD patients. The endpoints of interest included cardiovascular mortality, all-cause mortality, or major adverse cardiovascular events (MACEs). The predictive value of CRP level was estimated by pooling the multivariable adjusted risk ratio with 95% confidence intervals (CI) compared the highest to the lowest CRP level.
Results:
Twenty-six studies involving of 22,602 patients with stable CAD satisfied the inclusion criteria. In a comparison of the highest with the lowest CRP level, the pooled multivariable adjusted risk ratio was 1.77 (95% CI 1.60-1.96) for MACEs, 1.64 (95% CI 1.13-2.33) for cardiovascular mortality, and 1.62 (95% CI 2.62-5.12) for all-cause mortality, respectively. Subgroup analyses indicated that the values of elevated CRP level in predicting MACEs were consistently observed in each subgroup.
Conclusion:
Elevated baseline CRP level was an independent predictor of MACEs, cardiovascular mortality, and all-cause mortality in patients with stable CAD. Baseline CRP level can provide important predictive information in stable CAD patients.
... After excluding 226 duplicate articles, 125 studies were initially included by reading the title and abstract. Fifty-five studies were finally included after further reading the full text, including six RCT post-hoc studies (15)(16)(17)(18)(19)(20) and 49 cohort studies (3, 5-8, 21-64) (Figure 1). ...
Background: Patients with metabolic syndrome (MetS) have a higher risk of developing cardiovascular diseases (CVD). However, controversy exists about the impact of MetS on the prognosis of patients with CVD.
Methods: Pubmed, Cochrane library, and EMBASE databases were searched. Cohort Studies and randomized controlled trials post hoc analyses that evaluated the impact of MetS on prognosis in patients (≥18 years) with CVD were included. Relative risk (RR), hazard rate (HR) and 95% confidence intervals (CIs) were calculated for each individual study by random-effect model. Subgroup analysis and meta-regression analysis was performed to explore the heterogeneity.
Results: 55 studies with 16,2450 patients were included. Compared to patients without MetS, the MetS was associated with higher all-cause death [RR, 1.220, 95% CI (1.103 to 1.349), P , 0.000], CV death [RR, 1.360, 95% CI (1.152 to 1.606), P , 0.000], Myocardial Infarction [RR, 1.460, 95% CI (1.242 to 1.716), P , 0.000], stroke [RR, 1.435, 95% CI (1.131 to 1.820), P , 0.000]. Lower high-density lipoproteins (40/50) significantly increased the risk of all-cause death and CV death. Elevated fasting plasma glucose (FPG) (>100 mg/dl) was associated with an increased risk of all-cause death, while a higher body mass index (BMI>25 kg/m ² ) was related to a reduced risk of all-cause death.
Conclusions: MetS increased the risk of cardiovascular-related adverse events among patients with CVD. For MetS components, there was an increased risk in people with low HDL-C and FPG>100 mg/dl. Positive measures should be implemented timely for patients with CVD after the diagnosis of MetS, strengthen the prevention and treatment of hyperglycemia and hyperlipidemia.
... In this study, a remarkably worse short-term prognosis was observed in patients with serum hs-CRP levels >4.45 mg/l. These results of the present study are compatible with previous findings [23][24][25][26][27]. In the past year, the CANTOS trial [28] demonstrated for the first time that anti-inflammatory effects can reduce the risk for cardiovascular diseases. ...
Aim: The present study aimed to examine the correlation between high-sensitivity C-reactive protein to albumin ratio (CAR) and in-hospital and short-term major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS). Materials & methods: We analyzed 652 consecutive patients who had been hospitalized for ACS. The MACEs were defined as cardiogenic shock, reinfarction, acute heart failure and all-cause death. Results: The incidence rate of MACEs was significantly higher in the high CAR (≥0.114) group than in the low CAR (<0.114) group. Multivariate analysis revealed that CAR, high-sensitivity C-reactive protein and albumin were independent predictors for increased risk for MACEs. Conclusion: The CAR was independently correlated with in-hospital and short-term MACEs and can be used for risk stratification in patients with ACS.
... 8 CRP is associated with all parameters of the MS 9 and has been acknowledged to be an independent but not causal 2,10 risk factor for incident CHD and to add prognostic value for CHD risk on top of the MS criteria. 3,9,[11][12][13][14] The presence of obesity-related metabolic disturbances varies widely among obese persons. Metabolically healthy obese persons are characterized by having excessive body fat while displaying a favorable metabolic profile characterized by high levels of insulin sensitivity; no hypertension; and a favorable lipid, inflammation, hormonal, liver enzyme, and immune profile. ...
Background:
Conflicting data exist about the cardiovascular risk of metabolically healthy obese persons. The prognostic value of C-reactive protein (CRP) in this intriguing group is unknown. We assessed the association between CRP levels and the risk of coronary heart disease (CHD) in metabolically healthy persons with abdominal obesity.
Methods and results:
In the European Prospective Investigation of Cancer-Norfolk prospective cohort, CRP levels and information on metabolic syndrome criteria were available for 7279 participants, of whom 825 (11%) developed CHD during a follow-up period of 10.9±1.8 years. There was a trend toward a higher multivariable-adjusted hazard ratio for CHD in metabolically healthy obese participants with CRP levels >2 mg/L compared with <2 mg/L (hazard ratio 1.59, 95% CI 0.97-2.62, P=0.066). Metabolically unhealthy obese participants had significantly higher CHD risk compared with metabolically healthy obese participants with CRP levels <2 mg/L (hazard ratio 1.88, 95% CI 1.20-2.94, P=0.006). Most important, we found that the risk of CHD among metabolically healthy obese persons with CRP levels <2 mg/L was comparable to that of metabolically healthy nonobese persons (hazard ratio 0.91, 95% CI 0.60-1.39, P=0.674).
Conclusions:
Among metabolically healthy obese persons, low CRP levels were associated with a CHD risk comparable to that of metabolically healthy nonobese persons. CRP appears to be an easy and widely available method for identifying a low-risk subpopulation among metabolically healthy obese persons.
... Obesity along with dyslipidemia, pro-inflammatory state and impaired glucose metabolism is considered as a group of atherosclerotic risk factors that tend to gather and increase the development of diabetes and the risk of cardiovascular (CV) disease, [1] like atrial fibrillation, acute coronary syndrome, cardiac death and overall mortality. [2] the present study was designed to assess the relationship of HRV indices with inflammatory markers in obese subjects with dyslipidemia and without diabetes mellitus. ...
... Introduction of the high-sensitivity CRP (hs-CRP) testing in recent years has given the investigators an opportunity to assess the cardiovascular risk more thoroughly. A significant association between elevated serum or plasma concentrations of hs-CRP, on the one hand, and the prevalence of coronary artery disease (CAD), the risk of recurrent cardiovascular events among those with established disease, and higher risk of severe cardiovascular events in apparently healthy individuals, on the other hand, has been documented in many studies [3][4][5]. ...
... Obesity along with dyslipidemia, pro-inflammatory state and impaired glucose metabolism is considered as a group of atherosclerotic risk factors that tend to gather and increase the development of diabetes and the risk of cardiovascular (CV) disease, [1] like atrial fibrillation, acute coronary syndrome, cardiac death and overall mortality. [2] the present study was designed to assess the relationship of HRV indices with inflammatory markers in obese subjects with dyslipidemia and without diabetes mellitus. ...
Background and Aim: It has been documented that obesity is associated with diabetes, hypertension and dyslipidemia
that are known cardiovascular (CV) risks. However, there are few obese individuals, who do not develop diabetes early. In
the present study, we have assessed the association of inflammatory markers in non‑diabetic dyslipidemic obese subjects, as
metabolic biomarkers have not been adequately studied in obesity without diabetes, especially in the assessment of CV risks.
Methods: Twenty non‑diabetic obese dyslipidemic subjects (study group) and 20 healthy non‑obese subjects (control group)
were included in this study. They were assessed for their body mass index (BMI) and heart rate variability (HRV) indices.
Glucose, insulin, lipid profile and inflammatory markers were estimated from the fasting serum sample. Association of HRV
with various parameters was determined by Pearson’s correlation analysis.
Results: The basal CV parameters, HRV, lipid profile, glucose, insulin and the inflammatory markers were significantly altered
and correlated with ratio of low frequency to high frequency (LF: HF ratio), a marker of sympathovagal imbalance (SVI) in the
study group when compared with the control group.
Conclusion: SVI in the form of increased sympathetic and decreased parasymapathetic activity occurs in non‑diabetic obese
dyslipidemic subjects. Association of BMI, metabolic parameters and chronic low grade inflammation with LF: HF ratio may
partly explain their augmented risks to future cardiac morbidities.
Key words: Autonomic imbalance, dyslipidemic, heart rate variability, inflammatory markers, non‑diabetic obese
... MS is associated with a marked increase in the risk of atherosclerotic cardiovascular disease. MS affects 24% of adults in the US and 13.8% of adults in China [3][4][5] . Arterial stiffness is a marker of arterial damage and its increase has been shown to be associated with an increased risk of cardiovascular events [6][7][8][9] . ...
The purpose of this study was to assess the relationship between arterial stiffness, as measured by brachial-ankle pulse wave velocity (baPWV), and the presence of the metabolic syndrome (MS) in a Chinese population. A total of 4,445 subjects were enrolled. The prevalence of MS in our study population was 21.7%, 17.2% and 25.6% for the general population, males and females, respectively. With adjustments for age, gender, cigarette smoking, heart rate, total cholesterol, low-density lipoprotein (LDL) cholesterol, and the use of anti-hypertensive drug, the stepwise regression analysis showed that baPWV had a significant relationship with components of MS, including systolic blood pressure (P < 0.001), diastolic blood pressure (P < 0.001), glucose (P < 0.001), high-density lipoprotein (HDL) cholesterol (P = 0.04), and triglycerides (P < 0.001), but no relationship with waist circumference (P = 0.25). With an increase in the number of the MS components, baPWV increased significantly both in women and men. This study indicated that the MS is indeed a risk factor for arterial stiffness. Monitoring of baPWV in patients with MS may help in identifying persons at high risk for cardiovascular disease.
... In the MIRACL, WIZARD, and TNT trials, patients with metabolic syndrome had a 33% to 44% increased risk of recurrent cardiovascular events. [17][18][19] Patients with diabetes were also at markedly elevated risk, with nearly double the event rate of those without diabetes in CARE (19.1% vs 10.5%), 20 and had an adjusted relative risk that ranged from 1.4 (95% CI 1.3-1.5) in LIPID to 1.62 (1.29-2.03) in 4S. 21,22 Preventing macrovascular events in patients with diabetes and the metabolic syndrome remains challenging, and many recent trials of intensive lipid, 23 blood pressure, 24 glucose lowering, 25,26 or early coronary revascularization 27 have failed to show reductions in cardiovascular events and mortality. ...
Inflammation plays a fundamental role in atherothrombosis. Yet, whether direct inhibition of inflammation will reduce the occurrence of adverse cardiovascular outcomes is not known.
The Cardiovascular Inflammation Reduction Trial (CIRT) (ClinicalTrials.govNCT01594333) will randomly allocate 7,000 patients with prior myocardial infarction (MI) and either type 2 diabetes or the metabolic syndrome to low-dose methotrexate (target dose 15-20 mg/wk) or placebo over an average follow-up period of 3 to 5 years. Low-dose methotrexate is a commonly used anti-inflammatory regimen for the treatment of rheumatoid arthritis and lacks significant effects on lipid levels, blood pressure, or platelet function. Both observational and mechanistic studies suggest that low-dose methotrexate has clinically relevant antiatherothrombotic effects. The CIRT primary end point is a composite of nonfatal MI, nonfatal stroke, and cardiovascular death. Secondary end points are all-cause mortality, coronary revascularization plus the primary end point, hospitalization for congestive heart failure plus the primary end point, all-cause mortality plus coronary revascularization plus congestive heart failure plus the primary end point, incident type 2 diabetes, and net clinical benefit or harm. CIRT will use standardized central methodology designed to ensure consistent performance of all dose adjustments and safety interventions at each clinical site in a manner that protects the blinding to treatment but maintains safety for enrolled participants.
CIRT aims to test the inflammatory hypothesis of atherothrombosis in patients with prior MI and either type 2 diabetes or metabolic syndrome, conditions associated with persistent inflammation. If low-dose methotrexate reduces cardiovascular events, CIRT would provide a novel therapeutic approach for the secondary prevention of heart attack, stroke, and cardiovascular death.
... Introduction of the high-sensitivity CRP (hs-CRP) testing in recent years has given the investigators an opportunity to assess the cardiovascular risk more thoroughly. A significant association between elevated serum or plasma concentrations of hs-CRP, on the one hand, and the prevalence of coronary artery disease (CAD), the risk of recurrent cardiovascular events among those with established disease, and higher risk of severe cardiovascular events in apparently healthy individuals, on the other hand, has been documented in many studies [3][4][5]. ...
High-sensitivity C-reactive protein (CRP) has been extensively used in recent years to assess cardiovascular risk more thoroughly. A significant association between elevated CRP, a prevalence of coronary artery disease (CAD) and adverse cardiac events has been found. Stress myocardial SPECT perfusion imaging (MPI) is an accurate noninvasive technique for detecting CAD. The aim of our study was to find out if there are any differences in the CRP levels between patients with normal myocardial perfusion and mild to moderate perfusion defects, detected with 99m-Tc sestamibi gated SPECT MPI. We prospectively studied 127 patients (79 men, 48 women) suspected of having CAD or with previously confirmed CAD, who were referred for MPI. According to the findings of the stress study, they were divided into two groups: with normal/ near normal myocardial perfusion (n = 85) and with a mild to moderate perfusion defect (n = 42). Levels of CRP in the former group were significantly lower (2.7 mg/L vs. 4.2 mg/L, p = 0.01). There were significantly more men (78.6% vs. 54%, p = 0.000*) and smokers (26% vs. 15%, p = 0.003), also the rates of PCI were significantly higher (36% vs. 15%, p = 0.006) in patients with mild to moderate perfusion defects. The two groups did not differ significantly in age, type of stress, presence of most risk factors for CAD, previous myocardial infarction and CABG. The results of our study have shown that patients with mild to moderate perfusion defects on stress myocardial perfusion SPECT imaging have significantly higher levels of C-reactive protein, compared to those with normal/near normal myocardial perfusion.
A consensus has not been reached on the association of metabolic syndrome (MetS) with adverse outcomes in patients with stable coronary artery disease (CAD). The purpose of this systematic review and meta-analysis was to summarize the prognostic implication of MetS in patients with stable CAD. We comprehensively searched articles indexing in PubMed and Embase databases until August 14, 2022. Original studies investigating the association of MetS with adverse outcomes in patients with stable CAD were included. Seven studies including 32,736 patients with stable CAD were identified. Depending on the definition of MetS, the reported prevalence of MetS ranged from 23.4% to 63%. Meta-analysis showed that patients with MetS conferred an increased risk of all-cause mortality (risk ratio [RR] 1.22; 95% confidence intervals [CI] 1.15–1.19), cardiovascular mortality (RR 1.49; 95%CI 1.16–1.92), and MACEs defined by death, myocardial infarction, revascularization, cardiac arrest, or angina admission (RR 1.47; 95%CI 1.20–1.79) respectively. Leave-one-out sensitivity analysis indicated the robustness of the value of MetS in prediction of all-cause mortality. MetS may be an independently predictor of adverse outcomes in patients with stable CAD. However, future studies are required to consolidate the current evidence due to the small number of studies included.
The development of atherosclerotic cardiovascular disease (ASCVD) is multifactorial and depends on the plasma concentration of lipids and mediators of inflammation. As the most common inflammatory biomarker used in the assessment of atherosclerotic cardiovascular disease risk, high-sensitivity C-reactive protein (hsCRP) has been shown to independently predict future cardiovascular events. As a risk enhancer in primary prevention, it can help guide decision-making around statin use; in secondary prevention, it can help identify residual inflammatory risk among those treated with optimal medical therapy. While many anti-inflammatory therapies have the potential to reduce cardiovascular risk, incorporation into routine clinical practice will depend on additional data related to efficacy, safety, and cost-effectiveness. Until then, statin therapy remains the first-line treatment for the reduction of atherosclerotic cardiovascular disease risk in primary and secondary prevention.KeywordsHigh-sensitivity C-reactive proteinAtherosclerotic cardiovascular diseaseResidual riskCardiovascular disease preventionInflammationAnti-inflammatory therapies
Introduction: Diabetes is often accompanied by undiagnosed dyslipidemia. The aim of the study is to investigate the clinical relevance of lipid profiles and lipid ratios as predictive biochemical models for glycemic control in patients with type 2 diabetes mellitus (T2DM).
Methods: This is a retrospective study recruiting 140 patients with T2DM during a one-year period, 2018–2019, at the Diabetic Center Sanglah General Hospital and Internal Medicine Polyclinic Puri Raharja General Hospital. Demographic characteristics, glycosylated hemoglobin (HBA1c) , and lipid profile were recorded and analyzed using SPSS version 25.0 for Windows. The sample is then classified into good (HBA1c≤7) and poor (HBA1c>7) glycemic control. Risk analysis model, receiver operator characteristics (ROC) analysis, and correlation test were used to evaluate the association of HBA1c level with lipid profile and lipid ratio parameters.
Result: Lipid profile findings such as total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) , triglycerides (TG), and lipid ratio parameter (LDL-C to high-density lipoprotein cholesterol (HDL-C) ratio) were higher in patients in the poor glycemic control group (p<0.05) and HDL-C was significantly lower in patients with poor glycemic control (p=0.001). There is a significant positive correlation between LDL, total cholesterol, LDL-C, TG, and TC to HDL-C ratio, triglycerides, and TC/HDL-C ratio with HBA1c level. Meanwhile, a negative correlation was observed on HDL-C with the HBA1c level. Only TC/HDL-C ratio and LDL-C/HDL-C ratio parameters may be used as predictive models (AUC>0.7), with cutoff point, sensitivity, and specificity of 4.68 (77%; 52%) and 3.06 (98%; 56%) respectively. A risk analysis model shows that the LDL-C/HDL-C ratio parameter is the most influential risk factor in the occurrence of poor glycemic control (adjusted OR =38.76; 95% CI: 27.32–56.64; p<0.001).
Conclusion: Lipid profiles (LDL-C) and lipid ratios (LDL-C/HDL-C and TC/HDL-C ratio) show potential markers that can be used in predicting glycemic control in patients with T2DM.
Background: Coronary artery disease (CAD) is a major cause of death in India. This study determined the characteristics, treatment and outcomes of acute coronary syndrome (ACS) at tertiary centre in north eastern Uttar Pradesh in India.Methods: We carried out observational study with 60-days follow-up of 80 ACS patients. Data are collected on different variables including Blood pressure, pulserate, BNP, TROP I, CKMB, patient’s demography, risk factors, laboratory values at admission and repeated as and when required. Results: T In our study most common presentation was chest pain, majority of patients presented after 12 hour of onset of symptoms, elevation of TROP I was higher in STEMI than NSTEMI, most common complication in NSTEMI was recurrent angina and in STEMI patients was heart failure, total 15 patients expired during study 11 during hospitalization and 4 patients within 60days of follow up, thrombolysed patients has less chances of regional wall motion abnormality.Conclusions: In our study elevation of TROP I was more in STEMI and there was less chances of RWMA in thrombolysed patients.
Aim: Pulse wave velocity (PWV) is thought to have different relationships with metabolic syndrome (MS) components, inflammatory markers, and oxidative stress, according to age. However, age-specific determinants of PWV have not yet been studied. We investigated age-dependent relationships among PWV and MS components, inflammatory markers, and oxidative stress.
Methods: A total of 4,318 subjects were divided into 4 groups: 19–34 y (n=687), 35–44 y (n=1,413), 45–54 y (n=1,384), and 55–79 y (n=834). MS components, brachial-ankle PWV (baPWV), high-sensitivity C-reactive protein (hs-CRP), and oxidative stress markers were measured.
Results: There were age-related increases in MS, body mass index (BMI), waist circumference, systolic blood pressure (SBP), diastolic BP (DBP), triglycerides, glucose, hs-CRP, oxidized low-density lipoprotein (LDL), 8-epi-prostaglandin F2α (8-epi-PGF2α), and baPWV. BaPWV was significantly associated with sex and elevated BP in the 19–34 y group; with age, sex, BMI, elevated BP and triglycerides in the 35–44 y group; with age, sex, elevated BP, fasting glucose, hs-CRP and oxidized LDL in the 45–54 y group; and with age, BMI, elevated BP, fasting glucose and oxidized LDL in the 55–79 y group.
Conclusions: Our results show that age-related increases in baPWV are associated with age-related changes in MS components, inflammatory markers, and oxidative stress. However, each of these factors has an age-specific, different impact on arterial stiffness. In particular, oxidative stress may be independently associated with arterial stiffness in individuals older than 45 y.
. A large number of clinical and laboratory markers have been appraised to predict prognosis in patients with stable angina, but uncertainty remains regarding which variables are the best predictors of prognosis. Therefore, we performed a meta-analysis of studies in patients with stable angina to assess which variables predict prognosis.
Methods
. MEDLINE and PubMed were searched for eligible studies published up to 2015, reporting multivariate predictors of major adverse cardiac events (MACE, a composite endpoint of death, myocardial infarction, and revascularization) in patients with stable angina. Study features, patient characteristics, and prevalence and predictors of such events were abstracted and pooled with random-effect methods (95% CIs). Major adverse cardiovascular event (MACE) was the primary endpoint.
Results
. 42 studies (104,559 patients) were included. After a median follow-up of 57 months, cardiovascular events occurred in 7.8% of patients with MI in 6.2% of patients and need for repeat revascularization (both surgical and percutaneous) in 19.5% of patients. Male sex, reduced EF, diabetes, prior MI, and high C-reactive protein were the most powerful predictors of cardiovascular events.
Conclusions
. We show that simple and low-cost clinical features may help clinicians in identifying the most appropriate diagnostic and therapeutic approaches within the broad range of outpatients presenting with stable coronary artery disease.
Cardiovascular and metabolic disorders represent today one of the main causes of morbidity and mortality in the world. We analysed different physiologic and metabolic disorders associated to metabolic syndrome, defined by NCEP criteria, within one thousand healthy aged subjects recruited from the electoral list of the town of Saint Etienne. Our main results are that 1) waist circumference presents the strongest relationship between metabolic syndrome and C-reactive protein (CRP), an inflammatory indicator; 2) nocturnal oxyhemoglobin desaturation index is the main marker of the relationship between metabolic syndrome and obstructive sleep apnoea ; 3) baroreflex sensibility is largely altered by the metabolic syndrome, in relation with its severity ; 4) the indices of heart rate variability evaluated by 24-hour ECG monitoring, constitute the best marker of autonomic activity decrease with metabolic syndrome ; 5) obesity, evaluated by Body Fat index, a new rnarker created in our laboratory, presents the best association with autonomic activity decrease. Metabolic syndrome is a cluster of interacting factors responsible of, or consecutive to muItiple metabolic dysfunctions. In that view, the combination of these factors worsens the autonomic nervous system deactivation, particularly in women. Our work demonstrates, globally, a strong degree of implication
Cardiovascular disease is more prevalent in type 1 and type 2 diabetes, and continues to be the leading cause of death among adults with diabetes. Although atherosclerotic vascular disease has a multi-factorial etiology, disorders of lipid metabolism play a central role. The coexistence of diabetes with other risk factors, in particular with dyslipidemia, further increases cardiovascular disease risk. A characteristic pattern, termed diabetic dyslipidemia, consists of increased levels of triglycerides, low levels of high density lipoprotein cholesterol, and postprandial lipemia, and is mostly seen in patients with type 2 diabetes or metabolic syndrome.
This review summarizes the trends in the prevalence of lipid disorders in diabetes, advances in the mechanisms contributing to diabetic dyslipidemia, and current evidence regarding appropriate therapeutic recommendations.
Objective
Determine the association between C-Reactive Protein (CRP), the Rankin scale score at discharge and the hospital stay days.
Worldwide, atherosclerotic cardiovascular disease (CVD) including coronary artery disease (CAD) is estimated to be the leading cause of death and loss of disability-adjusted life years. Unfortunately, while the incidence and prevalence of CVD is now declining in the developed countries, it continues to increase exponentially in the developing nations. Reddy reported that from 1970 to 2015, mortality from CVD was projected to almost double in the developing countries while it was projected to decline during the same period in the developed nations.1 The Global Burden of Diseases (GBD) study reported the estimated mortality from CAD in India to be roughly 1.6 million in the year 2000.2
Several modifiable and non-modifiable risk factors have been identified to cause CVD. The major modifiable risk factors include hypertension (HTN), diabetes (DM), smoking and hyperlipidemia and whereas non-modifiable risk factors include age, gender and family history of premature CAD. However, not all coronary events can be predicted by these risk factors. In particular, nearly half of all myocardial infarctions or stroke occurs among individuals without hyperlipidemia. Consequently, alternate risk assessment approaches are being explored to facilitate early and accurate identification of individuals at risk of having CVD. Since atherosclerosis is an inflammatory process, several markers of inflammation have been evaluated for this purpose. Among them, high-sensitive C-reactive protein (hs-CRP) has emerged as the most important CV risk marker. More than a simple marker of inflammation, hs-CRP may influence vascular vulnerability directly through several mechanisms including, enhanced expression of adhesive molecules, reduced nitric oxide, increased expression of endothelial PAI-1 and altered LDL uptake by macrophages. A scientific statement issued by Centre for Disease Control (CDC) and American Heart Association (AHA) has mentioned hs-CRP as the only inflammatory marker that can be used for risk prediction both for primary and secondary prevention of cardiovascular events.3 However, very limited information is available about the relationship between various CV risk factors and hs-CRP levels and the significance of elevated hs-CRP in Indian patients, who as compared to the western populations have vast differences in CVD epidemiology. Therefore, this study was sought to assess the relationship between the levels of hs-CRP and clinical profile, CV risk factors and the coronary angiographic findings in Indian patients presenting with acute coronary syndrome (ACS).
One possible mechanism of higher cardiovascular mortality associated with the metabolic syndrome (MetS) may be through abnormal modulation in autonomic tone.
We examined the association between the MetS and autonomic tone as measured by heart rate variability (HRV) among 288 twins from the Twins Heart Study (THS). Of the 288 participants, 151 (52%) had the MetS. The MetS was associated with decreased HRV across all frequency ranges, and each additional MetS risk factor was associated with lower HRV. After adjustment for several potential confounders, very-low frequency (P < 0.001), low frequency (P < 0.001), and total power (P = 0.02) spectra of HRV remained significantly lower in twins with a progressively higher number of MetS components (18-50% decrease comparing twins with 5 risk factors to those with no risk factors). Among 87 twin pairs who were discordant for the number of MetS components, a one-unit increment in MetS components was associated with an 8% smaller very-low frequency (p = 0.03) and a 15% smaller low frequency spectrum (P = 0.002) comparing each twin with his brother.
MetS was associated with lower HRV in a well-characterized sample of middle-aged male twins. This association persisted even after controlling for genetic and shared environmental factors accounted for by comparison within twin pairs. Abnormalities of autonomic tone, as evidenced by lower HRV, may be partly responsible for the higher rate of atrial fibrillation, coronary heart disease, cardiac death, and overall mortality seen in patients with the MetS.
Depression is common in patients with coronary artery disease (CAD) and is associated with higher risk of cardiovascular adverse events. We aimed to explore the prognostic role of mild depression on cardiovascular mortality and compare its prognostic value with C-reactive protein (CRP) levels in patients with stable CAD.
We initially recruited 523 consecutive patients with stable CAD. Glucose, lipids and CRP levels were measured and an echocardiographic study was performed. In addition, depressive symptomatology was assessed with the Zung Depression Rating Scale (ZDRS, range 20-80). Patients on antidepressant treatment or with ZDRS score ≥60 were excluded. Patients were followed up at 6 month intervals (median 33 months, interquartile range 24-40 months) by telephone interview.
Follow-up data were obtained from 485 patients (92.7%). Nineteen patients with baseline CRP levels >10 mg/L and eight with non-cardiovascular death were excluded from analysis. Of the remaining 458 patients 113 (24.7%) presented cardiac events. Of them 21 died (4.6%), 42 developed acute coronary syndrome (9.2%), 27 (5.9%) had a revascularization procedure due clinical deterioration, two had a stroke (0.44%) and 21 (4.6%) an arrhythmic event. Multivariate Cox regression analysis showed that ZDRS score was independent predictor of cardiovascular death (hazard ratio [HR]: 1.104 with 95% confidence interval [CI]: 1.039-1.172, p = 0.001) after adjustment for conventional risk factors and CRP. The Wald test statistic of CRP was 2.59, whereas the Wald test statistic of ZDRS score was 3.23, indicating better predictability of ZDRS score. ZDRS score was also independent predictor of both cardiovascular death and arrhythmic event (HR: 1.102 with 95% CI: 1.051-1.156, p < 0.001) after adjustment for conventional risk factors and CRP levels. The main limitations of our study were the evaluation of depression at one point in time and the assessment of inflammatory burden by measuring only CRP levels.
Mild depression is associated with increased cardiovascular mortality and is a better predictor than CRP levels in patients with stable CAD.
Patients with stable coronary artery disease (CAD) have a poor prognosis. The aim of the study was to evaluate the extent to which serum high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement alone or together could be prognostic biomarkers in patients with stable CAD.
During the 2.6-year follow-up period 270 patients among the 4264 patients with stable CAD in the CLARICOR trial suffered myocardial infarction (MI) and 377 died (187 cardiovascular deaths (CVD)).
Serum NT-proBNP was significantly associated with MI (hazard ratio (HR), 1. 65 (refers to a 2.72 fold increase in serum level, p = 0.0005), CVD (HR, 2.42, p < 0.0005) and non-CVD (HR, 1.79, p < 0.0005). When correcting for hs-CRP, NT-proBNP was still significantly associated with MI (HR, 1.63, p = 0.0005), CVD (HR, 2.36, p < 0.0005) and non-CVD (HR, 1.66, p < 0.0005). Serum hs-CRP was compared to NT-proBNP less associated with MI (HR, 1.20, p = 0.001), CVD (HR, 1.39, p < 0.0005) and non-CVD (HR, 1.67, p < 0.0005). When corrected for NT-proBNP, hs-CRP was only associated with non-CVD (HR, 1.51, p < 0.0005). When adjusting for cardiovascular risk factors hs-CRP predicted non-CVD (HR, 1.46) and all-cause death (HR, 1.24) and NT-proBNP predicted MI (HR, 1.50), CVD (HR, 1.98), non-CVD (HR, 1.39), and all-cause death (HR, 1.62)(p < 0.0005 for all).
Increased serum NT-proBNP was a stronger predictor of MI, cardiovascular death and non-cardiovascular death than hs-CRP in patients with stable CAD. Once NT-proBNP was taken into account, hs-CRP did not improve predictions.
Autonomic nervous system (ANS) activity decrease has been associated with a higher risk of sudden cardiovascular and cerebrovascular disease. Thus, we explored the relationship between ANS control of the cardiovascular system and metabolic syndrome.
We analyzed the relationship with both short-term and long-term heart rate variability (HRV) and metabolic syndrome in the cross-sectional PROgnostic indicator OF cardiovascular and cerebrovascular events (PROOF) cohort study of 1,011 elderly subjects recruited amongst the inhabitants of the city of Saint Etienne, France, aged 65.6 ± 0.8 years at the inclusion date. Physical examination included measurements of height, weight, systolic and diastolic blood pressure, waist circumference, and biological parameters. HRV variables were measured over 5-min, nighttime, and 24-h periods using Holter monitoring.
After adjustment for current type 2 diabetes, depression, and smoking, we found that metabolic syndrome status, high-density lipoprotein cholesterol (HDL-C), and waist circumference were significantly (p < 0.05) associated with total power, very-low frequency, low-frequency/high-frequency (LF/HF) ratio, and normalized LF. HDL-C and metabolic syndrome status were significantly associated with decreased long-term HRV variables. Both nighttime and 24-h HRV showed closer associations with metabolic syndrome than did short-term HRV (5-min). Metabolic syndrome severity was associated with a decrease in both the long-term and short-term HRV variables.
ANS control alteration of the cardiovascular system was more pronounced when evaluated by long-term than short-term HRV recordings, particularly in women.
To determine the effectiveness and cost-effectiveness of a range of strategies based on conventional clinical information and novel circulating biomarkers for prioritising patients with stable angina awaiting coronary artery bypass grafting (CABG).
MEDLINE and EMBASE were searched from 1966 until 30 November 2008.
We carried out systematic reviews and meta-analyses of literature-based estimates of the prognostic effects of circulating biomarkers in stable coronary disease. We assessed five routinely measured biomarkers and the eight emerging (i.e. not currently routinely measured) biomarkers recommended by the European Society of Cardiology Angina guidelines. The cost-effectiveness of prioritising patients on the waiting list for CABG using circulating biomarkers was compared against a range of alternative formal approaches to prioritisation as well as no formal prioritisation. A decision-analytic model was developed to synthesise data on a range of effectiveness, resource use and value parameters necessary to determine cost-effectiveness. A total of seven strategies was evaluated in the final model.
We included 390 reports of biomarker effects in our review. The quality of individual study reports was variable, with evidence of small study (publication) bias and incomplete adjustment for simple clinical information such as age, sex, smoking, diabetes and obesity. The risk of cardiovascular events while on the waiting list for CABG was 3 per 10,000 patients per day within the first 90 days (184 events in 9935 patients with a mean of 59 days at risk). Risk factors associated with an increased risk, and included in the basic risk equation, were age, diabetes, heart failure, previous myocardial infarction and involvement of the left main coronary artery or three-vessel disease. The optimal strategy in terms of cost-effectiveness considerations was a prioritisation strategy employing biomarker information. Evaluating shorter maximum waiting times did not alter the conclusion that a prioritisation strategy with a risk score using estimated glomerular filtration rate (eGFR) was cost-effective. These results were robust to most alternative scenarios investigating other sources of uncertainty. However, the cost-effectiveness of the strategy using a risk score with both eGFR and C-reactive protein (CRP) was potentially sensitive to the cost of the CRP test itself (assumed to be 6 pounds in the base-case scenario).
Formally employing more information in the prioritisation of patients awaiting CABG appears to be a cost-effective approach and may result in improved health outcomes. The most robust results relate to a strategy employing a risk score using conventional clinical information together with a single biomarker (eGFR). The additional prognostic information conferred by collecting the more costly novel circulating biomarker CRP, singly or in combination with other biomarkers, in terms of waiting list prioritisation is unlikely to be cost-effective.
Patients with end stage renal disease (ESRD) have a 20-100 fold risk of premature cardiovascular death compared to age matched controls from the general population. These patients have many ‘conventional’ cardiovascular risk factors such as diabetes, ischaemic heart disease, hypertension, cigarette smoking and hyperlipidaemia. However, the relationship between the presence of these risk factors and cardiovascular outcomes is less clear in ESRD than in the general population. In the cases of hyperlipidaemia and hypertension a paradoxical relationship has been demonstrated where lower cholesterol or blood pressure is associated with an increased risk of cardiovascular events. One factor previously demonstrated to be associated with poor prognosis is the presence of uraemic cardiomyopathy, found in approximately 70% of ESRD patients at initiation of dialysis therapy, usually defined echocardiographically as the presence of left ventricular (LV) abnormalities, including left ventricular hypertrophy (LVH), LV dilatation and LV systolic dysfunction. However, echocardiography makes assumptions regarding LV geometry, which is frequently distorted in patients with ESRD. Furthermore any errors in measurements are amplified by the changes in hydration status which occur during the dialysis cycle, leading to changes in LV chamber dimensions. For these reasons, cardiac magnetic resonance imaging (CMR), by providing high fidelity measurements, potentially offers a ‘volume independent’ method of quantifying LV dimensions. Furthermore, by using gadolinium based contrast agents, tissue abnormalities particularly myocardial fibrosis, indicated by late gadolinium enhancement (LGE) may by identified. The work contained in this thesis examines the relationship between cardiac dimensions, as defined by CMR and cardiovascular risk factors (both conventional and specific to uraemia). In a study of 145 patients with ESRD using CMR with gadolinium, two specific pathological processes were demonstrated. First, the presence of subendocardial LGE indicating previous myocardial infarction was associated with the presence of conventional cardiovascular risk factors such as previous ischaemic heart disease and diabetes. Patients with subendocardial LGE frequently had LV systolic dysfunction. Second, diffuse LGE, representing fibrosis throughout the LV wall was identified in patients with LVH. This was an unexpected finding and appears specific to uraemia. Using CMR, isolated LV dilatation was rare. These findings suggest that in uraemia two forms of cardiomyopathy exist- LV systolic dysfunction due to underling myocardial ischaemia and LVH which is a true ‘uraemic cardiomyopathy’ associated with diffuse myocardial fibrosis. Attempts were made to reassess the relationship between CMR and echocardiographic measures of cardiac dimensions. In keeping with a previous study, it was demonstrated that M-mode echocardiography overestimates LV mass compared to CMR in this population. Thus, CMR may be used to optimise echocardiographic formulae to calculate LV mass. Furthermore, it appeared that either by echocardiography or by CMR the chief determinant of LVH in this population was blood pressure, in particular systolic blood pressure. This has implications for treatment as recent studies aimed at correcting anaemia, previously associated with LVH, either to reduce LV mass or to improve survival, have generally demonstrated increased cardiovascular events with higher haemoglobin. Therefore, if LV mass is a goal of treatment, attempts should be made to reduce blood pressure further in this population. The patients studied in these investigations were candidates for renal transplantation, the definitive treatment for chronic renal failure. Cardiovascular disease is the leading cause of death both in patients on the renal transplant list, as well as post successful transplantation. There is a great deal of interest in identifying patients at high cardiovascular risk, to allow strategies to be adopted to minimise this risk, frequently by undertaking invasive investigation such as coronary angiography. In a survival study of 300 potential renal transplant recipients, factors associated with increased risk of mortality were increased age, ischaemic heart disease whilst receipt of a renal transplant was protective. Although the presence of LGE was associated with poorer outcome, this finding was not independent of other variables. One interesting finding was that patients with greater exercise tolerance, measured objectively using the full Bruce exercise test had better outcomes. This observation represents a simple pragmatic method to risk-stratify such patients. A study using the biomarker brain natriuretic peptide (BNP) a peptide released from the LV in response to stretch and hypertrophy, in 114 patients, demonstrated that whilst BNP has potential as a diagnostic tool for the presence of uraemic cardiomyopathy, in particular LVH, this peptide added little prognostic value. As familiarity with CMR techniques developed, it became clear that vascular function could be investigated with this imaging modality. Previous studies using alternative measures of vascular function have suggested that arterial stiffness is an important predictor of long term outcome in patients with ESRD. A study of 147 uraemic patients using aortic distensibilty and aortic volumetric arterial strain as CMR measures of aortic stiffness demonstrated that both these parameters were associated with an increased risk of cardiovascular events and mortality. To date there do not appear to be any similar outcome studies using these measures, although a number of authors have noted an association between aortic distensibilty and cardiovascular risk factors. These factors may represent potential targets for therapy aimed at reduction of cardiovascular risk in patients with ESRD. One unfortunate development during the period during which these studies were undertaken, was the emergence of a link between exposure to gadolinium based contrast agents and nephrogenic systemic fibrosis (NSF), a potentially life threatening skin disorder in patients with advanced renal failure. This finding lead to the cessation of contrast CMR studies. A retrospective investigation of factors present in patients in North Glasgow affected by NSF, confirmed that patients with NSF were more likely to have undergone contrast based imaging than unaffected patients, frequently undergoing multiple scans, with high doses of gadodiamide used. Until this issue is clarified, future scans using these agents in this population should be undertaken with caution. These studies have characterised for the first time the relationship between both uraemic cardiomyopathy and uraemic arterial stiffness and both cardiovascular risk factors and long term outcome. CMR measures of cardiac dimensions and vascular function represent future targets for interventions aimed at reducing cardiovascular risk in patients with advanced renal failure.
To compare the levels of C-reactive protein (CRP) in a range of chronic disorders such as osteoporosis, asthma, diabetes, chronic bronchitis/emphysema, myocardial infarction, current oral infections, stroke, angina pectoris, hay fever, and fibromyalgia/chronic pain syndrome.
In all, 5,323 men took part in the first and second health screening of the Oslo Study in 1972/73 and 2000. Questionnaire information on medical history recorded at the second screening was used to identify men with relevant diseases. Serum samples collected in 2000 were stored for later analyses of CRP. In 2000 the men were aged 48-77 years.
Men with self-reported myocardial infarction, asthma, diabetes, chronic bronchitis/ emphysema, osteoporosis or fibromyalgia/chronic pain syndrome had significantly elevated mean levels of CRP versus non-cases. Men with osteoporosis had the highest mean values of 6.53 versus 3.55 mg/l in participants without this disease. Cases of asthma also had an increased mean CRP level of 5.01 versus 3.47 mg/l in non-cases and in chronic bronchitis/emphysema the corresponding levels were 4.42 versus 3.59 mg/l. Men with diabetes had 4.53 versus 3.53 mg/l and men with myocardial infarction had 4.27 versus 3.59 mg/l. In fibromyalgia/chronic pain syndrome the values were 4.79 mg/l and 3.60 mg/l respectively.
Elevated CRP levels were observed in elderly men in a number of chronic diseases, indicating a persistent inflammatory response. Mean levels varied according to the disease and indicated a baseline level in the individuals with a particular disorder. This is useful knowledge when CRP is used in the clinic for infection and inflammation status.
Macrophages in atherosclerotic plaques secrete YKL-40. We tested the hypothesis if high serum YKL-40 concentration predicts coronary events and death of patients with stable coronary artery disease (CAD).
During the 2.6 years follow-up period (median 2.77 year, interquartile range 0.23 year), 270 patients among the 4298 patients with stable CAD in the CLARICOR trial suffered myocardial infarction (MI) and 377 died (187 classified as cardiovascular death). Serum YKL-40 transformed as Y=log[max(82, serum YKL-40/microg/L)] was significantly associated with cardiovascular death [hazard ratio (HR) = 1.88, 95% confidence interval (CI) = 1.54-2.31, P < 0.001], all-cause mortality (HR = 2.01, 95% CI = 1.75-2.31, P < 0.001), and MI (HR = 1.38, 95% CI = 1.13-1.68, P = 0.002). Following multivariable adjustment for cardiovascular risk factors (age, sex, previous MI, smoking status, hypertension, diabetes mellitus) and selected medical treatments Y contributed significantly to prediction of all-cause mortality (P < 0.001) and cardiovascular mortality (P = 0.001), but not MI (P = 0.25).
High serum YKL-40 is associated with MI, cardiovascular and all-cause mortality in patients with stable CAD.
Associations between inflammation, metabolic syndrome (MetS), and cardiovascular disease have been reported. Limited information, however, is available on the prevalence of MetS and its relation to inflammation among Georgian cardiology patients. We investigated MetS components (elevated blood pressure, abdominal obesity, elevated triglyceride concentrations, decreased HDL-cholesterol concentrations, and elevated fasting glucose) and their relationships with C-reactive protein (CRP) concentrations in this population.
A total of 167 patients (mean age 53.1 years, 54% male) who attended an Emergency Cardiology Center in Tbilisi, Republic of Georgia were enrolled in this cross-sectional study. In-person interviews and clinical exams, as well as laboratory studies, were conducted to characterize MetS (using the ATP III criteria) and cardiac conditions in the study population. CRP concentrations were determined using standardized immunoassays.
Overall prevalence of MetS was 40.7%. Patients with coronary heart disease (CHD) had higher CRP concentrations compared with non-CHD patients. A linear relationship between increase in number of MetS components and CRP concentrations was observed among females (p value for linear trend <0.05), but not males. Further, among females, all components of MetS except HDL-C concentrations were correlated with CRP concentrations after adjustment for age and body mass index (all p values <0.05). However, among males, only abdominal obesity was significantly correlated with CRP.
MetS is prevalent among Georgian cardiology patients. CRP concentrations are positively associated with MetS. Further prospective studies are required to determine whether combining MetS and CRP data may have utility in the assessment of risk for developing future cardiovascular events in both males and females.
The current National Cholesterol Education Program Adult Treatment Panel III guidelines recommend specific target levels of LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) for determining cardiovascular disease (CVD) risk and evaluating the effectiveness of lipid-lowering therapies. While there is a growing consensus that levels of apolipoprotein (apo) B and the ratio of apo B/apo A-I are more accurate predictors of CVD risk, the question has been raised as to whether it is realistic to expect patients and health professionals to switch from cholesterol-based guidelines to apolipoprotein-based guidelines. Because it will take time before apolipoprotein terminology is recognized by the general public and recommended by the NCEP Adult Treatment panel to evaluate risk, it may be more efficacious to continue adhering to the already familiar and proven measurements of the LDL-C/HDL-C ratio. The following review provides evidence that the LDL-C/HDL-C ratio continues to be a valuable and standard tool to evaluate CVD risk in all populations.
Although the metabolic syndrome (MetS) is positively associated with high-sensitivity C-reactive protein (hsCRP), negatively associated with N-terminal pro-brain natriuretic peptide (Nt-proBNP) and inconsequently related to urine albumin/creatinine ratio (UACR) they are all associated with cardiovascular events. Therefore, we wanted to determine the influence of MetS on the predictive values of UACR, hsCRP and Nt-proBNP. On the basis of the definition of MetS by the International Diabetes Federation, a Danish population sample of 1983 apparently healthy subjects was divided into three groups: 530 subjects without any elements of MetS, 1093 subjects with some elements of MetS and 360 subjects with MetS. During the following 9.5 years the composite end point of cardiovascular death, non-fatal myocardial infarction or stroke (composite cardiovascular end point, CEP) occurred in 204 subjects. In Cox-regression analyses adjusting for age, gender and smoking, all three cardiovascular risk markers predicted CEP independently of MetS. Despite no significant interaction with MetS, high log(hsCRP) was associated with CEP primarily in subjects without any elements of MetS (hazard ratio (HR)=4.5 (1.5-14.0), P<0.01), log(Nt-proBNP) primarily in subjects with some elements of MetS (HR=3.0 (1.6-5.6), P<0.01), and logUACR independently of elements of MetS. Pre-specified gender-adjusted (men/women) cutoff values of hsCRP > or = 6.0/7.3 mg l(-1) predicted CEP in subjects without elements of MetS with positive and predictive values of 11.5 and 98%, respectively. UACR > or = 0.73/1.06 mg mmol(-1) predicted CEP in subjects with MetS with positive and predictive values of 23.5 and 93%, respectively. In apparently healthy subjects, high hsCRP was associated with CEP primarily in subjects without MetS, high Nt-proBNP in subjects with elements of MetS and UACR independently of MetS.
The metabolic syndrome (MetS) confers an increased risk for diabetes and cardiovascular disease. Although high-sensitive C-reactive protein (hsCRP) concentrations are higher and adiponectin concentrations lower in MetS, there is no reliable biochemical measure that can capture its various features. We evaluated whether hsCRP, adiponectin, or the ratio of adiponectin or its oligomers, especially the high-molecular-weight (HMW) oligomer, to hsCRP predict MetS in 123 subjects with MetS compared with that in 91 healthy control subjects. MetS subjects had significantly higher hsCRP levels and lower total adiponectin and oligomer levels relative to control subjects (P < .0001). The HMW/total adiponectin and adiponectin/CRP ratios were significantly lower in MetS subjects than control subjects (P < .005). The odds ratio (OR) of MetS using the 75th percentile cutoff for CRP was 3.8 (95% confidence interval [CI], 2.1-6.8) and equivalent to low total adiponectin (OR, 2.5; 95% CI, 1.3-4.5), its oligomers, or the adiponectin/ hsCRP ratio (OR, 2.6; 95% CI, 1.5, 4.8). Thus, measurements of CRP, adiponectin, or its oligomers provide robust biomarkers for predicting MetS.
Mounting evidence supports the contention that atherosclerosis is an inflammatory disease. Recently a possible role for infectious
microorganisms has gathered attention. Chlamydia pneumoniae is one possible pathogen. If C. pneumoniae is a target organism, antibiotics with antichlamydial activity may be able to ameliorate plaque instability. The WIZARD trial
is a secondary prevention study that is assessing the impact of a 3-month course of azithromycin compared with placebo on
the progression of clinical coronary heart disease. The study will enroll 3300 patients who have had a prior myocardial infarction
and who have a C. pneumoniae IgG titer of ⩾ 1:16. The primary end point is a composite of time to either recurrent myocardial infarction, death, a revascularization
procedure, or hospitalization for angina. This study is the first of a series of adequately powered clinical trials that will
attempt to bridge insights from preclinical investigations to interventions applicable to patient care.
To assess the association of circulating levels of C-reactive protein, a sensitive systemic marker of inflammation, with different components of the metabolic syndrome.
Total cholesterol (TC), HDL cholesterol, triglycerides, uric acid, BMI , and prevalence of diabetes and hypertension were assessed in 747 men and 956 women aged 18-89 years who were participating in the population-based National Health and Nutrition Survey, which was carried out in former West Germany in 1987-1988.
There was a statistically significant positive crude correlation between C-reactive protein and TC (R = 0.19), TG (R = 0.29), BMI (R = 0.32), glucose (R = 0.11), and uric acid (R = 0.14) (all P < 0.0001). A negative correlation was found between C-reactive protein and HDL cholesterol (R = 0.13, P < 0.0001). The age-adjusted geometric means of C-reactive protein concentrations in subjects grouped according to the presence of 0-1, 2-3, and > or =4 features of the metabolic syndrome were 1.11, 1.27, and 2.16 mg/l, respectively, with a statistically highly significant trend (P < 0.0001).
The data suggest that a variety of features of the metabolic syndrome are associated with a systemic inflammatory response.
Waist circumference is a simpler measure of abdominal adiposity than waist/hip ratio (WHR), but few studies have directly compared the two measures as predictors of coronary heart disease (CHD) in men. In addition, whether the association of abdominal adiposity is independent of total adiposity as measured by body mass index (BMI) in men remains uncertain.
To compare waist circumference and WHR as predictors of CHD in men, and to determine whether the association is independent of BMI.
Prospective cohort study.
We compared WHR, waist circumference and BMI with risk of CHD (myocardial infarction or coronary revascularization) among men in the Physicians' Health Study, a randomized trial of aspirin and beta-carotene among 22 071 apparently healthy US male physicians, aged 40-84 y at baseline in 1982. Men reported height at baseline, and weight, waist and hip measurements on the 9 y follow-up questionnaire.
Among the 16 164 men who reported anthropometric measurements and were free from prior CHD, stroke or cancer, a total of 552 subsequent CHD events occurred during an average follow-up of 3.9 y. After adjusting for age, randomized study agent, smoking, physical activity, parental history of myocardial infarction, alcohol intake, multivitamin and aspirin use, men in the highest WHR quintile (>or=0.99) had a relative risk (RR) for CHD of 1.50 (95% CI 1.14-1.98) compared with those in the lowest quintile (<0.90). Men in the highest waist circumference quintile (>or=103.6 cm) had a RR of 1.60 (CI, 1.21-2.11) for CHD compared with men in the lowest quintile (<88.4 cm). Further adjustment for BMI substantially attenuated these associations: men in the highest WHR and waist circumference quintiles had relative risks for CHD of 1.23 (CI, 0.92-1.66) and 1.06 (CI, 0.74-1.53), respectively. Men in the highest BMI quintile (>or=27.6 kg/m(2)) had a multivariate RR of CHD of 1.73 (CI, 1.29-2.32), after adjustment for WHR. No significant effect modification by age of the relationship between either measure of abdominal adiposity and risk of CHD was observed.
These data support a modest relationship between abdominal adiposity, as measured by either WHR or waist circumference, and risk of CHD both in middle-aged and older men. However, abdominal adiposity did not remain an independent predictor of CHD after adjustment for BMI.
The metabolic syndrome, a concurrence of disturbed glucose and insulin metabolism, overweight and abdominal fat distribution, mild dyslipidemia, and hypertension, is associated with subsequent development of type 2 diabetes mellitus and cardiovascular disease (CVD). Despite its high prevalence, little is known of the prospective association of the metabolic syndrome with cardiovascular and overall mortality.
To assess the association of the metabolic syndrome with cardiovascular and overall mortality using recently proposed definitions and factor analysis.
The Kuopio Ischaemic Heart Disease Risk Factor Study, a population-based, prospective cohort study of 1209 Finnish men aged 42 to 60 years at baseline (1984-1989) who were initially without CVD, cancer, or diabetes. Follow-up continued through December 1998.
Death due to coronary heart disease (CHD), CVD, and any cause among men with vs without the metabolic syndrome, using 4 definitions based on the National Cholesterol Education Program (NCEP) and the World Health Organization (WHO).
The prevalence of the metabolic syndrome ranged from 8.8% to 14.3%, depending on the definition. There were 109 deaths during the approximately 11.4-year follow-up, of which 46 and 27 were due to CVD and CHD, respectively. Men with the metabolic syndrome as defined by the NCEP were 2.9 (95% confidence interval [CI], 1.2-7.2) to 4.2 (95% CI, 1.6-10.8) times more likely and, as defined by the WHO, 2.9 (95% CI, 1.2-6.8) to 3.3 (95% CI, 1.4-7.7) times more likely to die of CHD after adjustment for conventional cardiovascular risk factors. The metabolic syndrome as defined by the WHO was associated with 2.6 (95% CI, 1.4-5.1) to 3.0 (95% CI, 1.5-5.7) times higher CVD mortality and 1.9 (95% CI, 1.2-3.0) to 2.1 (95% CI, 1.3-3.3) times higher all-cause mortality. The NCEP definition less consistently predicted CVD and all-cause mortality. Factor analysis using 13 variables associated with metabolic or cardiovascular risk yielded a metabolic syndrome factor that explained 18% of total variance. Men with loadings on the metabolic factor in the highest quarter were 3.6 (95% CI, 1.7-7.9), 3.2 (95% CI, 1.7-5.8), and 2.3 (95% CI, 1.5-3.4) times more likely to die of CHD, CVD, and any cause, respectively.
Cardiovascular disease and all-cause mortality are increased in men with the metabolic syndrome, even in the absence of baseline CVD and diabetes. Early identification, treatment, and prevention of the metabolic syndrome present a major challenge for health care professionals facing an epidemic of overweight and sedentary lifestyle.
Several lines of evidence have implied an association between Chlamydia pneumoniae infection and atherogenesis.
To determine the effect of 12 weeks of antibiotic therapy on coronary heart disease events in patients with stable coronary artery disease and known C pneumoniae exposure.
Randomized, placebo-controlled trial of 7747 adults with previous myocardial infarction that had occurred at least 6 weeks previously (median, 2.6 years) and a C pneumoniae IgG titer of 1:16 or more. Patients were recruited from 271 clinical practices in North America, Europe, Argentina, and India, from October 10, 1997, to July 22, 2001.
The patients received either azithromycin (600 mg/d for 3 days during week 1, then 600 mg/wk during weeks 2-12; n = 3879) or placebo (n = 3868).
The primary event was the first occurrence of death from any cause, nonfatal reinfarction, coronary revascularization, or hospitalization for angina. Patients were followed up until 1038 events accrued.
After a median of 14 months of follow-up, there was no significant risk reduction in the likelihood of a primary event with azithromycin vs placebo (7% [95% confidence interval, -5% to 17%], P =.23). Analysis of hazard ratios suggested early benefits of azithromycin on the primary event and on death or reinfarction, but these decreased over time. There were no significant risk reductions for any of the components of the primary end point including death (8%), recurrent myocardial infarction (7%), revascularization procedures (5%), or hospitalizations for angina (-1%). Adverse events related to study drug were reported by 13.2% of those randomized to receive azithromycin, predominantly a result of diarrhea, compared with 4.6% randomized to receive placebo, and resulted in discontinuation of drug in 1.6% of those taking azithromycin and 0.4% taking placebo.
Among stable patients with previous myocardial infarction and with evidence of C pneumoniae exposure, a 3-month course of azithromycin did not significantly reduce the clinical sequelae of coronary heart disease.
Insulin resistance is associated with a low chronic inflammatory state. In this study we investigated the relationship between impaired insulin sensitivity and selected markers of inflammation and thrombin generation in obese healthy women. We examined 32 healthy obese women (body mass index > or = 28), with normal insulin sensitivity (NIS, n = 14) or impaired insulin sensitivity (n = 18), and 10 nonobese women (body mass index < 25). Impaired insulin sensitivity patients had significantly higher levels of C-reactive protein (CRP), TGF-beta 1, plasminogen activator inhibitor-1 (PAI-1), activated factor VII (VIIa), and prothrombin fragment 1 + 2 (F1 + 2) compared with either control subjects or NIS patients. On the other hand, NIS patients had higher CRP, TGF-beta 1, PAI-1, and factor VIIa, but not F1 + 2, levels than controls. Significant inverse correlations were observed between the insulin sensitivity index and TGF-beta 1, CRP, PAI-1, factor VIIa, and F1 + 2 levels. Moreover, significant direct correlations were noted between TGF-beta 1 and CRP, PAI-1, factor VIIa, and F1 + 2 concentrations. Finally, multiple regressions revealed that TGF-beta 1 and the insulin sensitivity index were independently related to F1 + 2. Our results are the first to document an in vivo relationship between insulin sensitivity and coagulative activation in obesity. The elevated TGF-beta 1 levels detected in the obese population may provide a biochemical link between insulin resistance and an increased risk for cardiovascular disease.
The prevalence of the metabolic syndrome is high among U.S. adults. Our purpose was to determine whether the prevalence of this syndrome has changed since 1988-1994.
A total of 6,436 men and women aged > or = 20 years from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and 1,677 participants from NHANES 1999-2000 were included in the analyses. We used the definition of the metabolic syndrome developed by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
The unadjusted prevalence of the metabolic syndrome was 23.1% in NHANES III and 26.7% in NHANES 1999-2000 (P = 0.043), and the age-adjusted prevalences were 24.1 and 27.0% (P = 0.088), respectively. The age-adjusted prevalence increased by 23.5% among women (P = 0.021) and 2.2% among men (P = 0.831). Increases in high blood pressure, waist circumference, and hypertriglyceridemia accounted for much of the increase in the prevalence of the metabolic syndrome, particularly among women.
The increased prevalence of the metabolic syndrome is likely to lead to future increases in diabetes and cardiovascular disease.
To assess the magnitude of the association between the National Cholesterol Education Program's Third Adult Treatment Panel Report (ATP III) definition of the metabolic syndrome and cardiovascular disease (CVD).
Cox regression was used to estimate the relative risk of incident coronary heart disease (CHD) and stroke among 12,089 black and white middle-aged individuals in the Atherosclerosis Risk in Communities (ARIC) study.
The metabolic syndrome was present in approximately 23% of individuals without diabetes or prevalent CVD at baseline. Over an average of 11 years of follow-up, 879 incident CHD and 216 ischemic stroke events occurred. Among the components of the metabolic syndrome, elevated blood pressure and low levels of HDL cholesterol exhibited the strongest associations with CHD. Men and women with the metabolic syndrome were approximately 1.5 and 2 times more likely to develop CHD than control subjects after adjustment for age, smoking, LDL cholesterol, and race/ARIC center (sex interaction P < 0.03). Similar associations were found between the metabolic syndrome and incident ischemic stroke. Comparison of receiver operating characteristic curves indicated that the metabolic syndrome did not materially improve CHD risk prediction beyond the level achieved by the Framingham Risk Score (FRS).
Individuals without diabetes or CVD, but with the metabolic syndrome, were at increased risk for long-term cardiovascular outcomes, although statistical models suggested that most of that risk was accounted for by the FRS. Nevertheless, identification of individuals with the metabolic syndrome may provide opportunities to intervene earlier in the development of shared disease pathways that predispose individuals to both CVD and diabetes.
OBJECTIVES
The aim of the study was to determine the value of a cluster of metabolic risk factors in predicting mortality after coronary artery bypass surgery (CABG).BACKGROUND
The “deadly quartet” of metabolic risk factors (i.e., obesity, diabetes, hypertension, and hypertriglyceridemia) has been associated with coronary heart disease in healthy population studies. The expected influence of the cluster on survival in secondary prevention remains untested overall as well as by gender.METHODS
Patients with lipid profiles undergoing primary isolated CABG (n = 6,428) between 1987 and 1992 were followed a median of eight years. Cox models were used to evaluate all-cause mortality. Metabolic risk factors were incorporated as the sum of deadly quartet risk factors present in each patient (0 to 4). The role of gender as it relates to survival and metabolic risk clusters was also examined.RESULTSThe sum of deadly quartet risk factors showed a significant relationship to mortality as the hazard ratio increased from 1.64 (confidence interval [CI] = 1.34–2.01) for one risk factor to 3.95 (2.73–5.69) for four risk factors. Annualized mortality ranged from 1% per year in patients with no risk factors to 3.3% per year in patients with all four risk factors. Within gender, the hazard ratio associated with four risk factors was 2.58 for men and 13.39 for women. The expected clustering of risk factors was 8% compared to the observed clustering of 10% in men and 21% in women.CONCLUSIONS
This cohort showed risk factor clustering beyond that expected due to chance, particularly in women. Even after revascularization, survival is diminished for patients with members of a family of metabolic risk factors at the time of surgery.
To estimate the prevalence of and the cardiovascular risk associated with the metabolic syndrome using the new definition proposed by the World Health Organization
A total of 4,483 subjects aged 35-70 years participating in a large family study of type 2 diabetes in Finland and Sweden (the Botnia study) were included in the analysis of cardiovascular risk associated with the metabolic syndrome. In subjects who had type 2 diabetes (n = 1,697), impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) (n = 798) or insulin-resistance with normal glucose tolerance (NGT) (n = 1,988), the metabolic syndrome was defined as presence of at least two of the following risk factors: obesity, hypertension, dyslipidemia, or microalbuminuria. Cardiovascular mortality was assessed in 3,606 subjects with a median follow-up of 6.9 years.
In women and men, respectively, the metabolic syndrome was seen in 10 and 15% of subjects with NGT, 42 and 64% of those with IFG/IGT, and 78 and 84% of those with type 2 diabetes. The risk for coronary heart disease and stroke was increased threefold in subjects with the syndrome (P < 0.001). Cardiovascular mortality was markedly increased in subjects with the metabolic syndrome (12.0 vs. 2.2%, P < 0.001). Of the individual components of the metabolic syndrome, microalbuminuria conferred the strongest risk of cardiovascular death (RR 2.80; P = 0.002).
The WHO definition of the metabolic syndrome identifies subjects with increased cardiovascular morbidity and mortality and offers a tool for comparison of results from diferent studies.
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
Many studies have shown that hyperinsulinemia and/or insulin resistance are related to various metabolic and physiological disorders including hypertension, dyslipidemia, and non-insulin-dependent diabetes mellitus. This syndrome has been termed Syndrome X. An important limitation of previous studies has been that they all have been cross sectional, and thus the presence of insulin resistance could be a consequence of the underlying metabolic disorders rather than its cause. We examined the relationship of fasting insulin concentration (as an indicator of insulin resistance) to the incidence of multiple metabolic abnormalities in the 8-yr follow-up of the cohort enrolled in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease in Mexican Americans and non-Hispanic whites. In univariate analyses, fasting insulin was related to the incidence of the following conditions: hypertension, decreased high-density lipoprotein cholesterol concentration, increased triglyceride concentration, and non-insulin-dependent diabetes mellitus. Hyperinsulinemia was not related to increased low-density lipoprotein or total cholesterol concentration. In multivariate analyses, after adjustment for obesity and body fat distribution, fasting insulin continued to be significantly related to the incidence of decreased high-density lipoprotein cholesterol and increased triglyceride concentrations and to the incidence of non-insulin-dependent diabetes mellitus. Baseline insulin concentrations were higher in subjects who subsequently developed multiple metabolic disorders. These results were not attributable to differences in baseline obesity and were similar in Mexican Americans and non-Hispanic whites. These results support the existence of a metabolic syndrome and the relationship of that syndrome to multiple metabolic disorders by showing that elevations of insulin concentration precede the development of numerous metabolic disorders.
The classification of diabetes mellitus and the tests used for its diagnosis were brought into order by the National Diabetes Data Group of the USA and the second World Health Organization Expert Committee on Diabetes Mellitus in 1979 and 1980. Apart from minor modifications by WHO in 1985, little has been changed since that time. There is however considerable new knowledge regarding the aetiology of different forms of diabetes as well as more information on the predictive value of different blood glucose values for the complications of diabetes. A WHO Consultation has therefore taken place in parallel with a report by an American Diabetes Association Expert Committee to re-examine diagnostic criteria and classification. The present document includes the conclusions of the former and is intended for wide distribution and discussion before final proposals are submitted to WHO for approval. The main changes proposed are as follows. The diagnostic fasting plasma (blood) glucose value has been lowered to > or =7.0 mmol l(-1) (6.1 mmol l(-1)). Impaired Glucose Tolerance (IGT) is changed to allow for the new fasting level. A new category of Impaired Fasting Glycaemia (IFG) is proposed to encompass values which are above normal but below the diagnostic cut-off for diabetes (plasma > or =6.1 to <7.0 mmol l(-1); whole blood > or =5.6 to <6.1 mmol l(-1)). Gestational Diabetes Mellitus (GDM) now includes gestational impaired glucose tolerance as well as the previous GDM. The classification defines both process and stage of the disease. The processes include Type 1, autoimmune and non-autoimmune, with beta-cell destruction; Type 2 with varying degrees of insulin resistance and insulin hyposecretion; Gestational Diabetes Mellitus; and Other Types where the cause is known (e.g. MODY, endocrinopathies). It is anticipated that this group will expand as causes of Type 2 become known. Stages range from normoglycaemia to insulin required for survival. It is hoped that the new classification will allow better classification of individuals and lead to fewer therapeutic misjudgements.
C-reactive protein, a hepatic acute phase protein largely regulated by circulating levels of interleukin-6, predicts coronary heart disease incidence in healthy subjects. We have shown that subcutaneous adipose tissue secretes interleukin-6 in vivo. In this study we have sought associations of levels of C-reactive protein and interleukin-6 with measures of obesity and of chronic infection as their putative determinants. We have also related levels of C-reactive protein and interleukin-6 to markers of the insulin resistance syndrome and of endothelial dysfunction. We performed a cross-sectional study in 107 nondiabetic subjects: (1) Levels of C-reactive protein, and concentrations of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, were related to all measures of obesity, but titers of antibodies to Helicobacter pylori were only weakly and those of Chlamydia pneumoniae and cytomegalovirus were not significantly correlated with levels of these molecules. Levels of C-reactive protein were significantly related to those of interleukin-6 (r=0.37, P<0.0005) and tumor necrosis factor-alpha (r=0.46, P<0.0001). (2) Concentrations of C-reactive protein were related to insulin resistance as calculated from the homoeostasis model assessment model, blood pressure, HDL, and triglyceride, and to markers of endothelial dysfunction (plasma levels of von Willebrand factor, tissue plasminogen activator, and cellular fibronectin). A mean standard deviation score of levels of acute phase markers correlated closely with a similar score of insulin resistance syndrome variables (r=0.59, P<0.00005), this relationship being weakened only marginally by removing measures of obesity from the insulin resistance score (r=0.53, P<0.00005). These data suggest that adipose tissue is an important determinant of a low level, chronic inflammatory state as reflected by levels of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein, and that infection with H pylori, C pneumoniae, and cytomegalovirus is not. Moreover, our data support the concept that such a low-level, chronic inflammatory state may induce insulin resistance and endothelial dysfunction and thus link the latter phenomena with obesity and cardiovascular disease.
Inflammation has been suggested as a risk factor for the development of atherosclerosis. Recently, some components of the insulin resistance syndrome (IRS) have been related to inflammatory markers. We hypothesized that insulin insensitivity, as directly measured, may be associated with inflammation in nondiabetic subjects.
We studied the relation of C-reactive protein (CRP), fibrinogen, and white cell count to components of IRS in the nondiabetic population of the Insulin Resistance Atherosclerosis Study (IRAS) (n=1008; age, 40 to 69 years; 33% with impaired glucose tolerance), a multicenter, population-based study. None of the subjects had clinical coronary artery disease. Insulin sensitivity (S(I)) was measured by a frequently sampled intravenous glucose tolerance test, and CRP was measured by a highly sensitive competitive immunoassay. All 3 inflammatory markers were correlated with several components of the IRS. Strong associations were found between CRP and measures of body fat (body mass index, waist circumference), S(I), and fasting insulin and proinsulin (all correlation coefficients >0.3, P<0.0001). The associations were consistent among the 3 ethnic groups of the IRAS. There was a linear increase in CRP levels with an increase in the number of metabolic disorders. Body mass index, systolic blood pressure, and S(I) were related to CRP levels in a multivariate linear regression model.
We suggest that chronic subclinical inflammation is part of IRS. CRP, a predictor of cardiovascular events in previous reports, was independently related to S(I). These findings suggest potential benefits of anti-inflammatory or insulin-sensitizing treatment strategies in healthy individuals with features of IRS.
Background:
Indian Asians in the United Kingdom have increased coronary heart disease (CHD) mortality compared with European whites, but the causes are not well understood. Increased circulating concentrations of C-reactive protein (CRP) are an independent risk factor for CHD. Therefore, we investigated this marker of inflammation in healthy UK Indian Asian and European white men. Methods and Results-- We measured serum CRP concentrations and conventional CHD risk factors in 1025 healthy male subjects (518 Indian Asians and 507 European whites) aged 35 to 60 years who were recruited at random from general practitioner lists. The geometric mean CRP concentration was 17% higher (95% confidence interval, 3% to 33%) in Indian Asians compared with European whites. CRP values were strongly associated with conventional CHD risk factors, measures of obesity, and metabolic disturbances associated with insulin resistance in both racial groups. The difference in CRP concentrations between Indian Asians and European whites remained after adjustment for conventional CHD risk factors but was eliminated by an adjustment for central obesity and insulin resistance score in Asians. On the basis of these results, we estimate that the processes underlying elevated CRP and/or increased CRP production itself are associated with an approximately 14% increase in population CHD risk among Indian Asians compared with European whites.
Conclusions:
CRP concentrations are higher in healthy Indian Asians than in European whites and are accounted for by greater central obesity and insulin resistance in Indian Asians. Our results suggest that inflammation or other mechanisms underlying elevated CRP values may contribute to the increased CHD risk among Indian Asians.
The Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) highlights the importance of treating patients with the metabolic syndrome to prevent cardiovascular disease. Limited information is available about the prevalence of the metabolic syndrome in the United States, however.
To estimate the prevalence of the metabolic syndrome in the United States as defined by the ATP III report.
Analysis of data on 8814 men and women aged 20 years or older from the Third National Health and Nutrition Examination Survey (1988-1994), a cross-sectional health survey of a nationally representative sample of the noninstitutionalized civilian US population.
Prevalence of the metabolic syndrome as defined by ATP III (>/=3 of the following abnormalities): waist circumference greater than 102 cm in men and 88 cm in women; serum triglycerides level of at least 150 mg/dL (1.69 mmol/L); high-density lipoprotein cholesterol level of less than 40 mg/dL (1.04 mmol/L) in men and 50 mg/dL (1.29 mmol/L) in women; blood pressure of at least 130/85 mm Hg; or serum glucose level of at least 110 mg/dL (6.1 mmol/L).
The unadjusted and age-adjusted prevalences of the metabolic syndrome were 21.8% and 23.7%, respectively. The prevalence increased from 6.7% among participants aged 20 through 29 years to 43.5% and 42.0% for participants aged 60 through 69 years and aged at least 70 years, respectively. Mexican Americans had the highest age-adjusted prevalence of the metabolic syndrome (31.9%). The age-adjusted prevalence was similar for men (24.0%) and women (23.4%). However, among African Americans, women had about a 57% higher prevalence than men did and among Mexican Americans, women had about a 26% higher prevalence than men did. Using 2000 census data, about 47 million US residents have the metabolic syndrome.
These results from a representative sample of US adults show that the metabolic syndrome is highly prevalent. The large numbers of US residents with the metabolic syndrome may have important implications for the health care sector.
Elevated serum levels of acute-phase proteins, indicating chronic subclinical inflammation, have been associated with cardiovascular disease as well as the insulin resistance syndrome. Chronic inflammation may also be a risk factor for developing type 2 diabetes. We studied the concentrations of C-reactive protein (CRP), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) in 1,047 nondiabetic subjects in relation to incident diabetes within 5 years in the Insulin Resistance Atherosclerosis Study. Subjects with diabetes at follow-up (n = 144) had higher baseline levels of fibrinogen (mean +/- SD; 287.8 +/- 58.8 vs. 275.1 +/- 56.0 mg/dl; P = 0.013) as well as of CRP (median [interquartile range]; 2.40 [1.29, 5.87] vs. 1.67 mg/l [0.75, 3.41]; P = 0.0001) and PAI-1 (24 [15, 37.5] vs. 16 ng/ml [9, 27]; P = 0.0001) than nonconverters. The odds ratio (OR) of converting to diabetes was significantly increased with increasing baseline concentrations of the inflammatory markers. In contrast to PAI-1, the association of CRP and fibrinogen with incident diabetes was significantly attenuated after adjustment for body fat (BMI or waist circumference) or insulin sensitivity (S(I)), as assessed by a frequently sampled intravenous glucose tolerance test. In a logistic regression model that included age, sex, ethnicity, clinical center, smoking, BMI, S(I), physical activity, and family history of diabetes, PAI-1 still remained significantly related to incident type 2 diabetes (OR [95% CI] for 1 SD increase: 1.61 [1.20-2.16]; P = 0.002). Chronic inflammation emerges as a new risk factor for the development of type 2 diabetes; PAI-1 predicts type 2 diabetes independent of insulin resistance and other known risk factors for diabetes.
The metabolic syndrome describes a high-risk population having 3 or more of the following clinical characteristics: upper-body obesity, hypertriglyceridemia, low HDL, hypertension, and abnormal glucose. All of these attributes, however, are associated with increased levels of C-reactive protein (CRP).
We evaluated interrelationships between CRP, the metabolic syndrome, and incident cardiovascular events among 14 719 apparently healthy women who were followed up for an 8-year period for myocardial infarction, stroke, coronary revascularization, or cardiovascular death; 24% of the cohort had the metabolic syndrome at study entry. At baseline, median CRP levels for those with 0, 1, 2, 3, 4, or 5 characteristics of the metabolic syndrome were 0.68, 1.09, 1.93, 3.01, 3.88, and 5.75 mg/L, respectively (P(trend) <0.0001). Over the 8-year follow-up, cardiovascular event-free survival rates based on CRP levels above or below 3.0 mg/L were similar to survival rates based on having 3 or more characteristics of the metabolic syndrome. At all levels of severity of the metabolic syndrome, however, CRP added prognostic information on subsequent risk. For example, among those with the metabolic syndrome at study entry, age-adjusted incidence rates of future cardiovascular events were 3.4 and 5.9 per 1000 person-years of exposure for those with baseline CRP levels less than or greater than 3.0 mg/L, respectively. Additive effects for CRP were also observed for those with 4 or 5 characteristics of the metabolic syndrome. The use of different definitions of the metabolic syndrome had minimal impact on these findings.
These prospective data suggest that measurement of CRP adds clinically important prognostic information to the metabolic syndrome.
Insulin resistance is associated with chronic subclinical inflammation, and both conditions are linked with increased risk for type 2 diabetes mellitus and atherothrombotic cardiovascular disease.
In a cross-sectional study conducted among participants in the Women's Health Study, an ongoing US primary prevention trial of cardiovascular disease and cancer, we evaluated the correlates of elevated fasting insulin, a marker of insulin resistance, among 349 healthy, nondiabetic women who remained free from clinically diagnosed type 2 diabetes mellitus during a 4-year period from biomarker assessment. Fasting insulin was strongly associated with body mass index (BMI) (r=0.53, P<0.001), C-reactive protein (CRP) (r=0.38, P<0.001), and interleukin-6 (r=0.33, P<0.001). Physical activity level, alcohol consumption, and use of hormone replacement therapy were also related to fasting insulin. However, in multivariable linear regression analysis, BMI and CRP were the only independent correlates of log-normalized fasting insulin. Overall, the final model explained 32% of the variance in log insulin level. In multivariable logistic regression, the fully adjusted odds ratio (OR) for elevated fasting insulin (>or=51.6 pmol/L) increased with tertile of BMI, CRP, and IL-6, such that the ORs in the highest versus lowest tertile of each parameter were 9.0 (95% confidence interval [CI], 4.4 to 18.7), 4.4 (95% CI, 1.9 to 10.1), and 2.0 (95% CI, 0.9 to 4.2), respectively. Furthermore, increasing levels of CRP were associated with a stepwise gradient in odds for elevated fasting insulin among both lean and overweight women.
CRP is independently associated with fasting hyperinsulinemia in nondiabetic women. These data provide additional support for previously reported associations between subclinical inflammation and the risk of type 2 diabetes and cardiovascular disease.
Several studies suggested that the insulin resistance-associated metabolic syndrome (MS) is a major risk factor for coronary artery disease (CAD), but the criteria to identify MS were only recently standardized by the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III.
We evaluated the incidence of the newly defined MS in patients with documented CAD and compared the characteristics of patients with and without this syndrome.
In a Canadian population with CAD (793 men and 315 women, age 58.1+/-9.8 years) 51% had MS. As compared to patients without the MS syndrome, these patients had significantly higher waist circumference, blood pressure levels and fasting glucose and triglyceride, but lower high-density lipoprotein (HDL)-cholesterol levels. Their homeostatic model assessment (HOMA) insulin resistance index was significantly higher, with indicators of highly atherogenic, small low-density lipoprotein (LDL) and HDL particles. Family history of diabetes and the use of hypoglycemic agents, beta-blockers and thiazides were more frequent, but physical exercise and alcohol consumption were less frequent in MS positive patients. Cumulative coronary stenosis score and the frequency of patients with >50% coronary artery narrowing were higher and there was a strong tendency for higher rates of previous myocardial infarction in MS positive patients.
In a CAD population documented in 1991-1992, 51% of participants had MS and in several respects a more advanced coronary disease than those without the syndrome. These results support the view of NCEP ATP III, that in CAD prevention, beyond lowering LDL-cholesterol levels, interventions concerning the constituents of MS should be important.
The prevalence of the metabolic syndrome (MS) and the effects of formal phase II cardiac rehabilitation and exercise training program have not been assessed in patients with coronary artery disease (CAD). The present study examines the prevalence of MS in patients with CAD after major coronary events and assesses the salutary effects of a rigorous program to produce therapeutic lifestyle change in these patients. We reviewed the case records of 235 consecutive patients with CAD who completed a 3-month formal program of cardiac rehabilitation and exercise training to ascertain relevant anthropometric, lipid, and clinical data. Detailed program components have been reviewed elsewhere, 1–3 but in brief, patients received individual and group counseling from a registered dietitian in dietary management as recommended by recent national guidelines. 4 Patients received formalized exercise instruction, met 3 times per week for group exercise classes, and were encouraged to exercise on their own (1 to 3 times per week) in between sessions. Patients’ exercise recommendations were tailored toward the anaerobic threshold achieved during entry testing. Specific weight management guidance was given to those subjects identified as overweight and obese. Educational classes were given with regard to all aspects of CAD risk, including hypertension, smoking cessation, and diabetes management. In all patients, fasting lipids, glucose, high-sensitivity C-reactive protein (hs-CRP), percent body fat, abdominal girth, and blood pressure at rest were obtained at entry and at completion of the formal program. Most subjects entered the program 3 to 5 weeks (mean 3.3 3.4) after hospital discharge. Percentage of body fat was determined by the skinfold technique, using the average of 3 skinfolds (thigh, chest, and abdomen in men; thigh, triceps, and suprailium in women). 5,6 All measurements were made in the early morning before exercise. A group of 42 subjects who planned to enter the rehabilitation program during the same time period and had their baseline laboratory work, but who dropped out before beginning active participation in the program, agreed to serve as a control group; these subjects had additional laboratory work free of charge for the purpose of monitoring risk factors over time. All subjects were initially evaluated 3 to 6 weeks after hospital discharge, and repeat measurements of these parameters were performed between 3 and 6 months after initial testing. The principal reasons for not participating in the program were financial (55%) and traveling distance to the rehabilitation facility (33%). Seventy-nine percent of the control subjects underwent percutaneous coronary intervention, 21% had coronary bypass, and 24% had myocardial infarction; the study cohort had similar percentages. Patients and control subjects who were taking either lipid-lowering medication (including statins: 65% of rehabilitation patients, 59% of control subjects) or hormone replacement therapy remained on constant doses for a period of 6 weeks before the initial assessment and throughout the evaluation period. The presence of MS was determined using the definition set forth by recent national gudelines. 4 Spe
The National Cholesterol Education Program (NCEP) recently proposed a simple definition for metabolic syndrome. Information on the prospective association of this definition for coronary heart disease (CHD) and type 2 diabetes is currently limited.
We used a modified NCEP definition with body mass index in place of waist circumference. Baseline assessments in the West of Scotland Coronary Prevention Study were available for 6447 men to predict CHD risk and for 5974 men to predict incident diabetes over 4.9 years of follow-up. Mean LDL cholesterol was similar but C-reactive protein was higher (P<0.0001) in the 26% of men with the syndrome compared with those without. Metabolic syndrome increased the risk for a CHD event [univariate hazard ratio (HR)=1.76 (95% CI, 1.44 to 2.15)] and for diabetes [univariate HR=3.50 (95% CI 2.51 to 4.90)]. Metabolic syndrome continued to predict CHD events (HR=1.30, 95% CI, 1.00 to 1.67, P=0.045) in a multivariate model incorporating conventional risk factors. Men with 4 or 5 features of the syndrome had a 3.7-fold increase in risk for CHD and a 24.5-fold increase for diabetes compared with men with none (both P<0.0001). C-reactive protein enhanced prognostic information for both outcomes. With pravastatin, men with the syndrome had similar risk reduction for CHD as compared with those without (HR, 0.73 and 0.69; pravastatin versus placebo).
A modified NCEP metabolic syndrome definition predicts CHD events, and, more strikingly, new-onset diabetes, and thus helps identify individuals who may receive particular benefit from lifestyle measures to prevent these diseases.
Accumulating data suggest a link between blood pressure and vascular inflammation.
We examined the relationship between blood pressure, C-reactive protein (CRP), and incident first cardiovascular events among 15 215 women followed prospectively over a median of 8.1 years. In cross-sectional analyses at baseline, median levels of CRP for women with blood pressure <120/75, 120 to 129/75 to 84, 130 to 139/85 to 89, 140 to 159/90 to 94, and > or =160/95 mm Hg were 0.96, 1.42, 2.20, 2.82, and 3.34 mg/L, respectively (P for trend <0.0001). Increasing categories of blood pressure were significant predictors of CRP levels at baseline. In prospective analyses, both elevated CRP levels (> or =3 mg/L) and increasing categories of blood pressure were independent determinants of future cardiovascular events, and CRP had incremental prognostic value at all levels of blood pressure. The adjusted hazard ratio for women with blood pressure > or =160/95 mm Hg and CRP levels > or =3 mg/L was 8.31 (95% CI, 4.44 to 15.55, P<0.0001) compared with those with blood pressure <120/75 and CRP levels <3 mg/L. After participants had been divided into 4 groups on the basis of CRP levels (<3 or > or =3 mg/L) and blood pressure levels (<130/85 or > or =130/85), the risk factor-adjusted hazard ratios were as follows: low CRP/low blood pressure, 1.0; high CRP/low blood pressure, 1.87 (P=0.002); low CRP/high blood pressure, 2.54 (P<0.0001); and high CRP/high blood pressure, 3.27 (P<0.0001).
CRP and blood pressure are independent determinants of cardiovascular risk, and their predictive value is additive.
The combination of cardiovascular risk factors known as the metabolic syndrome is receiving increased attention from physicians, but data on the syndrome's association with morbidity are limited.
Applying National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria, we evaluated 10 357 NHANES III subjects for the 5 component conditions of the metabolic syndrome: insulin resistance, abdominal obesity based on waist circumference, hypertriglyceridemia, low HDL cholesterol (HDL-C), and hypertension, as well as the full syndrome, defined as at least 3 of the 5 conditions. Logistic regression was used to estimate the cross-sectional association of the syndrome and each of its 5 component conditions separately with history of myocardial infarction (MI), stroke, and either MI or stroke (MI/stroke). Models were adjusted for age, sex, race, and cigarette smoking. The metabolic syndrome was significantly related in multivariate analysis to MI (OR, 2.01; 95% CI, 1.53 to 2.64), stroke (OR, 2.16; 95% CI, 1.48 to 3.16), and MI/stroke (OR, 2.05; 95% CI, 1.64 to 2.57). The syndrome was significantly associated with MI/stroke in both women and men. Among the component conditions, insulin resistance (OR, 1.30; 95% CI, 1.03 to 1.66), low HDL-C (OR, 1.35; 95% CI, 1.05 to 1.74), hypertension (OR, 1.44; 95% CI, 1.00 to 2.08), and hypertriglyceridemia (OR, 1.66; 95% CI=1.20 to 2.30) were independently and significantly related to MI/stroke.
These results indicate a strong, consistent relationship of the metabolic syndrome with prevalent MI and stroke.
C-reactive protein (CRP), a marker of subclinical inflammation, predicts the occurrence of coronary heart disease in healthy subjects. Hyperglycaemia is known to stimulate the release of inflammatory cytokines from various cell types and can lead to the induction and secretion of acute-phase reactants by adipocytes. The aim of the present study was to determine the relation between glycaemic status and CRP in healthy subjects.
We studied the relation of high-sensitivity CRP to fasting glucose and other components of the metabolic syndrome in a population-based cross-sectional study (n = 1000; age 50 +/- 9 years).
Plasma CRP levels increased continuously from the lowest quartile of normal fasting glucose level to impaired fasting glucose and to diabetes (ln CRP 0.47 +/- 0.09, 0.95 +/- 0.12, and 1.11 +/- 0.13, respectively; Ptrend < 0.0001). Increasing CRP with higher fasting glucose levels was apparent even among subjects with fasting glucose in the normal range (Ptrend = 0.039), and subjects with fasting glucose level in the upper quartile of normal fasting glucose had higher CRP levels compared with subjects in the lower quartile (P = 0.035). There was a positive crude correlation between CRP and smoking, post-menopausal hormone use, body mass index, fasting glucose, triglycerides, hypertension, and uric acid (r = 0.11-0.36, P = 0.002-0.0001). A negative correlation was found between CRP and HDL-cholesterol (r = 0.12, P < 0.0001) and physical activity (r = 0.11, P = 0.002). After adjustment for potential confounders in a stepwise multivariate linear regression model, fasting glucose remained significantly and independently related to CRP levels (correlation coefficient 0.06; 95% confidence interval 0.014-0.11, P = 0.011).
Fasting glucose is significantly and positively associated with plasma CRP in middle-aged subjects. CRP levels increase continuously across the spectrum of fasting glucose, beginning in the lowest quartile of normal fasting glucose. This finding suggests that a proinflammatory effect may contribute to the adverse cardiovascular outcome associated with diabetes, impaired fasting glucose, and increasing glucose levels within the normal range.
The metabolic syndrome, which is a set of lipid and nonlipid risk factors of metabolic origin linked with insulin resistance, is believed to be associated with an elevated risk for cardiovascular disease, but few have studied this association in prospective long-term cardiovascular outcomes trials. Placebo data from the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) were used post hoc to estimate the long-term relative risk of major coronary events (MCEs) associated with the metabolic syndrome, after excluding diabetes mellitus. In 4S and AFCAPS/TexCAPS, respectively, placebo-treated patients with the metabolic syndrome were 1.5 (95% confidence interval 1.2 to 1.8) and 1.4 (95% confidence interval 1.04 to 1.9) times more likely to have MCEs than those without it. Of the components of the metabolic syndrome, low high-density lipoprotein levels were associated with elevated risk of MCEs in both studies, whereas high triglycerides in 4S and elevated blood pressure and obesity in AFCAPS/TexCAPS were associated with significantly increased relative risk. Patients with the metabolic syndrome showed increased risk of MCEs irrespective of their Framingham-calculated 10-year risk score category (>20% vs </=20%). These data demonstrate that the metabolic syndrome is associated with increased risk of MCEs in both hypercholesterolemic patients with coronary heart disease in 4S and in those with low high-density lipoprotein cholesterol but without coronary heart disease in AFCAPS/TexCAPS. It appears that the metabolic syndrome is associated with risk that is not entirely accounted for by traditional risk scoring paradigms.
Inflammation (assessed by C-reactive protein [CRP]) and the metabolic syndrome (MetS) are associated with cardiovascular disease (CVD), but population-based data are limited.
We assessed the cross-sectional relations of CRP to the MetS (National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III definition) in 3037 subjects (1681 women; mean age, 54 years) and the utility of CRP and the MetS to predict new CVD events (n=189) over 7 years. MetS (> or =3 of 5 traits) was present in 24% of subjects; mean age-adjusted CRP levels for those with 0, 1, 2, 3, 4, or 5 MetS traits were 2.2, 3.5, 4.2, 6.0, or 6.6 mg/L, respectively (P trend <0.0001). In persons with MetS, age-adjusted CRP levels were higher in women than men (7.8 versus 4.6 mg/L; P<0.0001). MetS and baseline CRP were individually related to CVD events (for MetS: age-sex-adjusted hazard ratio [HR], 2.1; 95% CI, 1.5 to 2.8; for highest versus lowest CRP quartile: HR, 2.2; 95% CI, 1.4 to 3.5). Greater risk of CVD persisted for MetS and CRP even after adjustment in a model including age, sex, MetS (HR, 1.8; 95% CI, 1.4 to 2.5), and CRP (HR, 1.9; 95% CI, 1.2 to 2.9). The c-statistic associated with the age- and sex-adjusted model including CRP was 0.72; including MetS, 0.74; and including CRP and MetS, 0.74.
Elevated CRP levels are related to insulin resistance and the presence of the MetS, especially in women. Although discrimination of subjects at risk of CVD events using both MetS and CRP is not better than using either phenotype alone, both CRP and MetS are independent predictors of new CVD events.
Mortality resulting from coronary heart disease (CHD), cardiovascular disease (CVD), and all causes in persons with diabetes and pre-existing CVD is high; however, these risks compared with those with metabolic syndrome (MetS) are unclear. We examined the impact of MetS on CHD, CVD, and overall mortality among US adults.
In a prospective cohort study, 6255 subjects 30 to 75 years of age (54% female) (representative of 64 million adults in the United States) from the Second National Health and Nutrition Examination Survey were followed for a mean+/-SD of 13.3+/-3.8 years. MetS was defined by modified National Cholesterol Education Program criteria. From sample-weighted multivariable Cox proportional-hazards regression, compared with those with neither MetS nor prior CVD, age-, gender-, and risk factor-adjusted hazard ratios (HRs) for CHD mortality were 2.02 (95% CI, 1.42 to 2.89) for those with MetS and 4.19 (95% CI, 3.04 to 5.79) for those with pre-existing CVD. For CVD mortality, HRs were 1.82 (95% CI, 1.40 to 2.37) and 3.14 (95% CI, 2.49 to 3.96), respectively; for overall mortality, HRs were 1.40 (95% CI, 1.19 to 1.66) and 1.87 (95% CI, 1.60 to 2.17), respectively. In persons with MetS but without diabetes, risks of CHD and CVD mortality remained elevated. Diabetes predicted all mortality end points. Those with even 1 to 2 MetS risk factors were at increased risk for mortality from CHD and CVD. Moreover, MetS more strongly predicts CHD, CVD, and total mortality than its individual components.
CHD, CVD, and total mortality are significantly higher in US adults with than in those without MetS.
To assess the utility of clinical definitions of the metabolic syndrome (MetS) to identify individuals with increased cardiovascular risk, we examined the relation between the MetS, using both the National Cholesterol Education Program (NCEP) and the World Health Organization definitions, and all-cause and cardiovascular mortality in San Antonio Heart Study participants enrolled between 1984 and 1988.
Among 2815 participants, 25 to 64 years of age at enrollment, 509 met both criteria, 197 met NCEP criteria only, and 199 met WHO criteria only. Over an average of 12.7 years, 229 deaths occurred (117 from cardiovascular disease). Moreover, in the primary prevention population of 2372 participants (ie, those without diabetes or cardiovascular disease at baseline), 132 deaths occurred (50 from cardiovascular disease). In the primary prevention population, the only significant association adjusted for age, gender, and ethnic group was between NCEP-MetS and cardiovascular mortality (hazard ratio [HR], 2.01; 95% CI, 1.13-3.57). In the general population, all-cause mortality HRs were 1.47 (95% CI, 1.13-1.92) for NCEP-MetS and 1.27 (95% CI, 0.97-1.66) for WHO-MetS. Furthermore, for cardiovascular mortality, there was evidence that gender modified the predictive ability of the MetS. For women and men, respectively, HRs for NCEP-MetS were 4.65 (95% CI, 2.35-9.21) and 1.82 (95% CI, 1.14-2.91), whereas HRs for WHO-MetS were 2.83 (95% CI, 1.55-5.17) and 1.15 (95% CI, 0.72-1.86).
In summary, although both definitions were predictive in the general population, the simpler NCEP definition tended to be more predictive in lower-risk subjects.
Despite its etiologic complexities, regulatory hurdles, and clinical uncertainties, metabolic syndrome must be recognized as a looming danger to public health in the United States. It demands the best efforts of clinicians, bench scientists, regulators, advocates, and clinical trialists to find viable solutions in the near future.
We aimed to assess the prevalence and prognostic role of metabolic syndrome (METS) and diabetes in post-myocardial infarction (MI) patients.
Diabetes is a well known risk factor for patients with previous MI, but glycemic dysmetabolism develops over a protracted period of time. Scanty data are available on the role of METS in patients with previous MI.
Adjusted Cox's regression models, having diabetes, death, major cardiovascular events (CVE), and hospitalization for congestive heart failure (CHF) during follow-up as outcome events, were fitted on 11,323 patients with prior MI enrolled in the GISSI-Prevenzione Trial.
At baseline, 21% and 29% of patients had diabetes mellitus and METS, respectively. The METS patients had a significant (93%) increased risk of diabetes during follow-up. As compared with control subjects, the probability of death and CVE were higher in both METS (+29%, p = 0.002; +23%, p = 0.005) and diabetic patients (+68%, p <0.0001; +47%, p <0.0001), although diabetic but not METS patients were more likely to be hospitalized for CHF (+89%, p <0.0003 and +24%, p = 0.241). Moderate (-6% to -10%) and substantial (>-10%) weight reduction were associated with a significant (18% and 41%, respectively) decreased risk of diabetes. Weight gain was significantly associated with increased risk of diabetes. The risk conferred by METS and diabetes tended to be higher among women.
In patients with MI, METS and diabetes were highly prevalent and are associated with increased risk of death and CVE. Diabetes is also associated with increased risk of hospitalization for CHF. Weight reduction significantly decreased the risk of becoming diabetic in patients with METS.
The metabolic syndrome, which is characterized by a constellation of fasting hyperglycemia, hypertriglyceridemia, low HDL cholesterol, hypertension, and/or abdominal obesity, is a risk factor for the development of coronary artery disease (CAD) and cardiovascular events. The interrelationship between metabolic status and CAD on cardiovascular risk in women is not known.
We evaluated interrelationships between angiographic CAD, the metabolic syndrome, and incident cardiovascular events among 755 women from the Women's Ischemia Syndrome Evaluation (WISE) study who were referred for coronary angiography to evaluate suspected myocardial ischemia; 25% of the cohort had the metabolic syndrome at study entry. Compared with women with normal metabolic status, women with the metabolic syndrome had a significantly lower 4-year survival rate (94.3% versus 97.8%, P=0.03) and event-free survival from major adverse cardiovascular events (death, nonfatal myocardial infarction, stroke, or congestive heart failure; 87.8% versus 93.5%, P=0.003). When the subjects were stratified by the presence or absence of angiographically significant CAD at study entry, in women with angiographically significant CAD, the metabolic syndrome resulted in significantly higher risk of cardiovascular events than in women with normal metabolic status (hazard ratio 4.93, 95% CI 1.02 to 23.76; P=0.05), whereas it did not result in increased 4-year cardiovascular risk in women without angiographically significant CAD (hazard ratio 1.41, 95% CI 0.32 to 6.32; P=0.65).
These data suggest that in women with suspected myocardial ischemia, the metabolic syndrome modifies the cardiovascular risk associated with angiographic CAD. Specifically, the metabolic syndrome was found to be a predictor of 4-year cardiovascular risk only when associated with significant angiographic CAD.
Metabolic syndrome: evaluation of pathological and therapeutic outcomes syndrome in relation to all-cause and cardiovascular mortality in the San Antonio Heart Study
- Miranda Pj Ra Defronzo
- Califf Rm
Miranda PJ, DeFronzo RA, Califf RM, et al. Metabolic syndrome: evaluation of pathological and therapeutic outcomes. Am Heart J 2005;149:20 -32. syndrome in relation to all-cause and cardiovascular mortality in the San Antonio Heart Study. Circulation 2004;110:1251 -7.
Prospective analysis of the insulin-resistance syndrome (syndrome X)
- Haffner
Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey
- Ford