Both the metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) confer an increased risk of coronary heart disease and cardiovascular disease (CVD). As MS and T2DM become more prevalent, there will be an associated rise in the number of individuals with or at risk for CVD and its related disorders. One major underlying cause of CVD in patients with MS or T2DM is a characteristic form of atherogenic dyslipidemia. This article reviews the evidence that demonstrates that individuals with MS or T2DM are at increased risk for CVD and highlights atherogenic dyslipidemia as an important risk factor for the development of CVD in these individuals. In an accompanying article, current pharmacotherapies available for the management of atherogenic dyslipidemia in individuals with MS or T2DM are discussed.

Diabetes and cardiovascular disease are so intertwined with one another that the presence of one prompts a search for the other. Diabetes has been considered to be equivalent to coronary heart disease (CHD), and conversely many patients with known CHD have concomitant diabetes or its pre-states. This review has been compiled based on the guidelines of the American Diabetes Association, the Third Report of the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III), the European Society of Cardiology, and the European Association for the Study of Diabetes. A systematic approach was developed by the European Society of Cardiology and the European Association for the Study of Diabetes recently to help detect CHD in patients with diabetes and to detect metabolic diseases in patients with CHD.This article is intended for the clinician in everyday practice focusing on the impact of recent advances in the prevention and management of CHD in diabetic patients and the background behind it.

Resveratrol (3,4',5 trihydroxystilbene), a naturally-occurring molecule known as a phytoalexin, is synthesized by plants in response to attacks by fungi, bacteria, or other injurious substances; it is also known to possess an array of cardioprotective effects. Recently, studies have shown resveratrol to protect against the metabolic changes associated with hypercaloric diets in mice with induced insulin resistance, hyperglycemia, and dyslipidemia. Despite impressive gains in diagnosis and treatment, cardiovascular disease (CVD) remains a serious clinical problem and threat to public health. The metabolic syndrome, which identifies persons at higher risk for diabetes mellitus and CVD, is approaching a prevalence of nearly 25% of the western world. If the metabolic syndrome can be considered a polar opposite to caloric restriction, then agents that mimic caloric restriction may offer a new therapeutic approach to preventing CVD. The authors discuss the cardioprotective effects of resveratrol and highlight its role in glucose homeostasis and lipid metabolism in mice. Armed with the ability to prevent the deleterious effects of excess caloric intake and prevent detrimental cardiovascular events, resveratrol merits proper clinical investigations for its efficacy in treating metabolic diseases and CVD.

Paralleling the rise in obesity, the cardiometabolic syndrome is a rapidly growing health problem in the United States. There is a 3-fold increase in the prevalence of coronary heart disease, myocardial infarction, and stroke due to the coagulation, hemodynamic, and metabolic abnormalities seen in these individuals. The use of aspirin for secondary prevention and, to a lesser degree, primary prevention of cardiovascular events is a well-established standard of care. However, in patients with diabetes or the cardiometabolic syndrome, the role of aspirin in prevention of cardiovascular events remains controversial. In this review, the authors examine the clinical trial data on the use of aspirin in diabetes and the cardiometabolic syndrome for cardiovascular protection. They also explore, in addition to aspirin's effects on platelet aggregation, some of the mechanisms by which aspirin may favorably alter the course of atherosclerosis, effects on endothelial function, and glycemia.

Obstructive sleep apnea (OSA) and the metabolic syndrome (MS) are independently associated with increased cardiovascular risk. The objective of the present study was to determine the prevalence of OSA among consecutive patients with MS and to determine whether OSA is associated with impaired glycemic control. Fifty consecutive patients with a recent diagnosis of MS and no previous diagnosis of OSA underwent a polysomnography and anthropometric and laboratory measurements. The prevalence of OSA (apnea-hypopnea index >or=15 events per hour of sleep) was 68% and in the same range of all other individual components of MS. Moreover, OSA was associated with increased levels of glucose (P=.03) and glycosylated hemoglobin (P=.03) but not with body mass index (P=.30). Glycosylated hemoglobin was independently associated with glucose (P<.001) and apnea-hypopnea index (P=.03). The prevalence of OSA is in the same range as all the individual components of MS and is independently associated with impaired glycemic control.

To test the hypothesis that the cardiac structural and functional abnormalities of the metabolic syndrome (MS) are independent of body mass index (BMI), 160 untreated patients (aged 47+/-1 years [mean +/- SEM], 53% male) underwent 2-dimensional echocardiography and tissue Doppler imaging and evaluation for MS. Participants with MS and controls were similar in age, BMI, and ejection fraction, but those with MS had greater left ventricular relative wall thickness (RWT) (0.43+/-0.008 vs 0.39+/-0.005, P<.001), reduced midwall fractional shortening (MFS) (13%+/-0.3% vs 14.2%+/-0.3%, P<.05), and reduced peak mitral annular velocity (Em) (9.9+/-0.5 vs 12.3+/-0.5 cm/sec, P<.01) than controls. There was a linear relationship between the number of features of MS and Em velocity (P<.001), RWT (P<.001), and MFS (P<.05). In a stepwise multiple regression analysis adjusting for likely determinants, MS was an independent predictor of Em in addition to age and nonindexed left ventricular mass. MS is associated with left ventricular concentric remodeling and reduced systolic and diastolic function independent of BMI.

The authors studied the effects on C-reactive protein (CRP) levels of an intensive intervention to reduce hemoglobin A(1c) (HbA(1c)) among 58 veterans with type 2 diabetes. Weekly group sessions of behavioral and pharmacologic intervention were conducted for 4 weeks at Providence Veterans Affairs Medical Center. Change in cardiovascular risk factors and CRP levels were compared at baseline and 3 months postintervention. There was a significant decrease in HbA(1c) (-0.7%+/-1.9%, P<.01), total cholesterol (-20.3+/-41.1 mg/dL, P=.01), low-density lipoprotein cholesterol (-11.7+/-31.4 mg/dL, P=.05), systolic blood pressure (-6.9+/-21.2 mm Hg, P=.03), and diastolic blood pressure (-6.0+/-10.6 mm Hg, P<.01) over 4 months. There was no significant change in CRP levels (1.1+/-6.6 mg/L, P=.2). These results suggest that CRP effects may not be adequate to predict changes in cardiovascular risk among diabetic patients and should not be a surrogate for achieving evidence-based goals in traditional cardiovascular risk factors.

The authors examined the clinical profile of the hypertensive population with the metabolic syndrome (MetS) and elevated pulse pressure (PP) in a sample of 5866 patients (3291 women and 2575 men) included in a large hypertension survey performed in primary care setting. Elevated PP was defined as >or=80 mm Hg in women and >or=75 mm Hg in men; 92.7% of women and 87.6% of men had normal PP values. Patients with higher PP levels were older, were more commonly diabetic, and exhibited more frequently target organ damage and associated clinical conditions. Blood pressure was less well controlled in the subgroup of patients with elevated PP: control rates were 4.1% vs 19.2%, P<.001; men, 3.9% vs 19.0%, P<.001; P=NS between sexes. Low-density lipoprotein cholesterol was similarly controlled regardless of PP: control rates were, 17.0% vs 17.8%; in women with high PP vs normal PP and 25.2% vs 25.1% in men with high PP vs normal PP, both P=NS; P<.001 between sexes with high PP. In the patients with high PP, the female subgroup was older, was more obese, and had more left ventricular hypertrophy and fewer associated clinical conditions than did men. The odds ratio of having high PP in women with MetS vs no MetS was 3.13 and in men was 1.9 (both P<.01).

The cardiometabolic syndrome (CMS) has been an organizing conceptual framework for subclinical cardiovascular pathophysiology. Using cross-sectional data from 338 healthy men and women aged 18 to 55 years, the study examined the role of central adiposity and insulin sensitivity and assessed potential relationships with other metabolic indices (insulin sensitivity, glucose tolerance, fibrinolysis, lipidemia, endothelial function, and inflammation) and measures of cardiac structure and function (cardiac mass, compliance and contractility, myocardial oxygen demand, and blood pressure). Structural equation modeling analyses, which controlled for sex, age, and race, demonstrated good fit to the data. The derived relationships provided a physiologically consistent model of CMS, with an initiating role for central adiposity and insulin resistance. The model accounted for 30% and 82% of the variance in diastolic blood pressure and myocardial oxygen demand, respectively. The findings suggest predominant pathways through which subclinical metabolic processes may exert pathogenic impact on the heart and vasculature.

Chronic kidney disease and cardiovascular disease share many risk factors, including hypertension, obesity, and insulin resistance. All of these are components of the cardiometabolic syndrome and are associated with increased risk of morbidity and mortality. One mechanism that links renal injury with the cardiometabolic syndrome is activation of the renin-angiotensin system. Chronic angiotensin II activation promotes development of renal disease through hemodynamic effects and up-regulation of inflammatory cytokines and growth factors. Inhibition of the renin-angiotensin system delays progression of renal disease and improves measures of renal function independent of blood pressure lowering in patients with the cardiometabolic syndrome or its components. Higher doses of renin-angiotensin system inhibitors may provide greater renoprotection in both normotensive and hypertensive patients with the cardiometabolic syndrome. Inhibition of the renin-angiotensin system in patients with risk factors or vascular disease with or without recognized glycemic abnormalities may be a useful strategy for preventing the progression of chronic kidney disease in patients with vascular disease and in those with the cardiometabolic syndrome or its components.

Type 1 diabetes (T1D) is a common disease of childhood with a current prevalence of almost 2 cases per 1000 adolescents, according to the third National Health and Nutrition Examination Survey. Modern insulin treatment has resulted in improved quality of life for children with this chronic disorder. However, T1D continues to carry a long-term burden of increased microvascular and macrovascular complications and mortality risk. Compared to the nondiabetic population, patients with T1D are more likely to have >or=1 cardiovascular risk factor and often at an earlier age. Since the prevalence of cardiovascular risk factors increases with age in young persons with T1D, there is a clear need for early screening and counseling to prevent their occurrence and manage long-term health ramifications. The purpose of this review is to describe how traditional risk factors for cardiovascular disease such as an abnormal lipid profile, hypertension, obesity, and insulin resistance contribute to the accelerated atherosclerosis seen in young persons with T1D. A summary is given of the guidelines and recommendations published for clinical care for these patients.

Nearly 1 in 4 adults in the United States is obese. The connection between obesity and insulin resistance, type 2 diabetes, and cardiovascular disease is a well researched one. The increasing prevalence of each of these diseases has become a growing concern for the medical community. Adiponectin is a collagen-like plasma protein secreted by adipocytes that has been suggested to play a causal role in the development of insulin resistance and cardiovascular disease. The protein has been found to be decreased in cases of insulin resistance, diabetes, atherosclerosis, and coronary artery disease. Up-regulation of adiponectin and its receptor, through the use of thiazolidinediones, has been found to be partially related to insulin sensitization and thus antidiabetic effects. In this review, we discuss adiponectin's antiatherogenic effects, its association with insulin resistance and obesity, and the possibility of using adiponectin and its receptor as a therapeutic target.

Highly active antiretroviral therapy (HAART) has dramatically improved the prognosis of HIV-positive patients. However, long-term adverse effects of this therapy include dyslipidemia, insulin resistance (IR), changes in body fat distribution (lipodystrophy), and cardiometabolic syndrome (CMS). IR in HIV-positive patients does not seem to represent a significant independent risk factor for the development of cardiovascular disease; nevertheless, the association with other metabolic complications (dyslipidemia, fat redistribution) and CMS may increase the risk of type 2 diabetes and cardiovascular disease. The use of nucleoside analogue reverse transcriptase inhibitors is associated with the development of upper trunk and visceral fat accumulation and may cause IR. The progression of IR toward diabetes may be impeded with the choice of HAART regimens with less IR effects and encouraging patients to adhere to a healthy lifestyle. For patients with marked IR but relatively preserved fat, the use of metformin may consent the improvement of CMS and lipodystrophy, especially when combined with an appropriate exercise program. Therapy with rosiglitazone is not indicated in these patients.

A number of metabolic syndrome (MS) definitions exist, and one's cardiovascular disease risk may depend on the definition used. The authors compared the association of subclinical atherosclerosis (coronary artery calcification [CAC] score >0] and inflammation (white blood cell [WBC] count greater than or equal to the highest quartile) with 3 definitions of MS (those of the National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III], the American Heart Association/National Heart, Lung and Blood Institute [AHA/NHLBI], and the International Diabetes Federation [IDF]) in 458 asymptomatic men (mean age, 46+/-7 years). MS was present in 28%, 29%, and 34% according to NCEP ATP III, AHA/NHLBI, and IDF criteria, respectively. CAC was observed in 40% and high WBC count in 24%. After adjustment for age, smoking, and low-density lipoprotein cholesterol, the odds ratios for CAC scores >0 with MS by NCEP ATP III, AHA/NHLBI, and IDF definitions were 1.67 (95% confidence interval [CI], 1.02-2.72), 1.67 (95% CI, 1.03-2.70), and 1.63 (95% CI, 1.03-2.57), respectively. The multivariate odds ratios for high WBC count with MS by NCEP ATP III, AHA/NHLBI, and IDF definitions were 1.69 (95% CI, 1.04-2.73), 1.84 (95% CI, 1.14-2.95), and 1.66 (95% CI, 1.05-2.62), respectively. MS is associated with increased subclinical atherosclerosis and inflammation irrespective of various definitions.