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Aims: To investigate the impact of intensive lipid-lowering with high-dose atorvastatin on the cardiovascular risk associated with individual metabolic syndrome components [high body mass index (BMI), elevated triglycerides, low high-density lipoprotein (HDL) cholesterol, hypertension and elevated fasting glucose] in patients with coronary heart disease (CHD)., Methods: Patients with clinically evident, stable CHD and low-density lipoprotein (LDL) cholesterol <3.4 mmol/l (130 mg/dl) were randomized to double-blind therapy with atorvastatin 10 mg/day (n = 5006) or 80 mg/day (n = 4995) after an 8-week open-label run-in with atorvastatin 10 mg. The median follow-up was 4.9 years. The impact of individual metabolic syndrome risk factors was tested on the primary endpoint, which was the occurrence of a first major cardiovascular event., Results: On-treatment LDL cholesterol was 2.6 mmol/l (101 mg/dl) with atorvastatin 10 mg and 2.0 mmol/l (77 mg/dl) with atorvastatin 80 mg. Among patients receiving atorvastatin 10 mg, the presence of each individual metabolic syndrome component significantly increased the risk of major cardiovascular events compared with the absence of each (BMI, p = 0.014; triglycerides, p = 0.006; HDL cholesterol, p = 0.0006; hypertension, p < 0.0001; and fasting glucose p < 0.0001). In patients receiving atorvastatin 80 mg, elevated triglycerides and fasting glucose were no longer significant predictors of major cardiovascular events. The predictive power of hypertension on the risk of major cardiovascular events was reduced in patients treated with atorvastatin 80 mg, although it remained a significant predictor., Conclusions: Treatment with high-dose atorvastatin to a mean LDL cholesterol level of 2.0 mmol/l (77 mg/dl) considerably attenuated the predictive power associated with three metabolic syndrome components., (© 2015 John Wiley & Sons Ltd.)

Background: Improvement in renal function and decreases in serum uric acid (SUA) have been reported following prolonged high-intensity statin (HMG-CoA reductase inhibitor) therapy. This post hoc analysis of the SAGE trial examined the effect of intensive versus less intensive statin therapy on renal function, safety, and laboratory parameters, including SUA, in elderly coronary artery disease (CAD) patients (65-85 years) with or without chronic kidney disease (CKD)., Methods: Patients were randomized to atorvastatin 80 mg/day or pravastatin 40 mg/day and treated for 12 months. Patients were stratified using Modification of Diet in Renal Disease (MDRD) estimated glomerular filtration rates (eGFRs) in CKD (eGFR <60 mL/min/1.73 m(2)) and non-CKD populations., Results: Of the 893 patients randomized, 858 had complete renal data and 418 of 858 (49%) had CKD (99% Stage 3). Over 12 months, eGFR increased with atorvastatin and remained stable with pravastatin (+2.38 vs. +0.18 mL/min/1.73 m(2), respectively; p < 0.0001). MDRD eGFR improved significantly in both CKD treatment arms; however, the increased eGFR in patients without CKD was significantly greater with atorvastatin (+2.08 mL/min/1.73 m(2)) than with pravastatin (-1.04 mL/min/1.73 m(2)). Modest reductions in SUA were observed in both treatment arms, but a greater fall occurred with atorvastatin than with pravastatin (-0.52 vs. -0.09 mg/dL, p < 0.0001). Change in SUA correlated negatively with changes in eGFR and positively with changes in low-density lipoprotein cholesterol. Reports of myalgia were rare (3.6% CKD; 5.7% non-CKD), and there were no episodes of rhabdomyolysis. Elevated serum alanine and aspartate transaminase to >3 times the upper limit of normal occurred in 4.4% of atorvastatin- and 0.2% of pravastatin-treated patients., Conclusion: Intensive management of dyslipidemia in older patients with stable coronary heart disease may have beneficial effects on renal function and SUA.

An Expert Panel convened by the National Lipid Association previously developed a consensus set of recommendations for the patient-centered management of dyslipidemia in clinical medicine (part 1). These were guided by the principle that reducing elevated levels of atherogenic cholesterol (non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol) reduces the risk for atherosclerotic cardiovascular disease. This document represents a continuation of the National Lipid Association recommendations developed by a diverse panel of experts who examined the evidence base and provided recommendations regarding the following topics: (1) lifestyle therapies; (2) groups with special considerations, including children and adolescents, women, older patients, certain ethnic and racial groups, patients infected with human immunodeficiency virus, patients with rheumatoid arthritis, and patients with residual risk despite statin and lifestyle therapies; and (3) strategies to improve patient outcomes by increasing adherence and using team-based collaborative care., (Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

End-stage renal disease (ESRD) patients have extraordinarily high cardiovascular risk and mortality, yet the benefit of statins in this population remains unclear based on the randomized trials. We investigated the prognostic value of statins in a large, pure cohort of prospectively recruited patients with ESRD awaiting renal transplantation, and being followed up in a dedicated cardiac clinic. We prospectively collected demographic, clinical, laboratory, and pharmacological data on 423 consecutive ESRD patients on hemodialysis awaiting renal transplantation. Survival analysis was performed as a function of statin therapy. The baseline characteristics were as follows: age 57 ± 11 years, males 64%, diabetes mellitus in 68%, known coronary artery disease in 30%, left ventricular (LV) ejection fraction 61 ± 11%. Over a mean follow-up of 2 years, there were 43 deaths. Adjusted for age, gender, hypertension, body mass index, diabetes mellitus, coronary artery disease, smoking, and treatment with angiotensin converting enzyme inhibitor, β blocker, and antiplatelet medications, statin use was a predictor of lower mortality (hazard ratio 0.30, 95% confidence interval 0.11-0.79, p = 0.01). This beneficial effect of statin was supported by propensity score analysis (p = 0.02) and was consistent across all clinical subgroups. The benefit of statins seemed to be greater in those with LV hypertrophy and smoking. Statin therapy in hemodialysis patients awaiting renal transplant is independently associated with better survival supporting its use in this high-risk population.

Objective: To determine epidemiology of cardiovascular risk factors according to geographic distribution and macrolevel social development index among urban middle class subjects in India., Methods: We performed cross-sectional surveys in 11 cities in India during years 2005-2009. 6198 subjects aged 20-75 years (men 3426, women 2772, response 62%) were evaluated for cardiovascular risk factors. Cities were grouped according to geographic distribution into northern (3 cities, n = 1321), western (2 cities, n = 1814), southern (3 cities, n = 1237) and eastern (3 cities, n = 1826). They were also grouped according to human social development index into low (3 cities, n = 1794), middle (5 cities, n = 2634) and high (3 cities, n = 1825). Standard definitions were used to determine risk factors. Differences in risk factors were evaluated using χ(2) test. Trends were examined by least squares regression., Findings: Age-adjusted prevalence (95% confidence intervals) of various risk factors was: low physical activity 42.1% (40.9-43.3), high dietary fat 49.9% (47.8-52.0), low fruit/vegetables 26.9% (25.8-28.0), smoking 10.1% (9.1-11.1), smokeless tobacco use 9.8% (9.1-10.5), overweight 42.9% (41.7-44.1), obesity 11.6% (10.8-12.4), high waist circumference 45.5% (44.3-46.7), high waist-hip ratio 75.7% (74.7-76.8), hypertension 31.6% (30.4-32.8), hypercholesterolemia 25.0% (23.9-26.9), low HDL cholesterol 42.5% (41.3-43.7), hypertriglyceridemia 36.9% (35.7-38.1), diabetes 15.7% (14.8-16.6), and metabolic syndrome 35.7% (34.5-36.9). Compared with national average, prevalence of most risk factors was not significantly different in various geographic regions, however, cities in eastern region had significantly lower prevalence of overweight, hypertension, hypercholesterolemia, diabetes and metabolic syndrome compared with other regions (P < 0.05 for various comparisons). It was also observed that cities with low human social development index had lowest prevalence of these risk factors in both sexes (P < 0.05)., Conclusions: Urban middle-class men and women in eastern region of India have significantly lower cardiometabolic risk factors compared to northern, western and southern regions. Low human social development index cities have lower risk factor prevalence.

Objective: To determine association of socioeconomic status, defined by educational status (ES), with awareness, treatment and control of cardiovascular risk factors., Methods: We performed an epidemiological study at 11 cities in India using cluster sampling. 6198 subjects (3426 men, 2772 women, response 62%, age 48±10 years) were evaluated for sociodemographic, lifestyle, anthropometric and biochemical factors. ES was categorised according to years of schooling into low (≤10 years), medium (11-15 years) and high (>15 years). Risk factors were diagnosed according to current guidelines. Awareness, treatment and control status were determined for hypertension, diabetes and hypercholesterolaemia. For smoking/tobacco use, quit rate was determined. Descriptive statistics are reported., Results: Age-adjusted and sex-adjusted prevalence (%) of various risk factors in low, medium and high ES subjects was hypertension 31.8, 29.5 and 34.1, diabetes 14.5, 15.3 and 14.3, hypercholesterolaemia 24.0, 23.9 and 27.3, and smoking/tobacco use 24.3, 14.4 and 19.0. Significantly increasing trends with low, medium and high ES were observed for hypertension awareness (30.7, 37.8, 47.0), treatment (24.3, 29.2, 35.5) and control (7.8, 11.6, 15.5); diabetes awareness (47.2, 51.5, 56.4), treatment (38.3, 41.3, 46.0) and control (18.3, 15.3, 22.8); hypercholesterolaemia awareness (8.9, 22.4, 18.4), treatment (4.1, 6.2, 7.9) and control (2.8, 3.2, 6.9), as well as for smoking/tobacco quit rates (1.6, 2.8, 5.5) (χ(2) for trend, p<0.05)., Conclusions: Low ES subjects in India have lower awareness, treatment and control of hypertension, diabetes and hypercholesterolaemia and smoking quit rates.

Type 2 diabetes (T2D) is a well-established risk factor for patients with coronary artery disease (CAD). Patients with CAD and comorbid T2D also have a higher risk of cardiovascular complications, such as silent ischemia and stable angina. In treating the symptoms of stable angina in patients with CAD and comorbid T2D, it is vital to utilize therapies that reduce symptoms and improve outcomes. At the same time, there is significant concern about the preservation of glycometabolic parameters, such as glycosylated hemoglobin (HbA1c), particularly because some antianginal therapies, such as β-blockers and calcium channel blockers-although effective at improving the symptoms of stable angina and reducing ischemia-may also worsen glycemic control by increasing HbA1c levels. Available trial data on the efficacy of antianginal agents in patients with stable angina and comorbid T2D are limited. Therefore, in patients with stable angina and T2D, a tailored approach to treatment of stable angina by selecting therapies with a neutral or positive glycometabolic profile may improve outcomes and increase treatment compliance. Additionally, patients with a dual diagnosis may benefit from therapies that have beneficial effects on both stable angina and T2D, thereby reducing polypharmacy. Prospective studies in patients with stable angina and T2D are needed to guide therapy decisions.

Objectives: To determine the prevalence of diabetes and awareness, treatment and control of cardiovascular risk factors in population-based participants in India., Methods: A study was conducted in 11 cities in different regions of India using cluster sampling. Participants were evaluated for demographic, biophysical, and biochemical risk factors. 6198 participants were recruited, and in 5359 participants (86.4%, men 55%), details of diabetes (known or fasting glucose >126 mg/dL), hypertension (known or blood pressure >140/>90 mm Hg), hypercholesterolemia (cholesterol >200 mg/dL), low high-density lipoprotein (HDL) cholesterol (men <40, women <50 mg/dL), hypertriglyceridemia (>150 mg/dL), and smoking/tobacco use were available. Details of awareness, treatment, and control of hypertension and hypercholesterolemia were also obtained., Results: The age-adjusted prevalence (%) of diabetes was 15.7 (95% CI 14.8 to 16.6; men 16.7, women 14.4) and that of impaired fasting glucose was 17.8 (16.8 to 18.7; men 17.7, women 18.0). In participants with diabetes, 27.6% were undiagnosed, drug treatment was in 54.1% and control (fasting glucose ≤130 mg/dL) in 39.6%. Among participants with diabetes versus those without, prevalence of hypertension was 73.1 (67.2 to 75.0) vs 26.5 (25.2 to 27.8), hypercholesterolemia 41.4 (38.3 to 44.5) vs 14.7 (13.7 to 15.7), hypertriglyceridemia 71.0 (68.1 to 73.8) vs 30.2 (28.8 to 31.5), low HDL cholesterol 78.5 (75.9 to 80.1) vs 37.1 (35.7 to 38.5), and smoking/smokeless tobacco use in 26.6 (23.8 to 29.4) vs 14.4 (13.4 to 15.4; p<0.001). Awareness, treatment, and control, respectively, of hypertension were 79.9%, 48.7%, and 40.7% and those of hypercholesterolemia were 61.0%, 19.1%, and 45.9%, respectively., Conclusions: In the urban Indian middle class, more than a quarter of patients with diabetes are undiagnosed and the status of control is low. Cardiovascular risk factors-hypertension, hypercholesterolemia, low HDL cholesterol, hypertriglyceridemia, and smoking/smokeless tobacco use-are highly prevalent. There is low awareness, treatment, and control of hypertension and hypercholesterolemia in patients with diabetes.

Objective: Metabolic syndrome is an important cardiovascular risk factor. To determine its prevalence among urban subjects in India we performed a multisite study., Methods: The study was performed at eleven cities using cluster sampling. 6198 subjects (men 3426, women 2772, response 62%, age 48±10 years) were evaluated for socio-demographic, lifestyle, anthropometric and biochemical factors. Prevalence of metabolic syndrome was determined using harmonized Asian-specific criteria. Significant socioeconomic and lifestyle associations were determined., Results: Age adjusted prevalence (%, 95% confidence intervals) of metabolic syndrome in men and women was 33.3 (31.7-34.9) and 40.4 (38.6-42.2) (harmonized criteria), 23.9 (22.4-26.4) and 34.5 (32.0-36.1) (modified Adult Treatment Panel-3, ATP-3) and 17.2 (15.3-19.1) and 22.8 (20.1-24.2) (ATP-3). Individual components of metabolic syndrome in men and women, respectively, were: high waist circumference 35.7 (34.1-37.3) and 57.5 (55.6-59.3), high blood pressure 50.6 (48.9-52.3) and 46.3 (44.4-48.1), impaired fasting glucose/diabetes 29.0 (27.5-30.5) and 28.0 (26.3-29.7), low HDL cholesterol 34.1 (32.5-35.7) and 52.8 (50.9-54.7) and high triglycerides 41.2 (39.5-42.8) and 31.5 (29.7-33.2) percent. Prevalence of metabolic syndrome was significantly greater in subjects with highest vs. lowest categories of education (45 vs. 26%), occupation (46 vs. 40%), fat intake (52 vs. 45%), sedentary lifestyle (47 vs. 38%) and body mass index (66 vs. 29%) (p<0.05)., Conclusion: There is high prevalence of metabolic syndrome in urban Indian subjects. Socioeconomic (high educational and occupational status) and lifestyle (high fat diet, low physical activity, overweight and obesity) factors are important., (Copyright © 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Chronic kidney disease (CKD) represents a serious public health concern. It has been associated with a significant burden of cardiovascular disease and studies have linked decreases in estimated glomerular filtration rate to higher incidences of cardiovascular events and mortality. Evidence from randomized clinical trials have shown that statins are a safe and effective treatment for improving cardiovascular outcomes in primary and secondary cardiovascular disease prevention in patients with CKD; despite this, statins are often underutilized in these patients. In addition to cardiovascular benefits, statin therapy may be associated with improvements in renal function in patients with kidney disease. Some statin treatment regimens have been shown to slow decline in kidney function, and some trials have found that intensive statin therapy improved kidney function. This review examines improved cardiovascular outcomes with statin treatment in patients with CKD (excluding end-stage renal disease) and investigates the effects of statin therapy on kidney function.

The prevalence of atrial fibrillation increases with age, augmenting the risk of embolic stroke in elderly individuals. Clinical practice guidelines recommend the long-term use of oral anticoagulation in elderly patients with atrial fibrillation to reduce risk of stroke. Until recently, vitamin K antagonists (eg, warfarin) were the only oral anticoagulants available, but using warfarin in elderly patients can be challenging. Newer oral anticoagulants may offer specific benefits and increased convenience for elderly patients, because they have predictable pharmacologic profiles, a rapid onset of action, a wide therapeutic window, no requirement for routine coagulation monitoring, and fewer and better-defined food and drug interactions compared with warfarin. This review highlights the benefits and challenges of warfarin use in elderly patients with atrial fibrillation and discusses potential efficacy and safety benefits for newer oral agents in these patients. The potential for increased rates of major bleeding in the elderly, particularly those with numerous concomitant medications or renal impairment, also is discussed. Practical considerations for the use of long-term anticoagulation in elderly patients also are discussed., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: We conducted a multisite study to determine the prevalence and determinants of normotension, prehypertension, and hypertension, and awareness, treatment, and control of hypertension among urban middle-class subjects in India., Methods: We evaluated 6,106 middle-class urban subjects (men 3,371; women, 2,735; response rate, 62%) in 11 cities for sociodemographic and biological factors. The subjects were classified as having normotension (BP < 120/80), prehypertension (BP 120-139/80-89), and hypertension (documented or BP ≥ 140/90). The prevalence of other cardiovascular risk factors was determined and associations evaluated through logistic regression analysis., Results: The age-adjusted prevalences in men and women of normotension were 26.7% and 39.1%, of prehypertension 40.2% and 30.1%, and of hypertension 32.5% and 30.4%, respectively. The prevalence of normotension declined with age whereas that of hypertension increased (P-trend < 0.01). A significant association of normotension was found with younger age, low dietary fat intake, lower use of tobacco, and low obesity (P < 0.05). The prevalence of hypercholesterolemia, diabetes, and metabolic syndrome was higher in the groups with prehypertension and hypertension than in the group with normotension (age-adjusted odds ratios (ORs) 2.0-5.0, P < 0.001). The prevalences in men and women, respectively, of two or more risk factors were 11.1% and 6.4% in the group with normotension, 25.1% and 23.3% in the group with prehypertension, and 38.3% and 39.1% in the group with hypertension (P < 0.01). Awareness of hypertension in the study population was in 55.3%; 36.5% of the hypertensive group were receiving treatment for hypertension, and 28.2% of this group had a controlled BP (< 140/90 mm Hg)., Conclusions: The study found a low prevalence of normotension and high prevalence of hypertension in middle-class urban Asian Indians. Significant associations of hypertension were found with age, dietary fat, consumption of fruits and vegetables, smoking, and obesity. Normotensive individuals had a lower prevalence of cardiometabolic risk factors than did members of the prehypertensive or hypertensive groups. Half of the hypertensive group were aware of having hypertension, a third were receiving treatment for it, and quarter had a controlled BP.

Background: Urban middle-socioeconomic status (SES) subjects have high burden of cardiovascular risk factors in low-income countries. To determine secular trends in risk factors among this population and to correlate risks with educational status we performed epidemiological studies in India., Methods: Five cross-sectional studies were performed in middle-SES urban locations in Jaipur, India from years 1992 to 2010. Cluster sampling was performed. Subjects (men, women) aged 20-59 years evaluated were 712 (459, 253) in 1992-94, 558 (286, 272) in 1999-2001, 374 (179, 195) in 2002-03, 887 (414, 473) in 2004-05, and 530 (324, 206) in 2009-10. Data were obtained by history, anthropometry, and fasting blood glucose and lipids estimation. Response rates varied from 55 to 75%. Mean values and risk factor prevalence were determined. Secular trends were identified using quadratic and log-linear regression and chi-squared for trend., Results: Across the studies, there was high prevalence of overweight, hypertension, and lipid abnormalities. Age- and sex-adjusted trends showed significant increases in mean body mass index (BMI), fasting glucose, total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (quadratic and log-linear regression, p < 0.001). Systolic blood pressure (BP) decreased while insignificant changes were observed for waist-hip ratio and low-density lipoprotein (LDL) cholesterol. Categorical trends showed increase in overweight and decrease in smoking (p < 0.05); insignificant changes were observed in truncal obesity, hypertension, hypercholesterolaemia, and diabetes. Adjustment for educational status attenuated linear trends in BMI and total and LDL cholesterol and accentuated trends in systolic BP, glucose, and HDL cholesterol. There was significant association of an increase in education with decline in smoking and an increase in overweight (two-line regression p < 0.05)., Conclusion: In Indian urban middle-SES subjects there is high prevalence of cardiovascular risk factors. Over a 20-year period BMI and overweight increased, smoking and systolic BP decreased, and truncal obesity, hypercholesterolaemia, and diabetes remained stable. Increasing educational status attenuated trends for systolic BP, glucose and HDL cholesterol, and BMI.

Heart failure (HF) remains a major growing public health problem in the United States. Despite extensive understanding of the mechanism at the molecular level and innovations in therapy, HF carries high morbidity and mortality rates, with frequent hospital admissions. In the Medicare population, HF is the leading cause for hospitalization, accounting for more than1 million admissions per year. The authors provide a review of the epidemiology and pathophysiology of HF., (Published by Elsevier Inc.)

Heart failure (HF) and atrial fibrillation (AF) are highly prevalent debilitating conditions that often coexist and are frequently encountered in clinical practice. The presence of chronic AF is a marker of worse prognosis in patients with HF, and the onset of new AF in those with chronic HF is associated with increased morbidity and mortality. Advances in the development of novel drugs, nonpharmacologic modalities, and therapeutic strategies, as well the increased understanding of the pathobiology of HF and AF, are key to mitigating the tremendous public health burden that is associated with these conditions., (Published by Elsevier Inc.)

Heart failure (HF) is a major public health problem associated with increased morbidity and mortality. As the US life expectancy increases and the population ages, the overall prevalence of HF will continue to escalate. The increasing use of effective selective therapies such as neurohormonal blockade in the treatment of patients with HF has led to considerable improvement in their prognosis. During the past several decades, some studies have demonstrated the benefits of treatment; based on the evidence available from these studies, various national and international guidelines have specific recommendations for the evidence-based therapy with these drugs in patients with HF., (Published by Elsevier Inc.)

Impaired kidney function often accompanies heart failure (HF) and is associated with a worse prognosis. This post hoc analysis of the Treating to New Targets (TNT) trial examined whether the observed decrease in HF hospitalizations with high- compared to low-dose atorvastatin could be related to improvements in kidney function. Of 10,001 TNT participants, 9,376 had estimated glomerular filtration rate (eGFR) measurements at baseline and 1 year and were included in this analysis. The association of change in year-1 eGFR and subsequent HF hospitalization was examined using Cox regression models. In total 218 participants developed subsequent HF hospitalization. Little change in eGFR occurred over 1 year in the atorvastatin 10-mg group, whereas eGFR improved in the 80-mg group by 1.48 ml/min/1.73 m(2) (95% confidence interval 1.29 to 1.67, p <0.0001). Subsequent HF was preceded by a decrease in eGFR over 1 year compared to modest improvement in those without subsequent HF (-0.09 ± 7.89 vs 0.81 ± 6.90 ml/min/1.73 m(2), p = 0.0015). After adjusting for baseline eGFR, each 5-ml/min/1.73 m(2) increase in eGFR at 1 year was associated with a lower risk of subsequent HF hospitalization (hazard ratio 0.85, 95% confidence interval 0.77 to 0.94, p = 0.002). This relation was independent of treatment effect or change in low-density lipoprotein cholesterol level at 1 year. In conclusion, treatment with high- compared to low-dose atorvastatin was associated with improvement in eGFR at 1 year, which was related to a decrease in subsequent HF hospitalization. This suggests that improvement in kidney function may be related to the beneficial effect of high-dose atorvastatin on HF hospitalization., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: To determine correlation of multiple parameters of socioeconomic status with cardiovascular risk factors in India., Methods: The study was performed at eleven cities using cluster sampling. Subjects (n = 6198, men 3426, women 2772) were evaluated for socioeconomic, demographic, biophysical and biochemical factors. They were classified into low, medium and high socioeconomic groups based on educational level (<10, 10-15 and >15 yr formal education), occupational class and socioeconomic scale. Risk factor differences were evaluated using multivariate logistic regression., Results: Age-adjusted prevalence (%) of risk factors in men and women was overweight or obesity in 41.1 and 45.2, obesity 8.3 and 15.8, high waist circumference 35.7 and 57.5, high waist-hip ratio 69.0 and 83.8, hypertension 32.5 and 30.4, hypercholesterolemia 24.8 and 25.3, low HDL cholesterol 34.1 and 35.1, high triglycerides 41.2 and 31.5, diabetes 16.7 and 14.4 and metabolic syndrome in 32.2 and 40.4 percent. Lifestyle factors were smoking 12.0 and 0.5, other tobacco use 12.7 and 6.3, high fat intake 51.2 and 48.2, low fruits/vegetables intake 25.3 and 28.9, and physical inactivity in 38.8 and 46.1%. Prevalence of > = 3 risk factors was significantly greater in low (28.0%) vs. middle (23.9%) or high (22.1%) educational groups (p<0.01). In low vs. high educational groups there was greater prevalence of high waist-hip ratio (odds ratio 2.18, confidence interval 1.65-2.71), low HDL cholesterol (1.51, 1.27-1.80), hypertriglyceridemia (1.16, 0.99-1.37), smoking/tobacco use (3.27, 2.66-4.01), and low physical activity (1.15, 0.97-1.37); and lower prevalence of high fat diet (0.47, 0.38-0.57),overweight/obesity (0.68, 0.58-0.80) and hypercholesterolemia (0.79, 0.66-0.94). Similar associations were observed with occupational and socioeconomic status., Conclusions: Low educational, occupational and socioeconomic status Asian Indians have greater prevalence of truncal obesity, low HDL cholesterol, hypertriglyceridemia, smoking or tobacco use and low physical activity and clustering of > = 3 major cardiovascular risk factors.

Coronary artery disease is a leading cause of death in the United States. Angina is encountered frequently in clinical practice. Effective management of patients with coronary artery disease and stable angina should consist of therapy aimed at symptom control and reduction of adverse clinical outcomes. Therapeutic options for angina include antianginal drugs: nitrates, beta-blockers, calcium channel blockers, ranolazine, and myocardial revascularization. Recent trials have shown that although revascularization is slightly better in controlling symptoms, optimal medical therapy that includes aggressive risk factor modification is equally effective in reducing the risk of future coronary events and death. On the basis of the available data, it seems appropriate to prescribe optimal medical therapy in most patients with coronary artery disease and stable angina, and reserve myocardial revascularization for selected patients with disabling symptoms despite optimal medical therapy., (Published by Elsevier Inc.)

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is an independent risk factor of potentially catastrophic cardioembolic strokes. AF patients are categorized into high-, intermediate-, and low-risk for thromboembolic complications using the CHADS(2) or CHA(2)DS(2)-VASc scoring system. Oral anticoagulation using warfarin has been the standard therapy for stroke prevention in intermediate- to high-risk AF patients. However, warfarin use has been limited by several factors such as narrow therapeutic windows, drug-drug and drug-food interactions, and hemorrhagic complications. Rigorous research evaluated dual antiplatelet therapy of clopidogrel and aspirin (acetylsalicylic acid) as a potential alternative to warfarin in the ACTIVE W trial. Dual antiplatelet therapy of clopidogrel and aspirin was found to be inferior to warfarin in preventing stroke and systemic embolism with increased bleeding risk. Other extensive research has led to the development of new antithrombotic agents. Recently, dabigatran etexilate 150 mg twice daily, a direct thrombin inhibitor, was approved by the US FDA for stroke prevention in patients with non-valvular AF after it was found to be superior to warfarin in preventing thromboembolic events and associated with less bleeding in the RE-LY trial. It was also cost effective when compared with warfarin. Dabigatran can be considered in high-risk AF patients who are unable or unwilling to comply with the frequent laboratory and clinic visits that are required when receiving treatment with warfarin. Factor Xa inhibitors are another class of new anticoagulants that have been developed. Oral rivaroxaban was non-inferior to warfarin in thromboprophylaxis and with similar bleeding in the ROCKET-AF trial (HR 0.88; p = 0.117). Apixaban, another factor Xa inhibitor, was superior to aspirin in reducing stroke and systemic embolism in patients with AF in the AVERROES trial (HR 0.45; p < 0.001). The results of the ARISTOTLE trial, which is evaluating apixaban against warfarin in ∼18 000 patients with AF, are expected to be available later this year. Edoxaban, another oral factor Xa inhibitor, is currently being evaluated against warfarin in the ENGAGE AF-TIMI 48 trial in ∼20 000 patients with AF. With these new developments, there is a necessity for the clinical practitioner to become familiar with these new and upcoming therapies and guidelines. This review provides an overview of the available data regarding the clinical usefulness of these agents.

Aims: To determine independent associations of diabetes mellitus with outcomes in a propensity-matched cohort of patients with acute myocardial infarction (AMI) and systolic heart failure (HF)., Methods and Results: In the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) trial, hospitalized AMI patients complicated by left ventricular ejection fraction ≤40% and symptoms of HF receiving standard therapy were randomized 3-14 days post-AMI to receive eplerenone 25-50 mg/day (n = 3319) or placebo (n = 3313). Of the 6632 patients, 2142 (32%) had a history of diabetes, who were older and sicker. Using propensity scores for diabetes, we assembled a cohort of 1119 pairs of patients with and without diabetes who were balanced on 64 baseline characteristics. Incident fatal or nonfatal recurrent AMI occurred in 136 (12%) and 87 (8%) of matched patients with and without diabetes, respectively, during 2.5 years of follow-up [hazard ratio (HR) when diabetes was compared with no-diabetes, 1.61; 95% confidence interval (CI), 1.23-2.10; P = 0.001]. Diabetes was associated with nonfatal AMI (HR, 1.68; 95% CI, 1.23-2.31; P = 0.001) but not with fatal AMI (HR, 1.42; 95% CI, 0.88-2.28; P = 0.146). Hazard ratios (95% CIs) for the association of diabetes with all-cause mortality, cardiovascular mortality, all-cause hospitalization, and cardiovascular hospitalization were 1.12 (0.93-1.37; P = 0.224), 1.11 (0.90-1.37; P = 0.318), 1.13 (1.00-1.27; P = 0.054), and 1.20 (1.01-1.44; P = 0.042), respectively., Conclusion: In post-AMI patients with systolic HF, diabetes mellitus is a significant independent risk factor for recurrent short-term nonfatal AMI, but had no association with fatal AMI.

Angina pectoris resulting from myocardial ischemia afflicts half of all patients with coronary heart disease (CHD). Chronic angina remains a major public health burden despite state-of-the-art therapies, and improvement in survival from myocardial infarction and CHD has only increased its prevalence. There is growing experimental and clinical evidence pointing to the anti-ischemic and anti-anginal properties of statins. Some data suggest that the degree of anti-ischemic efficacy of statins may be comparable to the current standard pharmacologic and mechanical strategies. The pleiotropic effects of statins are postulated to be primarily responsible for their anti-ischemic and anti-anginal properties. These include improvement of endothelial function, enhancement of the ischemic vasodilatory response, modulation of inflammation, and protection from ischemia-reperfusion injury. The anti-ischemic effects of statins further strengthen their role as a crucial component of the optimal medical therapy for CHD.

Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease (CVD) morbidity and mortality worldwide. Renin-angiotensin system (RAS) blockers have been indispensable in diminishing the macrovascular and microvascular complications of diabetes. In addition, cumulative evidence from retrospective studies pointed toward a beneficial effect of RAS agents in preventing the development and progression of T2DM. This disease-modifying potential of RAS blockers has been substantiated by recent prospective trials. Contemporary concepts regarding the natural history of T2DM and the pathophysiologic processes involved have increased our understanding of the mechanisms underlying the therapeutic potential of these agents in diabetes management. In addition to their established roles in the primary prevention of CVD in patients with diabetes, RAS blockers might be considered a suitable therapeutic choice for preventing the development of frank diabetes in high-risk patients.

Chronic heart failure and atrial fibrillation are 2 major disorders that are closely linked. Their coexistence is associated with adverse prognosis. Both share several common predisposing conditions, but their interaction involves complex ultrastructural, electrophysiologic, and neurohormonal processes that go beyond mere sharing of mutual risk factors. Rate control approach remains the standard therapy for atrial fibrillation in heart failure because current strategies at rhythm control have so far failed to positively impact mortality and morbidity. This is largely because of the shortcomings of current pharmacologic anti-arrhythmic agents. Surgical and catheter-based therapies are promising, but long-term data are lacking. The role of non-anti-arrhythmic therapeutic agents also is being explored. Further progress toward improved understanding the complex relationship between atrial fibrillation and heart failure should improve management strategies., (Published by Elsevier Inc.)

Beta adrenergic blockers have had a long history as frontline agents in hypertension therapy. They are the mainstay of treatment in ischemic heart disease, heart failure, high risk coronary artery disease and arrhythmias, as their importance in these compelling indications are well-established. However, the efficacy and relevance of beta blockers in the treatment of uncomplicated hypertension have been questioned because the traditional agents were deemed not atpar with drugs from other classes in terms of cardiovascular outcomes. Although atenolol and other traditional agent s have lost favor, the other cardioselective agents have been shown to be at least as efficacious in hypertension as the other classes of drugs. Their use in hypertension therapy should continue, especially in young and diabetic individuals where high sympathetic tone and high renin levels are the primary features. The newer-generation vasodilating beta blockers have favorable hemodynamic and metabolic properties, better side effect profile and improved efficacy in treating uncomplicated hypertension. With the advent of these new agents, the beta blocker class should remain as a viable first-line option in antihypertensive therapy.

Analyses of randomized clinical trials are usually restricted to examination of time to first event. However, because many patients have multiple events, this approach precludes much potentially useful clinical and economic data. To assess the effect on overall disease burden in the Treating to New Targets (TNT) study, we evaluated the effect of treatment with atorvastatin 80 versus 10 mg in the period after the occurrence of a first cardiovascular event. In TNT, 10,001 patients with stable coronary heart disease received double-blind therapy with atorvastatin 80 or 10 mg and were followed for 4.9 years. Post hoc time-to-event analysis was used to estimate separate hazard ratios for time to any first, second, third, fourth, and fifth recurrent cardiovascular events. During TNT, 3,082 patients had a first recurrent cardiovascular event, with 1,516, 698, 345, and 197 developing second, third, fourth, and fifth recurrent events, respectively. In patients receiving atorvastatin 80 mg, the relative risk of a first recurrent event was significantly decreased compared to those receiving atorvastatin 10 mg. Significant benefit with the 80-mg dose was also observed for second, third, fourth, and fifth recurrent events. Similar findings were recorded in 5,854 patients with type 2 diabetes mellitus and/or metabolic syndrome and in 3,809 patients > or = 65 years of age compared to younger patients. In conclusion, treatment with atorvastatin 80 mg continued to significantly decrease the risk of any cardiovascular event over time compared to atorvastatin 10 mg in patients who had survived previous events. In TNT, analyses limited to the primary end point significantly underestimated the decrease in total cardiovascular disease burden achieved by intensive low-density lipoprotein cholesterol lowering., (Copyright 2010 Elsevier Inc. All rights reserved.)

Systolic dysfunction and heart failure are major public health problems associated with a significant risk of morbidity and mortality. During the past 2 decades, considerable progress has been made in defining the underlying pathophysiology and the appropriate therapies in heart failure. In patients with chronic heart failure (CHF), sustained sympathetic overactivation leads to down-regulation of beta receptors and uncoupling of the receptors from adenylate cyclase. The clear understanding of the pivotal role of sympathetic overactivation in CHF has led to the evaluation of beta- blocker therapy in CHF. A number of large randomized clinical trials have been conducted with a variety of beta-blockers, and although most of them have shown benefit, there have been differing findings with different molecules. beta-blockers are now considered part of the standard therapy for all patients with symptomatic CHF. Despite the strong evidence supporting their use, beta-blockers continue to be underutilized in CHF.

Background: Lipid levels among contemporary patients hospitalized with coronary artery disease (CAD) have not been well studied. This study aimed to analyze admission lipid levels in a broad contemporary population of patients hospitalized with CAD., Methods: The Get With The Guidelines database was analyzed for CAD hospitalizations from 2000 to 2006 with documented lipid levels in the first 24 hours of admission. Patients were divided into low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride categories. Factors associated with LDL and HDL levels were assessed along with temporal trends., Results: Of 231,986 hospitalizations from 541 hospitals, admission lipid levels were documented in 136,905 (59.0%). Mean lipid levels were LDL 104.9 +/- 39.8, HDL 39.7 +/- 13.2, and triglyceride 161 +/- 128 mg/dL. Low-density lipoprotein cholesterol <70 mg/dL was observed in 17.6% and ideal levels (LDL <70 with HDL > or =60 mg/dL) in only 1.4%. High-density lipoprotein cholesterol was <40 mg/dL in 54.6% of patients. Before admission, only 28,944 (21.1%) patients were receiving lipid-lowering medications. Predictors for higher LDL included female gender, no diabetes, history of hyperlipidemia, no prior lipid-lowering medications, and presenting with acute coronary syndrome. Both LDL and HDL levels declined over time (P < .0001)., Conclusions: In a large cohort of patients hospitalized with CAD, almost half have admission LDL levels <100 mg/dL. More than half the patients have admission HDL levels <40 mg/dL, whereas <10% have HDL > or =60 mg/dL. These findings may provide further support for recent guideline revisions with even lower LDL goals and for developing effective treatments to raise HDL.

The identification of patients at high risk for cardiovascular events is imperative in the reduction of cardiovascular mortality and morbidity. Although coronary artery disease, peripheral arterial disease, cerebrovascular disease, hypertension, and diabetes mellitus contribute to the risk of developing cardiovascular events, we are now faced with emerging fronts because of an increase in life expectancy and the epidemic of hypertension, obesity, metabolic syndrome, and diabetes. Recent data emphasize the beneficial role of renin-angiotensin-aldosterone system (RAAS) blockers. This article addresses the role of RAAS activation in the high-risk metabolic milieu and the role of angiotensin receptor blockers in targeting and inhibiting the RAAS for cardiovascular protection.

This article reviews the results from several recent reports describing the safety and efficacy of statin therapy in the setting of heart failure. It additionally discusses the ongoing controversy regarding the lipid paradox and possible mechanisms responsible for potential benefit of statin therapy in heart failure.

This post-hoc analysis of the Treating to New Targets (TNT) study evaluated the joint effects of managing low-density lipoprotein cholesterol (LDL-C) and systolic blood pressure (SBP) on cardiovascular outcomes. Patients (N=9739) with clinically evident, stable coronary heart disease (CHD) were randomized to atorvastatin 10 or 80 mg/d. The primary end point was occurrence of a first major cardiovascular event. At 3 months' follow-up, patients were stratified according to SBP (< 140 mm Hg vs > or = 140 mm Hg) and tertiles of LDL-C. At 4.9 years' median follow-up, the rate of major cardiovascular events was reduced most in patients with lower LDL-C (P < .001) and in patients with SBP < 140 mm Hg (P = .014). A 42% relative risk reduction was observed for patients in the lowest LDL-C tertile with an SBP < 140 mm Hg, compared with patients in the highest LDL-C tertile with an SBP > or = 140 mm Hg. The effect of lower SBP on stroke was most pronounced in the lowest LDL-C tertile.

Objective: The impact of rising population-wide obesity on cardiovascular risk factors has not been well studied in low-income countries. To correlate the prevalence of obesity with risk factors we performed epidemiological studies in India., Methods: Multiple cross-sectional epidemiological studies, Jaipur Heart Watch (JHW), were performed in India in rural and urban locations. From these cohorts, subjects aged 20-59 years (men 4102, women 2872) were included. Prevalence of various risk factors: smoking/tobacco use, overweight/obesity (body mass index > or = 25 kg/m2) truncal obesity (waist:hip > or = 0.95 men, > or = 0.85 women), hypertension, dyslipidemias, metabolic syndrome and diabetes was determined. Trends were examined using least squares regression., Results: Smoking/tobacco use was more in rural men (50.0% vs 40.6%) and urban women (8.9% vs 4.5%, p < 0.01). Obesity, truncal obesity, hypertension, hypercholesterolemia, diabetes, and metabolic syndrome were more in urban cohorts (p < 0.001). Age-adjusted prevalence (%) of obesity in various cohorts, rural JHW, and urban JHW-1, JHW-2, JHW-3, and JHW-4 respectively, in men was 9.4, 21.1, 35.6, 54.0, and 50.9 (r2 = 0.92, p = 0.009) and in women 8.9, 15.7, 45.1, 61.5, and 57.7 (r2 = 0.88, p = 0.018). Prevalence of truncal obesity in men was 3.2, 19.6, 39.6, 41.4, and 31.1 (r2 = 0.60, p = 0.124) and in women 10.1, 49.5, 42.1, 51.7, and 50.5 (r2 = 0.56, p = 0.1467). In successive cohorts increasing trends were observed in the prevalence of hypertension (r2 = 0.93, p = 0.008) and metabolic syndrome (r2 = 0.99, p = 0.005) with weaker trends for hypercholesterolemia (r2 = 0.41, p = 0.241) and diabetes (r2 = 0.79, p = 0.299) in men. In women, significant trends were observed for hypertension (r2 = 0.98, p = 0.001) and weaker trends for others. Increase in generalized obesity correlated significantly with hypertension (two-line regression r2, men 0.91, women 0.88), hypercholesterolemia (0.53, 0.44), metabolic syndrome (0.87, 0.94) and diabetes (0.84, 0.93). Truncal obesity correlated less strongly with the risk factors like hypertension (0.50, 0.57), hypercholesterolemia (0.88, 0.61), metabolic syndrome (0.76, 0.33), and diabetes (0.75, 0.33)., Conclusions: In Asian Indian subjects, escalating population-wide generalized obesity correlates strongly with increasing cardiovascular risk factors.

Ischemic heart disease is the foremost cause of death in the United States and the developed countries. Stable angina is the initial manifestation of ischemic heart disease in one half of the patients and becomes a recurrent symptom in survivors of myocardial infarction (MI) and other forms of acute coronary syndromes (ACS). There are multiple therapeutic modalities currently available for treatment of anginal symptoms in patients with stable CAD. These include anti-anginal drugs and myocardial revascularization procedures such as coronary artery bypass graft surgery (CABGS), percutaneous transluminal coronary angioplasty (PTCA) and percutaneous coronary intervention (PCI). Anti-anginal drug therapy is based on treatment with nitrates, beta blockers, and calcium channel blockers. A newly approved antianginal drug, ranolazine, is undergoing phase III evaluation. Not infrequently, combination therapy is often necessary for adequate symptom control in some patients with stable angina. However, there has not been a systematic evaluation of individual or combination antianginal drug therapy on hard clinical end points in patients with stable angina. Most revascularization trials that have evaluated treatment with CABGS, PTCA, or PCI in patients with chronic CAD and stable angina have not shown significant improvement in survival or decreased incidence of non-fatal MI compared to medical treatment. In the CABGS trials, various post-hoc analyses have identified several smaller subgroups at high-risk in whom CABGS might improve clinical outcomes. However, there are conflicting findings in different reports and these findings are further compromised due to the heterogeneous groups of patients in these trials. Moreover, no prospective randomized controlled trial (RCT) has confirmed an advantage of CABGS, compared to medical treatment, in reduction of hard clinical outcomes in any of the high-risk subgroups. Based on the available data, it appears reasonable to conclude that for most patients (except perhaps in those with presence of left main disease > 50% stenosis) there is no apparent survival benefit of CABGS compared to medical therapy in stable CAD patients with angina. Although these trial have reported better symptom control associated with the revascularization intervention in most patients, this has not been adequately compared using modern medical therapies. Available data from recent studies also suggest treatment with an angiotensin converting enzyme inhibitor (ACEI), a statin and a regular exercise regimen in patients with stable CAD and angina pectoris., (Copyright (c) 2007 Wiley Periodicals, Inc.)

Rosuvastatin, which was approved by the FDA in 2003 and has been available in Europe since 2002, is the newest and most efficacious of the currently available 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins). More than 8 million patients have now been treated with rosuvastatin for up to 3 years, and initial concerns about the tolerability of this agent, prompted by the withdrawal of cerivastatin, have been answered. In fact, the lack of interactions of rosuvastatin with drugs metabolized by cytochrome P450 3A4 may provide a safety advantage not shared by other potent statins. Finally, rosuvastatin enables the majority of patients to achieve their cholesterol goals at initial doses, without the need for further dose titration and associated costs, and studies in both the USA and the UK have established its cost-effectiveness.

The metabolic syndrome or cardiovascular dysmetabolic syndrome is characterized by obesity, central obesity, insulin resistance, atherogenic dyslipidemia, and hypertension. The major risk factors leading to this syndrome are physical inactivity and an atherogenic diet and cornerstone clinical feature is abdominal obesity or adiposity. In addition, patients usually have elevated triglycerides, low HDL cholesterol, elevated LDL cholesterol, other abnormal lipid parameters, hypertension, and elevated fasting blood glucose. Impaired fibrinolysis, increased susceptibility to thrombotic events, and raised inflammatory markers are also observed. Given that India has the largest number of subjects with type-2 diabetes in the world it can be extrapolated that this country also has the largest number of patients with the metabolic syndrome. Epidemiological studies confirm a high prevalence. Therapeutic approach involves intervention at a macro-level and control of multiple risk factors using therapeutic lifestyle approaches (diet control and increased physical activity, pharmacotherapy - anti-obesity agents) for control of obesity and visceral obesity, and targeted approach for control of individual risk factors. Pharmacological therapy is a critical step in the management of patients with metabolic syndrome when lifestyle modifications fail to achieve the therapeutic goals. Anti-obesity drugs such as sibutramine and orlistat can be tried to reduce weight and central obesity and jointly control the metabolic syndrome components. Other than weight loss, there is no single best therapy and treatment should consist of treatment of individual components of the metabolic syndrome. Newer drugs such as the endocannabinoid receptor blocker,rimonabant, appear promising in this regard. Atherogenic dyslipidemia should be controlled initially with statins if there is an increase in LDL cholesterol. If there are other lipid abnormalities then combination therapy of statin with fibrates, nicotinic acid, or ezetimibe should be considered. For insulin resistance, drugs such as thiazolidinediones and renin-angiotensin system blockers are available. Available evidence suggests that angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBS) may be more beneficial for treatment of hypertension in patients with metabolic syndrome compared to others as these drugs also prevent development of diabetes. Patients with metabolic syndrome also have elevations in fibrinogen and other coagulation factors leading to prothrombotic state and aspirin may be beneficial for primary prevention in these patients. The new developments in the treatment of metabolic syndrome with drugs, such as peroxisome proliferator-activated receptor (PPAR) agonists and cannabinoid receptor-1 antagonists, will broaden the horizons of the current treatment options. Fixed-dose combination polypharmacy using a single pill is an interesting concept that needs to be evaluated in long-term prospective trials in such patients.

This was a post hoc analysis of data collected in the National Cholesterol Education Program (NCEP) Evaluation Project Utilizing Novel E-Technology II (NEPTUNE II) survey conducted in 2003. Among 4885 dyslipidemic patients receiving lipid management in the United States, estimates of the prevalence of the metabolic syndrome according to the 2001 NCEP Third Adult Treatment Panel (ATP III), the 2005 American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement, and the 2005 International Diabetes Federation definitions were 55%, 62%, and 63%, respectively. Metabolic syndrome prevalence among patients with coronary heart disease and risk equivalents was 69%, 74%, and 74%, according to these respective definitions. Notably, in the coronary heart disease and risk equivalents category, the prevalence was similar to that of the multiple risk factor category when patients with diabetes mellitus were excluded from the analysis (46% by ATP III). The metabolic syndrome is common in patients receiving lipid-lowering therapy in an office-based setting. Three recent definitions resulted in similar estimates of its prevalence.

Background: The MERIT-HF trial demonstrated improved survival and fewer hospitalizations for worsening heart failure with extended-release (ER) metoprolol succinate in patients with heart failure. This study sought to estimate the economic implications of this trial from a US perspective., Methods and Results: A discrete event simulation was developed to examine the course of patients with heart failure. Characteristics of the population modeled, probabilities of hospitalization and death with standard therapy, and risk reductions with ER metoprolol succinate were obtained from Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) and evaluated in weekly cycles. Direct medical costs were estimated from US databases in 2001 US dollars. Uncertainty in inputs was incorporated and analyses were carried out to estimate events prevented total and net costs. The model predicts that ER metoprolol succinate will prevent approximately 7 deaths and 15 hospitalizations from heart failure per 100 patients over 2 years. Compared with standard therapy alone, this translates to a cost reduction between $395 and $1112 per patient, depending on whether the costs of hospitalizations for other causes are included. Savings were maintained in 90% of the simulations., Conclusion: This analysis predicts that the positive effect of ER metoprolol succinate on mortality and morbidity demonstrated in MERIT-HF leads to substantial savings.

As the prevalence of diabetes continues to increase worldwide, diabetes-related macrovascular morbidity and mortality are becoming major health care problems. Epidemiologic evidence suggests this relationship begins early in the progression from normal glucose tolerance to frank diabetes. This report reviews this epidemiologic evidence linking early stages of glucose dysregulation with cardiovascular disease and discusses the results of major clinical trials demonstrating that lifestyle or pharmacologic intervention can reduce the incidence of diabetes in high-risk individuals. These observations indicate that early identification and aggressive treatment of subjects with impaired fasting glucose or impaired glucose tolerance have the potential to reduce both the incidence of diabetes and its related cardiovascular disease. Three clinical trials are being conducted to test whether early pharmacotherapy can reduce or delay the incidence of diabetes, and their results may well begin to shift the treatment paradigm toward earlier intervention.

The metabolic syndrome is defined as a condition characterized by a set of clinical criteria: insulin resistance, visceral obesity, atherogenic dyslipidemia, and hypertension. The major risk factors leading to the epidemic of this syndrome in the United States are visceral obesity, physical inactivity, and an atherogenic diet. The available current evidence suggests that the first step in management of patients with metabolic syndrome should be focused on lifestyle modifications (eg, weight loss and physical activity). The treatment should be based on two major components: behavioral change to reduce caloric intake and an increase in physical activity. A realistic goal for weight reduction should be 7% to 10% over 6 to 12 months. The general dietary recommendations include low intake of saturated fats, trans fats and cholesterol, and diets with low glycemic index. Soy protein could be more beneficial than animal protein in weight reduction and correction of dyslipidemia. Physical activity is associated with successful weight reduction and these therapeutic lifestyle changes can reduce by half the progression to new-onset diabetes in patients with metabolic syndrome. Physical activity recommendations should include practical, regular, and moderated regimens of exercise, with a daily minimum of 30 to 60 minutes. An equal balance between aerobic exercise and strength training is advised. Medication therapy is a critical step in the management of patients with metabolic syndrome when lifestyle modifications fail to achieve the therapeutic goals. There is no single best therapy and the treatment should consist of treatment of individual component(s). Atherogenic dyslipidemia should be controlled with statins if there is concomitant increase in low-density lipoprotein cholesterol and if indicated with combination therapy, including fibrates, nicotinic acid, bile acid-binding resins, or ezetimibe. Drugs such as thiazolidinediones and renin-angiotensin system blockers are a few of the available agents in this category. Some evidence suggests that angiotensin-converting enzyme inhibitors and b blockers are more beneficial for treatment of hypertension in patients with metabolic syndrome. Patients with metabolic syndrome also have elevations in fibrinogen and other coagulation factors leading to prothrombotic state and aspirin may be beneficial for primary prevention in these patients. The new developments in the treatment of metabolic syndrome with drugs, such as peroxisome proliferator-activated receptor agonists, will broaden the horizons of the current treatment options in metabolic syndrome.

The role of the RAAS in development and maintenance of blood pressure is well established. In addition, the deleterious effects of angiotensin II on the heart, vasculature, and kidneys have been clearly defined. There seems to be a close relationship between endothelial dysfunction, insulin resistance (a precursor to diabetes and coronary artery disease) and angiotensin II. The signaling pathways for insulin in the vascular wall interacts with the angiotensin signaling, giving rise to potential mechanisms for development of diabetes and resulting harmful effects. A large number of clinical trials using ACE inhibitors or ARBs have shown significant reduction in secondary endpoints in the development of new onset of diabetes. Ongoing prospective studies involving ARBs (eg, the Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research trial) and ACE inhibitors (eg, the Diabetes Re-duction Assessment with Ramipril and Rosiglita-zone Medication trial) are testing the ability of certain agents to prevent type 2 diabetes. In the meantime, it is important to recognize insulin resistance and metabolic syndrome as entities that increase the risk for cardiovascular disease. In addition to lifestyle modifications, managing endothelial dysfunction and protecting the vasculature will help prevent diabetes and cardiovascular disease.

Large, placebo-controlled RCTs that involve only diabetic patients who have hypertension have not been performed. Subgroup analyses of hyper-tension control from several recent RCTs un-equivocally demonstrated greater benefit in diabetic populations (see Table 3) with ACE inhibitors, TDs, and CCBs. Treatment with fBs(atenolol) also was beneficial in diabetic patients who had hypertension in the actively-controlled UKPDS. The results of three RCTs support intensive BP control in diabetic patients (see Table 4). In these trials, diabetic patients gained more benefit than nondiabetic patients. Such an effect is consistent with the fact that diabetics are at higher risk for CV events. Although there are limited data from RCTs with head-to-head comparison of newer agents (eg,ACE inhibitors, ARBs, CCBs) to show that these drugs are better than diuretics and betaBs in reducing CV events by treating hypertension in the diabetic population, the available data support ACE inhibitors (and ARBs if ACE inhibitors are not tolerated) as an initial drug of choice in diabetic,hypertensive patients (see Table 5). Most diabetic patients require three or four drugs to control their BP to target range; as such, it is not necessary to justify the choice of any single class of drug. Tight BP control is cost-effective and is more rewarding than hyperglycemic control in diabetic,hypertensive patients. The optimal goal in diabetics should be to achieve BP that is less than 130/80 mm Hg. Appropriate action should be taken if BP is greater than 140/85 mm Hg. In subjects who have diabetes and renal insufficiency,the BP should be decreased to less than 125/75 mm Hg to delay the progression of renal failure. Limited data suggest that an ACE inhibitor or an ARB is the agent of choice, especially in patients who have proteinuria or renal insufficiency. betaBs can be the first-line agent in diabetics who have CAD. TDs and CCBs are the second line drugs.AAAs should be avoided. Most hypertensive patients require more than one agent to adequately control their BP. There is no evidence to support one combination regimen over the others, nevertheless, the combination of an ACE inhibitor with a TD or a fPB may be more beneficial and cost effective than other combinations in the diabetic population. Large outcome studies that compare different combination therapies in hypertensive,diabetic patients are needed.

The metabolic syndrome (MS) is a constellation of coronary risk factors. Atherogenic dyslipidemia is an important factor in cardiovascular risk in these patients, and treatment of atherogenic dyslipidemia has been identified as an important goal of therapy in patients with MS. This post hoc analysis of data from a 6-week, randomized, open-label, parallel-group, comparative trial (Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin [STELLAR]) assessed the effects of rosuvastatin 10, 20, and 40 mg, atorvastatin 10, 20, 40, and 80 mg, simvastatin 10, 20, 40, and 80 mg, and pravastatin 10, 20, and 40 mg on plasma lipids in hypercholesterolemic patients (low-density lipoprotein cholesterol >/=160 and <250 mg/dl; triglycerides <400 mg/dl) who had >/=3 of the 5 National Cholesterol Education Program Adult Treatment Panel III criteria for MS (body mass index >30 kg/m(2) substituted for waist circumference). Of 2,268 patients, 811 met criteria for MS. Percent reductions in low-density lipoprotein cholesterol ranged from 20% in the pravastatin 10-mg group to 55% in the rosuvastatin 40-mg group. In patients with MS, triglyceride reductions were 22% to 34% with rosuvastatin, 23% to 33% with atorvastatin, 15% to 23% with simvastatin, and 12% to 15% with pravastatin. High-density lipoprotein cholesterol increased by 8% to 11% with rosuvastatin, 5% to 9% with atorvastatin, 8% to 10% with simvastatin, and 3% to 7% with pravastatin. Rosuvastatin, atorvastatin, simvastatin, and pravastatin treatment had favorable effects in hypercholesterolemic patients on the atherogenic dyslipidemia associated with MS. Rosuvastatin had the most favorable effect on the atherogenic lipid profile of MS overall.

Background: The objective of the current study was to examine the efficacy and tolerability of the beta-blocker metoprolol succinate controlled release/extended release (CR/XL) in patients with diabetes in the Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF)., Methods: The Cox proportional hazards model was used to calculate hazard ratios (HR) for convenience expressed as relative risks (risk reduction = 1-HR), and 95% confidence intervals (CI)., Results: The risk of hospitalization for heart failure was 76% higher in diabetics compared to non-diabetics (95% CI 38% to 123%). Metoprolol CR/XL was well tolerated and reduced the risk of hospitalization for heart failure by 37% in the diabetic group (95% CI 53% to 15%), and by 35% in the non-diabetic group (95% CI 48% to 19%). Pooling of mortality data from the Cardiac Insufficiency Bisoprolol Study II (CIBIS II), MERIT-HF, and the Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) showed similar survival benefits in patients with diabetes (25%; 95% CI 40% to 4%) and without diabetes (36%; 95% CI 44% to 27%); test of diabetes by treatment interaction was non-significant. Adverse events were reported more often on placebo than on metoprolol CR/XL., Conclusions: Patients with heart failure and diabetes have a much higher risk of hospitalization than patients without diabetes. Regardless of diabetic status, a highly significant reduction in hospitalizations for heart failure was observed with metoprolol CR/XL therapy, which was very well tolerated also by patients with diabetes. Furthermore, the pooled data showed a statistically significant survival benefit in patients with diabetes.

Background: The effects of beta-blockade with different extent of angiotensin-converting enzyme inhibitors (ACEI) and digitalization are unknown. To assess the effect of metoprolol succinate controlled release/extended release (CR/XL) combined with high versus low doses of ACEI and digitalis, we analyzed data from The Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) in which patients with heart failure and left ventricular ejection fraction < or =40% were randomized to metoprolol CR/XL versus placebo., Methods and Results: Outcome was analyzed separately for those on a low dose (< or =median) of the ACEI or digitalis versus high dose (> median). The mean dose of ACEI in the high-dose group (n = 1457) was 3 times higher than that in the low-dose group (n = 2094). Mortality was reduced to a similar extent in the high- and low-dose ACEI subgroups (RR = .69 versus .64, respectively). Corresponding figures for combined mortality/all hospitalization and for mortality/hospitalization for heart failure were .85 versus .83, and .70 versus .68, respectively. Likewise, reduction in total mortality with metoprolol CR/XL was similar in patients receiving no digitalis (n = 1447; RR = .56), low dose (n = 1122; RR = .71), or high dose (n = 1421; RR = .71)., Conclusion: This analysis of MERIT-HF demonstrates consistent and similar improvement in outcome of patients receiving metoprolol CR/XL when combined with either a high or low dose of an ACEI or digitalis, or no digitalis at all. Thus regardless of ACEI and digitalis dose and whether patients are treated with digitalis or not, it is very important to add a beta-blocker to the existing heart failure therapy. beta-blockers should not be withheld until target doses of ACEI have been achieved.

Background: Patients with stable CHD who experience episodes of ischemia during routine daily activities are at increased risk of coronary events. Older patients are at a particularly high risk. Few trials have specifically investigated the effects of lipid-lowering therapy with statins in older patients., Methods: The SAGE trial is a prospective, randomized, double-blind, parallel-arm study enrolling men and women with stable CHD at 192 centers worldwide. Qualifying participants (aged 65-85 years; low-density lipoprotein cholesterol 100-250 mg/dL) have had at least 1 episode of myocardial ischemia with total ischemia duration >or=3 minutes on 48-hour ambulatory electrocardiographic (AECG) monitoring performed during routine daily activities. Participants have been randomized to either atorvastatin 80 mg/day (aggressive lipid lowering) or pravastatin 40 mg/day (moderate lipid lowering). The primary efficacy measure is the absolute change in the total duration of myocardial ischemic events on 48-hour AECG monitoring from baseline to month 12., Results: SAGE is fully enrolled and 893 patients have been randomized. The majority of the study participants are white (97%) men (69%). The mean age of the participants is 72 years. Most participants (94%) have a history of angina. Other high-risk patient groups included in the study are patients with hypertension (65%), patients with diabetes (23%), and patients with peripheral vascular disease (12%)., Conclusions: SAGE will evaluate the effect of aggressive versus moderate lipid lowering on the total duration of myocardial ischemia in older ambulatory patients with CHD. It is likely to provide valuable data on the benefits of statins in this patient population.

As we enter the twenty-first century, the burden of chronic diseases, such as obesity, type 2 diabetes, and CVDs, is expected to increase dramatically. These diseases are a consequence of several factors that include an aging population,changes in demographic composition, and an excess of contemporary lifestyle. The prevention and control of overweight, obesity, metabolic syndrome, and diabetes pose special challenges for clinical and public heath practice as well as for basic, clinical, and population science research.

Diabetes is a vascular disease. Endothelial dysfunction is the initial process in vascular manifestations of diabetes mellitus (DM). There are multiple pathways involved in the pathophysiologic process related to endothelial dysfunction in DM. Most of these abnormalities occur secondary to insulin resistance. In this article the role of insulin, glucose,dyslipidemia, oxidative stress and various cellular mechanisms related to endothelial dys-function in diabetes are discussed in detail.

Objectives: To determine prevalence of the metabolic syndrome using United States Adult Treatment Panel-3 (ATP-3) guidelines in an urban Indian population., Methods: Randomly selected adults >20 years were studied using stratified sampling. Target study sample was 1800 with population proportionate distribution (men 960, women 840). Evaluation of anthropometric variables, blood pressure, fasting blood glucose and lipids was performed. Subjects (1123; response 62.4%) were examined, fasting blood samples were available in 1091 (532 men, 559 women) and analysed for prevalence of metabolic syndrome. Atherosclerosis risk factors were determined using the current guidelines. Metabolic syndrome was diagnosed when any three of the following were present: central obesity, raised triglycerides >/=150 mg/dl (>/=1.7 mmol/l), low high-density lipoprotein (HDL) cholesterol, blood pressure >/=130/>/=85 mm Hg, and diabetes or fasting glucose >110 mg/dl (>6.1 mmol/l). Intergroup comparisons were performed using t-test or chi-square test., Results: Metabolic syndrome was present in 345 (31.6%) subjects; prevalence was 122 (22.9%) in men and 223 (39.9%) in women (p<0.001); the age-adjusted prevalence was 24.9%, 18.4% in men and 30.9% in women. There was a significant age-related increase in its prevalence (Mantel-Haenzel chi(2) for trend p<0.05). Prevalence of components of metabolic syndrome in men and women was: central obesity (waist, men >102 cm, women >88 cm) in 116 (25.6%) and 246 (44.0%); low HDL cholesterol (men<40 mg/dl, <1.0 mmol/l), women<50 mg/dl, <1.3 mmol/l) in 292 (54.9%) and 504 (90.2%); high triglycerides >/=150 mg/dl (>/=1.7 mmol/l) in 172 (32.3%) and 160 (28.6%); and impaired fasting glucose or diabetes in 90 (16.9%) and 90 (16.1%). The prevalence of physical inactivity, hypertension, hypercholesterolemia (>/=200 mg/dl, >/=5.2 mmol/l) and high LDL cholesterol (>/=130 mg/dl, >/=3.4 mmol/l) was greater in the metabolic syndrome group in both men and women (p<0.05)., Conclusions: There is a high prevalence of metabolic syndrome in an urban Indian population. Focus of cardiovascular prevention should be at this high-risk group.