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Objective: To examine the association between income and cardiovascular disease (CVD) in community-dwelling older adults., Methods: Of the 5795 Medicare-eligible community-dwelling older Americans aged 65-100 years in the Cardiovascular Health Study (CHS), 4518 (78%) were free of baseline CVD, defined as heart failure, acute myocardial infarction, stroke, or peripheral arterial disease. Of them, 1846 (41%) had lower income, defined as a total annual household income <$16,000. Using propensity scores for lower income, estimated for each of the 4518 participants, we assembled a matched cohort of 1078 pairs balanced on 42 baseline characteristics. Outcomes included centrally adjudicated incident CVD and mortality., Results: Matched participants (n = 2156) had a mean age of 73 years, 63% were women, and 13% African American. During an overall follow-up of 23 years, incident CVD, all-cause mortality and the combined endpoint of incident CVD or mortality occurred in 1094 (51%), 1726 (80%) and 1867 (87%) individuals, respectively. Compared with the higher income group, hazard ratio (HR) for time to the first occurrence of incident CVD in the lower income group was 1.16 with a 95% confidence interval (CI) of 1.03 to 1.31. A lower income was also associated with a significantly higher risk of all-cause mortality (HR, 1.19; 95% CI, 1.08-1.30), and consequently a higher risk of the combined endpoint of incident CVD or death (HR, 1.20; 95% CI, 1.09-1.31)., Conclusion: Among community-dwelling older Americans free of baseline CVD, an annual household income <$16,000 is independently associated with significantly higher risks of new-onset CVD and death., (Copyright © 2021. Published by Elsevier Inc.)

Cardiovascular disease remains the leading cause of death in patients with diabetes. Cardiovascular disease in diabetes is multifactorial, and control of the cardiovascular risk factors leads to substantial reductions in cardiovascular events. The 2015 American Heart Association and American Diabetes Association scientific statement, "Update on Prevention of Cardiovascular Disease in Adults With Type 2 Diabetes Mellitus in Light of Recent Evidence," highlighted the importance of modifying various risk factors responsible for cardiovascular disease in diabetes. At the time, there was limited evidence to suggest that glucose-lowering medications reduce the risk of cardiovascular events. At present, several large randomized controlled trials with newer antihyperglycemic agents have been completed, demonstrating cardiovascular safety and reduction in cardiovascular outcomes, including cardiovascular death, myocardial infarction, stroke, and heart failure. This AHA scientific statement update focuses on (1) the evidence and clinical utility of newer antihyperglycemic agents in improving glycemic control and reducing cardiovascular events in diabetes; (2) the impact of blood pressure control on cardiovascular events in diabetes; and (3) the role of newer lipid-lowering therapies in comprehensive cardiovascular risk management in adults with diabetes. This scientific statement addresses the continued importance of lifestyle interventions, pharmacological therapy, and surgical interventions to curb the epidemic of obesity and metabolic syndrome, important precursors of prediabetes, diabetes, and comorbid cardiovascular disease. Last, this scientific statement explores the critical importance of the social determinants of health and health equity in the continuum of care in diabetes and cardiovascular disease.

Abstract: Cardiovascular disease (CVD) is a major cause of death and disability among people with type 2 diabetes (T2D), presenting a significant impact on longevity, patient quality of life, and health care costs. In the United States, attainment of recommended glycemic targets is low and T2D-related cardiovascular complications remain a significant burden. Many glucose-lowering treatment options are available, but glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are recommended in recent guidelines as the preferred add-on therapy to metformin to improve glycemic control. This is particularly the case for patients with T2D and established atherosclerotic CVD, at high risk of atherosclerotic CVD, and/or with chronic kidney disease. Recommendations were based on GLP-1RA and SGLT-2 inhibitor cardiovascular outcomes trials (CVOTs), which consistently showed that these agents pose no additional cardiovascular risk compared with placebo. Three GLP-1RAs (liraglutide, dulaglutide, and subcutaneous semaglutide) demonstrated significantly lower major adverse cardiovascular events versus placebo and are now approved for this indication. However, to realize improvement in outcomes in the clinical setting, organized, systematic, and coordinated approaches to patient management are also needed. For example, nurse-led diabetes self-management education and support programs have been shown to be effective. This article explores T2D management with emphasis on cardiovascular risk and CVOTs performed to date and reviews the clinical experience with GLP-1RAs for managing hyperglycemia and their impact on cardiovascular risk. In addition, practical guidance is given for key health care providers involved in the care of patients with T2D with cardiovascular risk outside of diabetes clinics/endocrinology centers., Competing Interests: Competing interests: P. C. Deedwania has acted as a consultant for Janssen and has received research grants for their institution from Boehringer Ingelheim, Novartis, and Sanofi. D. Hinnen has attended advisory boards and served on speakers' bureaus for Eli Lilly and Co., Janssen Pharmaceuticals, Novo Nordisk, and Sanofi. M. Magwire has attended advisory boards and acted as a consultant for Boehringer Ingelheim/Lilly and Novo Nordisk. The remaining authors report no conflicts of interest., (Copyright © 2022 American Association of Nurse Practitioners.)

Obesity and type 2 diabetes mellitus are highly prevalent and increasing in the United States among racial/ethnic minority groups. Type 2 diabetes mellitus, which is driven by many factors including elevated levels of adiposity, is an exemplar health disparities disease. Pervasive disparities exist at every level from risk factors through outcomes for U.S. racial/ethnic minority groups, including African American, Hispanic/LatinX American, and Asian American populations. Disparities in clinical care exist including hemoglobin A1c control, lower prescription rates of newer antihyperglycemic medications, along with greater rates of complications postbariatric surgery. Underpinning these disparities are the social determinants of health affecting provider-patient interactions, access to resources, and healthy built environments. We review the best practices to address cardiometabolic disparities in the current cardiovascular guidelines and describe recommendations for cross-cutting strategies to advance equity in obesity and type 2 diabetes across U.S. racial/ethnic groups., Competing Interests: Funding Support and Author Disclosures Dr Golden has been a member of the health equity advisory board for Midtronics, Inc; and has been a member of the health disparities advisory committee for Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Hyperuricemia and gout have been linked to an increased risk for cardiovascular (CV) disease, stroke, hypertension, heart failure, and chronic kidney disease, possibly through a proinflammatory milieu. However, not all the drugs used in gout treatment improve CV outcomes; colchicine has shown improved CV outcomes in patients with recent myocardial infarction and stable coronary artery disease independent of lipid-lowering effects. There is resurging interest in colchicine following publication of the COLCOT, LoDoCo, LoDoCo2, LoDoCo-MI trials, and COLCORONA trial which will shed light on its utility in COVID-19. Our aim is to review the CV use of colchicine beyond pericardial diseases, as well as CV outcomes of the available gout therapies, including allopurinol and febuxostat. The CARES trial and its surrounding controversies, which lead to the US FDA 'black box' warning on febuxostat, in addition to the recent FAST trial which contradicts this and finds febuxostat to be non-inferior, are discussed in this paper., (© 2020. Springer Nature Switzerland AG.)

Importance: The PCSK9 inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER randomized clinical trial. Patients with metabolic syndrome (MetS) are at increased cardiovascular risk., Objective: To investigate outcomes with evolocumab in patients with and without MetS., Design, Setting, and Participants: The FOURIER trial randomized patients worldwide with stable atherosclerotic cardiovascular disease receiving statin to evolocumab vs placebo with follow-up for a median of 2.2 years. Data were collected February 2013 to November 2016. For this prespecified analysis, patients with the requisite data were stratified based on the National Cholesterol Education Program Adult Treatment Panel III MetS criteria; in secondary analyses, patients were further substratified by diabetes at baseline. Analysis was intention to treat. Analysis began March 2018 and ended April 2020., Interventions: Patients were randomized to evolocumab or placebo., Main Outcomes and Measures: The primary end point was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary end point was cardiovascular death, myocardial infarction, or stroke., Results: Of 27 342 patients (mean [SD] age, 63 [9] years; 20 623 men [75.4%]) included in this analysis, 16 361 (59.8%) with baseline MetS were, when compared with patients without MetS, at higher risk of cardiovascular events (adjusted hazard ratio [95% CI], 1.31 [1.18-1.46]; P < .001 for the primary and 1.38 [1.20-1.57]; P < .001 for the key secondary end point). Evolocumab reduced low-density lipoprotein cholesterol similarly in patients with MetS (median [interquartile range], 92 [79-109] mg/dL vs 30 [19-48] mg/dL; P < .001) and without MetS (median [interquartile range], 92 [81-108] mg/dL vs 29 [18-44] mg/dl; P < .001). For the primary end point, the hazard ratios (95% CI) with evolocumab vs placebo were 0.83 (0.76-0.91) and 0.89 (0.79-1.01) in patients with and without MetS (P for interaction = .39). For the key secondary end point, the corresponding hazard ratios (95% CIs) were 0.76 (0.68-0.86) and 0.86 (0.74-1.01) (P for interaction = .23), respectively. Evolocumab did not increase the risk of new-onset diabetes or other major safety outcomes including worsening glycemic control, compared with placebo in patients with MetS., Conclusions and Relevance: Patients with atherosclerotic cardiovascular disease and MetS have substantial residual risk of cardiovascular events despite statin therapy. Evolocumab significantly reduced low-density lipoprotein cholesterol and cardiovascular risk in patients with MetS without increasing new-onset diabetes, worsening glycemic control, or other major safety events. These data suggest the addition of evolocumab to statin therapy in patients with atherosclerotic cardiovascular disease and MetS is safe and efficacious to reduce residual cardiovascular risk., Trial Registration: ClinicalTrials.gov Identifier: NCT01764633.

Implementation of prevention policies has often been impeded or delayed due to the lack of randomized controlled trials (RCTs) with hard clinical outcomes (eg, incident disease, mortality). Despite the prominent role of RCTs in health care, it may not always be feasible to conduct RCTs of public health interventions with hard outcomes due to logistical and ethical considerations. RCTs may also lack external validity and have limited generalizability. Currently, there is insufficient guidance for policymakers charged with establishing evidence-based policy to determine whether an RCT with hard outcomes is needed before policy recommendations. In this context, the purpose of this article is to assess, in a case study, the feasibility of conducting an RCT of the oft-cited issue of sodium reduction on cardiovascular outcomes and then propose a framework for decision-making, which includes an assessment of the feasibility of conducting an RCT with hard clinical outcomes when such trials are unavailable. We designed and assessed the feasibility of potential individual- and cluster-randomized trials of sodium reduction on cardiovascular outcomes. Based on our assumptions, a trial using any of the designs considered would require tens of thousands of participants and cost hundreds of millions of dollars, which is prohibitively expensive. Our estimates may be conservative given several key challenges, such as the unknown costs of sustaining a long-term difference in sodium intake, the effect of differential cotreatment with antihypertensive medications, and long lag time to clinical outcomes. Thus, it would be extraordinarily difficult to conduct such a trial, and despite the high costs, would still be at substantial risk for a spuriously null result. A robust framework, such as the one we developed, should be used to guide policymakers when establishing evidence-based public health interventions in the absence of trials with hard clinical outcomes.

Fatty acids derived from fish oil are long-chain omega-3 (n-3) polyunsaturated fatty acids. The important polyunsaturated fatty acids of fish oil are eicosapentaenoic acid, and docosahexaenoic acid. For decades, there has been a debate about the use of omega-3 fatty acids and their benefits on cardiovascular health. The more recent trials including the JELIS, VITAL, STRENGTH, and ASCEND trials, addressed the paucity of data of omega-3 fatty acids on primary and secondary prevention of cardiovascular events and the risk-benefit balance of these supplements. Prior to these studies, many large randomized controlled trials have shown conflicting results on the effect of polyunsaturated fatty acids in patients with prior coronary artery disease, stroke, or major vascular events. These inconsistent results warrant a better understanding of the effects of omega-3 fatty acids on the subtypes of cardiovascular diseases, and their use in primary and secondary prevention. More recently, icosapent ethyl showed a significant reduction in cardiovascular mortality and ischemic events in patients with elevated triglyceride (TG) and established cardiovascular disease or diabetes. The REDUCE-IT trial paved the way to further reduce cardiovascular risk in patients with high TG despite being on a maximally tolerated statin. The aim of this review is to discuss these recent updates on the use of various forms of fish oil, including prescription form and supplement in cardiometabolic diseases, and their surrounding controversies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Differences in lipid and cardiovascular risk profiles have been observed in African-American/black (AA/B), white (W), and Hispanic/Latino (H/L) individuals. Efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, may vary by race and ethnicity and has not been analyzed., Objective: This post hoc analysis evaluated alirocumab efficacy and safety vs control in 3 pooled ODYSSEY phase 3 trials (COMBO I, COMBO II, and LONG TERM) by race (AA/B [n = 154] vs W [n = 1982]) and ethnicity (H/L [n = 174] vs non-H/L [n = 3149])., Methods: Patients with elevated low-density lipoprotein cholesterol (LDL-C) despite maximally tolerated statin received alirocumab (75 mg up to 150 mg every 2 weeks [COMBO I & II] or 150 mg every 2 weeks [LONG TERM]) or control (placebo [COMBO I and LONG TERM] or ezetimibe [COMBO II])., Results: At baseline, LDL-C levels were similar across treatment groups; median lipoprotein(a) levels were higher in AA/B (33.0-120.0 mg/dL) vs W (7.1-66.3 mg/dL) and lower in H/L (5.0-38.3 mg/dL) vs non-H/L (7.7-69.0 mg/dL). At week 24, alirocumab significantly reduced LDL-C vs control. Alirocumab also reduced lipoprotein(a) compared with control across the subgroups. Treatment-emergent adverse events were similar between alirocumab (68.9-85.0%) and control (70.6-82.4%) regardless of race and ethnicity., Conclusion: Alirocumab significantly reduced LDL-C and Lp(a) levels compared with control, regardless of race and ethnicity, with overall safety comparable to control across most of the racial and ethnic groups analyzed., (Copyright © 2019 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Concerns of elevated cardiovascular disease (CVD) risk with some anti-diabetic medications warranted phase 4 clinical trials to demonstrate CVD safety of newly marketed anti-diabetic drugs. Although initially designed to evaluate safety, some of these CVD outcome trials (CVOTs) have in fact shown CVD benefits. New medication classes, like glucagon-like peptide 1 (GLP-1) analogues and sodium-glucose co-transporter 2 (SGLT2) inhibitors, have shown reductions in the risk of major adverse cardiovascular events (MACE) including, myocardial infarction, stroke, CV death, and heart failure (HF). Perhaps more importantly, SGLT2 inhibitors demonstrated reduction in the risk of HF hospitalizations, being the first class of anti-diabetic drugs to do so. Conversely, dipeptidyl peptidase 4 (DPP-4) inhibitors did not significantly affect atherosclerotic CVD end-points and some actually increased the risk of HF hospitalizations. Further, the adverse/beneficial CVD effects of these medications may not be class specific. This review focuses on the main results of these CVOTs while highlighting the heterogeneity of CVD end-points within each class and discusses important mechanistic insights and adverse effect profiles., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Diabetes mellitus is a major risk factor for cardiovascular (CV) disease. Conversely, CV disease is responsible for a majority of the deaths in patients with diabetes. Many drug trials have concentrated on blood glucose (hemoglobin A 1c ) reduction. This strategy, while reducing microvascular outcomes like nephropathy and neuropathy, has little or no effect on reducing macrovascular events like heart attack, stroke, and heart failure. It has been postulated that hypoglycemia may counterbalance some of the beneficial effects of anti-hyperglycemic agents, but this is not proven. Further, trial evidence for thiazolidinediones (rosiglitazone and pioglitazone) showed increased risk of heart failure and raised concerns about increased myocardial infarction. This heightened awareness of potentially harmful CV effects of otherwise effective hypoglycemic drugs resulted in regulatory mandates for CV outcome trials to ascertain the safety of newer anti-hypoglycemic agents appearing on the market. Three new classes of anti-hyperglycemic agents have been introduced in recent years. While dipeptidyl peptidase-4 (DPP-4) inhibitors exhibited increased heart failure hospitalization in the SAVOR-TIMI 53 trial evaluating saxagliptin and in the secondary analysis of the EXAMINE trial for alogliptin, the effects of glucagon-like peptide-1 (GLP-1) analogs and sodium-glucose co-transporter-2 (SGLT2) inhibitors on CV outcomes in diabetes have largely been positive. The LEADER and SUSTAIN-6 trials evaluating the safety and efficacy of the GLP-1 analogs liraglutide and semaglutide, respectively, showed a statistically significant reduction in the primary outcome (major adverse cardiac events [MACE]: CV death, myocardial infarction, and stroke) and the secondary combined outcome when compared to placebo. Results of the TECOS trial for sitagliptin were, however, neutral (no net CV benefit or harm), questioning the class effect of GLP-1 analogs. Results of the SGLT2 inhibitor trials were more uniform. While EMPA-REG (evaluating empagliflozin) and CANVAS (evaluating canagliflozin) showed a reduction in the MACE end point, dapagliflozin had a net neutral effect on MACE in DECLARE-TIMI 58. All three SGLT2 inhibitors, however, showed a significant reduction in heart failure hospitalizations. Although initially designed to keep potentially harmful anti-hyperglycemic agents off the market, the CV outcome trials have provided clinicians with a new set of anti-hyperglycemic drugs with proven CV benefit in patients with diabetes and CV disease, thus expanding the field of CV secondary prevention. There is a need to inculcate GLP-1 analogs and SGLT2 inhibitors that reduce major CV events and heart failure hospitalizations (alongside lifestyle management and metformin) in the treatment of patients with diabetes and CV disease.

Background: Rates of cardiometabolic-renal disease are extremely high among South Asians (India, Pakistan, Bangladesh, Sri Lanka, Bhutan, the Maldives, and Nepal) residing in their home countries and worldwide. The Cardio Renal Society of America, National Kidney Foundation of Arizona, and Twinepidemic Inc. convened a task force to examine evidence and reach consensus regarding cardiometabolic-renal disease prevention in South Asians. The task force distilled the findings from 5 years of face-to-face and virtual meetings addressing questions derived from expert reviews of published data using the Delphi technique to create these consensus statements., Summary: Several high-quality observational studies document the high and increasing incidence and prevalence of cardiometabolic-renal disease among South Asians, starting well before adulthood, owing to genetic, cultural, and environmental factors. Despite the need for additional prospective studies, especially randomized trials, of educational, screening, and other prevention efforts, sufficient information is already available to expand and intensify ongoing efforts in professional and lay education to help control this epidemic. The task force proposes to provide this expansion over the next 10 years through scientific and lay publications and other educational programs to promote more effective action among the public, health care professionals, payers, and regulators in screening for and treating cardiometabolic-renal risk factors and preventing disease in South Asians, starting at an early age. Key Messages: These consensus statements describe risk factors and prognoses characteristic of South Asians regarding cardiometabolic-renal diseases, to aid physician decision-making, health care system delivery, and research initiatives to improve the quality of care for South Asians worldwide., (© 2019 S. Karger AG, Basel.)

Objectives: We evaluated trends in hypertension prevalence, awareness, treatment and control in an Indian urban population over 25 years. Trends were projected to year 2030 to determine attainment of World Health Organization (WHO) Global Monitoring Framework targets., Methods: Adult participants (n=7440, men 4237, women 3203) enrolled in successive population based studies in Jaipur, India from years 1991 to 2015 were evaluated for hypertension prevalence, awareness, treatment and control. The studies were performed in years 1991-93 (n=2212), 1999-01 (n=1123), 2003-04 (n=458), 2006-07 (n=1127), 2009-10 (n=739) and 2012-15 (n=1781). Descriptive statistics are reported. We used logarithmic forecasting to year 2030 and compared outcomes to WHO target of 25% lower prevalence and >50% control., Results: The age-adjusted hypertension prevalence (%) among adults in successive studies increased from 29.5, 30.2, 36.5, 42.1, 34.4 to 36.1 (R 2 =0.41). Increasing trends were observed for hypertension awareness (13, 44, 49, 44, 49, 56; R 2 =0.63); treatment in all (9, 22, 38, 34, 41, 36; R 2 =0.68) and aware hypertensives (61, 66, 77, 79, 70, 64; R 2 =0.46); and control in all (2, 14, 13, 18, 21, 21; R 2 =0.82), aware (12, 33, 27, 46, 37, 37; R 2 =0.54) and treated (9, 20, 21, 48, 36, 49; R 2 =0.80) hypertensive participants. Projections to year 2030 show increases in prevalence to 44% (95% CI 43-45), awareness to 82% (81-83), treatment to 62% (61-63), and control to 36% (35-37)., Conclusion: Hypertension prevalence, awareness, treatment and control rates are increasing among urban populations in India. Better awareness is associated with greater control. The rates of increase are off-target for WHO Global Monitoring Framework and UN Sustainable Development Goals., (Copyright © 2017. Published by Elsevier B.V.)

Background: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab reduced LDL cholesterol and cardiovascular events in the FOURIER trial. In this prespecified analysis of FOURIER, we investigated the efficacy and safety of evolocumab by diabetes status and the effect of evolocumab on glycaemia and risk of developing diabetes., Methods: FOURIER was a randomised trial of evolocumab (140 mg every 2 weeks or 420 mg once per month) versus placebo in 27 564 patients with atherosclerotic disease who were on statin therapy, followed up for a median of 2·2 years. In this prespecified analysis, we investigated the effect of evolocumab on cardiovascular events by diabetes status at baseline, defined on the basis of patient history, clinical events committee review of medical records, or baseline HbA 1c of 6·5% (48 mmol/mol) or greater or fasting plasma glucose (FPG) of 7·0 mmol/L or greater. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, hospital admission for unstable angina, or coronary revascularisation. The key secondary endpoint was a composite of cardiovascular death, myocardial infarction, or stroke. We also assessed the effect of evolocumab on glycaemia, and on the risk of new-onset diabetes among patients without diabetes at baseline. HbA 1c was measured at baseline then every 24 weeks and FPG was measured at baseline, week 12, week 24, and every 24 weeks thereafter, and potential cases of new-onset diabetes were adjudicated centrally. In a post-hoc analysis, we also investigated the effects on glycaemia and diabetes risk in patients with prediabetes (HbA 1c 5·7-6·4% [39-46 mmol/mol] or FPG 5·6-6·9 mmol/L) at baseline. FOURIER is registered with ClinicalTrials.gov, number NCT01764633., Findings: At study baseline, 11 031 patients (40%) had diabetes and 16 533 (60%) did not have diabetes (of whom 10 344 had prediabetes and 6189 had normoglycaemia). Evolocumab significantly reduced cardiovascular outcomes consistently in patients with and without diabetes at baseline. For the primary composite endpoint, the hazard ratios (HRs) were 0·83 (95% CI 0·75-0·93; p=0·0008) for patients with diabetes and 0·87 (0·79-0·96; p=0·0052) for patients without diabetes (p interaction =0·60). For the key secondary endpoint, the HRs were 0·82 (0·72-0·93; p=0·0021) for those with diabetes and 0·78 (0·69-0·89; p=0·0002) for those without diabetes (p interaction =0·65). Evolocumab did not increase the risk of new-onset diabetes in patients without diabetes at baseline (HR 1·05, 0·94-1·17), including in those with prediabetes (HR 1·00, 0·89-1·13). Levels of HbA 1c and FPG were similar between the evolocumab and placebo groups over time in patients with diabetes, prediabetes, or normoglycaemia. Among patients with diabetes at baseline, the proportions of patients with adverse events were 78·5% (4327 of 5513 patients) in the evolocumab group and 78·3% (4307 of 5502 patients) in the placebo group; among patients without diabetes at baseline, the proportions with adverse events were 76·8% (6337 of 8256 patients) in the evolocumab group and 76·8% (6337 of 8254 patients) in the placebo group., Interpretation: PCSK9 inhibition with evolocumab significantly reduced cardiovascular risk in patients with and without diabetes. Evolocumab did not increase the risk of new-onset diabetes, nor did it worsen glycaemia. These data suggest evolocumab use in patients with atherosclerotic disease is efficacious and safe in patients with and without diabetes., Funding: Amgen., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Coronary heart disease risk factors are widely prevalent among urban subjects in India but the prevalence of good cardiovascular health is unknown., Objectives: This multisite study sought to determine the prevalence of American Heart Association-defined ideal cardiovascular health factors., Methods: The study was performed in 11 cities using cluster sampling. Middle-class urban subjects ages 20 to 75 years (N = 6,198; men: 3,426; women: 2,772, response: 62%) were evaluated for socioeconomic, biophysical, and biochemical factors. Prevalence of ideal cardiovascular health using 7-factor American Heart Association metric (nonsmoking, moderate or greater physical activity, low-fat, high-fruit/vegetable diet, body mass index <25 kg/m 2 , untreated blood pressure <120/<80 mm Hg, cholesterol <200 mg/dl, and fasting glucose <100 mg/dl) was determined. Descriptive statistics are reported., Results: Age-adjusted prevalences of ideal health factors in men and women, respectively, were non-tobacco use in 72.0% and 89.6%, moderate physical activity in 20.1% and 20.6%, healthy diet in 10.6% and 10.6%, normal body mass index in 57.7% and 52.8%, normotension in 17.1% and 22.4%, normocholesterolemia in 72.4% and 72.7%, and normoglycemia in 57.4% and 59.5%. Prevalence of all the 7 health factors was in <1.0% in both men and women, any 6 in 3.4% and 3.5%, any 5 in 12.7% and 17.8%, any 4 in 36.9% and 44.7%, any 3 in 67.2% and 70.8%, any 2 in 89.1% and 92.4%, and 1 in 98.2% and 99.1%. Cardiovascular health was poor (1 to 3 factors) in 62.4% of men and 54.9% of women, average (4 to 5 factors) in 34.1% and 41.5%, and good (≥6 factors) in 3.5% and 3.6%. With increasing age, the behavioral health factors (tobacco use, physical activity, healthy diet) did not change, whereas others declined (p trend < 0.01). Clustering of average and good health factors also declined with age (p trend < 0.01). There were no socioeconomic status-related differences in prevalence of good cardiovascular health., Conclusions: Good cardiovascular health factors-physical activity, healthy diet, and desirable body mass index, blood pressure, and glucose levels-are low in urban Asian Indians., (Copyright © 2015 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.)

Background: Traditional cardiovascular risk factors, such as hypertension and dyslipidemia, predispose individuals to cardiovascular disease, particularly patients with diabetes. We investigated the predictive value of baseline systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) on the risk of vascular outcomes in a large population of patients at high risk of future cardiovascular events., Methods: Data were pooled from the TNT (Treating to New Targets), CARDS (Collaborative Atorvastatin Diabetes Study), and IDEAL (Incremental Decrease in End-Points Through Aggressive Lipid Lowering) trials and included a total of 21,727 patients (TNT: 10,001; CARDS: 2838; IDEAL: 8888). The effect of baseline SBP and LDL-C on cardiovascular events, coronary events, and stroke was evaluated using a multivariate Cox proportional-hazards model., Results: Overall, risk of cardiovascular events was significantly higher for patients with higher baseline SBP or LDL-C. Higher baseline SBP was significantly predictive of stroke but not coronary events. Conversely, higher baseline LDL-C was significantly predictive of coronary events but not stroke. Results from the subgroup with diabetes (5408 patients; TNT: 1501; CARDS: 2838; IDEAL: 1069) were broadly consistent with those of the total cohort: baseline SBP and LDL-C were significantly predictive of cardiovascular events overall, with the association to LDL-C predominantly related to an effect on coronary events. However, baseline SBP was not predictive of either coronary or stroke events in the pooled diabetic population., Conclusions: In this cohort of high-risk patients, baseline SBP and LDL-C were significantly predictive of cardiovascular outcomes, but this effect may differ between the cerebrovascular and coronary systems., Trial Registration Number: NCT00327691 (TNT); NCT00327418 (CARDS); NCT00159835 (IDEAL)., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Cardiovascular morbidity and mortality as a result of inhaled tobacco products continues to be a global healthcare crisis, particularly in low- and middle-income nations lacking the infrastructure to develop and implement effective public health policies limiting tobacco use. Following initiation of public awareness campaigns 50 years ago in the United States, considerable success has been achieved in reducing the prevalence of cigarette smoking and exposure to secondhand smoke. However, there has been a slowing of cessation rates in the United States during recent years, possibly caused by high residual addiction or fatigue from cessation messaging. Furthermore, tobacco products have continued to evolve faster than the scientific understanding of their biological effects. This review considers selected updates on the genetics and epigenetics of smoking behavior and associated cardiovascular risk, mechanisms of atherogenesis and thrombosis, clinical effects of smoking and benefits of cessation, and potential impact of electronic cigarettes on cardiovascular health., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease risk factor control as primary prevention in patients with type 2 diabetes mellitus has changed substantially in the past few years. The purpose of this scientific statement is to review the current literature and key clinical trials pertaining to blood pressure and blood glucose control, cholesterol management, aspirin therapy, and lifestyle modification. We present a synthesis of the recent literature, new guidelines, and clinical targets, including screening for kidney and subclinical cardiovascular disease for the contemporary management of patients with type 2 diabetes mellitus., (© 2015 by the American Diabetes Association and the American Heart Association, Inc.)

Resting heart rate is central to cardiac output and is influenced by changes occurring in numerous diseases. It predicts longevity and cardiovascular diseases, and current evidence suggests that it is also an important marker of outcome in cardiovascular disease, including heart failure. Beta-blockers improve outcomes in heart failure; however, they have effects outside reducing heart rate. Ivabradine has demonstrated efficacy in reducing rehospitalizations and mortality in heart failure and in improving exercise tolerance and reducing angina attacks in patients with coronary artery disease, whereas selective heart rate reduction may also prove to be beneficial in therapeutic areas outside those in which ivabradine has already demonstrated clinical efficacy. This review provides an update on the associations between heart rate and cardiovascular outcomes in various conditions, the experimental effects of heart rate reduction with ivabradine, and the potential new indications in cardiovascular disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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.

We used baseline data from the NAVIGATOR trial to (1) identify risk factors for diabetes progression in those with impaired glucose tolerance and high cardiovascular risk, (2) create models predicting 5-year incident diabetes, and (3) provide risk classification tools to guide clinical interventions. Multivariate Cox proportional hazards models estimated 5-year incident diabetes risk and simplified models examined the relative importance of measures of glycemia in assessing diabetes risk. The C-statistic was used to compare models; reclassification analyses compare the models' ability to identify risk groups defined by potential therapies (routine or intensive lifestyle advice or pharmacologic therapy). Diabetes developed in 3,254 (35%) participants over 5 years median follow-up. The full prediction model included fasting and 2-hour glucose and hemoglobin A1c (HbA1c) values but demonstrated only moderate discrimination for diabetes (C = 0.70). Simplified models with only fasting glucose (C = 0.67) or oral glucose tolerance test values (C = 0.68) had higher C statistics than models with HbA1c alone (C = 0.63). The models were unlikely to inappropriately reclassify participants to risk groups that might receive pharmacologic therapy. Our results confirm that in a population with dysglycemia and high cardiovascular risk, traditional risk factors are appropriate predictors and glucose values are better predictors than HbA1c, but discrimination is moderate at best, illustrating the challenges of predicting diabetes in a high-risk population. In conclusion, our novel risk classification paradigm based on potential treatment could be used to guide clinical practice based on cost and availability of screening tests., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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.

Context: β-Blockers remain the standard of care after a myocardial infarction (MI). However, the benefit of β-blocker use in patients with coronary artery disease (CAD) but no history of MI, those with a remote history of MI, and those with only risk factors for CAD is unclear., Objective: To assess the association of β-blocker use with cardiovascular events in stable patients with a prior history of MI, in those with CAD but no history of MI, and in those with only risk factors for CAD., Design, Setting, and Patients: Longitudinal, observational study of patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry who were divided into 3 cohorts: known prior MI (n = 14,043), known CAD without MI (n = 12,012), or those with CAD risk factors only (n = 18,653). Propensity score matching was used for the primary analyses. The last follow-up data collection was April 2009., Main Outcome Measures: The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure., Results: Among the 44,708 patients, 21,860 were included in the propensity score-matched analysis. With a median follow-up of 44 months (interquartile range, 35-45 months), event rates were not significantly different in patients with β-blocker use compared with those without β-blocker use for any of the outcomes tested, even in the prior MI cohort (489 [16.93%] vs 532 [18.60%], respectively; hazard ratio [HR], 0.90 [95% CI, 0.79-1.03]; P = .14). In the CAD without MI cohort, the associated event rates were not significantly different in those with β-blocker use for the primary outcome (391 [12.94%]) vs without β-blocker use (405 [13.55%]) (HR, 0.92 [95% CI, 0.79-1.08]; P = .31), with higher rates for the secondary outcome (1101 [30.59%] vs 1002 [27.84%]; odds ratio [OR], 1.14 [95% CI, 1.03-1.27]; P = .01) and for the tertiary outcome of hospitalization (870 [24.17%] vs 773 [21.48%]; OR, 1.17 [95% CI, 1.04-1.30]; P = .01). In the cohort with CAD risk factors only, the event rates were higher for the primary outcome with β-blocker use (467 [14.22%]) vs without β-blocker use (403 [12.11%]) (HR, 1.18 [95% CI, 1.02-1.36]; P = .02), for the secondary outcome (870 [22.01%] vs 797 [20.17%]; OR, 1.12 [95% CI, 1.00-1.24]; P = .04) but not for the tertiary outcomes of MI (89 [2.82%] vs 68 [2.00%]; HR, 1.36 [95% CI, 0.97-1.90]; P = .08) and stroke (210 [6.55%] vs 168 [5.12%]; HR, 1.22 [95% CI, 0.99-1.52]; P = .06). However, in those with recent MI (≤1 year), β-blocker use was associated with a lower incidence of the secondary outcome (OR, 0.77 [95% CI, 0.64-0.92])., Conclusion: In this observational study of patients with either CAD risk factors only, known prior MI, or known CAD without MI, the use of β-blockers was not associated with a lower risk of composite cardiovascular events.

Background: Carriers of the KIF6 719Arg variant may be at increased risk for CVD and may benefit more from statin therapy, in terms of CVD risk reduction, than noncarriers. Our objective was to investigate whether carriers of the KIF6 719Arg genetic variant (rs20455) are at increased cardiovascular risk and obtain more benefit from high-dose statin therapy than do noncarriers., Methods and Results: We used an adjusted Cox proportional hazard model to assess the hazard ratio (HR) for the reduction of major cardiovascular events by 80 mg/d atorvastatin over 10 mg/d atorvastatin in 4599 patients of the Treating to New Targets (TNT) study and by 80 mg/d atorvastatin over 20-40 mg/d simvastatin in 6541 patients of the Incremental Decrease in End Points Through Aggressive Lipid-Lowering (IDEAL) study. A total of 381 and 648 patients had a cardiovascular event during follow-up in TNT and IDEAL, respectively. Heterozygotes and homozygotes for the minor allele were not at increased risk compared with noncarriers. In TNT, for noncarriers of the 719Arg allele, the HR for high- versus low-dose atorvastatin was 0.81 (95% confidence interval, 0.59-1.11). In carriers of 1 or 2 minor alleles, the HR was 0.85 (0.66-1.11) and carriers of 2 copies of the minor allele obtained a significant risk reduction (HR: 0.44, 95% confidence interval, 0.23-0.84). In IDEAL, the respective HRs were 0.85 (0.67-1.10), 0.88 (0.62-1.07) and 0.91 (0.58-1.43). The interaction term for carrier status by treatment was also nonsignificant (P=0.810 in TNT and P=0.909 in IDEAL)., Conclusions: In these 2 large, randomized clinical trials, carriers of the KIF6 719Arg allele were not at increased cardiovascular risk and did not obtain consistent cardiovascular benefit from high-dose statin therapy compared with noncarriers.

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.

The renin-angiotensin-aldosterone system (RAAS) plays a significant role in pathophysiology of multiple disease states. RAAS blockade is beneficial in patients with hypertension, acute myocardial infarction, chronic heart failure, stroke, and diabetic renal disease. RAAS blockade with the combination angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) has demonstrated conflicting results in recent clinical trials. This article reviews the latest evidence of isolated ACEI or ARB use, their combination, and the role of aldosterone blockers and direct renin inhibitors in patients at risk, and makes recommendations for their use in the prevention of morbidity and mortality in cardiovascular disease., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Cardiovascular disease prevention is a continuum that encompasses the life-course. This article discusses preventive strategies focusing on policy and clinical initiatives including primordial prevention (lifestyle changes involving smoking, diet and exercise), primary prevention (risk factor control), and secondary prevention (acute and chronic disease management). Combined use of all the three strategies can have an immediate and large impact on reducing CVD morbidity and mortality., (Copyright © 2011. Published by Elsevier Inc.)

The majority of individuals with diabetes die from cardiovascular disease (CVD) and related complications. The risk of CVD is 2 to 4 fold greater in diabetes and largely magnified by co-morbidities that aggregate along with it. Sufficient evidence-based data now exist to support multifactorial risk intervention with specific targets for goal-directed therapy for both primary and secondary prevention. These interventions have shown survival benefit in addition to prevention of vascular complications. Prevention of diabetes and delaying its onset should also be an important aspect in future health care strategy and research to confront the oncoming tsunami of CVD related to diabetes., (Published by Elsevier Inc.)

Cardiovascular disease (CVD) still ranks as the top cause of mortality worldwide. Lipid-modifying therapy has revolutionized the treatment of the disease and is partly responsible for the recent decline in deaths due to CVD. Treatment strategies have evolved since the introduction of the earlier lipid-lowering agents (fibrates, niacin, bile acid resins) to the advent of statins, which have become the standard drugs in cholesterol therapy. The strategy of using high-intensity statin therapy as the initial treatment approach in high-risk individuals, rather than focusing on specific cholesterol levels alone, remains a subject of debate., (Published by Elsevier Inc.)

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.

Cardiovascular disease (CVD) remains the top cause of global mortality. There is considerable evidence that supports the mortality and morbidity benefit of statin therapy in coronary heart disease (CHD) and stroke, both in primary and secondary prevention settings. Data also exist pointing to the advantage of statin treatment in other high-risk CVD conditions, such as diabetes, CKD, CHF, and PVD. National and international clinical guidelines in the management of these CVD conditions all advocate for the utilization of statin therapy in appropriate patients. However, overall compliance to statin therapy remains suboptimal. Patient-, physician-, and economic-related factors all play a role. These factors need to be considered in devising approaches to enhance adherence to guideline-based therapies. To fully reap the benefits of statin therapy, interventions which improve long-term treatment compliance in real-world settings should be encouraged.

Background: It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance., Methods: In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization., Results: The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P=0.85)., Conclusions: Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.), (2010 Massachusetts Medical Society)

Background: The ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown., Methods: In a double-blind, randomized clinical trial, we assigned 9306 participants with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors to receive nateglinide (up to 60 mg three times daily) or placebo, in a 2-by-2 factorial design with valsartan or placebo, in addition to participation in a lifestyle modification program. We followed the participants for a median of 5.0 years for incident diabetes (and a median of 6.5 years for vital status). We evaluated the effect of nateglinide on the occurrence of three coprimary outcomes: the development of diabetes; a core cardiovascular outcome that was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; and an extended cardiovascular outcome that was a composite of the individual components of the core composite cardiovascular outcome, hospitalization for unstable angina, or arterial revascularization., Results: After adjustment for multiple testing, nateglinide, as compared with placebo, did not significantly reduce the cumulative incidence of diabetes (36% and 34%, respectively; hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15; P=0.05), the core composite cardiovascular outcome (7.9% and 8.3%, respectively; hazard ratio, 0.94, 95% CI, 0.82 to 1.09; P=0.43), or the extended composite cardiovascular outcome (14.2% and 15.2%, respectively; hazard ratio, 0.93, 95% CI, 0.83 to 1.03; P=0.16). Nateglinide did, however, increase the risk of hypoglycemia., Conclusions: Among persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes. (ClinicalTrials.gov number, NCT00097786.), (2010 Massachusetts Medical Society)

It is well established that low high-density lipoprotein (HDL) cholesterol is a risk factor for coronary artery disease (CAD). Growing evidence from epidemiologic as well as intervention studies have identified that a low level of HDL cholesterol contributes to cardiovascular disease risk. In addition, a number of clinical trials have substantiated that an inverse association between HDL cholesterol concentrations and cardiovascular risk exists. Decreasing low-density lipoprotein cholesterol levels with statins has a major impact on cardiovascular risk reduction, and statin therapy plays a significant role in the management of CAD. However, low levels of HDL cholesterol remain as a cardiovascular risk factor despite statin therapy. This article presents an overview of statin clinical trials and discusses implications for the clinical management of patients with low HDL cholesterol levels and increased cardiovascular risk.

Cardiometabolic risk factors affect more than 47 million adults in the United States today. Although certain risk factors (e.g., obesity, dyslipidemia, hypertension, and hyperglycemia) contribute independently to the global risk, dyslipidemia is one of the most important risk factors for cardiovascular disease. Successful treatment requires a well-coordinated multifaceted approach, with commitment to a long-term program for disease management. Although initial attempts should focus on dietary changes and increased physical activity, most patients also need effective, safe, and well-monitored pharmacotherapy. Experimental studies have shown that overactivation of the endocannabinoid system-a physiologic signaling system involved in regulating energy intake, fatty acid synthesis and storage, and glucose and lipid metabolism-is associated with obesity, dyslipidemia, and insulin resistance. In clinical trials, selective blockade of CB1 receptors has resulted in substantial weight loss and significant improvement in lipid profiles. The effects of rimonabant, the first selective CB1 receptor blocker, were evaluated in 6600 obese or overweight adults who participated in one of 4 multicenter, placebo-controlled, randomized clinical trials for at least 1 year. Significant improvement in lipid profiles (specifically HDL and triglyceride levels and ratio of total cholesterol to HDL cholesterol) was seen in the 2503 patients taking rimonabant 20 mg/day, independent of its substantial effects on weight loss. No significant changes in LDL or total cholesterol were observed. Results of clinical trials with rimonabant are promising. Additional long-term controlled studies with appropriate follow-up are warranted to confirm the clinical potential of this drug, particularly its effects on dyslipidemia and other cardiovascular endpoints.

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.

Objective: To investigate the effect of intensive lipid lowering with high-dose atorvastatin on the incidence of major cardiovascular events compared with low-dose atorvastatin in patients with coronary artery disease and type 2 diabetes, with and without chronic kidney disease (CKD)., Patients and Methods: Following 8 weeks' open-label therapy with atorvastatin (10 mg/d), 10,001 patients with coronary artery disease were randomized to receive double-blind therapy with either 80 mg/d or 10 mg/d of atorvastatin between July 1, 1998, and December 31, 1999. Of 1501 patients with diabetes, renal data were available for 1431. Patients with CKD were defined as having a baseline estimated glomerular filtration rate (eGFR) below 60 mL/min per 1.73 m2, using the Modification of Diet in Renal Disease equation., Results: After a median follow-up of 4.8 years, 95 (17.4%) of 546 patients with diabetes and CKD experienced a major cardiovascular event vs 119 (13.4%) of 885 patients with diabetes and normal eGFRs (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.00-1.72; P<.05). Compared with 10 mg of atorvastatin, 80 mg of atorvastatin reduced the relative risk of major cardiovascular events by 35% in patients with diabetes and CKD (20.9% [57/273] vs 13.9% [38/273]; HR, 0.65; 95% CI, 0.43-0.98; P=.04) and by 10% in patients with diabetes and normal eGFR (14.1% [62/441] vs 12.8% [57/444]; HR, 0.90; 95% CI, 0.63-1.29; P=.56). The absolute risk reduction in patients with diabetes and CKD was substantial, yielding a number needed to treat of 14 to prevent 1 major cardiovascular event over 4.8 years. Both treatments were well tolerated., Conclusion: Patients with diabetes, stable coronary artery disease, and mild to moderate CKD experience marked reduction in cardiovascular events with intensive lipid lowering, in contrast to previous observations in patients with diabetes and end-stage renal disease., Trial Registration: clinicaltrials.gov identifier: NCT00327691.

Type 2 diabetes has reached epidemic proportions and is now recognized as a coronary heart disease equivalent. While the most common metabolic abnormality associated with diabetes is hyperglycemia, there are also abnormalities in carbohydrate, fat and protein metabolism. These abnormalities increase oxidative stress and activate the renin-angiotensin system leading to endothelial dysfunction and, thereafter, to systemic atherosclerosis. This systemic atherosclerosis is responsible for the increased cardiovascular morbidity and mortality related to diabetes. In this article, we review the evidence and discuss the rationale for comprehensive risk reduction to prevent and treat vascular disease in individuals with diabetes mellitus. The components of comprehensive risk reduction strategy consist of lifestyle changes, glycemic control, control of dyslipidemia and hypertension.