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      Benefits & risks of statin therapy for primary prevention of cardiovascular disease in Asian Indians – A population with the highest risk of premature coronary artery disease & diabetes

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          Abstract

          Several reviews and meta-analyses have demonstrated the incontrovertible benefits of statin therapy in patients with cardiovascular disease (CVD). But the role for statins in primary prevention remained unclear. The updated 2013 Cochrane review has put to rest all lingering doubts about the overwhelming benefits of long-term statin therapy in primary prevention by conclusively demonstrating highly significant reductions in all-cause mortality, major adverse cardiovascular events (MACE) and the need for coronary artery revascularization procedures (CARPs). More importantly, these benefits of statin therapy are similar at all levels of CVD risk, including subjects at low (<1% per year) risk of a MACE. In addition to preventing myocardial infarction (MI), stroke, and death, primary prevention with statins is also highly effective in delaying and avoiding expensive CARPs such as angioplasties, stents, and bypass surgeries. There is no evidence of any serious harm or threat to life caused by statin therapy, though several adverse effects that affect the quality of life, especially diabetes mellitus (DM) have been reported. Asian Indians have the highest risk of premature coronary artery disease (CAD) and diabetes. When compared with Whites, Asian Indians have double the risk of CAD and triple the risk of DM, when adjusted for traditional risk factors for these diseases. Available evidence supports the use of statin therapy for primary prevention in Asian Indians at a younger age and with lower targets for low-density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein (non-HDL-C), than those currently recommended for Americans and Europeans. Early and aggressive statin therapy offers the greatest potential for reducing the continuing epidemic of CAD among Indians.

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          Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus.

          In persons with diabetes, chronic hyperglycemia (assessed by glycosylated hemoglobin level) is related to the development of microvascular disease; however, the relation of glycosylated hemoglobin to macrovascular disease is less clear. To conduct a meta-analysis of observational studies of the association between glycosylated hemoglobin and cardiovascular disease in diabetic persons. Search of the MEDLINE database by using Medical Subject Heading search terms and key words related to glycosylated hemoglobin, diabetes, and cardiovascular disease. Prospective cohort studies with data on glycosylated hemoglobin levels and incident cardiovascular disease. Relative risk estimates were derived or abstracted from each cohort study that met the inclusion criteria. Adjusted relative risk estimates for glycosylated hemoglobin (total glycosylated hemoglobin, hemoglobin A1, or hemoglobin A1c levels) and cardiovascular disease events (coronary heart disease and stroke) were pooled by using random-effects models. Three studies involved persons with type 1 diabetes (n = 1688), and 10 studies involved persons with type 2 diabetes (n = 7435). The pooled relative risk for cardiovascular disease was 1.18; this represented a 1-percentage point increase in glycosylated hemoglobin level (95% CI, 1.10 to 1.26) in persons with type 2 diabetes. Results in persons with type 1 diabetes were similar but had a wider CI (pooled relative risk, 1.15 [CI, 0.92 to 1.43]). This review largely reflects the limitations of the literature. Important concerns were residual confounding, the possibility of publication bias, the small number of studies, and the heterogeneity of study results. Pending confirmation from large, ongoing clinical trials, this analysis shows that observational studies are consistent with limited clinical trial data and suggests that chronic hyperglycemia is associated with an increased risk for cardiovascular disease in persons with diabetes.
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            Risk factors for early myocardial infarction in South Asians compared with individuals in other countries.

            South Asians have high rates of acute myocardial infarction (AMI) at younger ages compared with individuals from other countries but the reasons for this are unclear. To evaluate the association of risk factors for AMI in native South Asians, especially at younger ages, compared with individuals from other countries. Standardized case-control study of 1732 cases with first AMI and 2204 controls matched by age and sex from 15 medical centers in 5 South Asian countries and 10,728 cases and 12,431 controls from other countries. Individuals were recruited to the study between February 1999 and March 2003. Association of risk factors for AMI. The mean (SD) age for first AMI was lower in South Asian countries (53.0 [11.4] years) than in other countries (58.8 [12.2] years; P or =once/wk, 10.7% vs 26.9%). However, some harmful factors were more common in native South Asians than in individuals from other countries (elevated apolipoprotein B(100) /apolipoprotein A-I ratio, 43.8% vs 31.8%; history of diabetes, 9.5% vs 7.2%). Similar relative associations were found in South Asians compared with individuals from other countries for the risk factors of current and former smoking, apolipoprotein B100/apolipoprotein A-I ratio for the top vs lowest tertile, waist-to-hip ratio for the top vs lowest tertile, history of hypertension, history of diabetes, psychosocial factors such as depression and stress at work or home, regular moderate- or high-intensity exercise, and daily intake of fruits and vegetables. Alcohol consumption was not found to be a risk factor for AMI in South Asians. The combined odds ratio for all 9 risk factors was similar in South Asians (123.3; 95% confidence interval [CI], 38.7-400.2] and in individuals from other countries (125.7; 95% CI, 88.5-178.4). The similarities in the odds ratios for the risk factors explained a high and similar degree of population attributable risk in both groups (85.8% [95% CI, 78.0%-93.7%] vs 88.2% [95% CI, 86.3%-89.9%], respectively). When stratified by age, South Asians had more risk factors at ages younger than 60 years. After adjusting for all 9 risk factors, the predictive probability of classifying an AMI case as being younger than 40 years was similar in individuals from South Asian countries and those from other countries. The earlier age of AMI in South Asians can be largely explained by higher risk factor levels at younger ages.
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              Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study.

              Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons. To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels. A randomized, double-blind, placebo-controlled trial. Outpatient clinics in Texas. A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51 st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile). Lovastatin (20-40 mg daily) or placebo in addition to a low-saturated fat, low-cholesterol diet. First acute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (1 83 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92; P =.006), and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P = .003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups. Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.
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                Author and article information

                Journal
                Indian J Med Res
                Indian J. Med. Res
                IJMR
                The Indian Journal of Medical Research
                Medknow Publications & Media Pvt Ltd (India )
                0971-5916
                0975-9174
                October 2013
                : 138
                : 4
                : 461-491
                Affiliations
                [1] Coronary Artery Disease in Asian Indians (CADI) Research Foundation, Lisle, IL, USA
                [* ] St. Peters Univeristy Hospital- Drexel University College of Medicine, New Brunswick, NJ, USA
                [** ] Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialities Centre, Chennai, India
                Author notes
                Reprint requests: Dr Enas A. Enas, Coronary Artery Disease in Asian Indians (CADI) Research Foundation, Lisle, IL, USA e-mail: cadiusa.org@ 123456gmail.com
                Article
                IJMR-138-461
                3868060
                24434254
                29b1fa07-8270-4fbf-9a1f-431f524811b7
                Copyright: © The Indian Journal of Medical Research

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 June 2013
                Categories
                Review Article

                Medicine
                asian indians,coronary artery disease,diabetes,myopathy,primary prevention,statin therapy
                Medicine
                asian indians, coronary artery disease, diabetes, myopathy, primary prevention, statin therapy

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