By impairing both function and survival, the severe reduction in oxygen availability associated with high-altitude environments is likely to act as an agent of natural selection. We used genomic and candidate gene approaches to search for evidence of such genetic selection. First, a genome-wide allelic differentiation scan (GWADS) comparing indigenous highlanders of the Tibetan Plateau (3,200-3,500 m) with closely related lowland Han revealed a genome-wide significant divergence across eight SNPs located near EPAS1. This gene encodes the transcription factor HIF2α, which stimulates production of red blood cells and thus increases the concentration of hemoglobin in blood. Second, in a separate cohort of Tibetans residing at 4,200 m, we identified 31 EPAS1 SNPs in high linkage disequilibrium that correlated significantly with hemoglobin concentration. The sex-adjusted hemoglobin concentration was, on average, 0.8 g/dL lower in the major allele homozygotes compared with the heterozygotes. These findings were replicated in a third cohort of Tibetans residing at 4,300 m. The alleles associating with lower hemoglobin concentrations were correlated with the signal from the GWADS study and were observed at greatly elevated frequencies in the Tibetan cohorts compared with the Han. High hemoglobin concentrations are a cardinal feature of chronic mountain sickness offering one plausible mechanism for selection. Alternatively, as EPAS1 is pleiotropic in its effects, selection may have operated on some other aspect of the phenotype. Whichever of these explanations is correct, the evidence for genetic selection at the EPAS1 locus from the GWADS study is supported by the replicated studies associating function with the allelic variants.chronic mountain sickness | high altitude | human genome variation | hypoxia | hypoxia-inducible factor

We found an incremental reduction in the use of evidence-based therapies with increasing age using a national ACS registry cohort. While survival benefit from more intensive management reduced with older age, better survival was associated with intensive management at all ages highlighting the requirement to improve standard of care in older patients with ACS.

ObjectiveTo determine whether the effect of South Asian ethnicity differs between studies of incidence and prognosis of coronary disease.DesignSystematic literature review and meta-analysis, and cohort analysis from a national acute coronary syndrome (ACS) registry linked to mortality (National Institute of Cardiovascular Outcomes Research/Myocardial Infarction National Audit Project).SettingInternational for the review, and England and Wales for the cohort analysis.PatientsThe numbers of South Asians included in the meta-analysis were 111 555 (incidence) and 14 531 (prognosis) of whom 8251 were from the ACS cohort.Main outcome measuresIncidence studies: non-fatal myocardial infarction or fatal coronary heart disease; prognostic studies: mortality; HRs for 1-year all-cause death in ACS cohort.ResultsSouth Asians had higher incidence of coronary disease compared with white subjects (HR 1.35 95% CI 1.30 to 1.40) based on meta-analysis of nine studies. Among 10 studies on prognosis, South Asians had better prognosis compared with white subjects (HR 0.78 95% CI 0.74 to 0.82). In the ACS cohort, the impact of diabetes (42.4% of South Asians, 16.9% of white subjects) on 1-year mortality was stronger in South Asians than white subjects (age-adjusted HR 1.83 95% CI 1.59 to 2.11 vs 1.53 95% CI 1.49 to 1.57). However, prognosis was better in South Asians even among diabetics, older people and those living in areas of the highest social deprivation.ConclusionsSouth Asian ethnicity is associated with higher incidence of coronary disease, but lower mortality once coronary disease is manifest. The dissociation between effects on incidence and prognosis suggests that public health initiatives to reduce inequalities in mortality between South Asian and white populations should focus on primary prevention.This is a CALIBER study with ClinicalTrials.gov Identifier: NCT01163513.

BackgroundWe aim to determine the prevalence of anemia in acute coronary syndrome (ACS) patients and compare their clinical characteristics, management, and clinical outcomes to those without anemia in an unselected national ACS cohort.Methods and ResultsThe Myocardial Ischemia National Audit Project (MINAP) registry collects data on all adults admitted to hospital trusts in England and Wales with diagnosis of an ACS. We conducted a retrospective cohort study by analyzing patients in this registry between January 2006 and December 2010 and followed them up until August 2011. Multiple logistic regressions were used to determine factors associated with anemia and the adjusted odds of 30‐day mortality with 1 g/dL incremental hemoglobin increase and the 30‐day and 1‐year mortality for anemic compared to nonanemic groups. Analyses were adjusted for covariates. Our analysis of 422 855 patients with ACS showed that 27.7% of patients presenting with ACS are anemic and that these patients are older, have a greater prevalence of renal disease, peripheral vascular disease, diabetes mellitus, and previous acute myocardial infarction, and are less likely to receive evidence‐based therapies shown to improve clinical outcomes. Finally, our analysis suggests that anemia is independently associated with 30‐day (OR 1.28, 95% CI 1.22‐1.35) and 1‐year mortality (OR 1.31, 95% CI 1.27‐1.35), and we observed a reverse J‐shaped relationship between hemoglobin levels and mortality outcomes.ConclusionsThe prevalence of anemia in a contemporary national ACS cohort is clinically significant. Patients with anemia are older and multimorbid and less likely to receive evidence‐based therapies shown to improve clinical outcomes, with the presence of anemia independently associated with mortality outcomes.

Background:Coronary heart disease (CHD) is the leading cause of morbidity and mortality worldwide. The growth of ageing populations in developing countries with progressively urbanized lifestyles are major contributors. The key risk factors for CHD such as hypercholesterolemia, diabetes mellitus, and obesity are likely to increase in the future. These risk factors are modifiable through lifestyle. Objectives: To review current literature on the potential benefit of cholesterol lowering in CHD risk reduction with a particular focus on the evidence of non-pharmacological/lifestyle management of hypercholesterolemia. Methods:Medline/PubMed systematic search was conducted using a two-tier approach limited to all recent English language papers. Primary search was conducted using key words and phrases and all abstracts were subsequently screened and relevant papers were selected. The next tier of searching was conducted by (1) reviewing the citation lists of the selected papers and (2) by using PubMed weblink for related papers. Over 3600 reports were reviewed.Results:Target cholesterol levels set out in various guidelines could be achieved by lifestyle changes, including diet, weight reduction, and increased physical activity with the goal of reducing total cholesterol to <200 mg/dL and LDL-C <100mg/dL. Various dietary constituents such as green tea, plant sterols, soy protein have important influences on total cholesterol. Medical intervention should be reserved for those patients who have not reached this goal after 3 months of non-pharmacological approach. Conclusion:CHD remains as a leading cause of death worldwide and hypercholesterolemia is an important cause of CHD. Non-pharmacological methods provide initial as well as long-term measures to address this issue.

No abstract

Some biological CVRFs were worse in higher SEP participants while some behavioural risk factors were worse in lower SEP participants. Lower SEP participants had less CVRF screening and knowledge of CVRFs. Those with knowledge of CVRFs were more likely to make healthy behavioural changes. Our findings suggest equipping rural Indians with knowledge about CVRFs may ameliorate projected future increases in CVD.

Objectives To determine whether coronary angiography for suspected stable angina pectoris is underused in older patients, women, south Asian patients, and those from socioeconomically deprived areas, and, if it is, whether this is associated with higher coronary event rates. Design Multicentre cohort with five year follow-up. Setting Six ambulatory care clinics in England. Participants 1375 consecutive patients in whom coronary angiography was individually rated as appropriate with the Rand consensus method. Main outcome measures Receipt of angiography (420 procedures); coronary mortality and acute coronary syndrome events.Results In a multivariable analysis, angiography was less likely to be performed in patients aged over 64 compared with those aged under 50 (hazard ratio 0.60, 95% confidence interval 0.38 to 0.96), women compared with men (0.42, 0.35 to 0.50), south Asians compared with white people (0.48, 0.34 to 0.67), and patients in the most deprived fifth compared with the other four fifths (0.66, 0.40 to 1.08). Not undergoing angiography when it was deemed appropriate was associated with higher rates of coronary event.Conclusions At an early stage after presentation with suspected angina, coronary angiography is underused in older people, women, south Asians, and people from deprived areas. Not receiving appropriate angiography was associated with a higher risk of coronary events in all groups. Interventions based on clinical guidance that supports individualised management decisions might improve access and outcomes.