Risk factors and in-hospital outcome of acute ST segment elevation myocardial infarction in young Bangladeshi adults

BackgroundSouth Asians have a higher overall incidence rate and younger age of onset for acute myocardial infarction (AMI) compared to Western populations. However, limited information is available on the association of preventable risk factors and outcomes of AMI among young individuals in Bangladesh. The aim of this study was to determine the risk factors and in-hospital outcome of AMI among young (age &le;40 years) adults in Bangladesh.MethodsWe conducted a prospective observational study among consecutive 50 patients aged &le;40 years and 50 patients aged &gt;40 years with acute ST Segment Elevation Myocardial Infarction (STEMI) and followed-up in-hospital at the National Institute of Cardiovascular Diseases (NICVD). Clinical characteristics, biochemical findings, diet, echocardiography and in-hospital outcomes were compared between the two groups. Multivariate logistic regression was performed to assess the association between risk factors and in-hospital outcome in young patients adjusting for other confounding variables.ResultsThe mean age of the young and older patient groups was 36.5&thinsp;&plusmn;&thinsp;4.6 years and 57.0&thinsp;&plusmn;&thinsp;9.1 years respectively. Male sex (OR 3.4, 95 % CI 1.2&thinsp;&minus;&thinsp;9.75), smoking (OR 2.4, 95 % CI 1.04&thinsp;&minus;&thinsp;5,62), family history of MI (OR 2.4, 95 % CI 1.11&thinsp;&minus;&thinsp;5,54), homocysteine (OR 1.2, 95 % CI 1.08&thinsp;&minus;&thinsp;1.36), eating rice &ge;2 times daily (OR 3.5, 95 % CI 1.15&thinsp;&minus;&thinsp;10.6) and eating beef (OR 4.5, 95 % CI 1.83&thinsp;&minus;&thinsp;11.3) were significantly associated with the risk of AMI in the young group compared to older group. In multivariate analysis, older patients had significantly greater chance of developing heart failure (OR 7.5, 95 % CI 1.51 to 37.31), re-infarction (OR 7.0, 95 % CI 1.08&thinsp;&minus;&thinsp;45.72), arrhythmia (OR 15.3, 95 % CI 2.69&thinsp;&minus;&thinsp;87.77) and cardiogenic shock (OR 69.0, 95 % CI 5.81&thinsp;&minus;&thinsp;85.52) than the younger group.ConclusionYounger AMI patients have a different risk profile and better in-hospital outcomes compared to the older patients. Control of preventable risk factors such as smoking, unhealthy diet, obesity and dyslipidemia should be reinforced at an early age in Bangladesh.<br /

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P &lt; 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

The Bangladesh Risk of Acute Vascular Events (BRAVE) Study: objectives and design.

During recent decades, Bangladesh has experienced a rapid epidemiological transition from communicable to non-communicable diseases. Coronary heart disease (CHD), with myocardial infarction (MI) as its main manifestation, is a major cause of death in the country. However, there is limited reliable evidence about its determinants in this population. The Bangladesh Risk of Acute Vascular Events (BRAVE) study is an epidemiological bioresource established to examine environmental, genetic, lifestyle and biochemical determinants of CHD among the Bangladeshi population. By early 2015, the ongoing BRAVE study had recruited over 5000 confirmed first-ever MI cases, and over 5000 controls "frequency-matched" by age and sex. For each participant, information has been recorded on demographic factors, lifestyle, socioeconomic, clinical, and anthropometric characteristics. A 12-lead electrocardiogram has been recorded. Biological samples have been collected and stored, including extracted DNA, plasma, serum and whole blood. Additionally, for the 3000 cases and 3000 controls initially recruited, genotyping has been done using the CardioMetabochip+ and the Exome+ arrays. The mean age (standard deviation) of MI cases is 53 (10) years, with 88 % of cases being male and 46 % aged 50 years or younger. The median interval between reported onset of symptoms and hospital admission is 5 h. Initial analyses indicate that Bangladeshis are genetically distinct from major non-South Asian ethnicities, as well as distinct from other South Asian ethnicities. The BRAVE study is well-placed to serve as a powerful resource to investigate current and future hypotheses relating to environmental, biochemical and genetic causes of CHD in an important but under-studied South Asian population.The Gates Cambridge Trust has supported Dr Chowdhury. Epidemiological fieldwork in BRAVE has been supported by grants to investigators at the Cardiovascular Epidemiology Unit, University of Cambridge. The Cardiovascular Epidemiology Unit is underpinned by programme grants from the British Heart Foundation (RG/13/13/30194), the UK Medical Research Council (MR/L003120/1), and the UK National Institute of Health Research Cambridge Biomedical Research Centre. BRAVE has received support for genetic assays from the European Research Council (ERC-2010-AdG-20100317), European Commission Framework 7 (Grant Agreement number: 279233), and the Cambridge British Heart Foundation Centre for Excellence in Cardiovascular Science; We would like to acknowledge the contributions of the following individuals: Cardiology Research Group in Bangladesh Mohammad Afzalur Rahman, Mohammad Abdul Kader Akanda, M Atahar Ali, Mir Jamal Uddin, SM Siddiqur Rahman, Amal Kumar Choudhury, Md. Mamunur Rashid, Nazir Ahmed Chowdhury, Mohammad Abdullahel Baqui, Kajal Kumar Karmoker, Mohammad Golam Azam; Setting up/implementation of fieldwork in Bangladesh Abbas Bhuiya, Susmita Chowdhury, Kamrun Nahar, Neelima Das, Proshon Roy, Sumona Ferdous, Taposh Kumar Biswas, Abu Sadat Mohammad Sayed Sharif, Ranjit Shingha, Rose Jinnath Tomas, Babulal Parshei, Mabubur Rahman, Mohammad Emon Hossain, Akhirunnesa Mily, AK Mottashir Ahmed, Sati Chowdhury, Sushila Roy, Dipak Kanti Chowdhury, Swapan Kumar Roy; Epidemiological/statistical support in Cambridge Stephen Kaptoge, Simon Thompson, Angela Wood, Narinder Bansal, Anna Ramond, Clare Oliver-Williams, Marinka Steur, Linda O’Keeffe, Eleni Sofianopoulou, Setor Kunutsor, Donal Gorman, Oscar H Franco, Malcolm Legget, Pinal Patel, Marc Suhrcke, Sylvaine Bruggraber, Jonathan Powell; Data management Matthew Walker, Steve Ellis, Shawkat Jahangir, Habibur Rahman, Rifat Hasan Shammi, Shafqat Ullah, Mohammad Abdul Matin and Administration Beth Collins, Hannah Lombardi, Binder Kaur, Rachel Henry, Marilena Papanikolaou, Robert Smith, Abdul Wazed, Robert Williams, Julie Jenkins, Keith Hoddy.This is the final published version of the article. It was originally published in the European Journal of Epidemiology (Chowdhury R, et al., European Journal of Epidemiology, 2015, doi:10.1007/s10654-015-0037-2). The final version is available at http://dx.doi.org/10.1007/s10654-015-0037-

Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease.

Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant)

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in A2ML1 and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention

36. Clinical profile of coronary slow flow phenomena – A cardiac Y syndrome

Coronary slow flow phenomenon (CSFP) is characterized by delayed progression of the contrast medium injected through the coronary tree during Coronary Angiogram (CAG). CSFP is usually observed in patient with various spectrum of Coronary Artery Disease including Acute Coronary Syndrome and Chronic Stable Angina (CSA). The exact pathogenesis of CSFP is unknown, but 80% of patients experience recurrent episodes of typical anginal pain which results in impairment of quality of the life. Endothelial Dysfunction, Inflammation and diffuse atherosclerosis are various proposed pathogenesis of CSFP. CSFP causes significant cardiovascular morbidity due to dynamic ECG changes and symptoms worsening necessitating recurrent hospitalization and they tend to undergo repeated investigations like Coronary Angiogram. Aim: To see clinical characteristics like risk factors and others of coronary slow flow phenomena. Methods: A total of 45 patients over a period of 6 months with Non Obstructive coronaries below the age group of 60 years who presented with Ischemic Heart Disease were studied. Coronary Slow Flow was identified using thrombolysis in myocardial infarction (TIMI) frame count (TFC) method introduced by Gibson. TIMI-2 flow grade (i.e. requiring ⩾3 beats to opacify the vessel) or a corrected TIMI frame count >27 frames have been frequently used. The later is based upon images acquired at 30 frames/second and a correction factor of 1.7 for the LAD Risk factors and profiles of all the patients were studied in detail. Those patients who had Coronary Artery ectasia, coronary aneurysm, ventricular dysfunction, valvular heart disease and connective tissue disorders. were excluded. Results: Out of 45 patients presented with CSFP 95% were males and 5% females with a mean age of 47 years. CSA with Positive Stress Test were 65%, 15% had Unstable Angina and 25% presented with Myocardial Infarction with Positive Troponin I test . Dynamic ECG changes were present in 30% of the cases. Analysing the risk factors, most of the patients had uncontrolled hypertension (75%) and also were smokers (65%). Diabetes was prevalent in 60% of cases and dyslipidemia in 35% of cases. There were no mortalities noted in hospitalized patients. Conclusion: CSFP was prevalent in wide spectrum if Ischemic Heart Disease presenting as CSA and Acute Coronary Syndrome. Most of the patients presented with CSFP were smokers and had uncontrolled Hypertension