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

Abstract

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.

Fig. 1

Location of the collaborating and recruitment centres in Dhaka

Fig. 2

BRAVE study flow diagram of surveillance, enrolment and data collection

Fig. 3

Genetic ancestry in the BRAVE population derived from Principal Component Analysis. The figures above indicate that Bangladeshis (i.e. the BRAVE study participants and those in the BEB 1000 Genomes study) cluster separately from major non-South Asian populations (a) and other South Asian (b) ethnic groups. BRAVE indicates the Bangladeshis from BRAVE study participants. The colours of points refer to the self-reported ethnicities in the BRAVE (n = 5756 and the 1000 Genomes (n = 2504) study participants: SAN, South Asians; ASN, East Asians; EUR, Europeans; AMR, admixed Americans; AFR, Africans; BEB, Bengalis in Bangladesh (Non-BRAVE); GIH, Gujrati Indians in Houston, US; ITU, Indian Telegus in the UK; PJL, Pakistani Punjabis in Pakistan; STU, Sri Lankan Tamils in the UK. Scatterplot are of the first 2 principal components. C1, first principal component; and C2, second principal component