IndEcho study: cohort study investigating birth size, childhood growth and young adult cardiovascular risk factors as predictors of midlife myocardial structure and function in South Asians

Abstract

Introduction: South Asians have high rates of cardiovascular disease (CVD) and its risk factors (hypertension, diabetes, dyslipidaemia and central obesity). Left ventricular (LV) hypertrophy and dysfunction are features of these disorders and important predictors of CVD mortality. Lower birth and infant weight and greater childhood weight gain are associated with increased adult CVD mortality, but there are few data on their relationship to LV function. The IndEcho study will examine associations of birth size, growth during infancy, childhood and adolescence and CVD risk factors in young adulthood with midlife cardiac structure and function in South Asian Indians.

Methods and analysis: We propose to study approximately 3000 men and women aged 43-50 years from two birth cohorts established in 1969-1973: the New Delhi Birth Cohort (n=1508) and Vellore Birth Cohort (n=2156). They had serial measurements of weight and height from birth to early adulthood. CVD risk markers (body composition, blood pressure, glucose tolerance and lipids) and lifestyle characteristics (tobacco and alcohol consumption, physical activity, socioeconomic status) were assessed at age ~30 years. Clinical measurements in IndEcho will include anthropometry, blood pressure, biochemistry (glucose, fasting insulin and lipids, urinary albumin/creatinine ratio) and body composition by dual energy X-ray absorptiometry and bioelectrical impedance. Outcomes are LV mass and indices of LV systolic and diastolic function assessed by two-dimensional and Doppler echocardiography, carotid intimal-media thickness and ECG indicators of ischaemia. Regression and conditional growth models, adjusted for potential confounders, will be used to study associations of childhood and young adult exposures with these cardiovascular outcomes.

Ethics and dissemination: The study has been approved by the Health Ministry Steering Committee, Government of India and institutional ethics committees of participating centres in India and the University of Southampton, UK. Results will be disseminated through scientific meetings and peer-reviewed journals.

Trial registration number: ISRCTN13432279; Pre-results.

Keywords: South Asians; adiposity; birth weight and early growth; echocardiography; indecho; left ventricular mass and function.

Figure 1

BMI SD scores from birth to adulthood for participants in each cohort who developed IGT or diabetes (n=219/1562 in NDBC and 424/2218 in VBC) in adult life relative to the whole cohort (dashed zero line). BMI, body mass index; IGT, impaired glucose intolerance; NDBC, New Delhi Birth Cohort; VBC, Vellore Birth Cohort.

Figure 2

Pathways to altered left ventricular (LV) structure and function that will be investigated in IndEcho. Factors contributing to LV hypertrophy. Intrauterine undernutrition alters the fetal circulation, which may have direct and persistent effects on ventricular structure. Intrauterine and infant undernutrition impairs the development of key metabolic tissues (muscle, pancreas, liver, blood vessels and kidneys) during critical periods of growth and increases adipose tissue deposition, leading to the ‘thin-fat’ phenotype and later obesity, T2DM, dyslipidaemia, hypertension and chronic renal disease, which adversely impact on LV size and function. BMI, body mass index; LV, left ventricular; T2DM, type 2 diabetes mellitus.

Figure 3

Flow chart of various stages of follow-up of the New Delhi and Vellore Birth cohorts and measurements recorded at each stage. BMI, body mass index; DXA, dual energy X-ray absorptiometry; HC, hip circumference; OGTT, oral glucose tolerance test; PA, physical activity; SES, socioeconomic status.