Heritability of cardiovascular health across three generations in South Africa: the Birth to Twenty-Plus cohort

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Abstract Objectives Cardiovascular disease is increasing in many low-middle income countries, including those in Africa. To inform strategies for the prevention of cardiovascular disease in South Africa, we sought to determine the broad heritability of phenotypic markers of cardiovascular risk across three generations. Design A cross-sectional study conducted in a longitudinal family cohort. Setting Research unit within a tertiary hospital in a historically disadvantaged, large urban township of South Africa. Participants 195 individuals from 65 biological families with all three generations including third generation children aged 4-10 years were recruited from the longest running intergenerational cohort study in Africa, the Birth to Twenty Plus cohort. All adults (grandparents and parents) were female, while children were male or female. Primary and secondary outcome measures The primary outcome was heritability of blood pressure (BP, brachial and central pressures). Secondary outcomes were heritability of arterial stiffness (pulse wave velocity), carotid intima media thickness (cIMT), and left ventricular mass indexed to body surface area (LVMI). Results While no significant intergenerational relationships of BP or arterial stiffness were found, there were significant relationships in LVMI across all three generations (p<0.04), and in cIMT between grandparents and parents (p=0.0166). Heritability estimates were 23-44% for cIMT and 21-39% for LVMI. Conclusions Structural indicators of vascular health, which are strong markers of future clinical cardiovascular outcomes transmit between generations within African families. Identification of these markers in parents may be useful to trigger assessments of preventable risk factors for cardiovascular disease in offspring. Strengths Intergenerational transmission was evaluated for a range of indicators of cardiovascular health within urban African families The sample included biological family members from three generations Heritability estimates were compared for three commonly used statistical methods. Limitations The sample size is a limitation with the random family statistical method used to increase the numbers of comparisons available. Only maternal family members were included.

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