Hyperglycemia, dyslipidemia and hyperhomocysteinemia are associated with both adult cardiovascular disease (CVD) and having a child with a congenital heart disease (CHD). We investigated associations between CVD in grandparents and the risk of CHD in grandchildren. In a case-control family study, we obtained detailed questionnaire information on CVD and CHD in 247 families with a CHD child and 203 families without a CHD child. Grandparents with CVD or intermittent claudication (IC) were significantly associated with an increased risk for CHD in grandchildren [OR 1.39 (95% CI 1.03-1.89) and OR 2.77 (95% CI 1.02-7.56), respectively]. The risk of CHD grandchildren was particularly increased in paternal grandfathers with CVD [OR 1.85 (95% CI 1.01-3.37)]. Overall, having a grandparent with CVD increased the risk for CHD in the grandchild by 1.65 (95% CI 1.12-2.41). After adjustment for potential maternal confounders, this risk was 1.44 (95% CI 0.94-2.21). Having two or more grandparents with CVD was associated with an approximately threefold risk for CHD grandchildren [OR adjusted 2.72 (95% CI 1.08-6.89)]. Our data suggest that CVD and IC in grandparents are associated with an increased risk of having a CHD grandchild. These first findings may be explained by shared causality of derangements in metabolic pathways and are in line with the fetal origins of health and disease.

cardiovascular disease, congenital heart disease, metabolic pathways, transgenerational
dx.doi.org/10.1017/S2040174414000026, hdl.handle.net/1765/62060
Journal of Developmental Origins of Health and Disease
Department of Gynaecology & Obstetrics

Wijnands, K.P.J, Obermann-Borst, S.A, Sijbrands, E.J.G, Wildhagen, M.F, Helbing, W.A, & Steegers-Theunissen, R.P.M. (2014). Cardiovascular diseases in grandparents and the risk of congenital heart diseases in grandchildren. Journal of Developmental Origins of Health and Disease, 5(2), 152–158. doi:10.1017/S2040174414000026