Cardiovascular risk factors in extended family members and birthweight in offspring

Low birthweight has been related to increased risk of adult cardiovascular disease (CVD). Transgenerational studies have been used to investigate likely mechanisms underlying this inverse association. However, previous studies mostly examined the association of offspring birthweight with CVD risk factors among parents. In this study, we investigated the association between offspring birthweight and individual cardiovascular disease (CVD) risk factors, an index of CVD risk factors, and education in their parents, aunts/uncles and aunts’/uncles’ partners. Birth data (Medical Birth Registry, Norway (1967-2012)) was linked to CVD risk factor data (the County Study, Age 40 program and CONOR) for the parents, aunts/uncles and their partners. For BMI, heart rate, systolic blood pressure, total cholesterol, triglycerides, and a risk factor index, the associations were examined by linear regression. For smoking and education, they were examined by logistic regression. Low birthweight was associated with an unfavorable risk factor profile in all familial relationships. For each kg increase in birthweight, the mean risk factor index decreased by -0.14 units (-0.15, -0.13) in mothers, -0.11 (-0.12, -0.10) in fathers, and -0.02 (-0.05, -0.00) to -0.07 (-0.09, -0.06) in aunts/uncles and their partners. The association in mothers was stronger than fathers but it was also stronger in aunts/uncles than their partners. Profound associations between birthweight and CVD risk factors in extended family members were observed that go beyond the expected genetic similarities in pedigrees, suggesting that mechanisms like environmental factors, assortative mating and genetic nurturing may explain these associations.