Elevated LDL Cholesterol in Mom, Increased LDL Cholesterol in Adult Offspring, Irrespective of Genetics

Individuals born to a mother with elevated LDL cholesterol levels are nearly four times more likely than those born to a mother with normal cholesterol levels to have dyslipidemia, according to a new analysis of the Framingham Heart Study (FHS). 

In 241 parent-offspring pairs, mean adult LDL cholesterol levels were 18 mg/dL higher among those exposed to elevated maternal pre-pregnancy LDL cholesterol levels than those born to mothers with normal cholesterol.

Writing in the latest cardiology journal to hit the medical stacks, JAMA: Cardiology, Mark Mendelson, MD (National Institutes of Health, Framingham, MA), and colleagues report that the association between elevated LDL cholesterol in women prior to the birth of the child and the elevated risk of dyslipidemia in their adult offspring remained even after adjusting for lifestyle, body mass index, and inherited genetic variants known to be linked with elevated LDL cholesterol levels.

In the mother-offspring pairings, each 10-mg/dL increase in the mother’s pre-pregnancy LDL cholesterol levels was associated with a 3.2-mg/dL increase in the offspring’s LDL cholesterol. For 297 father-offspring pairs, each 10-mg/dL increase in pre-pregnancy LDL cholesterol levels was associated with a 1.3 mg/dL increase in the offspring’s LDL cholesterol. In contrast with the mothers, the association between LDL cholesterol levels in the adult offspring and the father’s LDL cholesterol level was not statistically significant after adjusting for confounding variables, such as lifestyle and an LDL cholesterol genetic risk score.

Pre-pregnancy LDL cholesterol in the mother’s explained 13% of the variation in the adult offspring LDL cholesterol levels, according to the investigators.

“An improved understanding of the CVD risk associated with the intrauterine environment may inform population-based lifestyle strategies for women in their childbearing years to identify those at risk and to direct lipid-specific nutritional and lifestyle interventions or therapeutics,” conclude the researchers.

Marc Sabatine, MD (Brigham and Women’s Hospital, Boston, MA), who wrote an editor’s note to accompany the study, agreed with researchers, noting that an association does not imply causality. He also added the analysis is based on data from the FHS Offspring story, where the mother’s dietary habits might have played a greater role than the father’s. That said, there is a “growing body of evidence that epigenetic regulation of gene expression can be influenced by environmental exposures,” something that will need to be studied further, according to Sabatine.

Source:
1. Mendelson MM, Lyass A, O’Donnell CJ, et al. Association of maternal pre-pregnancy dyslipidemia with adult offspring dyslipidemia in excess of anthropometric, lifestyle, and genetic factors in the Framingham Heart Study. JAMA Cardiol. 2016;Epub ahead of print.
2. Sabatine MS. Nurturing nature—exploring the possible role of epigenetics in dyslipidemia. JAMA Cardiol. 2016;Epub ahead of print.

Disclosures:

• Authors report no conflicts of interest.

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