Association of Maternal Prepregnancy Dyslipidemia With Adult Offspring Dyslipidemia in Excess of Anthropometric, Lifestyle, and Genetic Factors in the Framingham Heart Study.

importanceDyslipidemia in young adults in the United States during their childbearing years is common, and the consequences for the next generation are poorly understood. Further understanding of the harmful consequences of elevated low-density lipoprotein cholesterol (LDL-C) levels in young adults may help to inform population screening and management strategies.

objectiveTo examine whether adult levels of serum LDL-C are associated with maternal prepregnancy LDL-C levels beyond that attributable to inherited genetic sequence polymorphisms, diet, physical activity, and body mass index. DESIGN, SETTING, AND

participantsThe Framingham Heart Study is a multigenerational, population-based inception cohort initiated in 1948 in Framingham, Massachusetts. In this study of families, the analyses included 538 parent-offspring pairs with parental LDL-C levels measured in the study prior to the offspring's birth. Parental prebirth, parental concurrent, and adult offspring assessments occurred in 1971-1983, 1998-2001, and 2002-2005, respectively. Data analyses were conducted between March 1, 2013, and May 30, 2015. EXPOSURES: Maternal prepregnancy LDL-C levels compared with paternal prepregnancy and parental concurrent LDL-C levels in association with adult offspring LDL-C levels. MAIN OUTCOMES AND MEASURES: Adult offspring LDL-C levels were examined as both a continuous and dichotomous outcome (using a threshold of 130 mg/dL).

resultsAmong the 538 parent-offspring pairs, there were 241 mother-offspring and 297 father-offspring pairs with a mean (SD) offspring age of 26 (3) years. Adult offspring LDL-C levels were associated with maternal prepregnancy LDL-C levels after adjustment for family relatedness and offspring lifestyle, anthropometric factors, and inherited genetic variants (β = 0.32 [SE, 0.05] mg/dL; P < .001). After multivariable adjustment, adults who had been exposed to elevated maternal prepregnancy LDL-C levels were at a 3.8 (95% CI, 1.5-9.8) times higher odds of having elevated LDL-C levels (P = .005) and had an adjusted LDL-C level of 18 mg/dL (95% CI, 9-27 mg/dL) higher than did those without such exposure. Maternal prepregnancy LDL-C levels explained 13% of the variation in adult offspring LDL-C levels beyond common genetic variants and classic risk factors for elevated LDL-C levels. CONCLUSIONS AND RELEVANCE: Adult offspring dyslipidemia is associated with maternal prepregnancy dyslipidemia in excess of measured lifestyle, anthropometric, and inherited genetic factors. The findings support the possibility of a maternal epigenetic contribution to cardiovascular disease risk in the general population. Further research is warranted to determine whether ongoing public health efforts to identify and reduce dyslipidemia in young adults prior to their childbearing years may have additional potential health benefits for the subsequent generation.