Maternal supraphysiological hypercholesterolemia and its adverse impact on transgenerational cardiometabolic health: a literature review

Aims: Among the risk factors leading to cardiovascular disease (CVD), hypercholesterolemia stands out as a key driver of vascular dysfunction and the development of atherosclerotic CVD. This review is aimed to highlight the emergent evidence showing that maternal supraphysiological hypercholesterolemia (MSPH) is a key risk factor for transgenerational CVD risk and to advocate for the development of strategies for the early prediction and prevention of MSPH. Data synthesis: Increasing evidence suggests that an individual's lifetime CVD risk may be modified by in utero exposure. However, the contribution of maternal lipid levels to pregnancy has been neglected. In women, chronic hypercholesterolemia occurs during pregnancy, during which total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels rise to meet fetal growth demands. Two patterns of increased pregnancy cholesterol levels have been described in the literature: i) those with maternal physiological hypercholesterolemia (MPH), characterized by increased TC levels at the end of gestation up to 280 mg/dl, and ii) those with MSPH, characterized by TC levels at the end of pregnancy above 280 mg/dl in combination with elevated LDL levels. This overlooked distinction is crucial considering the increased evidence linking MSPH to elevated cardiovascular risk in both mothers and offspring. Conclusion: Available data suggest that MSPH is associated with increased CVD risk in mothers in addition to fetal atherogenesis and increased lifetime risk of CVD in offspring. The implementation of early detection and interventions to mitigate MSPH could potentially improve acute and long-term health outcomes for both mothers and babies.