Altered PCSK9 plasma levels after preeclampsia in the PERLA-Brazil study

Preeclampsia (PE) is a major contributor to maternal morbidity and mortality, particularly in low- and middle-income countries. Women with a history of PE face a higher long-term risk of developing cardiovascular disease, but the mechanisms underlying this association remain poorly understood. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of plasma low-density lipoprotein cholesterol and has been linked to atherosclerosis and metabolic dysfunction. This study aimed to evaluate plasma PCSK9 levels in women with a history of PE, compared to those with history of normotensive pregnancies, and to explore the relationship between PCSK9, LDLc, and markers of cardiovascular disease.

A total of 205 women (103 with a history of PE and 102 with a history of normotensive pregnancies) were included, 6-15 years after delivery. PCSK9 concentrations were measured using ELISA.

Women with PE history exhibited significantly lower PCSK9 plasma levels compared to the normotensive group, despite presenting with higher LDLc, body mass index, fat percentage, and waist circumference. In the PE history group, PCSK9 levels were weakly correlated with markers of adiposity.

These findings suggest that lower PCSK9 levels may be associated with increased adipogenesis and could reflect compensatory mechanisms related to inflammation or metabolic alterations in women with a history of PE. While PCSK9 downregulation may confer vascular benefits, it appears insufficient to mitigate elevated LDLc or obesity indices. Further studies are needed to elucidate PCSK9's role in the pathophysiology of CVD after PE.