Recent studies have highlighted the association between polycystic ovary syndrome (PCOS) and cardiometabolic diseases, leading to an improved understanding of the underlying mechanistic factors. PCOS significantly increases cardiovascular risk by predisposing individuals to various subclinical and clinical conditions, including atherosclerosis and type 2 diabetes mellitus. Additionally, it interacts synergistically with other traditional cardiovascular risk factors, such as obesity, hyperlipidemia, and insulin resistance. Several molecular mechanisms involving genetics, epigenetics, adipokine secretion, hyperandrogenemia, and hyperinsulinemia play a role in the relationship between PCOS and these comorbidities. For instance, androgen excess has been implicated in the development of hypertension, type 2 diabetes mellitus, endothelial dysfunction, and ultimately, broader cardiovascular disease. A deeper understanding of these underlying mechanisms facilitates the development of diagnostic, preventative, and therapeutic strategies directed at reducing cardiometabolic morbidity. This narrative review summarizes the current evidence, explores the potential clinical implications of these findings, and discusses emerging therapies to reduce cardiometabolic morbidity in women with PCOS.

Background: Preeclampsia is associated with maternal and perinatal morbidity. Besides acute therapy for severe hypertension, best practices are lacking for intrapartum hypertension management. Our objective was to test the hypothesis that intrapartum initiation of extended-release nifedipine in individuals with preeclampsia with severe features prevents severe hypertension. Methods: Randomized, triple-blind, placebo-controlled trial of individuals with preeclampsia with severe features undergoing labor induction between 22 ^0/7 and 41 ^6/7 weeks gestation. Participants were randomized to oral extended-release nifedipine 30 mg or identical placebo every 24 hours. Primary outcome is defined as receipt of ≥1 dose of acute hypertension therapy for severe blood pressure (≥160/110 mm Hg) sustained ≥10 minutes. Secondary outcomes included route of delivery, neonatal intensive care unit admission, and a composite of adverse neonatal outcomes. Results: Of 365 individuals screened, 55 were randomized to nifedipine and 55 to placebo. Primary outcome was observed in 34.0% of individuals in nifedipine group versus 55.1% in placebo group (relative risk [RR] 0.62 [95% CI, 0.39–0.97]); number needed to treat to prevent receipt of acute treatment was 4.7 (95% CI, 2.5–44.3). Fewer individuals in nifedipine group required cesarean delivery compared with placebo group (20.8% versus 34.7%, RR, 0.60 [95% CI, 0.31–1.15]). Neonatal intensive care unit admission rate was lower in nifedipine group compared with placebo (29.1% versus 47.1%; RR 0.62 [95% CI, 0.37–1.02]). Neonatal composite was similar between groups (35.8% versus 41.2%, RR, 0.83 [95% CI, 0.51–1.37]). Conclusions: Initiation of extended-release nifedipine is effective in reducing intrapartum acute hypertensive therapy among individuals with preeclampsia with severe features. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04392375.