Reproductive-associated risk factors and incident coronary heart disease in women: an umbrella review

Background: Reproductive risk factors influence women's risk of cardiovascular disease (CVD), particularly coronary heart disease (CHD). Despite growing evidence and recent guideline recommendations, their integration into cardiovascular risk screening and assessment remains limited. Evaluating the effect sizes of reproductive-associated risk factors along with temporal trends, homogeneity, and additive effects could provide critical insights to guide future research and inform evidence-based policies for CHD prevention in women. Methods: This umbrella review synthesizes evidence from systematic reviews and meta-analyses examining reproductive-associated risk factors and their impact on incident coronary heart disease. A comprehensive search of PubMed and CINAHL databases was conducted for studies published between 2013 and 2024. Eligible articles were independently screened by two reviewers. Data were extracted using the Joanna Briggs Institute form and synthesized for effect sizes related to incident CHD. Prospective studies were used to assess temporality, and study quality was evaluated using the AMSTAR 2 tool. Forest plots were used for the effect size analysis based on comparative or time-to-event data. Results: Of 902 articles, 29 met the inclusion criteria. Female reproductive risk factors from menarche to menopause across three categories (adverse pregnancy outcomes, reproductive endocrine disorders, and emerging reproductive risk factors) were associated with elevated CHD risk. Recurrent preeclampsia was identified as a significant risk factor, markedly increasing the risk of CHD. Additionally, cardiovascular events, including ischemic heart disease, were most frequent within the first decade postpartum in women with a history of gestational diabetes. Notably, none of the included studies evaluated the combined effects of multiple reproductive risk factors on CHD outcome. Conclusion: Reproductive history is a critical factor in assessing CHD risk in women, with certain factors having temporal effects that correspond to heightened risk periods. Integrating these factors into screening tools, considering exposure and risk timing, may enable earlier intervention and improved outcomes.