Association of cardiovascular health with reproductive lifespan and pregnancy loss: insights from NHANES 2005-2018

Yang Yan¹Jiajia Chen¹Jinlong Qin^2*Min Yu^1*Meirong Du^1,3*

• ¹Laboratory of Reproduction Immunology, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University Shanghai Medical College, Shanghai, China
• ²Department of Obstetrics and Gynecology, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, China
• ³State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau, China

Background: Altered reproductive timing of females have close relations to long-term health. Since the cardiovascular system delivers oxygen, nutrients, and hormones throughout the body, cardiovascular health (CVH) may significantly impact hormonally controlled events such as pregnancy, the menarche, and the menopause. This study sought to determine whether CVH is associated with reproductive lifespan and pregnancy loss, and the mediating role of inflammation.Methods: 3964 females from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 were employed in this cross-sectional investigation. The Life’s Essential 8 (LE8) score was categorized into low (<50), moderate (50-79), and high (≥80) CVH. The years between menarche and menopause age was computed as reproductive lifespan. Pregnancy loss was determined by the discrepancy between the total number of pregnancies and the number of live births. We conducted multivariable linear regression models and zero-inflated negative binomial regression models to investigate the prospective association of CVH with reproductive lifespan and pregnancy loss while accounting for various potential confounders. Mediation analysis was applied to explore the function of inflammation.Results: After multivariate adjustment, higher CVH levels were notably associated with lower reproductive lifespan (β=-0.32, 95% CI: -0.47, -0.17, P<0.001) and lower number of pregnancy losses (β=-0.04, 95% CI: -0.07, -0.01, P=0.012). Specifically, increased CVH levels were associated with increased age at menarche (β=0.14, 95% CI: 0.10, 0.18, P<0.001) and decreased age at menopause (β=-0.18, 95% CI: -0.33, -0.04, P=0.014). Furthermore, a linear correlation was observed between CVH and reproductive lifespan (P<0.001), while the number of pregnancy losses decreased as CVH levels increase within a certain range and approximately presented an L-shaped relationship (P=0.009). Subgroup analyses proved a stronger inverse association between CVH and reproductive lifespan among never-married women (P for interaction<0.001), whereas no significant interaction existed between CVH and pregnancy loss. Inflammation biomarker alkaline phosphatase (ALP) mediated 9.4% of the association between CVH and reproductive lifespan (P=0.048).Conclusions: Higher CVH levels were associated with shorter reproductive lifespan and lower prevalence of pregnancy loss at population level, and inflammation may mediate the association of CVH with reproductive lifespan. Comprehensive management of CVH in female may be vital to safeguard their reproductive health.