Reproductive risk factors and prevalence of cardiovascular-kidney-metabolic syndrome among young women

Introduction: Cardiovascular-Kidney-Metabolic (CKM) syndrome provides a framework for early cardiometabolic and kidney dysfunction. While reproductive risk factors are associated with cardiovascular disease, their relationship to CKM syndrome stages remains unclear. We estimated CKM prevalence among reproductive-aged US women and evaluated associations with reproductive risk factors. Methods: Using the National Health and Nutrition Examination Survey (2013-2020), we included 3,917 non-pregnant women aged 20-49 years. Reproductive risk factors included early menarche (≤10 years), infertility, gestational diabetes, delivery of a large-for-gestational-age neonate, and grand multiparity (≥ 5 births). CKM stages were classified as stage 0 (no risk factors), stage 1 (excess or dysfunctional adiposity), stage 2 (metabolic risk factors or chronic kidney disease), stage 3 (subclinical cardiovascular disease), stage 4 (clinical cardiovascular disease). Adjusted prevalence ratios (aPRs) for CKM stage ≥ 2 were estimated using Poisson regression accounting for sociodemographic and behavioral factors. Results: Approximately 34.7% (95% CI: 32.3, 37.1) of women reported at least one reproductive risk factor. Overall, 55.1% (95% CI: 52.9, 57.3) were classified as CKM stage ≥ 2. Women with reproductive risk factors were more likely to be in higher CKM stages. Significant associations with CKM stage ≥ 2 were observed for gestational diabetes (aPR, 1.25; 95% CI: 1.13, 1.39) and infertility (aPR, 1.14; 95% CI: 1.04, 1.26). Conclusion: CKM syndrome is highly prevalent among reproductive-aged women in the US. Histories of gestational diabetes and infertility were associated with higher CKM stages. Incorporating reproductive factors into clinical tools could support targeted prevention of CKM progression and future CVD.