CKD Confers Increased Excess Risks of Mortality and Cardiovascular Events in Women Compared with Men

Background: In the general population, women exhibit a lower cardiovascular risk and increased life expectancy compared to men. While studies in dialysis and post-transplant patients suggested that this relationship is attenuated or absent, direct comparisons between men and women with and without chronic kidney disease (CKD) are currently lacking. This study aims to address this gap by evaluating cardiovascular events and mortality in women and men to assess whether CKD confers greater excess risk in women. Methods: In this retrospective observational cohort study, we analyzed de-identified patient-level data from electronic medical records captured within the TriNetX US Collaborative Network encompassing 69 health care organizations. Adults aged 18-90 years with an eGFR≥15 ml/min/1.73m2 and no history of prior kidney replacement therapy were included and categorized into four groups: women with CKD, women without CKD, men with CKD, and men without CKD. Primary outcomes were all-cause mortality and cardiovascular composite outcome (acute myocardial infarction, unstable angina, stroke, peripheral artery disease and ischemic heart disease). Analyses were adjusted for age, sociodemographic factors, cardiovascular risk factors, laboratory measurements, medications, and history of CVD. Descriptive statistics and adjusted Cox regression analyses were conducted using the built-in tools of the TriNetX research platform or R 4.3.2. Results: Within 328,431 eligible individuals, 43,830 were women with CKD, 45,173 were men with CKD, 127,383 were women without CKD and 112,045 were men without CKD. In individuals without CKD, women displayed a reduced risk of all-cause mortality (HR 0.53; 95% CI 0.49-0.58) and cardiovascular events (HR 0.70; 95% CI 0.68-0.71) than men. However, this risk reduction in women compared to men was significantly attenuated in individuals with CKD both for all-cause mortality (HR 0.73; 95%CI 0.69-0.77) and for cardiovascular events (HR 0.80; 95% 0.78-0.82). Consequently, CKD conferred significantly greater excess risks of mortality and cardiovascular events in women compared to men. Conclusion: The cardiovascular and survival advantage typically observed in women compared to men in the general population is markedly diminished among individuals with CKD.