Purpose: This study aimed to clarify the relationship between serum high-density lipoprotein cholesterol (HDL-C) level and incidence of CV events. Moreover, the relationship stratified by gender was evaluated. Methods: The study database was derived from a multicenter, prospective, cohort study that included 1520 incident dialysis patients in Aichi Prefecture, Japan. Baseline was defined as the time of dialysis initiation and outcome as incidence of CV event. The enrolled patients were first classified into four quartile groups (Q1, Q2, Q3, and Q4; Q1 was the lowest serum HDL-C) based on serum HDL-C level. A multivariate Cox proportional hazards analysis was conducted using the stepwise regression method to determine factors associated with outcomes and was performed in each gender. Results: The log-rank test revealed significant differences in the incidence of CV events between not only the four groups (p = 0.003) but also the male and female patients (HR, 0.74; 95% CI, 0.59–0.92; p < 0.001). Stepwise regression analysis indicated that higher serum HDL-C level was significantly associated with lower incidence of CV events (HR, 0.88; 95% CI, 0.82–0.95; p = 0.001). The association between serum HDL-C and incidence of CV events could be clarified in only female patients (male patients; HR, 0.92; 95% CI, 0.84–1.01; p = 0.067 and female patients; HR, 0.81; 95% CI, 0.72–0.92; p = 0.001). Conclusions: HDL-C level at the initiation of dialysis was associated with the incidence of CV events. Moreover, the association was prominent in female patients. Trial registration: The trial registration number of the study is UMIN 7096, registered on January 18, 2012.
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