Are there sex differences in cardiovascular outcomes in non-dialysis CKD patients?

Abstract

Background: Sex differences for cardiovascular (CV) risk and outcomes in chronic kidney disease (CKD) patients not on dialysis have been scarcely or never investigated. We therefore studied this important aspect in a cohort of CKD stage 2-5 in the south of Italy.

Methods: We tested the relationship between sex and fatal and non-fatal major CV events in a cohort of 759 stage 2-5 CKD patients followed up for a median time of 36 months.

Results: Out of 759 patients, 455 were males (60%) and the remaining 304 patients were females (40%). During the follow-up, 42 patients died, and 118 had fatal and non-fatal CV events. On univariate Cox regression analyses, the male sex failed to be associated with all-cause mortality but was strongly related to the incidence rate of fatal and non-fatal major CV events [hazard ratio (HR) 1.75, 95% confidence interval (CI) 1.18-2.60, P = .006]. Data adjustment for a series of major potential confounders did not materially affect the strength of this relationship (HR 1.78, 95% CI 1.03-3.09). Further analysis testing the effect of age on major CV outcomes by sex showed an effect modification by this risk factor on the same outcome (P = .037) because the HR of male versus female CV events increased progressively with aging.

Conclusion: Male patients in stage G2-5 CKD had a higher risk for CV events compared with female patients. Age was shown to be a risk modifier for the association between sex and CV events and this risk increased linearly across a wide age spectrum in CKD patients.

Keywords: CKD; cardiovascular disease; female; risk assessment; risk difference.

Figure 1:

Kaplan–Meier analysis of fatal and non-fatal CV events according to sex. See ‘Results’ section for more detail.

Figure 2:

Effect modification analysis by age on the association between sex (males versus females) and fatal and nonfatal CV events. Data are HR and 95% CI. The P-value for effect modification was calculated by the linear combination method. See ‘Results’ section for more detail.