Sex Differences in Cardiovascular Outcomes in CKD: Findings From the CRIC Study

Abstract

Rationale & objective: Cardiovascular events are less common in women than men in general populations; however, studies in chronic kidney disease (CKD) are less conclusive. We evaluated sex-related differences in cardiovascular events and death in adults with CKD.

Study design: Prospective cohort study.

Setting & participants: 1,778 women and 2,161 men enrolled in the Chronic Renal Insufficiency Cohort (CRIC).

Exposure: Sex (women vs men).

Outcome: Atherosclerotic composite outcome (myocardial infarction, stroke, or peripheral artery disease), incident heart failure, cardiovascular death, and all-cause death.

Analytical approach: Cox proportional hazards regression.

Results: During a median follow-up period of 9.6 years, we observed 698 atherosclerotic events (women, 264; men, 434), 762 heart failure events (women, 331; men, 431), 435 cardiovascular deaths (women, 163; men, 274), and 1,158 deaths from any cause (women, 449; men, 709). In analyses adjusted for sociodemographic, clinical, and metabolic parameters, women had a lower risk of atherosclerotic events (HR, 0.71 [95% CI, 0.57-0.88]), heart failure (HR, 0.76 [95% CI, 0.62-0.93]), cardiovascular death (HR, 0.55 [95% CI, 0.42-0.72]), and death from any cause (HR, 0.58 [95% CI, 0.49-0.69]) compared with men. These associations remained statistically significant after adjusting for cardiac and inflammation biomarkers.

Limitations: Assessment of sex hormones, which may play a role in cardiovascular risk, was not included.

Conclusions: In a large, diverse cohort of adults with CKD, compared with men, women had lower risks of cardiovascular events, cardiovascular mortality, and mortality from any cause. These differences were not explained by measured cardiovascular risk factors.

Keywords: Atherosclerotic event; cardiac biomarker; cardiovascular disease (CVD); cardiovascular outcomes; chronic kidney disease (CKD); female; heart failure; male; mortality; myocardial infarction (MI); risk assessment; sex differences; sex factors.

Figure 1.. Multivariable-adjusted risk models.

Hazards ratios with 95% confidence interval for (A) atherosclerotic composite outcome, incident heart failure, cardiovascular death, and all-cause death; and (B) myocardial infarction, stroke and peripheral artery disease. Model 1: Stratified by clinical site and adjusted for age, race/ethnicity, baseline estimated glomerular filtration rate (eGFR), urine protein-to-creatinine ratio, education, marital status, nephrology care, smoking, physical activity, body mass index, waist circumference, systolic blood pressure, diabetes, cardiovascular disease, albumin, HDL-cholesterol, LDL-cholesterol, triglycerides, hemoglobin, angiotensin converting enzyme/angiotensin II receptor blocker use, aspirin, statin, fibroblast growth factor 23, calcium and phosphorus Model 2: Model 1 + log-transformed high-sensitivity C-reactive protein Model 3: Model 1 + log-transformed N-terminal prohormone of brain natriuretic peptide Model 4: Model 1 + high-sensitivity troponin T sex-specific categories Model 5: Model 1 + time-updated eGFR

Figure 2.

Primary outcomes in women vs men, by subgroups according to age, self-reported cardiovascular disease (CVD) and estimated glomerular filtration rate (eGFR) at baseline. Hazard ratios (HR) lower than one indicate a lower risk of the outcome in women vs. men, and are stratified by clinical site and adjusted for the following baseline characteristics: Age, race/ethnicity, eGFR, urine protein-to-creatinine ratio, education, marital status, nephrology care, smoking, physical activity, body mass index, waist circumference, systolic blood pressure, diabetes, self-reported CVD, albumin, HDL-cholesterol, LDL-cholesterol, triglycerides, hemoglobin, angiotensin converting enzyme/angiotensin II receptor blocker use, aspirin, statin, fibroblast growth factor 23, calcium and phosphorus.