The exclusion of women and people with kidney disease from cardiovascular disease clinical trials has resulted in a knowledge gap regarding how cardiovascular health status might differ between men and women with kidney failure. This is of particular importance because cardiovascular disease is the leading cause of morbidity and mortality among individuals with kidney failure.
To help address this gap, a group of researchers, including Silvi Shah, MD, examined sex differences in cardiovascular events, cardiovascular death, and all-cause mortality using data from the United States Renal Data System (USRDS). Their findings were published in the Journal of the American Heart Association.
The study cohort comprised 508,822 patients from USRDS with linked claims for Medicare Part A and Part B or Medicare Primary Other as the primary payer, who had incident end-stage renal disease and started dialysis between January 1, 2005, and December 31, 2014. All patients were ≥18 years of age, and the mean age at the start of the study was 69.9 ± 12.4 years; 44.7% were women; 61.6% were White, 23.5% were Black, 10.6% were Hispanic, 3.4% were Asian, and 0.9% were Native American. The mean age was higher for women than men (70.3 ± 12.3 years vs 69.7 ±1 2.5 years), and women were more likely to be Black (27.2% vs 20.5%) and less likely to be White (57.7% vs 64.8%) than men.
Most (91.4%) study subjects had a history of cardiovascular disease. Women were more likely than men to have comorbidities of diabetes (56.0% vs 52.3%) and poor functional status (19.9% vs 15.6%) but less likely to have the comorbidity of smoking (4.3% vs 6.1%). Women were more likely than men to experience kidney failure due to malignancy (3.0% vs 2.1%) or glomerulonephritis (4.8% vs 3.9%). Women were also more likely to have unfavorable laboratory measurements of albumin <3.5 mg/dL and hemoglobin <11 g/dL than men.
The primary outcomes for the study were the occurrence of a composite cardiovascular event, defined as hospitalization with a primary diagnosis of acute coronary syndrome (ACS; myocardial infarction or unstable angina), heart failure, or stroke; separate occurrence of ACS, heart failure, or stroke; cardiovascular death; and all-cause death. The researchers studied the association of sex with these outcomes using adjusted time-to-event models.
The analysis found that women on dialysis, compared with men, had a 14% higher risk of cardiovascular events (hazard ratio [HR], 1.14; 95% CI, 1.13-1.16), a 16% higher risk of heart failure (HR, 1.16; 95% CI, 1.15-1.18), and a 31% higher risk of stroke (HR, 1.31; 95% CI, 1.28-1.34). The risk of ACS was comparable between women and men (HR, 1.01; 95% CI, 0.99-1.03).
The event rates for cardiovascular death and all-cause death were lower for women than men. Cardiovascular death rates were 104 per thousand person-years (PTPY; 95% CI, 103-105) for women and 116 PTPY (95% CI, 115-117) for men; all-cause death rates were 275 PTPY (95% CI, 273-276) for women versus 285 PTPY (95% CI, 284-286) for men. In the time-to-event model, women’s risk of cardiovascular death (HR, 0.89; 95% CI, 0.88-0.90) was lower than men’s. In the model predicting all-cause death, women had a lower risk (HR, 0.96; 95% CI, 0.95-0.97) than men.
The authors acknowledge several limitations of the study. They could not determine causality due to the study’s observational design. Only patients with Medicare as their primary payer were included in the follow-up period. Comorbidity reporting on the Medical Evidence Report form was not validated, possibly leading to some nondifferential misclassification. Quality and completeness of data on form 2728 of the USRDS data varied. Researchers were unable to assess cardiovascular health-seeking behavior in women compared with men and could not account for endogenous hormone levels, which may play a role in the sex differences observed. Men and women may have been coded differently in terms of cardiovascular events, including fluid overload with heart failure. The authors lacked information on laboratory parameters and medications used to treat cardiovascular disease.
“In conclusion,” the authors wrote, “women with kidney failure have higher risks of cardiovascular events, including those of heart failure and stroke but lower risks of cardiovascular mortality than men. These differences were not explained by age, race or ethnicity, or history of prior cardiovascular disease. Women with kidney failure should be considered at high cardiovascular risk, and sex-specific interventions should focus on early diagnosis and prevention and optimal management of cardiovascular disease in patients with kidney failure.”
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