Frailty and Cardiovascular Outcomes in Adults With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Abstract

Rationale & objective: Frailty is common in individuals with chronic kidney disease (CKD) and increases the risk of adverse outcomes in adults with kidney failure requiring dialysis. However, this relationship has not been thoroughly evaluated among those with non-dialysis-dependent CKD.

Study design: Prospective cohort study.

Setting & participants: 2,539 adults in the Chronic Renal Insufficiency Cohort Study.

Exposure: Frailty status assessed using 5 criteria: slow gait speed, muscle weakness, low physical activity, exhaustion, and unintentional weight loss.

Outcome: Atherosclerotic events, incident heart failure, all-cause death, and cardiovascular death.

Analytical approach: Cause-specific hazards models.

Results: At study entry, the participants' mean age was 62 years, 46% were female, the mean estimated glomerular filtration rate was 45.4mL/min/1.73m², and the median urine protein was 0.2mg/day. Frailty status was as follows: 12% frail, 51% prefrail, and 37% nonfrail. Over a median follow-up of 11.4 years, there were 393 atherosclerotic events, 413 heart failure events, 497 deaths, and 132 cardiovascular deaths. In multivariable regression analyses, compared with nonfrailty, both frailty and prefrailty status were each associated with higher risk of an atherosclerotic event (HR, 2.03 [95% CI, 1.41-2.91] and 1.77 [95% CI, 1.35-2.31], respectively) and incident heart failure (HR, 2.22 [95% CI, 1.59-3.10] and 1.39 [95% CI, 1.07-1.82], respectively), as well as higher risk of all-cause death (HR, 2.52 [95% CI, 1.84-3.45] and 1.76 [95% CI, 1.37-2.24], respectively) and cardiovascular death (HR, 3.01 [95% CI, 1.62-5.62] and 1.78 [95% 1.06-2.99], respectively).

Limitations: Self-report of aspects of the frailty assessment and comorbidities, which may have led to bias in some estimates.

Conclusions: In adults with CKD, frailty status was associated with higher risk of cardiovascular events and mortality. Future studies are needed to evaluate the impact of interventions to reduce frailty on cardiovascular outcomes in this population.

Plain-language summary: Frailty is common in individuals with chronic kidney disease (CKD) and increases the risk of adverse outcomes. We sought to evaluate the association of frailty status with cardiovascular events and death in adults with CKD. Frailty was assessed according to the 5 phenotypic criteria detailed by Fried and colleagues. Among 2,539 participants in the CRIC Study, we found that 12% were frail, 51% were prefrail, and 37% were nonfrail. Frailty status was associated with an increased risk of atherosclerotic events, incident heart failure, and death.

Keywords: Atherosclerotic events; cardiovascular events; chronic kidney disease; frailty; mortality.

Figure 1.

Analytic cohort.

Figure 2.

The association of frailty status and outcomes. ⁺ Adjusted for clinical center, age, sex, race, ethnicity, education, marital status, smoking, body mass index, systolic blood pressure, diabetes, CV disease, ACE inhibitor/ARB use, aspirin, statin, LDL cholesterol, eGFR, and urine protein/creatinine ratio. Abbreviations: HR, hazard ratio; CI, confidence interval; CV, cardiovascular.