All-Cause and Cardiovascular-Related Mortality in CKD Patients With and Without Heart Failure: A Population-Based Cohort Study in Kaiser Permanente Southern California

RATIONALE & OBJECTIVE: Heart failure and chronic kidney disease (CKD) frequently coexist reflective of the strong interplay between these organ systems. A better understanding of the prevalence of different types of heart failure (preserved and reduced ejection fraction) and their subsequent mortality risks among advanced CKD patients would provide important epidemiologic insights and may pave the way for more focused and proactive management strategies. STUDY DESIGN: Retrospective cohort study. SETTING & POPULATION: Patients aged ≥18 years with incident CKD (estimated glomerular filtration rate ≤45 mL/min/1.73 m(2)) with and without heart failure in a large integrated health care system in Southern California. EXPOSURE: Heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF). OUTCOMES: All-cause and cardiovascular-related mortality within one year of CKD identification. ANALYTICAL APPROACH: HRs were estimated using Cox proportional-hazards model for risk of all-cause mortality and Fine-Gray subdistribution hazard model for risk of cardiovascular-related mortality within 1 year. RESULTS: The study cohort included 76,688 patients with incident CKD between 2007 and 2017, of which 14,249 (18.6%) had prevalent heart failure. Among these patients, 8,436 (59.2%) had HFpEF and 3,328 (23.3%) had HFrEF. Compared with patients without heart failure, the HR for 1-year all-cause mortality was 1.70 (95% CI, 1.60-1.80) among patients with heart failure. The HRs were 1.59 (95% CI, 1.48-1.70) for patients with HFpEF and 2.43 (95% CI, 2.23-2.65) for patients with HFrEF. Compared with patients without heart failure, the 1-year cardiovascular-related mortality HR for patients with heart failure was 6.69 (95% CI, 5.93-7.54). Cardiovascular-related mortality HR was even higher among those with HFrEF (HR, 11.47; 95% CI, 9.90-13.28). LIMITATIONS: Retrospective design with a short 1-year follow-up period. Additional variables including medication adherence, medication changes, and time-varying variables were not accounted for in this intention-to-treat analysis. CONCLUSIONS: Among patients with incident CKD, heart failure was highly prevalent with HFpEF accounting for over 70% among patients with known ejection fraction. Although the presence of heart failure was associated with higher 1-year all-cause and cardiovascular-related mortality, patients with HFrEF were the most vulnerable.