Chronic kidney disease associated mortality in diastolic versus systolic heart failure: a propensity matched study

Abstract

Chronic kidney disease (CKD) is common and is associated with increased mortality in heart failure (HF). However, it is unknown whether the effect of CKD on mortality varies by left ventricular ejection fraction (LVEF). We evaluated the effect of CKD on mortality in patients with systolic (LVEF <or=45%) and diastolic (LVEF >45%) HF. Of the 7,788 patients in the Digitalis Investigation Group trial, 3,527 (45%) had CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2). We calculated the propensity score for CKD for each patient, using a multivariate logistic regression model (c statistic 0.76, postmatch absolute standardized differences <5% for all 32 co-variates). We matched 2,399 pairs of patients with and without CKD with similar propensity scores. There were 757 (rate 1,049/10,000 person-years) and 882 (rate 1,282/10,000 person-years) deaths, respectively, in patients without and with CKD (hazard ratio 1.22, 95% confidence interval 1.09 to 1.36, p <0.0001). CKD-associated mortality was higher in those with diastolic HF (371 extra deaths/10,000 person-years, hazard ratio 1.71, 95% confidence interval 1.21 to 2.41, p = 0.002) than in systolic HF (214 extra deaths/10,000 person-years, hazard ratio 1.19, 95% confidence interval 1.07 to 1.32, p = 0.001), which was significant (adjusted p for interaction = 0.034). A graded association was found between CKD-related deaths and LVEF. The hazard ratios for CKD-associated mortality for the LVEF subgroups of <35%, 35% to 55%, and >55% were 1.15 (95% confidence interval 1.02 to 1.29), 1.35 (95% confidence interval 1.11 to 1.64), and 2.33 (95% confidence interval 1.34 to 4.06). In conclusion, CKD-associated mortality was higher in those with diastolic than systolic HF. Patients with diastolic HF should be evaluated for CKD, and the role of inhibitors of the renin-angiotensin system in these patients needs to be investigated.

Figure 1

Absolute standardized differences in baseline covariates between patients with and without chronic kidney disease, before and after propensity score matching (post-match standardized difference <5% indicate excellent covariate balance).

Figure 2

Kaplan-Meier plots for cumulative risk of all-cause death associated with chronic kidney disease (CKD) (SHF=systolic heart failure or heart failure with ejection fraction ≤ 45% and DHF=diastolic heart failure or heart failure with ejection fraction >45%)

Figure 3

Hazard ratios and 95% confidence intervals for mortality associated with chronic kidney disease (CKD) in subgroups of patients with heart failure (ACEI=angiotensin-converting enzyme inhibitor, DM=diabetes, EF=ejection fraction, NYHA=New York Heart Association)