Effects of diabetes mellitus in patients with heart failure and chronic kidney disease: A propensity-matched study of multimorbidity in chronic heart failure

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Abstract

Background

Chronic kidney disease (CKD) and diabetes mellitus (DM) are common comorbidities in heart failure (HF) and each is associated with poor outcomes. However, the effects of multimorbidity related to having both CKD and DM compared to CKD alone have not been well studied in a propensity-matched population of chronic HF patients.

Methods

Of the 7788 ambulatory chronic HF patients in the Digitalis Investigation Group trial, 3527 had CKD, of whom 1095 had DM. Based on the absence or presence of DM, patients were categorized CKD-only and CKD-DM, respectively. Propensity scores for CKD-DM were calculated for each patient and were used to match 987 pairs of CKD-only and CKD-DM patients. Hazard ratios (HR) and 95% confidence intervals (CI) comparing CKD-DM patients with CKD-only patients were estimated using matched Cox regression models.

Results

All-cause mortality occurred in 47.0% (rate, 1783/10,000 person-years of follow-up) of CKD–DM patients and 39.6% (rate, 1414/10,000 person-years) of CKD-only patients (HR when CKD-DM is compared with CKD-only, 1.25; 95%–CI, 1.07–1.46; p = 0.006). All-cause hospitalization occurred in 75.4% (rate, 5710/10,000 person-years) and 67.8% (rate, 4213/10,000 person-years) of CKD-DM and CKD-only patients respectively (HR, 1.32; 95%–CI, 1.15–1.52; p < 0.0001). Respective HR and 95%–CI for other outcomes were: cardiovascular mortality (1.27; 1.06–1.52; p = 0.009), HF mortality (1.34; 1.04–1.72; p = 0.025); cardiovascular hospitalization (1.29; 1.12–1.49; p = 0.001) and HF hospitalization (1.37; 1.16–1.63; p < 0.0001).

Conclusions

Compared with comorbidity due to CKD alone, multimorbidity with CKD and DM was associated with poor outcomes in chronic HF patients.

Introduction

Multimorbidity is common in patients with heart failure (HF) [1]. Chronic kidney disease (CKD) and diabetes mellitus (DM) are common comorbidities in HF and are individually associated with poor outcomes [2], [3]. However, the association of multimorbidity and outcomes in chronic HF has not been well studied. The objective of this study was to test the hypothesis that in patients with chronic HF, compared with the comorbidity due to CKD alone, multimorbidity due to both CKD and DM is associated with increased mortality and hospitalization.

Section snippets

Study design and patients

This is a secondary analysis of the Digitalis Investigation Group (DIG) trial, which was a randomized, double-blind, placebo-controlled trial of digoxin in chronic HF patients conducted in the United States (186 centers) and Canada (116 centers) during 1991 to 1995. The design and the results of the DIG trial are well described in the literature [4], [5], [6].

Patients

All 7788 DIG participants were in normal sinus rhythm, 6800 had left ventricular ejection fraction ≤ 45%, and over 90% were receiving

Patient characteristics

Baseline characteristics for both groups before and after matching are displayed in Table 1 and Fig. 1. Values of absolute standardized differences for all covariates were < 5% after matching, suggesting substantial bias reduction (Fig. 1).

CKD–DM and mortality

Overall, 855 (43.3%) patients died from all causes. All-cause mortality occurred in 47.0% (rate, 1783/10,000 person-years) of CKD–DM patients, and 39.6% (rate, 1414/10,000 person-years) of patients with CKD (matched hazard ratio {HR} when CKD–DM was compared

Key study findings

In the current analysis, we demonstrate that in patients with chronic HF, the risk of adverse outcomes associated with CKD is further increased by the presence of additional comorbidity due to DM. These findings are important as HF is common among older adults who also suffer from multimorbidity. To the best of our knowledge, this is the first report of a propensity-matched study of associations of multimorbidity associated with DM with outcomes in chronic HF patients with CKD.

Mechanistic insights to study findings

All patients in

Conclusions

In conclusion, in this propensity-matched study of chronic HF patients with CKD, in which patients with and without DM were well-balanced on all measured baseline characteristics, the presence of DM was associated with significant increases in mortality and hospitalization. These findings highlight the importance of multimorbidity associated with DM and CKD on outcomes relative comorbidity due to CKD in patients with chronic HF. Future studies need to prospectively test preventive and

Acknowledgement

The Digitalis Investigation Group (DIG) study was conducted and supported by the NHLBI in collaboration with the DIG Investigators. This Manuscript was prepared using a limited access dataset obtained from the NHLBI and does not necessarily reflect the opinions or views of the DIG Study or the NHLBI.

The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [21].

References (21)

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Funding/Support: Dr. Ritchie is supported by the National Institute on Aging Geriatric Academic Leadership Award (1K07AG031779-01A1). Dr. Ahmed is supported by the National Institutes of Health through grants from the National Heart, Lung, and Blood Institute (5-R01-HL085561-02 and P50-HL077100), and a generous gift from Ms. Jean B. Morris of Birmingham, Alabama.

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