Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction

Abstract

Objectives: The aim of this study was to evaluate the prevalence and prognostic impacts of noncardiac comorbidities in patients with heart failure (HF) with preserved ejection fraction (HFpEF) compared with those with HF with reduced ejection fraction (HFrEF).

Background: There is a paucity of information on the comparative prognostic significance of comorbidities between patients with HFpEF and those with HFrEF.

Methods: In a national ambulatory cohort of veterans with HF, the comorbidity burden of 15 noncardiac comorbidities and the impacts of these comorbidities on hospitalization and mortality were compared between patients with HFpEF and those with HFrEF.

Results: The cohort consisted of 2,843 patients with HFpEF and 6,599 with HFrEF with 2-year follow-up. Compared with patients with HFrEF, those with HFpEF were older and had higher prevalence of chronic obstructive pulmonary disease, diabetes, hypertension, psychiatric disorders, anemia, obesity, peptic ulcer disease, and cancer but a lower prevalence of chronic kidney disease. Patients with HFpEF had lower HF hospitalization, higher non-HF hospitalization, and similar overall hospitalization compared with those with HFrEF (p < 0.001, p < 0.001, and p = 0.19, respectively). An Increasing number of noncardiac comorbidities was associated with a higher risk for all-cause admissions (p < 0.001). Comorbidities had similar impacts on mortality in patients with HFpEF compared with those with HFrEF, except for chronic obstructive pulmonary disease, which was associated with a higher hazard (1.62 [95% confidence interval: 1.36 to 1.92] vs. 1.23 [95% confidence interval: 1.11 to 1.37], respectively, p = 0.01 for interaction) in patients with HFpEF.

Conclusions: There is a higher noncardiac comorbidity burden associated with higher non-HF hospitalizations in patients with HFpEF compared with those with HFrEF. However, individually, most comorbidities have similar impacts on mortality in both groups. Aggressive management of comorbidities may have an overall greater prognostic impact in HFpEF compared to HFrEF.

Figure 1. Stacked bar chart showing relative composition of the HF population (HFpEF vs. HFrEF) stratified by the total number of non-cardiac comorbidities

X-axis represents the total number of prevalent comorbidities, and the Y-axis demonstrates the relative proportion of patients with HFpEF and HFrEF for each category. As the number of prevalent comorbidities increases, there is a greater proportion of patients with HFpEF compared to patients with HFrEF (p<0.001 by trend analysis).

Figure 2. Incidence of death and at least one all-cause admission, heart failure (HF) admission, and non-HF related admission, in HFpEF and HFrEF patients

The median (inter quartile range) follow up for these end-points were 730 days (730 to 730 days), 518 days (138 to 730 days), 730 days (474 to 730 days) and 518 days (138 to 730 days), respectively. *p < 0.001

Figure 3. Kaplan Meier curves for hospitalization in patients with HFpEF and HFrEF

A) Heart failure admissions, and B) Non-heart failure admissions. Hazard ratios (HR) shown are calculated using univariate Cox proportional hazards models.

Figure 4. Risk of all-cause hospitalization vs. number of non-cardiac comorbidities

Log hazard ratios are based on Cox proportional hazard model (p<<0.001). Number of non-cardiac comorbidities used as a categorical variable. Error bars represent the upper limit of the 95% confidence interval.