Abstract
Monocytes are a heterogeneous population of effector cells with key roles in tissue integrity restoration and maintenance. Here, we explore the association of monocyte subsets and prognosis in patients with ambulatory heart failure (HF). Monocyte subsets were classified as classical (CD14++/CD16–), intermediate (CD14++/CD16+), or non-classical (CD14+/CD16++). Percentage distribution and absolute cell count were assessed in each subset, and multivariable Cox regression analyses were performed with all-cause death, HF-related hospitalization, and the composite end-point of both as dependent variables. 400 patients were consecutively included (72.8% male, age 69.4±12.2 years, 45.5% from ischemic aetiology, left ventricle ejection fraction (LVEF) 41.6% ±14.5, New York Heart Association (NYHA) class II 62.8% and III 30.8%). During a mean follow-up of 2.6±0.9 years, 107 patients died, 99 had a HF-related hospitalization and 160 suffered the composite end-point of all-cause death or HF-related hospitalization. Monocyte subsets assessed in percentages were not independently associated to any of the end-points. When considering number of cells/μL, intermediate subset was independently associated with an increase of all-cause death (HR 1.25 [95% CI 1,02–1.52], p = 0.03), and the composite end-point HR 1.20 [95% CI 1,03–1.40], p = 0.02). The presented findings show that absolute cell count of monocyte subsets was preferred over monocyte percentage for prognosis stratification for outpatients with HF. The intermediate monocyte subset provides information on increased risk of all-cause death and the composite end-point.
Highlights
Heart failure (HF) is a syndromic disease associated with significant economic burden and clinical manifestations [1,2]
When the monocyte subset distribution was assessed according to the different etiologies of HF, globally there were no statistically significant differences when percentages of subsets were considered, but a significant difference was observed in the non-classic subset when number of cells was measured (p = 0.04)
We investigated two main questions in this study: first, what is the distribution of the three subsets of monocytes in outpatients with HF diagnosis, and second, can this distribution be related to the main events of the study, and play predictive role for HF patients? In this context, we found a significant difference in the percentages of monocyte subsets relative to previous studies performed in healthy controls [20]
Summary
Heart failure (HF) is a syndromic disease associated with significant economic burden and clinical manifestations [1,2]. Morbidity and mortality continues to be unacceptably high for patients with HF, despite significant research and medical progress. A better risk stratification by an improved understanding of the underlying pathogenic mechanisms and potentially valuable prognostic markers could be a key for the optimal determination of patients who would benefit from close follow-up and more aggressive treatment. Established prognostic factors including the New York Heart Association (NYHA) functional classification, the left ventricle ejection fraction (LVEF), age, sex, aetiology, comorbidities and laboratory markers all fail to completely and individually predict disease progression and mortality [3,4,5,6]. Risk stratification could be improved by the incorporation of biomarkers associated with different pathophysiological pathways, not reflected by established mortality risk factors. The search for biomarkers for HF diagnosis and prognosis has become a major research focus over the last decade [6,7,8]
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