Circulating monocyte subsets and heart failure prognosis

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.

Phenotypic and Functional Heterogeneity of Monocyte Subsets in Chronic Heart Failure Patients

“…Several studies have demonstrated that Mon1 was the predominant subset in HF (87-48%) and it was followed by the Mon2 (5-44%) and Mon3 subsets (7.1-8.4%) [85,[93][94][95][96]. Thus, the data indicate a significant expansion of Mon2 subset in HF patients if compared to healthy controls (see also Table 3).…”

“…Noteworthy, M1 and M2 macrophage subsets in human heart tissues are defined by the expression of specific C-C chemokine receptor 2 (CCR2) [85]. CCR2 − macrophages (or M2) are tissue-resident and maintained through local proliferation, while CCR2 + (or M1) macrophages are derived from both monocyte recruitment and local proliferation [81].…”

“…It is intriguing that the role of monocytes under different CHF conditions is complex and, depending on the different monocyte subset number, encompasses inflammatory processes leading to tissue damage or repair [85,[90][91][92]. We summarized the articles, where monocyte subset (CD14++; CD16-, CD14++; CD16+, CD14+; CD16++) distribution in CHF patients was investigated; however, we did not evaluate works in which monocyte subsets were classified differently.…”

“…Another study examined CHF patients with idiopathic dilated cardiomyopathy (65% of investigated population) and ischemic heart disease (the remainder part of population, in total n=20), and found a higher total leukocyte count and a higher absolute monocyte count in CHF group when compared with healthy persons, but no differences in monocyte subset ratio (but not the cells count) between healthy and diseased persons [93]. However, under ambulatory treated HF conditions the Mon1 and Mon2 subsets (50.0±17.2% and 42±17.2%, respectively) outnumbered the Mon3 monocytes (8.1±4.0%) [85]. In contrast, the Mon1 subset significantly prevailed over the other two in healthy persons (see Table 3).…”

Integrated Analysis of Immunocyte Infiltration and Differential Gene Expression in Hypertrophic Obstructive Cardiomyopathy

“…In addition, CCL2 and TNFRSF1A were validated by PCR. Monocytes can differentiate into macrophages and have a proved signi cant relationship with HF and myocardial infarction in both animal and human research [17,18]. Additionally, monocytes in ltration can cause cardiac hypertrophy and remodeling [19].…”