Background Monocytes play important roles in inflammation, angiogenesis and tissue repair and may contribute to the pathophysiology of heart failure (HF). We examined differences in monocyte subset numbers and expression of cell surface markers of activation (CD14) and chemotaxis (CCR2) in patients with acute HF (AHF), stable HF (SHF) and controls and evaluated their impact on clinical outcomes.
Methods Three monocyte subsets [CD14++CD16−CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2− (Mon3)] were analysed by flow cytometry in 51 patients with AHF, 42 patients with SHF, 44 patients with stable coronary artery disease (CAD) and 40 healthy controls (HC). Surface marker expression of CD14 and CCR2 was also measured and expressed as median fluorescent intensity (MFI). The prognostic impact of monocyte subsets was examined in patients with AHF.
Results Patients with AHF had significantly higher Mon1 counts compared to other groups (p<0.001 for all) (Abstract 115 table 1). Similarly, Mon2 counts were increased in AHF compared to SHF (p=0.011), CAD (p<0.001) and HC (p<0.001). Mon2 counts were also increased in SHF compared to both CAD and HC groups (p=0.023, p=0.035 respectively). In AHF, CD14 expression by Mon2 was significantly higher than in CAD patients (1481±473 vs 1228±408, p=0.039) and in SHF patients, CD14 expression by Mon2 was significantly higher than in CAD patients (1502±484 vs 1228±408, p=0.031). CCR2 expression by Mon2 in AHF was higher than in HC (128±43.9 vs 104±28.5, p=0.013) and CCR2 expression by Mon2 was higher in SHF compared to HC (126±36.2 vs 104±28.5, p=0.032). 20 patients (39.2%) with AHF reached the primary end point of death or re-hospitalisation, with a median time to event of 129 (IQR 70.0–209) days. In Cox regression analysis, after adjustment for age, left ventricular ejection fraction, serum creatinine and brain natriuretic peptide, Mon2 count remained an independent negative predictor of combined death and re-hospitalisation [HR (for an increase of 10 cells/μl) 0.829 (CI 0.713 to 0.964; p=0.015)]. In Kaplan–Meier analysis AHF patients with Mon2 above median (59.9 cells/μl) had significantly better outcomes compared to those below the median (Abstract 115 figure 1).
Conclusion We have shown for the first time that CD14++CD16+ monocytes (Mon2) are an independent negative predictor of adverse prognosis in patients with AHF. This subset is phenotypically different from the other monocyte subsets, with increased expression of markers of activation (CD14) and chemotaxis (CCR2). Consequently, the Mon2 subset merits further evaluation as a prognostic marker and potential therapeutic target in patients with HF.
- heart failure