Levels of Circulating Pro-angiogenic Cells Predict Cardiovascular Outcomes in Patients With Chronic Heart Failure
Received 24 October 2008; received in revised form 17 April 2009; accepted 21 May 2009. published online 06 July 2009.
Abstract
Background
Circulating pro-angiogenic cells (PACs) contribute to vascular and myocardial regeneration. A low level of PACs is associated with worse outcome in patients with coronary heart disease. However, little is known about PACs in heart failure (HF).
Methods and Results
Blood was sampled at baseline in 111 patients with HF, 67 from 5 Italian Centers and 44 from Frankfurt, Germany. In cultured mononuclear cells from peripheral blood, PACs were counted as double-stained by tetramethylindocarbocyanine-labeled acetylated LDL and fluorescein-5-isothiocyanate–labeled lectin. Mean age of the patients was 62 years, 12 were females, 66 had ischemic etiology, 26 were in New York Heart Association Class >II. Cutoffs for PACs were assessed by receiver operating characteristic curves, to identify the optimal cutoffs for PAC level in predicting outcomes. Mean level of PACs was 35±29 (mean±SD) cells/mm2, 2- to 3-fold lower than in age-matched healthy volunteers, but unrelated to severity of HF, age, or sex. Over 2.5 years, 12 cardiovascular deaths and 47 first hospitalizations for cardiovascular reasons were recorded. After adjustment for demographic and clinical variables, elevated creatinine and natriuretic peptides, and PACs ≤30.5/mm2 were associated with a 2-fold higher risk of cardiovascular death and hospitalization, as shown by survival curves and by Cox multivariable.
Conclusions
The level of circulating PACs is an independent predictor of cardiovascular death and hospitalization in patients with chronic HF, it can be assessed in blood samples collected in a multicenter setting, and may offer an accessible tool to assess the role of vascular regeneration in patients with HF.
11Department of Medicine, New York Medical College, Valhalla, NY
Reprint requests: Roberto Latini, Dept. of Cardiovascular Research, Mario Negri Institute for Pharmacological Research, via La Masa 19, 20156 Milano, Italy. Tel: +39 0239 014454; Fax: +39 0233 200049.
This work stems from the European Vascular Genomics Network (http://www.evgn.org), a Network of Excellence supported by the European Community's sixth Framework Programme for Research Priority 1 “Life sciences, genomics and biotechnology for health” (contract no. LSHM-CT-2003-503254), and the Consortium Agreement European Community “Heart failure and cardiac repair,” IP 018630.
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