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Previous Volume 353:999-1007 September 8, 2005 Number 10 Next

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ABSTRACT

Background Endothelial progenitor cells derived from bone marrow are believed to support the integrity of the vascular endothelium. The number and function of endothelial progenitor cells correlate inversely with cardiovascular risk factors, but the prognostic value associated with circulating endothelial progenitor cells has not been defined.

Methods The number of endothelial progenitor cells positive for CD34 and kinase insert domain receptor (KDR) was determined with the use of flow cytometry in 519 patients with coronary artery disease as confirmed on angiography. After 12 months, we evaluated the association between baseline levels of endothelial progenitor cells and death from cardiovascular causes, the occurrence of a first major cardiovascular event (myocardial infarction, hospitalization, revascularization, or death from cardiovascular causes), revascularization, hospitalization, and death from all causes.

Results A total of 43 participants died, 23 from cardiovascular causes. A first major cardiovascular event occurred in 214 patients. The cumulative event-free survival rate increased stepwise across three increasing baseline levels of endothelial progenitor cells in an analysis of death from cardiovascular causes, a first major cardiovascular event, revascularization, and hospitalization. After adjustment for age, sex, vascular risk factors, and other relevant variables, increased levels of endothelial progenitor cells were associated with a reduced risk of death from cardiovascular causes (hazard ratio, 0.31; 95 percent confidence interval, 0.16 to 0.63; P=0.001), a first major cardiovascular event (hazard ratio, 0.74; 95 percent confidence interval, 0.62 to 0.89; P=0.002), revascularization (hazard ratio, 0.77; 95 percent confidence interval, 0.62 to 0.95; P=0.02), and hospitalization (hazard ratio, 0.76; 95 percent confidence interval, 0.63 to 0.94; P=0.01). Endothelial progenitor-cell levels were not predictive of myocardial infarction or of death from all causes.

Conclusions The level of circulating CD34+KDR+ endothelial progenitor cells predicts the occurrence of cardiovascular events and death from cardiovascular causes and may help to identify patients at increased cardiovascular risk.

Source Information

From the Division of Cardiology, Angiology, and Intensive Care Medicine, Department of Internal Medicine, University of Saarland, Homburg–Saar, Germany.

Address reprint requests to Dr. Nickenig at the Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, D-66421, Homburg–Saar, Germany, or at nickenig{at}med-in.uni-sb.de.

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Related Letters:

Circulating Endothelial Progenitor Cells
Kim D. H., Leu H.-B., Chen J.-W., Lin S.-J., Ott H. C., Taylor D. A., Bertolini F., Mancuso P., Kerbel R. S., Boos C. J., Goon P. K.Y., Lip G. Y.H., Werner N., Nickenig G.
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N Engl J Med 2005; 353:2613-2616, Dec 15, 2005. Correspondence

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• Authors/Task Force Members:, , Mancia, G., De Backer, G., Dominiczak, A., Cifkova, R., Fagard, R., Germano, G., Grassi, G., Heagerty, A. M., Kjeldsen, S. E., Laurent, S., Narkiewicz, K., Ruilope, L., Rynkiewicz, A., Schmieder, R. E., Struijker Boudier, H. A.J., Zanchetti, A., ESC Committee for Practice Guidelines (CPG):, , Vahanian, A., Camm, J., De Caterina, R., Dean, V., Dickstein, K., Filippatos, G., Funck-Brentano, C., Hellemans, I., Kristensen, S. D., McGregor, K., Sechtem, U., Silber, S., Tendera, M., Widimsky, P., Zamorano, J. L., ESH Scientific Council:, , Kjeldsen, S. E., Erdine, S., Narkiewicz, K., Kiowski, W., Agabiti-Rosei, E., Ambrosioni, E., Cifkova, R., Dominiczak, A., Fagard, R., Heagerty, A. M., Laurent, S., Lindholm, L. H., Mancia, G., Manolis, A., Nilsson, P. M., Redon, J., Schmieder, R. E., Struijker-Boudier, H. A.J., Viigimaa, M., Document Reviewers:, , Filippatos, G., Adamopoulos, S., Agabiti-Rosei, E., Ambrosioni, E., Bertomeu, V., Clement, D., Erdine, S., Farsang, C., Gaita, D., Kiowski, W., Lip, G., Mallion, J.-M., Manolis, A. J., Nilsson, P. M., O'Brien, E., Ponikowski, P., Redon, J., Ruschitzka, F., Tamargo, J., van Zwieten, P., Viigimaa, M., Waeber, B., Williams, B., Zamorano, J. L. (2007). 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 0: ehm236v1-75 [Full Text]  
• Cubbon, R. M, Rajwani, A., Wheatcroft, S. B (2007). The impact of insulin resistance on endothelial function, progenitor cells and repair. Diabetes and Vascular Disease Research 4: 103-111 [Abstract]  
• Asosingh, K., Swaidani, S., Aronica, M., Erzurum, S. C. (2007). Th1- and Th2-Dependent Endothelial Progenitor Cell Recruitment and Angiogenic Switch in Asthma. J. Immunol. 178: 6482-6494 [Abstract] [Full Text]  
• Theiss, H. D., David, R., Engelmann, M. G., Barth, A., Schotten, K., Naebauer, M., Reichart, B., Steinbeck, G., Franz, W.-M. (2007). Circulation of CD34+ progenitor cell populations in patients with idiopathic dilated and ischaemic cardiomyopathy (DCM and ICM). Eur Heart J 28: 1258-1264 [Abstract] [Full Text]  
• Boos, C. J., Soor, S. K., Kang, D., Lip, G. Y.H. (2007). Relationship between circulating endothelial cells and the predicted risk of cardiovascular events in acute coronary syndromes. Eur Heart J 28: 1092-1101 [Abstract] [Full Text]  
• Fadini, G. P., Sartore, S., Agostini, C., Avogaro, A. (2007). Significance of Endothelial Progenitor Cells in Subjects With Diabetes. Diabetes Care 30: 1305-1313 [Full Text]  
• Thum, T., Fraccarollo, D., Thum, S., Schultheiss, M., Daiber, A., Wenzel, P., Munzel, T., Ertl, G., Bauersachs, J. (2007). Differential Effects of Organic Nitrates on Endothelial Progenitor Cells Are Determined by Oxidative Stress. Arterioscler. Thromb. Vasc. Bio. 27: 748-754 [Abstract] [Full Text]