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.

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Objective-Endothelial dysfunction predicts morbidity and mortality in patients at cardiovascular risk. Endothelial function may be decisively influenced by the degree of endothelial cell apoptosis. Methods and Results-To test this hypothesis in humans, endothelial-dependent vasodilatation was invasively assessed in 50 patients with coronary artery disease (CAD) by quantitative coronary angiography during intracoronary acetylcholine infusion. Flow cytometry was used to assess endothelial cell apoptosis by quantification of circulating CD31 ϩ /annexin V ϩ apoptotic microparticles in peripheral blood. Increased apoptotic microparticle counts positively correlated with impairment of coronary endothelial function. Multivariate analysis revealed that increased apoptotic microparticle counts predict severe endothelial dysfunction independent of classical risk factors, such as hypertension, hypercholesterolemia, smoking, diabetes, age, or sex. Conclusions-In patients with CAD, endothelial-dependent vasodilatation closely relies on the degree of endothelial cell apoptosis, which is readily measurable by circulating CD31 ϩ /annexin V ϩ apoptotic microparticles. These findings possibly provide new options for risk assessment and may have implications for future treatment strategies of CAD.

Conclusion: Endothelial progenitor cells positive for CD-34 and kinase domain receptor (KDR) predict occurrence of death from cardiovascular causes and cardiovascular events. Summary: Endothelial progenitor cells can differentiate into endothelial cells and proliferate. They may be candidates for mediating vascular regeneration. These cells, derived from the bone marrow, are thought to support vascular endothelium integrity. Levels of endothelial progenitor cells correlate inversely with cardiovascular risk factors. The authors sought to study the prognostic value associated with circulating endothelial progenitor cells. Endothelial progenitor cells positive for CD-34 and KDR were determined using flow cytometry. Five hundred and nineteen patients with coronary artery disease confirmed by angiography were studied. After twelve months of follow-up, association between death from cardiovascular causes, the occurrence of a first major cardiovascular event (defined as myocardial infarction, hospitalization, revascularization, or death from cardiovascular cause), revascularization, hospitalization, and death from all causes was correlated with baseline levels of endothelial progenitor cells. Two hundred and fourteen patients had a first major cardiovascular event, 43 participants died, with 23 of these deaths from cardiovascular causes. Adjusting for age, vascular risk factors, sex, and other variables relevant to cardiovascular disease, increased levels of endothelial progenitor cells were associated with a reduced risk of a first major cardiovascular event (Hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.62 to 0.89; P ϭ .002), death from cardiovascular causes, (HR 0.31; 95% CI 0.16 to 0.63; P ϭ .001), hospitalization (HR 0.76; 95% CI 0.63 to 0.94; P ϭ .01), and revascularization (HR 0.77; 95% CI 0.62 to 0.95; P ϭ .02). Myocardial infarction and death from all causes were not predicted by endothelial progenitor-cell levels. Comment: The role of endothelial progenitor cells in rejuvenation of vascular endothelium is currently an area of intensive investigation. It appears these immature cells may modify the pathogenesis of atherosclerotic disease. Measurement of endothelial progenitor cells may improve risk stratification in patients with cardiovascular disease.

Endothelial progenitor cells (EPC) predict morbidity and mortality in patients at cardiovascular risk.Patients with low EPC counts and impaired endothelial colony forming activity have a higher incidence for cardiovascular events compared to patients with high EPC counts and favorable colony forming activity. The pathophysiological basis for this finding may be an insufficient endothelial cell repair by EPC.We postulate that EPC influence coronary endothelial function which itself is relevant for the outcome of patients at cardiovascular risk. To test this hypothesis in humans, endothelial function was invasively assessed in 90 patients with coronary heart disease by quantitative coronary angiography during intracoronary acetylcholine infusion. Flow cytometry of mononuclear cells isolated from peripheral blood was performed to assess CD133(+) or CD34(+)/KDR(+) EPC. EPC function was assessed ex vivo by determination of endothelial colony forming units. Low EPC number as well as impaired endothelial colony forming activity correlated with severely impaired coronary endothelial function in univariate analysis. Multivariate analysis revealed that only the number of EPC predicts severe endothelial dysfunction independent of classical cardiovascular risk factors. Endothelial function closely correlates with the number of circulating EPC providing new mechanistic insights and options for risk assessment in patients with coronary heart disease.