Homburg-Saar, Germany - In a prospective study of more than 500 patients with CAD, measurement of the level of circulating endothelial progenitor cells (EPCs)—a complex test—was useful to stratify the risk of dying from cardiovascular causes in the next year[1]. The findings, by Dr Nikos Werner (University of Saarland, Homburg-Saar, Germany) and colleagues, are published in the September 8, 2005 issue of the New England Journal of Medicine.

Study author Dr Georg Nickenig (University of Saarland) told heartwire, "We have evidence from cell-culture [studies] that these endothelial progenitor cells derived from bone marrow can regenerate and be involved in the healing process in various organs. We and others have done animal studies, but nobody knows the role of these cells in the pathogenesis of coronary artery disease in humans."

The team hypothesized that the number of EPCs was related to clinical outcomes in patients with CAD. They looked at 519 patients (mean age 66.6±10.8) who underwent coronary angiography that confirmed CAD. Flow cytometry was used to determine the baseline number of circulating EPCs that were positive for CD34 and for kinase insert domain receptor (KDR). EPC counts were classed into three groups according to level.

The investigators evaluated the association between the baseline level of EPCs and outcomes at one year. During this time, 43 patients died. A total of 23 patients died from cardiovascular causes: 14, six, and three patients in the low-, medium-, and high-EPC-level groups, respectively. After adjustment for relevant variables, increased levels of EPCs were linked with a reduced risk of death from cardiovascular causes, first major cardiovascular event, revascularization, or hospitalization but were not predictive of MI or death from any cause.

"We are in the beginning of understanding," Nickenig told heartwire. "There are two issues: first, to understand the pathophysiology, and second, to be able to use this for risk stratification, since patients with fewer numbers of cells are at higher risk of dying from cardiovascular causes."

He added, "A major point is that it is not easy to measure EPCs (but a few years ago, troponin was not easy to measure). We need larger studies in various patient groups, including healthy patients, to confirm that the findings from this study are true. The method is very definitive and absolutely valid, but it is [suitable] for a research team and right now is too complicated and expensive for a clinical lab."

In an accompanying editorial, Dr Anthony Rosenzweig (Harvard Medical School, Boston, MA) describes how this study advances knowledge [2]. "It demonstrates for the first time that the number of EPCs circulating in the blood of patients with coronary disease is an independent predictor of coronary death and overall cardiovascular clinical events during the subsequent year," he told heartwire.

"Clinically, it suggests that cells represent a new class of biomarkers that help assess risk and that EPCs in particular provide additional useful information about coronary risk in this population. It lends additional support to considering therapeutic approaches to enhance the number of EPCs, including redoubling efforts at standard therapy (mitigating other risk factors, statins, etc). . . . On a fundamental level, this study lends support to the hypothesis that atherosclerosis results from a balance of injury . . . and repair and that EPCs may (still a hypothesis) play a role in restoring and maintaining vascular function."