Elsevier

Atherosclerosis

Volume 191, Issue 1, March 2007, Pages 115-120
Atherosclerosis

Decreased number of circulating CD34+KDR+ cells in asymptomatic subjects with preclinical atherosclerosis

https://doi.org/10.1016/j.atherosclerosis.2006.02.041Get rights and content

Abstract

Objectives

To assess whether circulating endothelial progenitor cells (CEPCs) can be considered as a cardiovascular risk marker before event has occurred, that is less firmly established than in clinically overt atherosclerosis.

Methods

Number of CD34+KDR+ cell number per ml blood was measured by flow cytometry in 84 untreated subjects without cardiovascular disease. Atherosclerotic plaque was detected by ultrasound in carotid, abdominal aortic and femoral sites and the number of sites affected by plaque among these three sites was counted as 0, 1, 2 or 3. Additionally, intima-media thickness (IMT) was measured by computerized ultrasound imaging of both common carotid segments.

Results

CD34+KDR+ cell number decreased by 48, 29 or 30% in the presence of carotid, aortic or femoral plaque (p < 0.001, 0.05, 0.05, respectively) as compared to the absence of plaque and by 70% in the presence of three sites affected with plaque as compared with 0 site with plaque (p < 0.01) but did not change with increasing IMT tertiles. Adjustment for Framingham risk score, that was also associated with decreased CD34+KDR+ cell number (p < 0.001), made CD34+KDR+ cell number associations with plaque insignificant, except at the carotid site (p < 0.01).

Conclusions

Reduced CEPC number may participate to preclinical stage of atherosclerosis and provide additional information to traditional risk factors as regards global risk assessment.

Introduction

Circulating endothelial progenitor cells (CEPCs) that are derived from bone marrow contribute to vascular homeostasis and repair, so that their impairment is likely to participate to the initiation and development of atherosclerotic disease [1], [2]. In patients with established cardiovascular disease, the number of CEPCs has been found lower than that of subjects free of cardiovascular disease [3]. Moreover it has been shown recently that reduced CEPC number was associated with increased risk of future cardiovascular events in secondary prevention patients with coronary artery disease [4], [5]. These results clearly emphasize the potential prognostic value of CEPCs as secondary risk markers. A challenging issue emerges from studies aimed at showing that CEPCs can be interpreted as primary risk markers in situations where no event has occurred. One study in healthy subjects has dealt with this issue by reporting that the number of colonies of cultured CEPCs was lower in the presence of cardiovascular risk factors (especially if multiple) than in their absence and decreased in parallel with impairment of brachial artery flow-mediated vasodilation, a functional marker of endothelial alteration [6]. In the present work, we measured directly the number of CEPCs by flow cytometry in relation with the presence and extent of preclinical atherosclerosis in extracoronary vessels of asymptomatic subjects without cardiovascular disease. For characterizing atherosclerosis, we used a structural surrogate marker, plaque, detected by ultrasound in three different carotid, abdominal aortic, and femoral sites prone to the early development of such lesions [7], [8].

Section snippets

Subjects

Eighty-four consecutive subjects of either sex (52 men and 32 women), referred between December 2003 and May 2005 to Preventive Cardiology Department for in-depth evaluation of cardiovascular risk status, were included in the study provided they fulfilled the following criteria: (i) absence of any present or past history of cardiovascular disease, (ii) absence of any drug treatment of risk reduction, (iii) availability of measurements of traditional cardiovascular risk factors and

Results

The distribution of CD34+KDR+ cell count per ml blood within the study population is shown in Fig. 1C. The prevalence of cardiovascular risk factors and preclinical atherosclerosis measures are shown in Table 1, Table 2. The Framingham risk score was higher in the presence than in the absence of carotid, aortic and femoral plaque (p < 0.001), increased in parallel with the number of diseased sites (p < 0.001), and was positively associated with carotid IMT (p < 0.01).

Discussion

To test whether monitoring CEPCs measurement may allow assessing better atherosclerotic risk burden in asymptomatic subjects without cardiovascular disease, we have counted the number of CD34+KDR+ cells in a relatively simple, inexpensive, and reproducible manner that is compatible with a potential clinical use in primary prevention.

Our main findings are that the number of CD34+KDR+ cells decreased with the presence and extent of preclinical atherosclerosis and risk factors accounted for such

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