Published Online
on July 15, 2002

A more recent version of this article appeared on August 13, 2002

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Submitted on April 15, 2002
Revised on May 29, 2002
Accepted on May 29, 2002

Soluble Intercellular Adhesion Molecule-1, Soluble Vascular Adhesion Molecule-1, and the Development of Symptomatic Peripheral Arterial Disease in Men

Aruna D. Pradhan MD, MPH, Nader Rifai PhD, and Paul M. Ridker MD, MPH^*

From the Center for Cardiovascular Disease Prevention (A.D.P., N.R., P.M.R.), the Leducq Center for Molecular and Genetic Epidemiology of Cardiovascular Disorders (A.D.P., N.R., P.M.R.), the Divisions of Cardiology (A.D.P., P.M.R.) and Preventive Medicine (A.D.P., P.M.R.), Brigham and Women's Hospital and Harvard Medical School, Boston, Mass; and the Department of Pathology (N.R.), Children's Hospital Medical Center and Harvard Medical School, Boston, Mass.

^* To whom correspondence should be addressed. E-mail: pridker{at}partners.org.

Background—Elevated levels of soluble cellular adhesion molecules have been linked to the development of occlusive coronary events in otherwise healthy individuals. It is not certain, however, whether similar relationships exist for the development of early systemic atherosclerosis.

Methods and Results—In a prospective, nested case-control study conducted among 14 916 middle-aged men, we evaluated the relationship between baseline levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and the subsequent development of symptomatic peripheral arterial disease (PAD) during a 9-year follow-up period. Median levels of sICAM-1 but not sVCAM-1 were significantly higher at baseline among men who developed PAD than among those who did not (285.2 versus 267.8 ng/mL [P=0.005] for sICAM-1 and 701.0 versus 709.3 ng/mL [P=0.8] for sVCAM-1). In analyses adjusted for age and smoking, the odds ratio in the highest compared with the lowest quartile of sICAM-1 was 3.9 (95% CI 1.7 to 8.6; P_trend=0.001). After additional adjustment for lipid and nonlipid risk factors, including C-reactive protein, elevated sICAM-1 remained significantly associated with subsequent PAD (OR 3.5, 95% CI 1.4 to 8.5, P_trend=0.008). Whereas a monotonic dose-response relationship was evident over the full spectrum of ICAM-1 levels, elevated sVCAM-1 was not associated with future PAD in either age- and smoking-adjusted or fully adjusted models.

Conclusions—Elevated levels of sICAM-1 are independently associated with the development of accelerated atherosclerosis among otherwise healthy men even in the absence of acute coronary occlusion.

Key words: cell adhesion molecules • peripheral vascular disease • men

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