Received on March 13, 2008
Accepted on August 14, 2008

Proteomics and Protein Markers

Association of Soluble Cell Adhesion Molecules with Ankle-Brachial Index in a Biethnic Cohort of Predominantly Hypertensive Individuals

¹ Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN
² Department of Medicine (Geriatrics), University of Mississippi Medical Center, Jackson, MS
³ Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN

^* To whom correspondence should be addressed. E-mail: kullo.iftikhar{at}mayo.edu.

BACKGROUND: Higher plasma concentrations of soluble adhesion molecules have been shown to be associated with increased risk of cardiovascular events. We investigated the association of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) with ankle-brachial index (ABI), a measure of peripheral arterial disease (PAD), in a biethnic cohort of adults without known coronary heart disease or stroke.

METHODS: Participants included 1102 blacks (mean 63 years old, 74% women) and 1013 non-Hispanic whites (mean 58 years old, 59% women) belonging to hypertensive sibships. We measured plasma concentrations of sICAM-1 and sVCAM-1 using high-sensitivity immunoassays and ABI using a standard protocol; PAD was defined as ABI <0.9. We used generalized estimating equations to assess whether sICAM-1 and sVCAM-1 were associated with ABI and PAD, independently of conventional risk factors.

RESULTS: After adjustment for conventional risk factors, blacks with sICAM-1 and sVCAM-1 concentrations in the highest quartiles had lower ABIs than those in the lowest quartiles (mean ABI 1.02 vs 0.98, P = 0.007, vs 1.02 vs 0.99, P = 0.003, respectively). In multivariable logistic regression analysis, sICAM-1 and sVCAM-1 concentrations in the highest quartiles were each associated with a higher odds ratio of having PAD, compared with the lowest quartiles: odds ratio (95% CI): 5.2 (1.8–15.2) and 2.2 (1.0–4.8), respectively. In contrast, in non-Hispanic whites, sICAM-1 and sVCAM-1 concentrations were not associated with ABI or PAD.

CONCLUSIONS: Higher sICAM-1 and sVCAM-1 concentrations were independently associated with lower ABI and PAD in blacks, but not in non-Hispanic whites.