Association of soluble cell adhesion molecules with ankle-brachial index in a biethnic cohort of predominantly hypertensive individuals

Abstract

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 age, 63 years; 74% women) and 1013 non-Hispanic whites (mean age, 58 years; 59% women) belonging to sibships ascertained on the basis of hypertension. 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.

Figure 1

The distribution of plasma concentrations of sICAM-1 based on genotypes at SNP rs5491 (A/T) in ICAM-1, in blacks.

Figure 2

Association of soluble cell adhesion molecules with PAD and ABI in blacks. A) Prevalence of PAD (ABI <0.9) in the quartiles of plasma concentrations of sICAM-1 and sVCAM-1 in blacks. B) Mean±SE of ABI in the quartiles of plasma concentrations of sICAM-1 and sVCAM-1 in blacks. * P value <0.05; † P value <0.01; ‡ P value <0.001