Soluble Vascular Cell Adhesion Molecules May be Protective of Future Cardiovascular Disease Risk: Findings from the PREVEND Prospective Cohort Study

Aim: Soluble cell adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1, E-selectin, and P-selectin, have been suggested to be associated with cardiovascular disease (CVD) risk; however, the nature and magnitude of the association between VCAM-1 and CVD risk is uncertain. We aimed to assess the association of VCAM-1 with CVD risk and determine its potential utility for CVD risk prediction. Methods: VCAM-1 concentrations were measured at baseline in the PREVEND prospective study of 2,638 participants. Hazard ratios (95% confidence intervals [CI]) and measures of risk discrimination for CVD (e.g., C-index) and reclassification (i.e., net reclassification improvement) of participants were assessed. Results: During a median follow-up of 9.9 years, 614 CVD events occurred. Plasma VCAM-1 was weakly associated with several cardiovascular risk markers. In analyses adjusted for established cardiovascular risk factors, the hazard ratio (95% CI) for CVD per 1 standard deviation increase in loge VCAM-1 was 0.91 (0.84-0.99; P=0.020), which remained consistent after additional adjustment for body mass index, alcohol consumption, triglycerides, renal function, and C-reactive protein; hazard ratio (95% CI) 0.89 (0.82-0.97; P=0.006). Comparing the top versus bottom quintiles of VCAM-1 levels, the corresponding adjusted hazard ratios were 0.74 (0.57-0.96; P=0.023) and 0.70 (0.54 -0.91; P=0.007) respectively. Adding VCAM-1 to a CVD risk prediction model containing conventional risk factors did not improve the C-index or net reclassification. Conclusions: Plasma VCAM-1 is inversely and independently associated with CVD. However, VCAM-1 provides no significant improvement in CVD risk assessment beyond conventional CVD risk factors.