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

Abstract

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.

Oxidative stress mediates renal endothelial cell damage in trichloroethylene-sensitized mice

“…VCAM-1 is important for mediating the adhesion of leukocytes and endothelial cells and can reflect endothelial cell disorders, but is not as specific as E-selectin. The expression of ICAM-1 is more extensive, not only in endothelial cells, but also in hematopoietic cells and fibroblasts (Kunutsor et al, 2017). In this study, E-selectin, VCAM-1 and ICAM-1 levels increased in the TCE sensitized group; eNOS, NO and NOS decreased in the TCE sensitized group, indicating that renal endothelial cells were damaged in the TCE sensitized group.…”

“…E-selectin is produced exclusively by endothelial cells and therefore is considered to be a superior biomarker of endothelial dysfunction compared to other cell adhesion molecules. E-selectin mediates the transient rolling of leukocytes along the endothelium while VCAM-1 and ICAM-1 mediate stronger attachment of leukocytes to the endothelium (Kunutsor et al, 2017). VCAM-1 is mainly expressed on endothelial cells, but is also expressed on leukocytes.…”

Inflammatory Markers for Arterial Stiffness in Cardiovascular Diseases

“…They are increased in endothelial dysfunction, vascular remodeling, and obesity. They are furthermore considered as biomarkers and mediators of cardiovascular disorders in several cardiovascular disorders, including hypertension, stroke, and coronary heart disease ( 34 , 105 , 106 ). They accelerate atherosclerosis by enabling attachment of circulating leukocytes to ECs ( 105 ).…”

“…They accelerate atherosclerosis by enabling attachment of circulating leukocytes to ECs ( 105 ). E-selectin and P-selectin mediate transient rolling of leukocytes along the endothelium and ICAM-1 and VCAM-1 mediate stronger attachment of leukocytes to the endothelium ( 106 ). Adhesion molecules can not only be detected on the endothelial surface but also as soluble adhesion molecules in the circulation, where they are reported as useful biomarkers to predict future fatal cardiovascular events in patients with angiographically documented CAD ( 107 ).…”

Soluble Vascular Cell Adhesion Molecule and Cardiovascular Disease: An Epidemiological View

“…In this issue of the Journal of Atherosclerosis and Thrombosis , Kunutsor et al examined the association between soluble VCAM-I plasma levels and incident cardiovascular disease (coronary heart disease and stroke) in the Prevention of Renal and Vascular Endstage Disease (PREVEND) Study, a prospective cohort study of a general population living in the city of Groningen, the Netherlands 4 ) . They found a weak correlation between VCAM-I and classical risk factors, and unexpectedly, an inverse association between VCAM-1 and risk of cardiovascular disease (primarily coronary heart disease) after adjustment for, or stratification by, classical risk factors.…”