Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes - The Hoorn study

Membrane-bound vascular cell adhesion molecule 1 (VCAM-1) allows the tether ing and rolling of monocytes and lymphocytes as well as firm attachment and transendothelial migration of leukocytes. Soluble forms of VCAM (sVCAM-1) may serve as monitors of increased expression of membrane-bound VCAM-1 and thus may reflect progressive formation of atherosclerotic lesions. Levels o f sVCAM-1 have been found to be increased among type 2 diabetic as compared with nondiabetic subjects. To study the association of plasma sVCAM-1 conc entration and risk of cardiovascular and all-cause mortality among nondiabe tic and diabetic subjects, we investigated an age-, sex-, and glucose-toler ance-stratified sample (n = 631) of a population-based cohort aged 50-75 ye ars that was followed prospectively. Plasma levels of sVCAM-1 were determin ed in frozen -70 degrees C baseline samples. After 7.4 years (mean) of foll ow-up, 107 (17%) subjects had died (42 of cardiovascular causes). In the en tire group, increased sVCAM-1 levels were significantly associated with inc reased risk of cardiovascular mortality (relative risks [RRs] per 100 ng/ml sVCAM-1 increase, 1.10 [1.05-1.15] after adjustment for age, sex, and gluc ose tolerance status). This RR was somewhat diminished by further adjustmen t for the presence of hypertension and cardiovascular disease; levels of to tal, HDL, and LDL cholesterol and homocysteine; the presence of microalbumi nuria (a putative marker of endothelial dysfunction); levels of von Willebr and factor (a marker of endothelial dysfunction) and C-reactive protein (a marker of low-grade inflammation); and estimates of glomerular filtration r ate. However, the RR remained statistically significant. The RR among type 2 diabetic subjects was 1.13 (1.07-1.20) per 100 ng/ml sVCAM-1 increase aft er adjustment for age and sex, which was somewhat higher but not significan tly different from the RR in nondiabetic subjects (P value for interaction term, 0.12). Further adjustment for other risk factors gave similar results . In conclusion, levels of sVCAM-1 are independently associated with the ri sk of cardiovascular mortality in type 2 diabetic subjects and therefore mi ght be useful for identifying subjects at increased cardiovascular risk. In creased plasma sVCAM-1 levels may reflect progressive formation of atherosc lerotic lesions, or sVCAM-1 itself may have bioactive properties related to cardiovascular risk. Our data, however, argue against the hypotheses of sV CAM-1 levels simply being a marker of endothelial dysfunction, of low-grade inflammation, or of an impaired renal function.