Circulating Cell Adhesion Molecules and Death in Patients With Coronary Artery Disease

Abstract

MD; for the AtheroGene InvestigatorsBackground-Vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, and E-selectin mediate adhesion and transmigration of leukocytes to the vascular endothelial wall and may promote plaque growth and instability. In a prospective study, we evaluated the effect of soluble adhesion molecules on the risk of future cardiovascular events among patients with angiographically documented coronary artery disease (CAD). Methods and Results-We obtained baseline samples from a prospective cohort of 1246 patients with CAD. Besides various markers of inflammation, soluble VCAM-1 (sVCAM-1), sICAM-1, and sE-selectin were determined. Follow-up information on cardiovascular events was obtained (mean, 2.7; maximum, 4.1 years). Independently higher levels of sVCAM-1 (1932 versus 1128 ng/mL; PϽ0.0001), sICAM-1 (353 versus 287 ng/mL; Pϭ0.015), and sE-selectin (81 versus 63 ng/mL; Pϭ0.003) were observed in patients with future death from cardiovascular causes. In a multivariate model, fatal risk was 2.1-fold (1.1 to 4.0) higher in patients within the top quartile of baseline sVCAM-1 concentrations compared with lower quartiles. This association was present independent of general inflammatory response as reflected by low or high C-reactive protein (hs-CRP) levels. In a model that simultaneously controlled for all inflammatory and soluble adhesion markers determined, only sVCAM-1 remained independently significant for future fatal cardiovascular events, with a 2.8-fold increase in risk (Pϭ0.003). Conclusions-Soluble adhesion molecules sVCAM-1, sICAM-1, and sE-selectin were significantly related to future death from cardiovascular causes among patients with documented CAD. Especially sVCAM-1 added to the predictive value of classic risk factors and hs-CRP in determining the risk of future cardiovascular death.

Endothelial dysfunction is associated with increased levels of biomarkers in essential hypertension

“…6 Other inflammatory biomarkers, such as high-sensitivity C-reactive protein, soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule or interleukin-6 did not correlate with endothelial function in this group of patients. Although they are also produced totally or partially in the endothelium, and they have been found increased in hypertension 13,14 or in patients with cardiovascular disease, 21 no clear relationship with the endothelial function was observed in this study. A possible explanation of this different behaviour could be found in the relative young age of the study population, which was recently diagnosed of essential hypertension and was free from overt cardiovascular disease.…”

“…30 They have all been related to the risk of future cardiovascular events in healthy women 31 and especially in patients with coronary artery disease. 21,22 We have previously reported increased levels of these biomarkers in salt-sensitive hypertensive patients, 25 irrespective of the level of salt intake, a group also characterized by a more impaired endothelial function. 6 Other inflammatory biomarkers, such as high-sensitivity C-reactive protein, soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule or interleukin-6 did not correlate with endothelial function in this group of patients.…”

“…19,20 Moreover, in patients with coronary heart disease some of these serum markers have prognostic implications. [21][22][23] The aim of this study was to evaluate the correlation between the degree of endothelial dys-function, as measured by the maximal acetylcholine-induced forearm vasodilation, and the serum level of biochemical markers of inflammation, remodeling and oxidative stress, in a group of newly diagnosed, never-treated, essential hypertensive patients.…”

Assessment of endothelial function in the patient with erectile dysfunction: an opportunity for the urologist

“…47,48 Elevated CRP levels have also been found to significantly correlate with vascular ED as measured by penile Doppler. 49 Finally, markers of cellular adhesion, such as E-selectin, 50 intercellular adhesion molecule-1 Assessment of endothelial function in men with ED R Tamler and N Bar-Chama (ICAM-1) 44,51 or vascular cell adhesion molecule-1 (VCAM-1) 46 and thrombogenesis, such as von Willebrand factor (vWF) 52 or plasminogen-activator inhibitor type-1 (PAI-1) 53 have also been associated with endothelial dysfunction and increased risk of CAD. 54 This underlines the importance of inflammation and cellular adhesion in early atherosclerosis, 55 but-with the exception of CRP-so far has not resulted in increased clinical usability.…”

Soluble integrin adhesion receptors and atherosclerosis: much heat and a little light?

“…This association was independent of other risk factors, including the nonspecific inflammatory indicator C-reactive protein, and, in a multivariable model, sVCAM-1 was the only independently predictive soluble cell adhesion molecule. 45 Several authors [46][47][48][49] have reported increased levels of sICAM-1 and sVCAM-1 in cohorts with unstable coronary heart disease. Nevertheless, subtle differences are once again apparent.…”