Soluble Intercellular Adhesion Molecule-1 and Risk of Future Ischemic Stroke

Abstract

Background and Purpose-Inflammation is considered to be involved in the pathogenesis of ischemic stroke. Our purpose was to assess the role of soluble intercellular adhesion molecule-1 (sICAM-1) concentration, a marker of inflammation, in predicting future ischemic stroke among patients at risk because of chronic coronary heart disease. Methods-We obtained baseline serum samples from patients with chronic coronary heart disease enrolled in the Bezafibrate Infarction Prevention trial (nϭ3090), which assessed the efficacy of bezafibrate in secondary prevention. Using a prospective nested case-control design, we measured baseline sICAM-1 concentration in sera of patients who developed ischemic stroke during a mean follow-up of 8.2 years (cases, nϭ134) and in age-and sex-matched controls without any subsequent cardiovascular events (nϭ134). Results-Baseline serum concentrations of sICAM-1 were significantly higher in cases compared with controls (379 versus 350 ng/mL, PϽ0.05). sICAM-1 concentration at the highest quartile (Ͼ394 ng/mL) was associated with significantly higher relative odds of ischemic stroke compared with the lower concentrations after adjustment for potential confounding variables (relative odds, 2.1; 95% CI, 1.1 to 4.3). After fibrinogen and total white blood cell count were added to the multivariable model, the relative odds were 2.1 (95% CI, 1.1 to 4.2) and 2.2 (95% CI, 1.1 to 4.8), respectively. The risk associated with raised concentrations of sICAM-1 seemed to be highest for large disabling strokes of cardioembolic origin. Conclusions-Elevated concentrations of sICAM-1, a marker of inflammation, are associated with increased risk of ischemic stroke, independent of other traditional cerebrovascular risk factors and of plasma fibrinogen, among patients at increased risk because of manifest coronary heart disease.

Are elevated circulating intercellular adhesion molecule 1 levels more strongly predictive of diabetes than vascular risk? Outcome of a prospective study in the elderly

“…These findings suggest ICAM-1 levels, in as much as they may reflect endothelial activation, are more strongly related to diabetes risk in the elderly than they are to cardiovascular risk. These data extend existing data in middle-aged individuals, since, in general, reported associations of circulating ICAM-1 with diabetes risk [3,4] appear to be of greater magnitude than their associations with CVD risk [5].…”

“…The study was conducted in the context of a randomised trial of statins [9]; however, baseline measures were taken before randomisation, and there was no significant interaction by randomised treatment. The study had an average 3.2 years of follow-up, although short follow-up may be appropriate in the more elderly because of the high event risk, and others have shown no difference in the association of ICAM-1 with vascular events by longer follow-up [4]. We acknowledge that the lack of OGTTs means that some individuals may have developed type 2 diabetes not detectable by changes in fasting glucose alone.…”

“…Early prospective studies showed significant associations between baseline circulating ICAM-1 levels and incident vascular events [1][2][3][4], but with larger studies and more rigorous adjustment for potential confounders, associations became far less marked [5]. More recently, circulating ICAM-1 levels have been shown to predict diabetes in middle-aged individuals [6,7] but data in the elderly are lacking.…”

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

“…17 Likewise, several large epidemiological studies have demonstrated that apparently healthy subjects with elevated levels of sICAM-1 are at increased risk of developing overt coronary heart disease, peripheral vascular disease, carotid atherosclerosis and stroke. [18][19][20][21][22][23] Although VCAM-1 appears to play an important role in atherogenesis, 24 the data relating sVCAM-1 levels to atherosclerosis are less consistent than those for sICAM-1. Several large studies that have demonstrated an association between sICAM-1 and incident vascular disease have failed to show a similar relation for sVCAM-1.…”

Association of polymorphism in ICAM-1 (K469E) and cytology parameters in patients’ initial blood test with acute ischemic stroke

“…Substantially increased expression of endothelial ICAM-1 was observed in brain autopsies of patients who died from ischemic stroke, indicating an association between ICAM-1 expression and ischemic stroke (Lindsberg et al, 1996). Increased levels of soluble ICAM-1 were also reported to be associated with higher susceptibility to ischemic stroke (Tanne et al, 2002;Simundic et al, 2004). A genetic polymorphism in ICAM-1, K469E (rs5498), causes an amino acid change from glutamic acid (E) to lysine (K) in the ICAM-1 protein, resulting in changes in protein structure and immunoglobulin binding.…”