Soluble Intercellular Adhesion Molecule-1, Soluble Vascular Adhesion Molecule-1, and the Development of Symptomatic Peripheral Arterial Disease in Men

Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass 02115-1204, USA.
Circulation (Impact Factor: 14.43). 09/2002; 106(7):820-5. DOI: 10.1161/01.CIR.0000025636.03561.EE
Source: PubMed


Elevated levels of soluble cellular adhesion molecules have been linked to the development of occlusive coronary events in otherwise healthy individuals. It is not certain, however, whether similar relationships exist for the development of early systemic atherosclerosis.
In a prospective, nested case-control study conducted among 14 916 middle-aged men, we evaluated the relationship between baseline levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and the subsequent development of symptomatic peripheral arterial disease (PAD) during a 9-year follow-up period. Median levels of sICAM-1 but not sVCAM-1 were significantly higher at baseline among men who developed PAD than among those who did not (285.2 versus 267.8 ng/mL [P=0.005] for sICAM-1 and 701.0 versus 709.3 ng/mL [P=0.8] for sVCAM-1). In analyses adjusted for age and smoking, the odds ratio in the highest compared with the lowest quartile of sICAM-1 was 3.9 (95% CI 1.7 to 8.6; P(trend)=0.001). After additional adjustment for lipid and nonlipid risk factors, including C-reactive protein, elevated sICAM-1 remained significantly associated with subsequent PAD (OR 3.5, 95% CI 1.4 to 8.5, P(trend)=0.008). Whereas a monotonic dose-response relationship was evident over the full spectrum of ICAM-1 levels, elevated sVCAM-1 was not associated with future PAD in either age- and smoking-adjusted or fully adjusted models.
Elevated levels of sICAM-1 are independently associated with the development of accelerated atherosclerosis among otherwise healthy men even in the absence of acute coronary occlusion.

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    • "Previous studies have shown associations between biomarkers of endothelial function such as transmembrane proteins intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and air pollution exposures [21]. ICAM-1 and VCAM-1 levels are associated with increased cardiovascular risk and are predictors of acute coronary events [22-24]. General markers of inflammation like interleukin-6 (IL-6) and C-reactive protein (CRP) have also been associated with cardiovascular risk [25,26] and air pollution [27,28]. "
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    ABSTRACT: Experimental evidence suggests that inhaled particles from vehicle exhaust have systemic effects on inflammation, endothelial activation and oxidative stress. In the present study we assess the relationships of short-term exposures with inflammatory endothelial activation and oxidative stress biomarker levels in a population of trucking industry workers. Blood and urine samples were collected pre and post-shift, at the beginning and end of a workweek from 67 male non-smoking US trucking industry workers. Concurrent measurements of microenvironment concentrations of elemental and organic carbon (EC & OC), and fine particulate matter (PM2.5) combined with time activity patterns allowed for calculation of individual exposures. Associations between daily and first and last-day average levels of exposures and repeated measures of intercellular and vascular cell adhesion molecule-1 (ICAM-1 & VCAM-1), interleukin 6 (IL-6) and C-reactive protein (CRP) blood levels and urinary 8-Hydroxy-2[prime]-Deoxyguanosine (8-OHdG) were assessed using linear mixed effects models for repeated measures. There was a statistically significant association between first and last-day average PM2.5 and 8-OHdG (21% increase, 95% CI: 2, 42%) and first and last-day average OC and IL-6 levels (18% increase 95% CI: 1, 37%) per IQR in exposure. There were no significant findings associated with EC or associations suggesting acute cross-shift effects. Our findings suggest associations between weekly average exposures of PM2.5 on markers of oxidative stress and OC on IL-6 levels.
    Environmental Health 12/2013; 12(1):105. DOI:10.1186/1476-069X-12-105 · 3.37 Impact Factor
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    • "There seem to be differences in the prognostic meaning of sICAM-1 and sVCAM: a previous observational study found a positive association between sICAM-1, but not sVCAM and atherosclerotic disease, in that case carotid or femoral plaque burden [23]. The same observation of sICAM-1 being a better predictor was found in a large cohort study of endothelial markers and symptomatic peripheral arterial disease [24]. This evidence suggests that the elevated sICAM-1 of individuals in the at risk group in our study signals an increased risk of future CVD despite their apparently healthy condition. "
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    ABSTRACT: Hispanics have a high rate of diabetes that exposes them to an increased risk of cardiovascular disease. We hypothesized that many of the pathophysiological mechanisms that cause atherosclerotic disease may be present in young Hispanics who do not have clinical diabetes but are at increased risk of developing it. We studied 36 young Hispanic adults without diabetes (ages 18--40). Seventeen participants were at increased risk of developing type 2 diabetes given by overweight and a family history of diabetes on one or both parents (at risk group). Nineteen participants with normal body-mass index and no parental history of diabetes constituted the control group. We measured and compared plasma markers of endothelial dysfunction, disturbed coagulation and fibrinolysis, subclinical inflammation and adipose tissue dysfunction in the at risk and control groups. Participants at risk of diabetes were more insulin-resistant according to different indicators, and had significantly higher levels of soluble intercellular adhesion molecule-1 (sICAM-1), tissue plasminogen activator (tPA), inhibitor of plasminogen activator-1 (PAi-1), high sensitivity C-reactive protein and free fatty acids, signaling the presence of multiple proatherogenic alterations despite the absence of overt diabetes. Levels of the prothrombotic molecule PAi-1 were most elevated in participants who were not only at risk of diabetes by the study definition, but also abdominally obese. Young adult Hispanics at risk of type 2 diabetes but without overt disease already bear considerably high levels of markers reflecting processes that lead to the development of atherosclerotic cardiovascular disease.
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    • "Adiponectin, a peptide with antiinflammatory properties, has in some studies been associated with a decreased risk of type 2 diabetes and CVD [35] [36]. Markers of endothelial dysfunction, like circulating levels of E-selectin, vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), as well as inflammatory parameters like CRP and IL-6, have been reported to be associated with CVD in several studies [37] [38] [39] [40] [41] [42]. Furthermore, the adhesion molecules E-selectin, VCAM-1, and ICAM-1 are thought to play a major role in the pathogenesis of vascular disease [6]. "
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