Baseline levels of sICAM-1 were independently associated with incident symptomatic peripheral arterial disease in women (adjusted HR for extreme tertiles 4.0; 95% CI 1.9-8.6).
Cohort (n=27,935)
Effect estimate: HR 4.0 (95% CI 1.9-8.6)
BACKGROUND: Most investigations of novel biomarkers for prediction of cardiovascular disease pertain to coronary artery disease. Few large-scale prospective studies have critically assessed plasma-based factors as predictors of peripheral arterial disease (PAD), and comparative data between individual biomarkers and lipid levels are sparse, especially among women. METHODS AND RESULTS: We evaluated the relationship between baseline levels of several novel biomarkers and confirmed incident symptomatic PAD (n=100) in a prospective cohort study (median follow-up, 12.3 years) involving 27,935 US female health professionals > or = 45 years of age without diagnosed vascular disease at baseline. Biomarkers assessed were high-sensitivity C-reactive protein, fibrinogen, soluble intercellular adhesion molecule-1 (sICAM-1), homocysteine, lipoprotein(a), hemoglobin A1c, creatinine, and conventional lipid levels. In univariate analyses, levels of high-sensitivity C-reactive protein, fibrinogen, sICAM-1, homocysteine, lipoprotein(a), creatinine clearance, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and the ratio of total cholesterol to HDL-C (TC:HDL-C) were significantly related to PAD (all P<0.05). However, after multivariable adjustment, risk associations were significant only for high-sensitivity C-reactive protein (adjusted hazard ratio HR extreme tertiles, 2.1; 95% confidence interval, 1.2 to 3.7), sICAM-1 (adjusted HR, 4.0; 95% confidence interval, 1.9 to 8.6), HDL-C (adjusted HR, 0.4; 95% confidence interval, 0.3 to 0.8), and TC:HDL-C (adjusted HR, 2.2; 95% confidence interval, 1.2 to 3.9). In a model simultaneously controlling for traditional risk factors plus these significant biomarkers, sICAM-1 remained independently predictive of PAD (adjusted HR in each tertile, 1.0 reference, 2.3, and 3.5). CONCLUSIONS: Among a broad range of biomarkers of cardiovascular risk, only 4 factors, sICAM-1, high-sensitivity C-reactive protein, HDL-C, and TC:HDL-C, were significantly associated with incident symptomatic PAD in women. Findings pertaining to novel biomarkers provide clinical confirmation of a prominent role of endothelial activation and leukocyte recruitment in lower-extremity arterial disease.
Pradhan et al. (Tue,) conducted a cohort in Peripheral arterial disease (PAD) (n=27,935). Novel biomarkers (including sICAM-1 and hs-CRP) vs. Lowest tertile was evaluated on Incident symptomatic peripheral arterial disease (HR 4.0, 95% CI 1.9-8.6). Baseline levels of sICAM-1 were independently associated with incident symptomatic peripheral arterial disease in women (adjusted HR for extreme tertiles 4.0; 95% CI 1.9-8.6).