Introduction:
Markers of endothelial function may be associated with increased risk for cardiovascular disease; however, prospective data for peripheral arterial disease (PAD) are limited. We evaluated the hypothesis that serum markers of endothelial dysfunction are associated with an increased risk of PAD among women.
Methods:
We conducted a nested case-control study within an ongoing prospective cohort of U.S. female nurses (Nurses’ Health Study). Among 32,826 NHS participants who provided blood samples in 1989-1990, after excluding those who had myocardial infarction, coronary heart disease, stroke, or carotid artery surgery prior to the PAD diagnosis, we included all incident PAD cases that occurred between 1990 and 2008 and were confirmed by medical records. Each case was individually matched with three eligible controls using risk-set sampling, by age, smoking, date of blood draw, and fasting status. We evaluated the association between serum levels of soluble intercellular adhesion molecule (ICAM-1), E-selectin, and the risk of PAD, using conditional logistic regression analysis.
Results:
Complete biomarker data from 1990 was available for 144 cases and 431 controls. After accounting for matching factors, baseline ICAM-1 levels were associated with higher risk of PAD (RR for highest (T3) vs. lowest (T1) tertile=1.75, 95% CI: 1.05-2.90). The association was attenuated and no longer significant (RR T3 vs. T1=1.37, 95% CI: 0.75-2.49) after adjusting for serum levels of HDL and LDL-cholesterol, family history of myocardial infarction, relative weight, reported aspirin and cholesterol-lowering medication use, hypertension and diabetes diagnoses, physical activity, and pack-years of smoking. Additional adjustment for CRP levels further attenuated the relative risk (RR T3 vs. T1= 1.24, 95% CI: 0.67-2.29). We did not observe any significant association between baseline E-selectin levels and the risk of PAD (multivariate- and CRP-adjusted RR T3 vs. T1=0.93, 95% CI: 0.54-1.59).
Conclusions:
There was no association between ICAM-1 and E-selectin and subsequent PAD in this cohort of U.S women.
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