Prevalent peripheral arterial disease and inflammatory burden

BACKGROUND: Strong evidence implicates inflammation in the development of atherosclerotic heart disease but less is known about peripheral arterial disease (PAD). Our objective was to test the hypothesis that a composite index of inflammatory burden is associated with PAD. METHODS: Cross-sectional analysis of a randomly-selected group of 903 community-dwelling men in the MrOS cohort recruited between 2000 and 2002. Using blood samples, we measured seven cytokines and related these levels to prevalent PAD (ankle-brachial index (ABI) <0.9) both individually and as part of an "inflammatory burden score" (a composite sum of the number of pro-inflammatory cytokines in the highest quartile). RESULTS: Overall, 6.75% of men had ABI <0.9. The odds of prevalent PAD were higher in men with the highest quartile (Q4) levels of interleukin-6 multivariable (MV) adjusted (odds ratio (OR) =3.95 (95% CI, 1.4-11.3), tumor necrosis factor alpha OR = 4.44 (95% confidence interval (CI), 1.5-12.8), and C-reactive protein OR = 3.63 (95% CI, 1.4-9.4) compared to men in Q1. The magnitude of the association of these cytokines with PAD was similar to the effect of being 10 years older, OR = 2.41 (95% CI, 1.16-3.7). These significant effects persisted after additional MV adjustment for smoking except for CRP. Men with the highest inflammatory burden score (≥3) had 3.6 (95% CI, 1.5-8.7) increased odds of PAD, p trend = 0.03. After smoking adjustment the linear trend was borderline statistically significant (p trend = 0.10). CONCLUSION: Inflammatory burden is associated with prevalent PAD, an association similar to aging 10 years. The inflammatory effects of smoking contributes to the underlying association between inflammation and PAD.