Prevalent peripheral arterial disease and inflammatory burden

Abstract

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.