Association between C-reactive protein level and peripheral arterial disease among US adults without cardiovascular disease, diabetes, or hypertension

Background Inflammatory processes are implicated in the development and progression of atherosclerotic cardiovascular disease (CVD). C-reactive protein (CRP), a specific marker of inflammation, has been found to be related to CVD and subclinical atherosclerosis, including peripheral arterial disease (PAD). However, it is not entirely clear whether CRP levels are related to subclinical CVD independent of traditional risk factors, including diabetes and hypertension. We examined the association between CRP levels and PAD among US adults free of CVD, diabetes, and hypertension. Methods Cross-sectional study was performed among 1611 National Health and Nutrition Examination Survey 1999-2002 participants aged ≥40 years and without CVD, diabetes, or hypertension. Main outcome of interest was PAD defined as ankle-brachial index <0.9. Results Higher CRP levels were positively associated with PAD, independent of smoking, waist circumference, body mass index, blood pressure, glycosylated hemoglobin, serum total cholesterol, and other confounders. Multivariable odds ratio (95% CI) comparing quartile 4 of CRP (>0.54 mg/dL) to quartile 1 (<0.09 mg/dL) was 6.38 (1.77-22.96); P trend = .005. This association persisted in separate analysis in men and women. Furthermore, the results were consistent in subgroup analyses by categories of age, education, smoking, and body mass index. In nonparametric models, the positive association between CRP and PAD seemed to be present across the full range of CRP without any apparent threshold. Conclusions Higher CRP levels are associated with PAD among US adults free of CVD, diabetes, and hypertension. These results suggest that inflammatory mechanisms related to atherosclerosis may be operative even among clinically healthy adults.