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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:166.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

Serum Total Bilirubin Level and Prevalent Lower-Extremity Peripheral Arterial Disease

National Health and Nutrition Examination Survey (NHANES) 1999 to 2004

Todd S. Perlstein; Reena L. Pande; Joshua A. Beckman; Mark A. Creager

From the Department of Medicine, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Todd S. Perlstein, MD, MMSc, Brigham and Women’s Hospital, Cardiovascular Division, 75 Francis Street, A Bldg, 3rd floor, Boston, MA 02115. E-mail tperlstein{at}partners.org

Abstract

Background— Bilirubin, with recently recognized antioxidant and antiinflammatory activity, has emerged as a candidate for atheroprotection. We hypothesized that higher levels of bilirubin would reduce susceptibility to peripheral arterial disease (PAD).

Methods and Results— We analyzed 7075 adults with data available on the ankle brachial index, serum total bilirubin level, and PAD risk factors in the National Health and Nutrition Examination Survey (1999 to 2004), a nationally representative cross-sectional examination of the United States population. A 0.1 mg/dL increase in bilirubin level was associated with a 6% reduction in the odds of PAD (OR 0.94 [95% CI 0.90 to 0.98]) after adjustment for age, gender, race/ethnicity, smoking status, diabetes, hypertension, hypercholesterolemia, chronic kidney disease, CRP, and homocysteine. This result was not dependent on bilirubin levels above the reference range, liver disease, or alcohol intake. The inverse association of bilirubin with PAD tended to be stronger among men (OR 0.90 [95% CI 0.85 to 0.96]) compared with women (OR 0.97 [95% CI 0.91 to 1.04]; P_interaction=0.05), and was stronger among active smokers (OR 0.81 [95% CI 0.73 to 0.90]) compared with nonsmokers (OR 0.97 [95% CI 0.93 to 1.02]; P_interaction<0.01).

Conclusions— Increased serum total bilirubin level is associated with reduced PAD prevalence. This result is consistent with the hypothesis that bilirubin is protective from PAD.

Bilirubin has antiinflammatory, antioxidant, and possibly atheroprotective properties. Among 7075 adults in the NHANES 1999 to 2004, we found that bilirubin was inversely associated with PAD prevalence independent of traditional and novel PAD risk factors. Higher bilirubin levels may therefore be associated with lessened susceptibility to PAD.

Key Words: bilirubin • peripheral vascular disease • PVD • epidemiology • Centers for Disease Control and Prevention • CDC • National Health and Nutrition Examination Survey • NHANES

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