Background: Bilirubin inhibits experimental atherosclerosis, is inversely associated with carotid plaque burden, and confers neuroprotection in experimental stroke. Clinical data addressing the association of bilirubin with stroke are not available. We hypothesized that higher bilirubin levels would be associated with reduced stroke prevalence and improved stroke outcomes.
Methods: We used the National Health and Nutrition Examination Survey 1999 to 2004, a nationally representative cross-sectional examination of the United States civilian population, to examine the association of bilirubin with stroke. Of 13,214 adult participants with data on stroke history, serum total bilirubin level, and stroke risk factors, 453 reported a history of stroke. Of these, 138 participants reported an adverse stroke outcome, defined as a long-term health problem or disability due to stroke. We performed multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) with adjustment for demographic characteristics and stroke risk factors.
Results: After multivariable adjustment, a 1.71 micromol/L (0.1 mg/dL) increment in bilirubin level was associated with a 9% reduced odds of stroke (OR 0.91; 95% CI, 0.86-0.96) among all participants and with a 10% reduced odds of an adverse stroke outcome (OR 0.90; 95% CI, 0.80-1.00) among participants with a history of stroke.
Conclusions: These results suggest that a higher serum total bilirubin level is associated with reduced stroke prevalence and improved stroke outcomes. Our findings support the hypothesis that bilirubin may protect from stroke events and from neurologic damage in stroke.