The American Journal of Medicine
Volume 121, Issue 9 , Pages 781-788.e1, September 2008

Serum Total Bilirubin Level, Prevalent Stroke, and Stroke Outcomes: NHANES 1999–2004

This work was presented as an abstract at the Society of Vascular Medicine and Biology annual meeting, Baltimore, Maryland, June 2007.

  • Todd S. Perlstein, MD

      Affiliations

    • Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass
    • Corresponding Author InformationRequests for reprints should be addressed to Todd S. Perlstein, MD, Division of Cardiovascular Medicine, Brigham and Women's Hospital, 75 Francis Street, A322, Boston, MA 02115
  • ,
  • Reena L. Pande, MD

      Affiliations

    • Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass
  • ,
  • Mark A. Creager, MD

      Affiliations

    • Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass
  • ,
  • Jennifer Weuve, ScD

      Affiliations

    • Department of Environmental Health, Harvard School of Public Health, Boston, Mass
  • ,
  • Joshua A. Beckman, MD

      Affiliations

    • Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass

Abstract 

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 μmol/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.

Keywords: Bilirubin, Epidemiology, Heme oxygenase, National Health and Nutrition Examination Survey, Nutrition survey, Stroke

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 Dr Perlstein was supported by the National Heart, Lung and Blood Institute (NHLBI) Training Grant T32 HL07604 and an American College of Cardiology Foundation/Merck Research Fellowship Award. Dr Beckman was supported by American Diabetes Association Career Development Award 1-06-CD-01. Dr Creager is the Simon C. Fireman Scholar in Cardiovascular Medicine. Dr Pande was supported by NHLBI training grant T32 HL07604 and by a Research Career Development Award (K12 HL083786) from the NHLBI. Dr Weuve is partially supported by National Institutes of Environmental Health Sciences R01ES005257. This work also was supported by NHLBI grant R01 HL075771.

PII: S0002-9343(08)00470-1

doi:10.1016/j.amjmed.2008.03.045

The American Journal of Medicine
Volume 121, Issue 9 , Pages 781-788.e1, September 2008