Sex Differences in the Association between Total Bilirubin and Cardiovascular Disease Outcomes
Aayush Visaria1, Louis Amorosa2. 1Rutgers New Jersey Medical School, Newark, New Jersey, United States, 2Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States
Purpose of Study Bilirubin (BR) has been noted to have anti-oxidant effects through its protection of serum lipid oxidation, but there is no consensus on whether BR improves Cardiovascular Disease (CVD) outcomes. We studied the associations between total BR and CVD mortality in men and women.
Methods Used A population of 5,424 males and 6,341 non-pregnant females >20 years with data on serum total BR levels and mortality were included in this secondary analysis of NHANES III (1988-1994), a U.S. nationally representative survey. Those with excessive alcohol consumption (>2 drinks/day for males & >1 drink/day for females) and/or history of hepatitis (as determined by hepatitis A, B, C serology) were excluded. BR values were categorized into gender-specific quartiles. Outcomes included myocardial infarction (MI) and CVD mortality. Multivariate logistic regression and Cox proportional hazard models were run adjusting for potential confounders (age, race/ethnicity, smoking status, metabolic syndrome, C-reactive protein, and albumin) and accounting for the complex survey design.
Summary of Results The mean (SD) total BR level was 0.526 (0.006) mg/dl for females [Quartiles= Q1:(0,0.3), Q2:(0.3,0.4), Q3:(0.4,0.5), Q4: >0.5]. The mean (SD) BR level for males was 0.714 (0.008) mg/dl [Q1:(0,0.4), Q2:(0.4,0.5), Q3:(0.6,0.8), Q4:>0.8]. Males and females in Q4 both had decreased odds of MI, although only significant in males (Male: aOR: 0.52 [0.30, 0.89], Female: aOR: 0.88 [0.43, 1.77]). Females in Q3, but not Q4, had an increased hazard of CVD mortality (unadjusted HR: 1.57 [1.10, 2.25]). Males in Q4 had a lower hazard of CVD mortality (unadjusted HR: 0.64 [0.39, 1.04]). Neither hazard stayed significant after adjustment. When cerebrovascular disease-related (CBVD) and heart disease-related (HD) mortality were isolated, females in Q3 had a higher hazard of CBVD mortality (aHR: 2.93 [1.46, 5.84]) but no significant increase in hazard for HD mortality (aHR: 1.30 [0.87, 1.94]).
Conclusions Increasing levels of BR are associated with decreased MI and CVD mortality in males. Females, however, have a non-linearly increased hazard of CVD mortality, specifically CBVD mortality.
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