Elevated serum bilirubin has been suggested to reduce the risk for mortality. Cardiorespiratory fitness (CRF) has also been reported to have inverse association with all-cause and cardiovascular disease (CVD) mortality. The association between serum bilirubin, all-cause and CVD mortality, and the effect of CRF on the observed association was investigated. A total of 1,279 men aged 30 to 82 years underwent baseline medical examinations from 1974 to 1997 at the Cooper Clinic in Dallas, Texas. During an average of 17 years of follow-up, 698 men died, with 253 deaths due to CVD (36%). Men in the highest bilirubin quartiles had significantly lower risk for all-cause mortality compared to men in the lowest quartiles (p for trend = 0.0043), after adjusting for age and examination year. This inverse association remained significant after further adjustment for known confounders (p for trend = 0.0018). Additional adjustment for treadmill time attenuated the association (p for trend = 0.0090). Similar patterns of association were observed between serum bilirubin quartiles and CVD mortality. CRF was inversely associated with all-cause mortality (p for trend <0.0001) after adjusting for age and examination year. This inverse association also was observed after further adjusting for known confounders (p for trend = 0.0004). After additional adjustment for serum bilirubin, the association between CRF and all-cause mortality remained significant (p for trend = 0.0012). All-cause mortality and CVD mortality were significantly lower in men in the moderate- to high-fitness quartiles in the low- and high-bilirubin groups. In conclusion, serum bilirubin level and CRF level were strongly and independently associated with all-cause and CVD mortality.
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