Preventive cardiology
Usefulness of Serum Bilirubin and Cardiorespiratory Fitness as Predictors of Mortality in Men

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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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Methods

This study was based on data from a prospective nested case-control study obtained from the Aerobics Center Longitudinal Study (ACLS).6 In the original study, case subjects were those who died from any cause during the follow-up period (through the end of 1997), and control subjects for cases were selected randomly from among survivors who met the matching criteria for age (±5 years). For the present study, we used the original study sample and followed up for mortality through 2003 using an

Results

In this study population, 698 men died during follow-up, with 253 deaths due to CVD (36%). The mean follow-up period was 17 ± 9 years, and the mean age was 52 ± 10 years. The baseline characteristics of the 1279 participants included in this study are listed in Table 1. The mean serum bilirubin in each quartile was 0.36 ± 0.06, 0.55 ± 0.05, 0.75 ± 0.05, and 1.12 ± 0.27 mg/dl, respectively, and ranged from 0.10 to 2.60 mg/dl. The correlation between bilirubin level and treadmill time in this

Discussion

The findings of the present study are consistent with previous studies of the association between total serum bilirubin level and all-cause mortality in men, which found a lower risk for mortality in the highest bilirubin quartiles.5, 6 Most of the studies that have examined the association between serum bilirubin level and CVD disease did not include death as an end point.1, 2, 4, 12, 13, 14 Furthermore, none of the previous studies took CRF, a strong and independent mortality predictor, into

Acknowledgments

We thank the Cooper Clinic physicians and technicians for collecting the baseline data and staff members at the Cooper Institute for data entry and data management.

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    This study was supported by grants AG06945, HL62508, and DK088195 from the National Institutes of Health, Bethesda, Maryland, and an unrestricted research grant from the Coca-Cola Company, Atlanta, Georgia. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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