The Relationship between Total Bilirubin Levels and Total Mortality in Older Adults: The United States National Health and Nutrition Examination Survey (NHANES) 1999-2004

ObjectiveDue to its anti-oxidant and anti-inflammatory properties, bilirubin has been associated with reduced cardiovascular risk. A recent study demonstrated an L-shaped association of pre-treatment total bilirubin levels with total mortality in a statin-treated cohort. We therefore investigated the association of total bilirubin levels with total mortality in a nationally representative sample of older adults from the general population.MethodsA total of 4,303 participants aged ≥60 years from the United States National Health and Nutrition Examination Survey 1999–2004 with mortality data followed up through December 31, 2006 were included in this analysis, with a mean follow-up period of 4.5 years.ResultsParticipants with total bilirubin levels of 0.1–0.4 mg/dl had the highest mortality rate (19.8%). Compared with participants with total bilirubin levels of 0.5–0.7 mg/dl and in a multivariable regression model, a lower total bilirubin level of 0.1–0.4 mg/dl was associated with higher risk of total mortality (hazard ratios, 1.36; 95% confidence interval, 1.07–1.72; P = 0.012), while higher levels (≥0.8 mg/dl) also tended to be associated with higher risk of total mortality, but this did not reach statistical significance (hazard ratios, 1.24; 95% confidence interval, 0.98–1.56; P = 0.072).ConclusionIn this nationally representative sample of older adults, the association of total bilirubin levels with total mortality was the highest among those with a level between 0.1 and 0.4 mg/dl. Further studies are needed to investigate whether higher total bilirubin levels could be associated with a higher mortality risk, compared to a level of 0.5–0.7 mg/dl.

研究目的：由于胆红素具有抗氧化与抗炎特性，其与心血管疾病风险降低存在关联。近期一项研究在他汀类药物治疗队列中证实，治疗前总胆红素水平与全因死亡率呈L型关联。因此本研究旨在探讨普通人群全国代表性老年样本中总胆红素水平与全因死亡率的关联。
研究方法：本分析纳入1999-2004年美国全国健康与营养调查（National Health and Nutrition Examination Survey, NHANES）中4303名年龄≥60岁的参与者，所有对象均带有截至2006年12月31日的死亡率随访数据，平均随访时长为4.5年。
研究结果：总胆红素水平处于0.1~0.4 mg/dl区间的参与者全因死亡率最高（19.8%）。以总胆红素水平0.5~0.7 mg/dl的参与者为参照组，在多变量回归模型中，0.1~0.4 mg/dl的较低总胆红素水平与更高的全因死亡风险显著相关（风险比HR=1.36；95%置信区间CI：1.07~1.72；P=0.012）；而总胆红素水平≥0.8 mg/dl的较高水平也呈现出与全因死亡风险升高相关的趋势，但未达到统计学显著性（HR=1.24；95%CI：0.98~1.56；P=0.072）。
研究结论：本研究针对全国代表性老年人群样本的分析显示，总胆红素水平与全因死亡率的关联中，0.1~0.4 mg/dl区间的参与者死亡风险最高。与0.5~0.7 mg/dl的胆红素水平相比，更高的总胆红素水平是否与更高的死亡风险相关，仍需进一步研究加以验证。