Patel Chirag J, Rehkopf David H, Leppert John T, Bortz Walter M, Cullen Mark R, Chertow Glenn M, Ioannidis John Pa
Stanford Prevention Research Center, Stanford University School of Medicine, CA, USA Division of General Medical Disciplines, Stanford University School of Medicine, CA, USA Department of Urology, Stanford University School of Medicine, CA, USA and Division of Nephrology, Department of Medicine, Stanford University School of Medicine, CA, USA.
Int J Epidemiol. 2013 Dec;42(6):1795-810. doi: 10.1093/ije/dyt208. Epub 2013 Dec 16.
Environmental and behavioural factors are thought to contribute to all-cause mortality. Here, we develop a method to systematically screen and validate the potential independent contributions to all-cause mortality of 249 environmental and behavioural factors in the National Health and Nutrition Examination Survey (NHANES).
We used Cox proportional hazards regression to associate 249 factors with all-cause mortality while adjusting for sociodemographic factors on data in the 1999-2000 and 2001-02 surveys (median 5.5 follow-up years). We controlled for multiple comparisons with the false discovery rate (FDR) and validated significant findings in the 2003-04 survey (median 2.8 follow-up years). We selected 249 factors from a set of all possible factors based on their presence in both the 1999-2002 and 2003-04 surveys and linkage with at least 20 deceased participants. We evaluated the correlation pattern of validated factors and built a multivariable model to identify their independent contribution to mortality.
We identified seven environmental and behavioural factors associated with all-cause mortality, including serum and urinary cadmium, serum lycopene levels, smoking (3-level factor) and physical activity. In a multivariable model, only physical activity, past smoking, smoking in participant's home and lycopene were independently associated with mortality. These three factors explained 2.1% of the variance of all-cause mortality after adjusting for demographic and socio-economic factors.
Our association study suggests that, of the set of 249 factors in NHANES, physical activity, smoking, serum lycopene and serum/urinary cadmium are associated with all-cause mortality as identified in previous studies and after controlling for multiple hypotheses and validation in an independent survey. Whereas other NHANES factors may be associated with mortality, they may require larger cohorts with longer time of follow-up to detect. It is possible to use a systematic association study to prioritize risk factors for further investigation.
环境和行为因素被认为与全因死亡率有关。在此，我们开发了一种方法，以系统地筛选和验证美国国家健康与营养检查调查（NHANES）中249种环境和行为因素对全因死亡率的潜在独立影响。
我们使用Cox比例风险回归，将249种因素与全因死亡率相关联，同时在1999 - 2000年和2001 - 2002年调查数据中对社会人口学因素进行调整（中位随访时间为5.5年）。我们通过错误发现率（FDR）控制多重比较，并在2003 - 2004年调查（中位随访时间为2.8年）中验证显著结果。我们基于这些因素在1999 - 2002年和2003 - 2004年调查中的存在情况以及与至少20名死亡参与者的关联，从所有可能因素中选择了249种因素。我们评估了已验证因素的相关模式，并建立了一个多变量模型来确定它们对死亡率的独立影响。
我们确定了七种与全因死亡率相关的环境和行为因素，包括血清和尿镉、血清番茄红素水平、吸烟（三级因素）和身体活动。在一个多变量模型中，只有身体活动、既往吸烟、参与者家中有人吸烟和番茄红素与死亡率独立相关。在调整了人口统计学和社会经济因素后，这三个因素解释了全因死亡率方差的2.1%。
我们的关联研究表明，在NHANES的249种因素中，身体活动、吸烟、血清番茄红素和血清/尿镉与全因死亡率相关，这与先前研究一致，且在控制多重假设并在独立调查中验证后得到确认。虽然NHANES中的其他因素可能与死亡率相关，但可能需要更大规模的队列和更长时间的随访才能检测到。使用系统关联研究来确定进一步研究的风险因素优先级是可行的。
