We obtained the relative risk (RR) per unit of exposure (for risks measured continuously) or for each exposure category (for risks measured in categories) for diseases with probable or convincing causal associations with each risk factor, based on the most recent published systematic reviews and meta-analyses of epidemiological studies or by conducting new systematic reviews and meta-analyses when they were not available in the published literature (
Tables 2–
7).
The studies used for etiological effect sizes included both randomized intervention studies of exposure reduction and observational studies (primarily prospective cohort studies) that estimated the effects of baseline exposure. The majority of observational studies used for effect sizes had adjusted for important potential confounding factors. Each RR used in our analysis represents the best evidence for the proportional effect of risk factor exposure on disease-specific mortality in the population based on the current causes and determinants of the population distribution of exposure (see also Discussion).
We used RRs for blood pressure, LDL cholesterol, and FPG that were adjusted for regression dilution bias using studies that had repeated exposure measurement [7] (
link),[11] (
link), [12] (
link); for blood pressure and LDL cholesterol, the adjusted magnitude is supported by effect sizes from randomized studies [13] (
link),[14] (
link). Evidence from a large prospective study with multiple measurements of weight and height showed that regression dilution bias did not affect the RRs for BMI, possibly because there is less variability [15] (
link). RRs for dietary salt and PUFA-SFA replacement were from intervention studies, and hence unlikely to be affected by regression dilution bias. RRs for dietary trans fatty acids were primarily from studies that had used cumulative averaging of repeated measurements [16] (
link) that reduces but may not fully correct for regression dilution bias. RRs for physical inactivity, alcohol use, smoking, and dietary omega-3 fatty acids and fruits and vegetables were not corrected for regression dilution bias due to insufficient current information from epidemiological studies on exposure measurement error and variability, which is especially important when error and variability of self-reported exposure may themselves differ across studies.
For each risk factor–disease pair, we used the same RR for men and women except where empirical evidence indicated that the RR differed by sex: colon and pancreas cancers caused by high BMI [17] (
link), and all disease outcomes caused by alcohol use and tobacco smoking, for which there are sex differences in factors such as smoking duration and intensity [18] (
link) and type of alcohol consumed [19] . The RRs for some risk factor–disease associations vary by age, especially for cardiovascular diseases. We used consistent age-varying distributions of RRs across risk factors and diseases (
Tables 2–
7).
The current evidence suggests that when measured comparably the proportional effects of the risk factors considered in this analysis are similar across populations, e.g., Western and Asian populations [7] (
link),[20] (
link),[21] (
link). The exception to this observation is the effects of alcohol use on ischemic heart disease (IHD) where the pattern of drinking (regular versus binge) determines the RR. We used both the average quantity of alcohol consumed as well as the drinking pattern in our analysis of exposure and RRs for alcohol use and IHD. The effects of alcohol on injuries and violence may also be modified by social, policy, and transportation factors. Therefore, we did not pool epidemiological studies on the injury effects of alcohol from different countries, but used data sources that appropriately measure effects in the US (
Table 4).
Danaei G., Ding E.L., Mozaffarian D., Taylor B., Rehm J., Murray C.J, & Ezzati M. (2009). The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors. PLoS Medicine, 6(4), e1000058.