Abstract
Few studies have examined multiple risk factors for mortality or formally compared their associations across specific causes of death. The authors used competing risks survival analysis to evaluate associations of lifestyle and dietary factors with all-cause and cause-specific mortality among 50,112 participants in the Nurses’ Health Study. There were 4,893 deaths between 1986 and 2004: 1,026 from cardiovascular disease, 931 from smoking-related cancers, 1,430 from cancers not related to smoking, and 1,506 from all other causes. Age, body mass index at age 18 years, weight change, height, current smoking and pack-years of smoking, glycemic load, cholesterol intake, systolic blood pressure and use of blood pressure medications, diabetes, parental myocardial infarction before age 60 years, and time since menopause were directly related to all-cause mortality, whereas there were inverse associations for physical activity and intakes of nuts, polyunsaturated fat, and cereal fiber. Moderate alcohol consumption was associated with decreased mortality. A model that incorporated differences in the associations of some risk factors with specific causes of death had a significantly better fit compared with a model in which all risk factors had common associations across all causes. In the future, this new model may be used to identify individuals at increased risk of mortality.
Generated Summary
This study, published in the American Journal of Epidemiology, utilized a prospective cohort study design to examine the relationship between lifestyle and dietary factors and mortality in a cohort of 50,112 nurses. The Nurses’ Health Study, which began in 1976, provided the data for this research, with follow-up for this analysis beginning in 1986. The study employed a competing risks survival analysis to evaluate associations of lifestyle and dietary factors with all-cause and cause-specific mortality. The researchers sought to compare the effects of risk factors across specific causes of death, including cardiovascular disease, smoking-related cancers, other cancers, and all other causes. The goal was to develop a comprehensive model for all-cause mortality based on these comparisons. Data on lifestyle factors, health behaviors, and medical histories were collected through questionnaires administered every two years. The primary outcome was death from all causes, and the causes of death were categorized according to the International Classification of Diseases, Eighth Revision (ICD-8). The study used Cox proportional hazards models to compute hazard ratios and 95% confidence intervals for associations between each risk factor and all-cause mortality, adjusting for all other risk factors. The study’s design allowed for a detailed assessment of various lifestyle and dietary factors and their relationship to mortality.
Key Findings & Statistics
- The study included 50,112 participants from the Nurses’ Health Study, with 4,893 deaths recorded between 1986 and 2004.
- The distribution of deaths was as follows: 1,026 from cardiovascular disease (21%), 931 from smoking-related cancers (19%), 1,430 from cancers not related to smoking (29%), and 1,506 from all other causes (31%).
- The hazard ratio (HR) for all-cause mortality increased significantly with age (HR per 19 years = 5.78).
- Body mass index (BMI) at age 18 years showed a positive association with all-cause mortality (HR per 7 kg/m² = 1.23).
- Weight change since age 18 was also associated with increased mortality risk.
- A height increase of 6 inches was associated with an HR of 1.16.
- Current smoking (HR vs. never = 1.48) and greater total pack-years of smoking (HR per 46 pack-years = 2.08) were associated with increased mortality risk.
- Physical activity was associated with decreased risk (HR per 33 MET-hours/week = 0.87).
- Alcohol consumption showed a small decrease in risk for 0.1 g/day-9.9 g/day and 10 g/day-29.9 g/day (HRs vs. none = 0.90 and 0.91, respectively), but not for ≥30 g/day.
- Glycemic load (HR per 41 units = 1.22) and cholesterol intake (HR per 105 mg/1,000 kcal = 1.17) were positively associated with mortality.
- Nut consumption (HR for ≥2 servings/week vs. none or almost none = 0.86), polyunsaturated fat intake (HR per 3% of total energy intake = 0.85), and cereal fiber intake (HR per 4 g = 0.84) were inversely associated with risk.
- Systolic blood pressure (HR for ≥ 160 vs. <120 mm Hg = 1.49), use of blood pressure medications (HR = 1.19), personal history of diabetes (HR = 2.45), parental myocardial infarction before age 60 years (HR = 1.14), and time since menopause (HR per 13 years = 1.15) were positively associated with all-cause mortality.
- The hazard ratio for all-cause mortality for the “worst” versus the “best” risk profile for all of the modifiable risk factors was 12.32.
- For cardiovascular disease mortality, the hazard ratio for the “worst” versus the “best” risk profile for the modifiable risk factors was 24.14, 16.02 for smoking-related cancer mortality, 5.73 for other cancer mortality, and 12.50 for other cause mortality.
- Height was not associated with risk of mortality from coronary heart disease (HR per 6 inches = 1.04), but was positively associated with other cardiovascular disease (HR per 6 inches = 1.52).
Other Important Findings
- The study found that the associations of risk factors with mortality differed across specific causes of death.
- For example, age was more strongly associated with death from cardiovascular disease and other causes than from smoking-related cancers.
- BMI at age 18 years was more strongly associated with death from cardiovascular disease than other causes.
- Weight change was positively associated with cardiovascular disease and other cancers but inversely associated with other causes.
- Current smoking was associated with increased risk of death from cardiovascular disease, smoking-related cancers, and other causes, but not from other cancers.
- Total pack-years of smoking was positively associated with death from all causes, most strongly for smoking-related cancers.
- Physical activity was most strongly inversely associated with the risk of death from other causes.
- The U-shaped association for alcohol consumption was observed only for the risk of death from cardiovascular disease and other causes.
- The model for all-cause mortality was developed in which risk factors had different effects across specific causes of death.
- Higher glycemic load, and parental myocardial infarction before age 60 years were associated with increased risk of death from all causes.
- Greater nut consumption and cereal fiber intake were associated with decreased risk.
Limitations Noted in the Document
- The study acknowledges that it did not update risk factors in the competing risks model, using only participants’ risk factor status at the beginning of the follow-up period, which might have attenuated associations.
- The restriction of the population to nurses could potentially limit the generalizability of the results.
- The study did not validate the model in an external population.
- The study’s reliance on self-reported data, common in large-scale cohort studies, introduces potential for measurement error.
- The observational nature of the study design means that causal inferences are limited.
- The study was limited by its inability to account for potential confounding factors that were not measured.
Conclusion
The Nurses’ Health Study provides compelling evidence that lifestyle and dietary factors significantly influence the risk of mortality in middle-aged women. The study’s findings highlight the importance of maintaining a low body mass index, avoiding weight gain, not smoking, and engaging in physical activity for reducing overall mortality risk. Furthermore, the research underscores the complex relationship between diet and health, emphasizing the benefits of consuming nuts, polyunsaturated fats, and cereal fiber, while cautioning against high glycemic load and cholesterol intake. A key insight from the study is that the impact of risk factors varies depending on the cause of death, revealing nuanced associations that can inform targeted interventions. “From a methodological standpoint, there are several advantages to using competing risks survival analysis to analyze the composite endpoint of all-cause mortality,” the authors note. The study’s competing risks model offers a more refined understanding of how different risk factors are linked to specific causes of death. The development of a model that can account for these varying effects represents a step towards more personalized risk assessment and ultimately, more effective preventative strategies. The findings suggest that promoting specific lifestyle and dietary changes could substantially reduce mortality risk in this population. The authors conclude that in the future, this new model may be used to identify individuals at increased risk of mortality. The implications of this research extend beyond the specific cohort studied, contributing to a broader understanding of the modifiable factors that impact lifespan.
IFFS Team Summary
- 2010 Nurses Health Study – 50 000 subjects
- multiple factor related to mortality include cholesterol intake, obesity, diabetes, blood pressure, glycemic load etc
- protective factors include, intake of polyunsaturated fat, nuts, cereal fibre intake etc
- reflects badly on animal based foods, good on whole grains, nuts, plant foods