In HPFS, with up to 22 years of follow-up (758524 person-years), we documented 8926 deaths, of which 2716 were CVD deaths and 3073 were cancer deaths. In NHS, with up to 28 years of follow-up (2199892 person-years), we documented 15000 deaths, of which 3194 were CVD deaths and 6391 were cancer deaths. Men and women with higher intake of red meat were less likely to be physically active, and more likely to be current smokers, drink alcohol and have higher BMI (). In addition, a higher red meat intake was associated with a higher intake of total energy, but lower intakes of whole grain, fruit and vegetables. Unprocessed and processed red meat consumption was moderately correlated (0.40 in HPFS and 0.37 in NHS). However, red meat consumption was less correlated with intakes of poultry or fish (Spearman correlation coefficients, −0.04 and −0.18 in HPFS, 0.05 and −0.12 in NHS, respectively). During the follow-up, red meat intake declined in both men and women (eFigure 1
). For example, the mean intake of unprocessed red meat dropped from 0.75 to 0.63 serving/d from 1986 to 2006 in men, and from 1.10 to 0.55 serving/d from 1980 to 2006 in women.
Baseline age-standardized characteristics of participants in the two cohorts according to quintiles of total red meat consumption
Both unprocessed and processed red meat intakes were associated with an increased risk of total, CVD and cancer mortality in both men and women in the age-adjusted and fully-adjusted models (-). When treating red meat intake as a continuous variable, the elevated risk of total mortality in the pooled analysis was 12% (HR, 1.12; 95% CI, 1.09-1.15) for 1-serving/d increase of total red meat, 13% (HR, 1.13; 95% CI, 1.07-1.20) for unprocessed red meat, and 20% (HR, 1.20; 95% CI, 1.15-1.24) for processed red meat. The HRs (95% CIs) for CVD mortality were 1.16 (1.12-1.20) for total red meat, 1.18 (1.13-1.23) for unprocessed red meat, and 1.21 (1.13-1.31) for processed red meat. The HRs (95% CIs) for cancer mortality were 1.10 (1.07-1.13) for total red meat, 1.10 (1.06-1.14) for unprocessed red meat, and 1.16 (1.09-1.23) for processed red meat. We found no statistically significant differences among specific unprocessed red meat items, or among specific processed red meat items for the associations with total mortality (eTable 1
). However, bacon and hot dogs tended to be associated with a higher risk than other items. Spline regression analysis showed that the association between red meat intake and risk of total mortality was linear (P for linearity <0.001; ). Furthermore, no significant interaction was detected between red meat intake and BMI or physical activity (P >0.10 for both tests).
Hazard ratio (HR) and 95% confidence interval (CI) of all-cause mortality according to red meat intake in the HPFS and NHS
Hazard ratio (HR) and 95% confidence interval (CI) of cancer mortality according to red meat intake in the HPFS and NHS
Dose-response relationship between red meat intake and risk of all-cause mortality in (A) Health Professionals Follow-up Study and (B) Nurses' Health Study
Additional adjustment for other foods (fish, poultry, nuts, beans, and dairy products) or nutrients (glycemic load, cereal fiber, magnesium, polyunsaturated and trans fatty acids) did not appreciably alter the results. Additional adjustment for saturated fat and cholesterol moderately attenuated the association between red meat intake and risk of CVD death, and the pooled HR dropped from 1.16 (95% CI, 1.12-1.20) to 1.12 (95% CI, 1.07-1.18). Similarly, additional adjustment for heme iron moderately attenuated the association, and the pooled HR dropped from 1.16 (95% CI, 1.12-1.20) to 1.11 (95% CI, 1.05-1.17). Additional adjustment for husband's education level as a surrogate of social-economic status in women did not change the results.
The results were not materially changed when we continuously updated dietary information even after diagnosis of chronic diseases (eTable 2
) or simply updated the dietary variables (eTable 3
). Also, using energy density of red meat intake as the exposure showed similar findings (eTable 4
). In the sensitivity analysis that accounted for measurement error in diet, the associations became even stronger. For example, the HR was 1.25 (95% CI, 1.16-1.35) for 1-serving/d increase of total red meat intake with mortality in HPFS, and it was 1.83 (95% CI, 1.54-2.20) in NHS. However, the associations were attenuated in analyses using only baseline dietary data (eTable 5
In the substitution analyses, replacing 1-serving/d of total red meat with 1-serving/d of fish, poultry, nuts, legumes, low-fat dairy products, or whole grains was associated with a lower risk of total mortality (): 7% (HR, 0.93; 95% CI, 0.90-0.97) for fish, 14% (HR, 0.86; 95% CI, 0.82-0.91) for poultry, 19% (HR, 0.81; 95% CI, 0.77-0.86) for nuts, 10% (HR, 0.90; 95% CI, 0.86-0.94) for legumes, 10% (HR, 0.90; 95% CI, 0.86-0.94) for low-fat dairy products, and 14% (HR, 0.86; 95% CI, 0.82-0.88) for whole grain. The corresponding substitution estimates were 5%, 13%, 18%, 8%, 9%, and 13% for replacement of unprocessed red meat, and 10%, 17%, 22%, 13%, 13%, and 16% for replacement of processed red meat.
Hazard ratios and 95% confidence intervals for total mortality associated with replacement of other food groups for red meat intake
We estimated that 9.3% (95% CI, 5.9%-12.7%) in men and 7.6% (95% CI, 3.5%-11.7%) in women of total deaths during the follow-up could be prevented if all participants consumed <0.5 serving/d of total red meat in our cohorts; the estimates were 8.6% (95% CI, 2.3%-14.7%) in men and 12.2% (95% CI, 3.3%-21.0%) in women for CVD deaths. However, only 22.8% of men and 9.6% of women were in the low risk category of total red meat.