Study Population and Design

The Nurses’ Health Study, a prospective study that was initiated in 1976, enrolled 121,700 registered nurses who were 30 to 55 years of age. The Health Professionals Follow-up Study, a prospective study that was initiated in 1986, enrolled 51,529 U.S. health professionals who were 40 to 75 years of age. Baseline and follow-up questionnaires were sent to participants every 2 years to update medical and lifestyle information over the follow-up period.20,21 In both studies, follow-up rates exceeded 90% in both cohorts.22

For the present study, the initial cycle was set at 1986, baseline was set at 1998 (changes in diet quality were calculated from 1986 through 1998), and the end of follow-up was 2010. We excluded participants who had a history of cardiovascular disease or cancer at or before baseline in 1998, missing information regarding diet and lifestyle covariates, or very low or high caloric intake (<800 kcal or >4200 kcal per day in men and <500 or >3500 kcal per day in women). We also excluded participants who died before 1998. The final analysis included 47,994 women and 25,745 men.

Study Oversight

The first author formulated the study question and design, performed the statistical analyses, interpreted the results, and wrote the first draft of the manuscript. The second and fifth authors contributed to the development of the study questions and statistical analyses. The seventh, eighth, and last authors contributed to the conception and design of the study and acquisition of the data. All the authors contributed to the interpretation of data and critical revision of the manuscript, approved the final version, and made the decision to submit the manuscript for publication. The first and last authors share primary responsibility for the final content and vouch for the accuracy and completeness of the data and analyses.

Dietary Assessment

At baseline and every 4 years thereafter, the participants reported information about their diets with the use of a validated food frequency questionnaire. They were asked how often, on average, they had consumed each food of a standard portion size in the past year. The reproducibility and validity of the food frequency questionnaires have been described previously.12,23,24

We calculated three diet-quality scores using food components and scoring criteria that have been described previously.25 Briefly, the Alternate Healthy Eating Index included 11 food components, each scored from 0 (unhealthy) to 10 (healthiest) and selected on the basis of evidence of an association with the risk of chronic disease.12 Total scores ranged from 0 to 110, with higher scores indicating a healthier diet. The Alternate Mediterranean Diet score included 9 components, each scored as 0 (unhealthy) or 1 (healthy) according to whether the participant’s intake was above or below the cohort-specific median levels.10,13 Total scores ranged from 0 to 9, with higher scores indicating a healthier diet. Finally, the DASH score included 8 components, each scored from 1 (unhealthy) to 5 (healthiest) according to a participant’s quintile of intake.14 Total DASH scores ranged from 8 to 40 points, with higher scores indicating a healthier diet. Further information is provided in Table S1 in the Supplementary Appendix, available with the full text of this article at NEJM.org.

Ascertainment of Deaths

Deaths were identified from state vital statistics records and the National Death Index or reported by the participants’ families and the U.S. postal system.26 Using these methods, we could ascertain 98% of the deaths in each cohort.26 We attempted to obtain the death certificate of each participant who had died, and when appropriate, we requested permission from the participant’s next of kin to review medical records. The underlying cause of death, according to the International Classification of Diseases, Eighth Revision and Ninth Revision, was assigned by physicians after they had reviewed death certificates and medical records.

Covariates

Information on the participants’ lifestyle and risk factors for cardiovascular disease was assessed and updated every other year. This information included the following: the participant’s age; weight; smoking status; use of aspirin, multivitamins, postmenopausal hormone-replacement therapy, and oral contraceptives; menopausal status; physical activity; and hypertension, hypercholesterolemia, or diabetes that had been recently diagnosed by a physician. Alcohol use was assessed, and this information was updated from the food frequency questionnaires every 4 years. The participant’s height and weight were used to calculate the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters). Detailed descriptions of the validity and reproducibility of body weight, physical activity, and alcohol consumption as reported by the participants have been published previously.27-29

Statistical Analysis

Changes in the three diet-quality scores were categorized into quintiles from the largest decrease (quintile 1) to the largest increase (quintile 5). Person-years were calculated from the date of return of the 1998 questionnaire to the date of death or the end of follow-up, whichever occurred first. Cox proportional-hazards models with time-varying covariates and age as the underlying time scale were used to estimate hazard ratios and 95% confidence intervals.

Model 1 was adjusted for the following factors: age; calendar year as the underlying time scale; initial diet-quality score (in quintiles); race; family history of myocardial infarction, diabetes, or cancer; use or nonuse of aspirin or multivitamins; initial BMI category; menopausal status and use or nonuse of hormone-replacement therapy in women; initial smoking status and changes in smoking status; initial smoking pack-year and changes in smoking pack-year (continuous variables) among participants with any history of smoking (ever smokers); and initial levels of physical activity and total energy intake and changes in these levels (in quintiles). In addition to these adjustments, model 2 was adjusted for a history of hypertension, hypercholesterolemia, or type 2 diabetes; change in weight; and the use or nonuse of cholesterol-lowering and antihypertensive medications. The model with the DASH score as the exposure was also adjusted for initial alcohol intake and changes in alcohol intake. Tests for trend were conducted by assigning a median value to each quintile. A 20-percentile increase in each score was calculated from the range of the diet score and the median value of each quintile. We also conducted restricted-cubic-spline regressions to flexibly model the association.

Shorter-term changes (baseline to 8-year follow-up, 1986–1994) and longer-term changes (baseline to 16-year follow-up, 1986–2002) in the three scores were tested for association with total and cause-specific mortality. We conducted several sensitivity analyses to test the robustness of our findings. First, we applied stratification analysis according to several potential confounding factors at baseline (e.g., age, BMI, diet, physical activity, and smoking status). Second, we conducted a 4-year lag analysis to account for the presence of any chronic diseases in the years after diagnosis that might have influenced dietary patterns. Third, because early detection and treatment of disease could confound results, in an additional model we adjusted for mammographic screening in women and physical checkups.

All analyses were performed separately for each cohort and then were pooled with the use of an inverse, variance-weighted meta-analysis with a fixed-effects model. Analyses were performed with the use of SAS software, version 9.4 for UNIX (SAS Institute). Statistical tests were two-sided, and P values of less than 0.05 were considered to indicate statistical significance.