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Dietary Patterns and Long-Term Survival: A Retrospective Study of Healthy Primary Care Patients

      Abstract

      Background

      Dietary patterns are related to mortality in selected populations with comorbidities. We studied whether dietary patterns are associated with long-term survival in a middle-aged, healthy population.

      Methods

      In this observational cohort study at the Cooper Clinic preventive medicine center (Dallas, Tex), a volunteer sample of 11,376 men and women with no history of myocardial infarction or stroke completed a baseline dietary assessment between 1987 and 1999 and were observed for an average of 18 years. Proportional hazard regressions, including a tree-augmented model, were used to assess the association of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern, Mediterranean dietary pattern, and individual dietary components with mortality. The primary outcome was all-cause mortality. The secondary outcome was cardiovascular mortality.

      Results

      Mean baseline age was 47 years. Each quintile increase in the DASH diet score was associated with a 6% lower adjusted risk for all-cause mortality (P < .02). The Mediterranean diet was not independently associated with all-cause or cardiovascular mortality. Solid fats and added sugars were the most predictive of mortality. Individuals who consumed >34% of their daily calories as solid fats had the highest risk for all-cause mortality.

      Conclusions

      The DASH dietary pattern was associated with significantly lower all-cause mortality over approximately 2 decades of follow-up in a middle-aged, generally healthy population. Added solid fat and added sugar intake were the most predictive of all-cause mortality. These results suggest that promotion of a healthy dietary pattern should begin in middle age, before the development of comorbid risk factors.

      Keywords

      Clinical Significance
      • In this observational study, the DASH diet was associated with decreased risk for all-cause mortality.
      • Vegetable intake in the DASH diet pattern was associated with decreased risk for all-cause mortality, and fruit/nut and grain intake in the Mediterranean diet pattern was associated with a decreased risk for cardiovascular mortality.
      • Solid fat and added sugar intake were the most predictive of all-cause mortality.
      • Dietary patterns were associated with all-cause mortality an average of 18 years after dietary assessment.

      Introduction

      Dietary pattern is a known modifiable risk factor for chronic diseases, including cardiovascular disease
      • Zarraga I.G.
      • Schwarz E.R.
      Impact of dietary patterns and interventions on cardiovascular health.
      and cancer.
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      Prioritizing genes for follow-up from genome wide association studies using information on gene expression in tissues relevant for type 2 diabetes mellitus.
      Dietary patterns have also been linked to chronic disease risk factors, such as lipids,
      • Zarraga I.G.
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      Impact of dietary patterns and interventions on cardiovascular health.
      blood pressure,
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      A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group.
      diabetes,
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      • Willett W.C.
      • Stampfer M.J.
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      Dietary patterns and risk for type 2 diabetes mellitus in U.S. men.
      body mass index (BMI),
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      Dietary patterns and changes in body mass index and waist circumference in adults.
      and atherosclerosis and inflammation.
      • Zarraga I.G.
      • Schwarz E.R.
      Impact of dietary patterns and interventions on cardiovascular health.
      However, the relationship between dietary pattern and mortality outcomes has been inconsistent.
      • Zarraga I.G.
      • Schwarz E.R.
      Impact of dietary patterns and interventions on cardiovascular health.
      • Schwingshackl L.
      • Hoffmann G.
      Diet quality as assessed by the Healthy Eating Index, the Alternate Healthy Eating Index, the Dietary Approaches to Stop Hypertension score, and health outcomes: a systematic review and meta-analysis of cohort studies.
      The Dietary Approaches to Stop Hypertension (DASH) diet, originally designed to reduce hypertension,
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      • Moore T.J.
      • Obarzanek E.
      • et al.
      A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group.
      has been shown to reduce overall mortality in select populations, such as adults with hypertension
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      • Lipsitz S.R.
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      Association between a DASH-like diet and mortality in adults with hypertension: findings from a population-based follow-up study.
      and women with heart failure
      • Levitan E.B.
      • Lewis C.E.
      • Tinker L.F.
      • et al.
      Mediterranean and DASH diet scores and mortality in women with heart failure: the Women's Health Initiative.
      over approximately 5 to 8 years of follow-up. Also, the DASH diet was associated with an approximately 17% decrease in the risk for all-cause and cardiovascular disease mortality in adults aged more than 60 years.
      • Reedy J.
      • Krebs-Smith S.M.
      • Miller P.E.
      • et al.
      Higher diet quality is associated with decreased risk of all-cause, cardiovascular disease, and cancer mortality among older adults.
      The Mediterranean dietary pattern has shown an inconsistent relationship with mortality.
      • Levitan E.B.
      • Lewis C.E.
      • Tinker L.F.
      • et al.
      Mediterranean and DASH diet scores and mortality in women with heart failure: the Women's Health Initiative.
      • Estruch R.
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      Primary prevention of cardiovascular disease with a Mediterranean diet.
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      • Clarke A.
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      “Mediterranean” dietary pattern for the primary prevention of cardiovascular disease.
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      Dietary patterns and the risk of major adverse cardiovascular events in a global study of high-risk patients with stable coronary heart disease.
      Individual foods and food groups, for example, fruits,
      • Bongard V.
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      Food groups associated with a reduced risk of 15-year all-cause death.
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      Fruit and vegetable consumption and mortality from all causes, cardiovascular disease, and cancer: systematic review and dose-response meta-analysis of prospective cohort studies.
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      Fruit and vegetable consumption and all-cause mortality: a dose-response analysis.
      vegetables,
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      • et al.
      Food groups associated with a reduced risk of 15-year all-cause death.
      • Wang X.
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      • Liu J.
      • et al.
      Fruit and vegetable consumption and mortality from all causes, cardiovascular disease, and cancer: systematic review and dose-response meta-analysis of prospective cohort studies.
      • Bellavia A.
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      • Wolk A.
      • Orsini N.
      Fruit and vegetable consumption and all-cause mortality: a dose-response analysis.
      dairy,
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      Food groups associated with a reduced risk of 15-year all-cause death.
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      Milk consumption and mortality from all causes, cardiovascular disease, and cancer: a systematic review and meta-analysis.
      sugars,
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      Added sugar intake and cardiovascular diseases mortality among US adults.
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      • Hollenbeck A.
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      Sugars and risk of mortality in the NIH-AARP Diet and Health Study.
      and fats,
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      • et al.
      Dietary fat intake and risk of cardiovascular disease and all-cause mortality in a population at high risk of cardiovascular disease.
      • de Souza R.J.
      • Mente A.
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      Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies.
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      • et al.
      Saturated fats compared with unsaturated fats and sources of carbohydrates in relation to risk of coronary heart disease: a prospective cohort study.
      have similarly demonstrated an inconsistent association with mortality outcomes. In a population of generally healthy, middle-aged individuals, we sought to assess the relationship of dietary patterns and food group intake at midlife with the long-term risk of all-cause and cardiovascular disease mortality.

      Materials and Methods

      Design and Participants

      The Cooper Center Longitudinal Study is a prospective study of predominantly non-Hispanic white patients at the Cooper Clinic in Dallas, Texas.
      • Blair S.N.
      • Kohl 3rd, H.W.
      • Barlow C.E.
      • Paffenbarger Jr, R.S.
      • Gibbons L.W.
      • Macera C.A.
      Changes in physical fitness and all-cause mortality. A prospective study of healthy and unhealthy men.
      The current study included men and women aged 20 years or older who completed a 3-day dietary record from 1987 to 1999 (n = 15,517). Participants were excluded if they were missing data on covariates (n = 3507), they reported prevalent cardiovascular disease (n = 466), their discretionary fat intake was recorded greater than total fat intake (n = 107), their total daily calorie intake was less than 500 kcal (n = 5) or greater than 5000 kcal (n = 31), or their physical activity exceeded 140 metabolic equivalent of task hours/week (n = 25). After exclusions, 11,376 individuals remained for primary analysis.
      The Cooper Center Longitudinal Study is reviewed annually by the Institutional Review Board at the Cooper Institute, and the present analysis was determined not to require review by the Stanford University Institutional Review Board.

      Dietary Variables

      Participants completed a 3-day diet record for which recording methods have been described.
      • Brodney S.
      • McPherson R.S.
      • Carpenter R.S.
      • Welten D.
      • Blair S.N.
      Nutrient intake of physically fit and unfit men and women.
      • Finley C.E.
      • Barlow C.E.
      • Halton T.L.
      • Haskell W.L.
      Glycemic index, glycemic load, and prevalence of the metabolic syndrome in the cooper center longitudinal study.
      Briefly, participants recorded their food intake and portion sizes on 1 weekend day and 2 weekdays. Clinic dietitians provided written instructions and photographs of serving sizes to assist in accurately recording food intake and portion sizes. Nutrient analysis was performed with the Food Intake Analysis System (University of Texas-Houston School of Public Health) using the US Agricultural Department (USDA) Survey Nutrient Database to supply nutrient intake information. Adjusted standard portion sizes were used when portion sizes were missing.
      • Welten D.C.
      • Carpenter R.A.
      • McPherson R.S.
      • et al.
      Comparison of a dietary record using reported portion size versus standard portion size for assessing nutrient intake.
      Diet record data were linked to the USDA Pyramid Servings database,
      Pyramid servings database for USDA survey food codes.
      which provided USDA food pyramid servings data and complete nutrient intakes for the diet records.
      To calculate the DASH diet score, average daily intakes of fruits, vegetables, nuts and legumes, dairy, whole grains, red meat, and added sugars were computed from the 3-day dietary record and converted to My Pyramid serving equivalents, similar to prior analyses.
      • Levitan E.B.
      • Lewis C.E.
      • Tinker L.F.
      • et al.
      Mediterranean and DASH diet scores and mortality in women with heart failure: the Women's Health Initiative.
      MyPyramid equivalents database, 2.0 for USDA survey foods, 2003-2004.
      These items, along with sodium intake, were ranked into quintiles. Participants were categorized by quintile of DASH diet score.
      To calculate the Mediterranean diet score, average daily intakes of vegetables (except potatoes), fruits and nuts, legumes, grains, fish, dairy, and meat (except fish) were computed from the 3-day dietary record and converted to My Pyramid equivalents.
      • Trichopoulou A.
      • Costacou T.
      • Bamia C.
      • Trichopoulos D.
      Adherence to a Mediterranean diet and survival in a Greek population.
      Quintiles of Mediterranean diet score categories were used in analysis.

      Outcome Measurements

      All-cause mortality was assessed via National Death Index records through December 31, 2010. Cardiovascular disease deaths were identified using the International Classification of Diseases, 9th Revision (codes 410.0-414.9 and 429.2) for deaths occurring before 1999 and 10th Revision (codes 120-126) for deaths between 1999 and 2010.

      Covariates

      Covariates were assessed at the baseline visit. Family history was defined as positive if a first-degree relative had cardiovascular disease before age 50 years. Alcohol use was measured as the number of drinks per week when not included in the diet exposure score. Smoking status was categorized as current versus nonsmokers. BMI was calculated as weight in kilograms divided by height in meters squared. Physical activity levels were defined by metabolic equivalent of task hours per week. Resting systolic and diastolic blood pressures were recorded in millimeters of mercury at the baseline visit. Fasting low-density lipoprotein (LDL) cholesterol and glucose levels were measured in milligrams/deciliter.

      Statistical Analysis

      Characteristics of participants at baseline were summarized in aggregate and within quintiles of total caloric intake. Trends of characteristics across ordered diet categories were tested using the nonparametric Jonckheere-Terpstra method.
      • Hollander M.
      • Wolfe D.A.
      Nonparametric Statistical Methods.
      To account for the effect of total calorie intake on dietary patterns, the total sample of participants was divided into quintiles of total calorie intake. Within each total calorie intake quintile, the dietary pattern exposure was calculated as described previously. Individuals grouped into the same dietary pattern score were combined into total calorie-adjusted dietary pattern groups for primary analysis.
      Hazard ratios (HRs) for all-cause and cardiovascular mortality were estimated using proportional hazards models. Age at baseline was used as an entry time to account for left truncation. Age at follow-up was used as the time scale to control for strong age dependence in mortality. All models included the diet score. Adjusted models included age and sex, or age, sex, family history of premature heart disease, BMI, physical activity, current smoking, alcohol use (except in the Mediterranean diet analysis, which includes alcohol in the score calculation), LDL cholesterol, systolic blood pressure, and glucose. Each aggregate diet score model had a companion model including the score components individually. Proportional hazards assumptions for each covariate included in regression models were confirmed by testing the Pearson correlation between the rank order of the age at follow-up and the corresponding Schoenfeld residuals.
      • Schoenfeld D.
      Partial residuals for the proportional hazards regression-model.
      • Harrell F.E.
      The PHGLM Procedure. SUGI Supplemental Library Guide.
      We further used a tree-augmented proportional hazards model to explore the relationship between dietary composition and all-cause and cardiovascular mortality controlling for age, sex, smoking, total caloric intake, and physical activity.
      • Su X.
      • Tsai C.L.
      Tree-augmented Cox proportional hazards models.
      We initially fit a proportional hazards model of right-censored age at death with entry age at dietary assessment. Deviance residuals reflective of excess deaths were then modeled at the individual level by recursive partitioning
      • Therneau T.M.
      • Grambsch P.M.
      • Fleming T.R.
      Martingale-based residuals for survival models.
      on 2 dietary compositions: one giving the allocation of total calories among 13 specific food groups (fruits, vegetables, legumes/nuts/seeds, dairy, poultry/eggs, fish, other meat, added oils, solid fats, added sugar, alcohol, whole grains, other grains) and another giving the allocation of total calories among the 4 macro-nutrients (protein, carbohydrate, fat, alcohol). The resulting tree was pruned back to the size that minimized average square error in 10-fold cross-validation.
      • Breiman L.
      Classification and Regression Trees.
      A categoric variable representing the nodes of the selected tree was then included as an additional covariate in the final proportional hazards model. All analyses were programmed in SAS/STAT, version 9.4 (SAS Institute, Inc, Cary, NC).

      Results

      Participant Characteristics

      Baseline participant characteristics in aggregate and by quintile of daily calorie intake are reported in Table 1. As baseline calorie intake increased, mean participant age decreased; alcohol use, LDL cholesterol, blood pressure, fasting glucose, smoking rates, and BMI increased; and participants were more predominantly men (P < .001 for all characteristics across calorie quintile).
      Table 1Participant Characteristics at Baseline Visit, by Total, and by Quintiles of Average Daily Calorie Intake
      TotalQuintile 1Quintile 2Quintile 3Quintile 4Quintile 5P
      P for trend of characteristic across diet category. Continuous data presented as mean (standard deviation). Frequency data presented as N (percent).
      N11,37622752275227622752275
      Energy, kcal (SD)2155 (641)1354 (214)1783 (92)2092 (89)2433 (113)3114 (445)<.001
      Age, y (SD)46.5 (10.0)47.7 (9.8)47.3 (10.2)46.8 (10.0)46.0 (9.9)44.5 (9.9)<.001
      Sex (% female)2799 (24.6)1125 (49.5)756 (33.2)497 (21.8)279 (12.3)142 (6.2)<.001
      Family history cardiovascular disease (%)2155 (18.6)430 (18.9)424 (18.6)447 (19.6)399 (17.5)415 (18.2).349
      Alcohol use (drinks/wk)5.9 (7.2)4.7 (6.0)5.5 (6.5)6.0 (6.7)6.5 (8.1)6.9 (8.4)<.001
      LDL cholesterol (mg/dL)131.4 (36.3)127.6 (37.2)131.4 (37.5)131.5 (35.0)133.1 (35.7)133.3 (35.9)<.001
      SBP (mm Hg)119.8 (14.3)118.1 (15.2)119.4 (14.9)119.6 (13.9)120.6 (13.9)121.4 (13.4)<.001
      DBP (mm Hg)80.2 (9.9)79.3 (10.4)79.8 (10.0)80.2 (9.8)80.7 (9.8)81.0 (9.4)<.001
      Fasting glucose (mg/dL)99.1 (15.9)98.4 (15.6)99.3 (18.3)99.0 (16.1)99.1 (12.3)99.7 (16.8)<.001
      Smoking (% current)1349 (11.9)248 (10.9)257 (11.3)271 (11.9)293 (12.9)280 (12.3).04
      BMI (kg/m2)25.8 (4.1)25.2 (3.9)25.4 (3.9)25.7 (4.0)26.1 (4.0)26.4 (4.3)<.001
      Physical activity (MET-h/wk)17.5 (19.5)16.6 (18.8)16.8 (18.5)17.7 (19.0)18.1 (20.1)18.6 (21.0).002
      BMI = body mass index; DBP = diastolic blood pressure; LDL = low-density lipoprotein; MET = metabolic equivalent of task; SBP = systolic blood pressure; SD = standard deviation.
      * P for trend of characteristic across diet category. Continuous data presented as mean (standard deviation). Frequency data presented as N (percent).

      Dietary Pattern, Dietary Components, and Mortality

      All-Cause Mortality

      There were 841 deaths from all causes over a mean of 18.0 years of follow-up. The relationship among baseline dietary pattern, dietary components, and all-cause mortality is shown in Table 2, Table 3. After adjustment for all covariates, the DASH diet score was associated with a lower risk of all-cause mortality (HR, 0.94 per quintile; 95% confidence interval [CI], 0.89-0.99). A 1-quintile increase in vegetable intake, as defined in the DASH diet score, was associated with a 7% lower risk for all-cause mortality (HR, 0.93; 95% CI, 0.88-0.98). Neither the Mediterranean diet score nor the dietary components in the Mediterranean diet score calculation were associated with all-cause mortality.
      Table 2Mortality Hazard Ratios for Dietary Approaches to Stop Hypertension Dietary Pattern Score and Components
      Basic Adjustment
      Adjusted for sex and age.
      Full Adjustment
      Adjusted for sex, age, smoking, calorie intake, physical activity, BMI, family history, cardiovascular disease, and baseline glucose, LDL, and SBP.
      All-cause mortality
       DASH diet score0.89 (0.85-0.94)
      P < .05.
      0.94 (0.89-0.99)
      P < .05.
       DASH score components
       Fruit0.97 (0.91-1.02)1.00 (0.94-1.06)
       Vegetable0.92 (0.88-0.97)
      P < .05.
      0.93 (0.88-0.98)
      P < .05.
       Nuts and legumes0.98 (0.93-1.02)0.98 (0.94-1.03)
       Dairy0.96 (0.91-1.01)0.96 (0.92-1.01)
       Whole grain0.94 (0.90-0.99)
      P < .05.
      0.97 (0.92-1.02)
       Sodium1.00 (0.95-1.05)1.00 (0.95-1.05)
       Red and processed meats1.02 (0.97-1.08)1.00 (0.95-1.06)
       Added sugar1.01 (0.96-1.06)1.02 (0.97-1.07)
      Cardiovascular mortality
       DASH diet score0.90 (0.82-0.99)
      P < .05.
      0.96 (0.86-1.06)
       DASH score components
       Fruit0.94 (0.85-1.04)0.97 (0.88-1.08)
       Vegetable0.93 (0.85-1.02)0.94 (0.85-1.03)
       Nuts and legumes0.97 (0.89-1.06)0.98 (0.90-1.07)
       Dairy1.02 (0.93-1.12)1.03 (0.94-1.13)
       Whole grain0.90 (0.82-0.99)
      P < .05.
      0.94 (0.85-1.03)
       Sodium1.02 (0.93-1.12)1.02 (0.93-1.13)
       Red and processed meats1.00 (0.91-1.10)0.98 (0.89-1.08)
       Added sugar1.04 (0.95-1.14)1.05 (0.96-1.15)
      DASH = Dietary Approaches to Stop Hypertension.
      DASH diet score data represent the HR (95% CI) for each 1 quintile increase in the DASH diet score. DASH diet components are scored by quintile. Component HRs represent 1 quintile increase in each respective component.
      * Adjusted for sex and age.
      Adjusted for sex, age, smoking, calorie intake, physical activity, BMI, family history, cardiovascular disease, and baseline glucose, LDL, and SBP.
      P < .05.
      Table 3Mortality Hazard Ratios for Mediterranean Dietary Pattern Score and Components
      Basic Adjustment
      Adjusted for sex and age.
      Full Adjustment
      Adjusted for sex, age, smoking, calorie intake, physical activity, BMI, family history cardiovascular disease, and baseline glucose, LDL, and SBP.
      All-cause mortality
       Mediterranean diet score0.96 (0.91-1.01)0.99 (0.94-1.04)
       Mediterranean score components
       Vegetable0.86 (0.74-0.98)
      P < .05.
      0.88 (0.77-1.02)
       Fruits and nuts0.81 (0.70-0.94)
      P < .05.
      0.88 (0.75-1.02)
       Legumes1.04 (0.91-1.19)1.06 (0.92-1.21)
       Grains0.90 (0.78-1.03)0.92 (0.80-1.06)
       Fish0.92 (0.90-1.06)0.92 (0.80-1.06)
       MUFA:SFA1.02 (0.88-1.18)1.03 (0.89-1.19)
       Dairy0.84 (0.73-0.97)
      P < .05.
      0.86 (0.75-1.00)
       Meat0.98 (0.85-1.14)0.92 (0.79-1.07)
       Alcohol0.95 (0.83-1.10)0.93 (0.81-1.08)
      Cardiovascular mortality
       Mediterranean diet score0.92 (0.84-1.01)0.93 (0.85-1.02)
       Mediterranean score components
       Vegetable1.02 (0.78-1.31)1.05 (0.81-1.37)
       Fruits and nuts0.65 (0.50-0.86)
      P < .05.
      0.70 (0.52-0.93)
      P < .05.
       Legumes1.24 (0.96-1.59)1.24 (0.96-1.60)
       Grains0.59 (0.45-0.77)
      P < .05.
      0.62 (0.48-0.82)
      P < .05.
       Fish0.91 (0.70-1.19)0.91 (0.70-1.18)
       MUFA:SFA0.97 (0.74-1.27)0.97 (0.74-1.27)
       Dairy0.96 (0.73-1.25)1.00 (0.76-1.30)
      MUFA = mono-unsaturated fatty acids; SFA = saturated fatty acids.
      Mediterranean diet score data represent the HR (95% CI) for each 1 quintile increase in the Mediterranean diet score. Mediterranean diet components are scored as being above/below median or for alcohol intake above/below a range of intake (see “Materials and Methods”). For all except alcohol intake, data presented as the HR (95% CI) for being above median intake, compared with below median intake, in each respective component. For alcohol intake, the referent group is low alcohol intake.
      * Adjusted for sex and age.
      Adjusted for sex, age, smoking, calorie intake, physical activity, BMI, family history cardiovascular disease, and baseline glucose, LDL, and SBP.
      P < .05.

      Cardiovascular Mortality

      There were 249 cardiovascular deaths over a mean 18 years of follow-up. Assessment of dietary pattern, dietary components, and risk for cardiovascular mortality is reported in Table 2, Table 3. After adjustment for all covariates, neither the DASH diet score nor the DASH diet score components were associated with cardiovascular mortality. Although the Mediterranean diet score was also not associated with risk of cardiovascular mortality, greater than median intake of fruits and nuts (HR, 0.70; 95% CI, 0.52-0.93), as well as grains (HR, 0.62; 95% CI, 0.48-0.82), was associated with a reduced risk of cardiovascular mortality (P < .05).

      Tree-Augmented Analysis of Dietary Components

      The optimized regression tree for all-cause mortality is displayed in Figure, which depicts a recursive process of identifying the predictor variable and threshold value that divides the sample into maximally disparate subgroups. In this tree, the initial sample of 11,376 participants was initially divided by percent of daily caloric intake from solid fats (node 2 includes individuals whose daily caloric intake was between 28.5% and 33.6% solid fats, and node 3 includes individuals whose daily caloric intake was >33.6% solid fats). The group of individuals who consumed less than 28.5% of their daily caloric intake in solid fats was further divided into 3 groups based on percent of daily intake from added sugars: node 4 (<3.5%), node 5 (between 3.5 and 9.1%), and node 6 (>9.1%).
      Figure
      FigureRegression tree of dietary components for all-cause mortality. *P < .05 for risk of all-cause mortality. CI = confidence interval; HR = hazard ratio.
      Individuals in node 5 (solid fats <28.5%, added sugar 3.5%-9.1%) had the lowest risk for all-cause mortality. Relative to individuals in node 5, participants in node 4 had a 36% higher risk for all-cause mortality (HR, 1.36; 95% CI, 1.11-1.66) and those in node 6 had a 39% higher risk for all-cause mortality (HR, 1.39; 95% CI, 1.18-1.63). Individuals in node 2 had a 69% increased risk for all-cause mortality (HR, 1.69; 95% CI, 1.29-2.21), regardless of amount of added sugar intake. Participants whose daily caloric intake was >33.6% added solid fats (node 3), regardless of added sugar intake, had a risk for all-cause mortality more than 3 times higher than people in node 5 (HR, 3.30; 95% CI, 2.29-4.74). A similar regression tree analysis was not pursued for cardiovascular mortality because the optimized tree had no dietary or macronutrient branches.

      Discussion

      In this generally healthy middle-aged population, the DASH diet was associated with a lower risk of all-cause mortality, even after adjustment for covariates with which dietary pattern are known to be related (eg, lipids, blood pressure, BMI). The DASH diet score was not associated with risk of cardiovascular mortality after accounting for cardiovascular disease risk factors. The Mediterranean dietary pattern was not associated with all-cause or cardiovascular mortality. In our analysis of dietary components and food groups, we found that solid fat and added sugar intake was most highly predictive of all-cause mortality. People who consumed more than one third of their daily calories as solid fats had more than 3 times the risk of dying from any cause over an average of 18 years of follow-up, compared with individuals who ate <28.5% of calories as solid fats and between 3.5% and 9.1% as added sugars. We found that individuals with the lowest risk were not those who ate the least added sugar, but instead consumed a moderate amount of added sugars (between 3.5% and 9.1% of their total daily caloric intake).
      Although the DASH diet has been associated with a lower risk of death in adults with hypertension, women with heart failure, older adults, and African-American women,
      • Parikh A.
      • Lipsitz S.R.
      • Natarajan S.
      Association between a DASH-like diet and mortality in adults with hypertension: findings from a population-based follow-up study.
      • Levitan E.B.
      • Lewis C.E.
      • Tinker L.F.
      • et al.
      Mediterranean and DASH diet scores and mortality in women with heart failure: the Women's Health Initiative.
      • Reedy J.
      • Krebs-Smith S.M.
      • Miller P.E.
      • et al.
      Higher diet quality is associated with decreased risk of all-cause, cardiovascular disease, and cancer mortality among older adults.
      • Boggs D.A.
      • Ban Y.
      • Palmer J.R.
      • Rosenberg L.
      Higher diet quality is inversely associated with mortality in African-American women.
      to our knowledge this is the first analysis to demonstrate a survival benefit associated with the DASH diet in a healthy middle-aged population. The magnitude of lower mortality risk we observed is similar to that observed in higher-risk populations.
      • Schwingshackl L.
      • Hoffmann G.
      Diet quality as assessed by the Healthy Eating Index, the Alternate Healthy Eating Index, the Dietary Approaches to Stop Hypertension score, and health outcomes: a systematic review and meta-analysis of cohort studies.
      Our finding that the DASH diet was associated with a lower risk of all-cause mortality after adjustment for key cardiovascular risk factors suggests that this dietary pattern has health benefits beyond its effect on cardiovascular risk factors, such as blood pressure, lipids, and glucose. These results do not clearly indicate a pathway through which the DASH dietary pattern may reduce all-cause mortality. Detailed analysis revealed modest benefit associated with vegetables within the DASH diet scheme. Existing evidence suggests that lower all-cause mortality associated with the DASH dietary pattern may be due to the influence of nutrients, displacement of other foods,
      • Levitan E.B.
      • Lewis C.E.
      • Tinker L.F.
      • et al.
      Mediterranean and DASH diet scores and mortality in women with heart failure: the Women's Health Initiative.
      reduced inflammation,
      • Miller 3rd, E.R.
      • Appel L.J.
      • Risby T.H.
      Effect of dietary patterns on measures of lipid peroxidation: results from a randomized clinical trial.
      • Fung T.T.
      • Chiuve S.E.
      • McCullough M.L.
      • Rexrode K.M.
      • Logroscino G.
      • Hu F.B.
      Adherence to a DASH-style diet and risk of coronary heart disease and stroke in women.
      • Coussens L.M.
      • Werb Z.
      Inflammation and cancer.
      reduced risk of multiple types of cancers,
      • Coussens L.M.
      • Werb Z.
      Inflammation and cancer.
      • Block G.
      • Patterson B.
      • Subar A.
      Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence.
      • Cummings J.H.
      • Bingham S.A.
      Diet and the prevention of cancer.
      • Dixon L.B.
      • Subar A.F.
      • Peters U.
      • et al.
      Adherence to the USDA Food Guide, DASH Eating Plan, and Mediterranean dietary pattern reduces risk of colorectal adenoma.
      and other unmeasured variables. Given the complexity of dietary intake, a combination of these effects likely underlies the lower risk of all-cause mortality.
      The unadjusted association of the DASH diet with cardiovascular disease mortality was significant; however, the association was no longer significant after adjusting for risk factors such as LDL cholesterol, glucose, and blood pressure. This is somewhat surprising, because the DASH diet lowers blood pressure in people with hypertension,
      • Appel L.J.
      • Moore T.J.
      • Obarzanek E.
      • et al.
      A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group.
      but prior studies in different populations had similar findings.
      • Folsom A.R.
      • Parker E.D.
      • Harnack L.J.
      Degree of concordance with DASH diet guidelines and incidence of hypertension and fatal cardiovascular disease.
      Our findings suggest that atherosclerosis risk factors may mediate the pathway from dietary pattern to mortality. The DASH diet was originally developed to treat hypertension, a known cardiovascular disease risk factor, and is also related to other cardiovascular risk factors such as diabetes, cholesterol, and BMI.
      • Zarraga I.G.
      • Schwarz E.R.
      Impact of dietary patterns and interventions on cardiovascular health.
      • Appel L.J.
      • Moore T.J.
      • Obarzanek E.
      • et al.
      A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group.
      • van Dam R.M.
      • Rimm E.B.
      • Willett W.C.
      • Stampfer M.J.
      • Hu F.B.
      Dietary patterns and risk for type 2 diabetes mellitus in U.S. men.
      • Newby P.K.
      • Muller D.
      • Hallfrisch J.
      • Qiao N.
      • Andres R.
      • Tucker K.L.
      Dietary patterns and changes in body mass index and waist circumference in adults.
      This finding supports the importance of primordial prevention or preventing the development of risk factors for cardiovascular disease. In the prevention of fatal cardiovascular events, adoption of a DASH-style diet may prevent progression down the cardiovascular disease pathophysiologic pathway.
      Although the DASH diet pattern showed associations with mortality in our population, the Mediterranean dietary pattern did not. The Mediterranean diet has been associated with a lower mortality risk in multiple studies.
      • Hu F.B.
      The Mediterranean diet and mortality–olive oil and beyond.
      Mediterranean dietary component analysis in the Cooper Clinic population suggests that fruit and nut intake, as well as grain intake, is protective, which is consistent with prior findings.
      • Wang X.
      • Ouyang Y.
      • Liu J.
      • et al.
      Fruit and vegetable consumption and mortality from all causes, cardiovascular disease, and cancer: systematic review and dose-response meta-analysis of prospective cohort studies.
      • Zong G.
      • Gao A.
      • Hu F.B.
      • Sun Q.
      Whole grain intake and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis of prospective cohort studies.
      • Bao Y.
      • Han J.
      • Hu F.B.
      • et al.
      Association of nut consumption with total and cause-specific mortality.
      The lack of association of the Mediterranean diet score as a whole with mortality in this population may be explained, in part, by the relatively small magnitude of association between score components and mortality, as well as the combination of components associated with both increased and decreased mortality (ie, averaging to no association).
      The regression tree analysis suggests that solid fat and added sugar intake are the most predictive of mortality. Both solid fat intake and sugar intake have been linked to mortality in prior studies.
      • Yang Q.
      • Zhang Z.
      • Gregg E.W.
      • Flanders W.D.
      • Merritt R.
      • Hu F.B.
      Added sugar intake and cardiovascular diseases mortality among US adults.
      • Tasevska N.
      • Park Y.
      • Jiao L.
      • Hollenbeck A.
      • Subar A.F.
      • Potischman N.
      Sugars and risk of mortality in the NIH-AARP Diet and Health Study.
      • Guasch-Ferre M.
      • Babio N.
      • Martinez-Gonzalez M.A.
      • et al.
      Dietary fat intake and risk of cardiovascular disease and all-cause mortality in a population at high risk of cardiovascular disease.
      • de Souza R.J.
      • Mente A.
      • Maroleanu A.
      • et al.
      Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies.
      Of note, in our analysis the participants who consumed a moderate amount of added sugar—not the least amount of added sugar—had the lowest mortality risk. There are multiple potential explanations for this finding. Perhaps participants in the lowest sugar intake group (node 4) were originally in the higher sugar intake groups (nodes 5 or 6), but were instructed to cut their sugar intake because of a poorer health status. These participants' sugar intake would thus be lower, but they may still have had a higher overall mortality risk. Alternatively, it is possible that individuals consuming healthful foods that do contain some added sugar (eg, yogurt) are represented in the lowest-risk category (node 5). A less plausible, but possible, explanation is that our results indicate a physiologic benefit to moderate sugar intake that is not yet well understood.

      Study Strengths and Limitations

      Strengths of our analysis include a large sample followed over approximately 2 decades. The dietary assessment allowed for calculation of dietary pattern using a validated nutrient analysis. The relatively homogenous baseline sample enhances internal validity of this analysis, but restricts applicability to other groups. However, our analysis was performed on a population who was generally healthy at baseline, unlike many prior studies conducted in older populations or those with comorbidities. As an observational study, our findings are primarily hypothesis generating; however, the tree-augmented model suggests relative contributions of diet components to the overall diet pattern that may influence mortality outcomes. The DASH diet may only be a marker of other healthy behaviors that directly reduce the risk of death. Although the dietary assessment was subject to recall bias, recall errors may be limited because intake was recorded in nearly real-time.
      An important limitation to this analysis is that dietary pattern data were only available at baseline. This precluded assessment of changes over time, which have shown associations with mortality.
      • Sotos-Prieto M.
      • Bhupathiraju S.N.
      • Mattei J.
      • et al.
      Changes in three diet quality scores and total and cause-specific mortality.
      Prior analysis in unrelated populations suggests that dietary patterns may persist for 7 years.
      • Weismayer C.
      • Anderson J.G.
      • Wolk A.
      Changes in the stability of dietary patterns in a study of middle-aged Swedish women.
      Consistent with this observation, our finding of a link between dietary pattern in middle-age and survival after an average of 18 years of follow-up suggest that dietary pattern in midlife is related to long-term outcomes. We also acknowledge that patients seen in a preventive medicine clinic may be more likely to follow a healthful diet, but the range in diet scores seen in our analysis suggests that individuals followed at the Cooper Clinic did not necessarily follow healthful dietary patterns.

      Conclusions

      Our results indicate that eating patterns in middle age may influence outcomes decades later, supporting the need for promotion of healthy dietary patterns early in life.

      Acknowledgments

      The authors thank Kenneth H. Cooper, MD, MPH, for establishing the Cooper Center Longitudinal Study, the Cooper Clinic for collecting the data, and The Cooper Institute for maintaining the database.

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