Nutrition-based approaches are recommended

Transcription

1 AJH 2000;13: ORIGINAL CONTRIBUTIONS The Effect of Dietary Patterns on Blood Pressure Control in Hypertensive Patients: Results From the Dietary Approaches to Stop Hypertension (DASH) Trial Paul R. Conlin, Dominic Chow, Edgar R. Miller III, Laura P. Svetkey, Pao-Hwa Lin, David W. Harsha, Thomas J. Moore, Frank M. Sacks, and Lawrence J. Appel, for the DASH Research Group To determine the impact of dietary patterns on the control of hypertension we studied the subgroup of 133 participants with systolic blood pressure (BP) of 140 to 159 mm Hg and/or diastolic BP of 90 to 95 mm Hg enrolled in the Dietary Approaches to Stop Hypertension (DASH) study. Participants were fed a control diet for a 3-week period and were then randomized to receive for 8 weeks either the control diet; a diet rich in fruits and vegetables, but otherwise similar to control; or a combination diet rich in fruits, vegetables, and low-fat dairy products, including whole grains, fish, poultry, and nuts, and reduced in fats, red meats, sweets, and sugar-containing beverages. Sodium intake and body weight were held constant throughout the study. The combination diet significantly reduced systolic BP ( 11.4 mm Hg, P <.001) and diastolic BP ( 5.5 mm Hg, P <.001). The fruits-andvegetables diet also significantly reduced systolic BP ( 7.2 mm Hg, P <.001) and diastolic BP ( 2.8 mm Hg, P.013). The combination diet produced significantly greater BP effects (P <.05) than the fruits-and-vegetables diet. Blood pressure changes were evident within 2 weeks of starting the intervention feeding. After the 8-week intervention period, 70% of participants eating the combination diet had a normal BP (systolic BP < 140 and diastolic BP < 90 mm Hg) compared with 45% on the fruits-and-vegetables diet and 23% on the control diet. In patients with hypertension, the DASH combination diet effectively lowers BP and may be useful in achieving control of Stage 1 hypertension. Am J Hypertens 2000;13: American Journal of Hypertension, Ltd. KEY WORDS: Hypertension, diet, fruit, vegetables, clinical trial, multicenter study. Nutrition-based approaches are recommended as first-line therapy for the prevention of hypertension in individuals with high normal blood pressure (BP) and to control BP in patients with Stage 1 hypertension. To date, most recommendations for lifestyle modifications have focused on reducing salt intake, weight loss, and moderation of alcohol consumption. Other dietary interventions, particularly modifying whole dietary patterns, might also effectively reduce BP and thereby control hypertension. The Dietary Approaches to Stop Hypertension Received July 15, Accepted December 6, From the Endocrinology-Hypertension Division, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts; Welch Center for Prevention, Epidemiology and Clinical Research, The Johns Hopkins Medical Institutions, Baltimore, Maryland; Duke Hypertension Center, Duke University Medical Center, Durham, North Carolina; Sarah W. Stedman Center for Nutritional Studies, Duke University Medical Center, Durham, North Carolina; Pennington Biomedical Research Center, Baton Rouge, Louisiana; Merck and Company, Westwood, Massachusetts; Channing Laboratory, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts; and Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts. Address correspondence and reprint requests to Paul R. Conlin, MD, Endocrinology-Hypertension Division, Brigham and Women s Hospital, 221 Longwood Avenue, Boston, MA 02115; pconlin@rics.bwh.harvard.edu 2000 by the American Journal of Hypertension, Ltd /00/$20.00 Published by Elsevier Science, Inc. PII S (99)

2 950 CONLIN ET AL AJH SEPTEMBER 2000 VOL. 13, NO. 9 (DASH) clinical trial tested the effects of modifying whole dietary patterns in 459 persons with a diastolic BP between 80 and 95 mm Hg and systolic BP less than 160 mm Hg. 1,2 The results of this trial showed that a diet that emphasizes fruits, vegetables, and low-fat dairy products, includes whole grains, poultry, fish, and nuts, and is reduced in fat, red meat, sweets, and sugar-containing beverages (combination diet) in the absence of weight loss or sodium restriction significantly lowered BP. Previous reports have suggested that the DASH combination diet provided greater BP lowering in the hypertensive subgroup, compared with normotensive individuals. 1,3 Because 29% of study participants had Stage 1 hypertension (systolic BP 140 mm Hg and/or diastolic BP 90 mm Hg) at entry into the study, we have performed detailed analyses focusing on this important subgroup. We report the clinical characteristics of the hypertensive participants, the patterns and magnitude of BP reduction across time, and the effects of the DASH diets on hypertension control. MATERIALS AND METHODS The DASH trial was a multicenter randomized controlled feeding study. Its design and main results have been previously published. 1,2 Participants were adults, 22 years of age or older, with a systolic BP 160 mm Hg and diastolic BP between 80 and 95 mm Hg. Of the 459 randomized participants, 133 were hypertensive as defined by an average baseline systolic BP 140 and/or diastolic BP 90 mm Hg (average of three pairs of measurements during the screening and four pairs during a 3-week run-in period). Persons previously using antihypertensive medication were eligible for entry into the trial only after a period of supervised medication withdrawal that preceded the formal screening process by at least 2 weeks. Exclusion criteria included poorly controlled diabetes mellitus, poorly controlled hyperlipidemia, a cardiovascular event within the prior 6 months, chronic diseases that might interfere with participation, pregnancy or lactation, body mass index (BMI) 35 kg/m 2, the concurrent use of medications that affect BP, unwillingness to discontinue vitamin and mineral supplements or antacids containing magnesium or calcium, renal insufficiency, and alcohol intake of more than 14 drinks per week. The study was conducted in three phases: screening for eligibility, a 3-week run-in feeding period, and an 8-week intervention feeding period. During the 3-week run-in period all participants ate a control diet. This diet was relatively low in fruits and vegetables (total of four servings per day), and the macronutrient profile corresponded to average U.S. dietary consumption. 2 At the end of the run-in period, participants were randomized to continue with one of three diets for an 8-week intervention period: the control diet, a fruits-and-vegetables diet, or the combination diet. Diet randomization was not stratified based on hypertension status. The fruits-and-vegetables diet provided approximately 10 servings of fruits and vegetables per day and was rich in potassium, magnesium, and fiber but was otherwise similar to the control diet. The combination diet emphasizes fruits, vegetables, and low-fat dairy products. It includes whole grains, poultry, fish, and nuts, and is reduced in fats, red meat, sweets, and sugar-containing beverages. Its nutrient content is increased in potassium, magnesium, calcium, and fiber, moderately increased in protein, and reduced in saturated fat, total fat, and cholesterol. Its sodium content is slightly below average U.S. consumption. Meals were prepared in metabolic kitchens and served to participants in outpatient dining facilities. Each weekday the participants ate one meal (either lunch or dinner) on-site. After the on-site meal they received prepackaged food to be consumed for the next 24 h (during weekdays) and their weekend food was provided on Fridays. Throughout the 11 weeks of feeding participants agreed to eat only the foods provided to them and nothing else. The weight of each participant was measured each weekday and caloric intake was adjusted to maintain weight within 2% of baseline. Sodium intake was maintained at a daily target of approximately 3 g per 2100 kcal in all diets. Participants were instructed to limit their alcohol consumption to no more than two alcoholic drinks per day. The total servings of tea, coffee, and/or carbonated beverages were limited to no more than three drinks per day. Blood pressure was measured by trained and certified staff members using a random-zero sphygmomanometer according to a common protocol adapted from the Trials of Hypertension Prevention (TOHP II). 4 At measurement sessions, participants had two BP measurements obtained after 5 min rest in the seated position. Mean screening BP was the average of three pairs of measurements during the three screening visits. During the run-in and intervention periods, BP was measured once weekly. Baseline BP was the average of screening measurements and four pairs of measurements during run-in. The end-of-intervention BP was the average of five pairs of measurements obtained during the last 13 days of the intervention feeding. Control of hypertension was defined as both systolic BP 140 and diastolic BP 90 mm Hg at the end of intervention. Patients with isolated systolic hypertension were defined as those with baseline systolic BP 140 mm Hg and diastolic BP 90 mm Hg.

3 AJH SEPTEMBER 2000 VOL. 13, NO. 9 DIETARY PATTERNS AND BP CONTROL 951 TABLE 1. BASELINE CHARACTERISTICS OF HYPERTENSIVE* PARTICIPANTS IN DAYS BY DIET ASSIGNMENT Control Fruits-and- Vegetables Combination All Number of participants Age (years) 48.1 (11.7) 49.7 (8.8) 49.9 (10.2) 49.2 (10.3) Female (%) Race (% black) Physician diagnosis of hypertension (%) History of antihypertensive medication use (%) Alcohol Intake Weekly users 34% 27% 41% 39% Drinks/week 1.4 (3.2) 0.6 (1.3) 1.1 (2.6) 1.2 (2.4) Weight (kg) 78.8 (12.3) 80.9 (13.8) 80.5 (11.4) 80.1 (12.6) BMI (kg/m 2 ) 27.3 (3.3) 28.6 (3.7) 27.9 (3.6) 28.0 (3.6) Estimated energy expenditure (cal/kg/day) 39.0 (8.4) 36.6 (7.6) 35.8 (4.1) 37.2 (7.2) Systolic blood pressure (mm Hg) (8.9) (8.6) (8.1) (8.5) Diastolic blood pressure (mm Hg) 90.1 (4.6) 90.0 (5.8) 88.3 (6.1) 89.6 (5.5) Urinary sodium (mg/24 h) 3504 (225) 3743 (323) 3440 (276) 3573 (160) Urinary potassium (mg/24 h) 2112 (156) 2169 (131) 2019 (170) 2107 (87) BMI body mass index. Continuous data are reported as means ( SD). * Hypertension defined as systolic blood pressure 140 mm Hg and/or diastolic blood pressure 90 mm Hg measured as mean of three screening visits and four visits during the run-in period. The estimated energy expenditure is derived from a 7-day physical activity recall performed at screening. Control of isolated systolic hypertension was defined as end-of-intervention systolic BP 140 mm Hg in these same individuals. Urinary excretions of sodium, potassium, calcium, and magnesium were determined from 24-h urine collections at the end of run-in and intervention periods. A 7-day activity recall was used to measure physical activity, ie, total daily energy expenditure, during screening and at the end of the intervention period. 5 Analyses Data are presented as mean SD. Analyses were performed on an intention-to-treat basis. Pairwise comparisons of changes in BP between the diets from baseline to the end of intervention were analyzed by Student s t test in unadjusted analyses and by ANOVA in adjusted analyses, using the STATA statistical package, version 5.0. The relative risks of hypertension at the end of the intervention period for each intervention group, compared with the control group, were computed with their 95% confidence intervals (CI) using EPI Info, version 6.0. All trial-wide data were compiled and verified by the DASH Coordinating Center. The authors performed all data analyses in this manuscript. RESULTS In the subgroup of 133 DASH participants with hypertension, the average age was years; 65% were black and 60% were women. Mean baseline urinary sodium excretion was 3573 mg/day and mean potassium excretion was 2107 mg/day. Other baseline characteristics, both overall and by diet assignment, are displayed in Table 1. Forty-seven participants received the control diet, 49 received the fruits-andvegetables diet, and 37 received the combination diet. Hypertensive participants assigned to each of the diets had similar characteristics, although the combination diet group tended to have fewer blacks and more participants who reported the consumption of alcohol on a regular basis. The percentage of hypertensive participants who completed the intervention phase on the control, fruits and vegetables, and combination diets were 94%, 96%, and 100%, respectively. Mean changes in weight from the end of run-in to the end of intervention were not significantly different from zero for any of the intervention groups: 0.33 kg in the control diet, 0.16 kg in the fruits and vegetables diet, and 0.55 kg in the combination diet. Mean changes in total daily energy expenditure between end of intervention and screening periods were also not significant: 0.12 kcal/kg/ day in the control diet, 0.12 kcal/kg/day in the fruits-and-vegetables diet, and 2.11 kcal/kg/day in the combination diet. Mean levels of urinary sodium, potassium, calcium, and magnesium excretion at end of run-in and end of intervention are displayed in Fig. 1. There was no significant change in sodium

4 952 CONLIN ET AL AJH SEPTEMBER 2000 VOL. 13, NO. 9 FIG. 1. Mean urinary sodium, potassium, calcium, and magnesium excretion at end of run-in (open bars) and end of intervention (solid bars). *P.01 v control diet. excretion from run-in to end of intervention within each group and across diets. At the end of intervention, urinary potassium and magnesium excretion were significantly greater in the fruits-and-vegetables (P.001) and combination diets (P.001), compared with the control diet. At the end of the intervention period the percent of hypertensive participants who remained hypertensive ( 140 and/or 90 mm Hg) was 77% in the control diet, 55% in the fruits-and-vegetables diet, and 30% in the combination diet (Table 2). The relative risk (95% CI) of hypertension at the end of the study was 0.72 (0.52, 0.97) (P.027) for the fruits-and-vegetables diet and 0.39 (0.23, 0.65) (P.001) for the combination diet, in comparison to the control diet. At the end of the intervention period, the prevalence of isolated systolic hypertension was 19/25 (76%) in the control diet, 13/24 (54%) in the fruits-and-vegetables diet, and 5/23 (22%) in the combination diet. The relative risk (95% CI) of isolated systolic hypertension at the end of the intervention was 0.71 (0.46, 1.09) for the fruits-and-vegetables diet and 0.29 (0.13, 0.64) (P.001) for the combination diet, compared with the control diet (Table 2). At the end of the 8-week intervention period, within-group changes in systolic BP in the control, fruitsand-vegetables, and combination diets were 0.5 mm Hg, 6.6 mm Hg, and 10.7 mm Hg, respectively. Corresponding changes in diastolic BP were 0.6 mm Hg, 2.4 mm Hg, and 4.7 mm Hg, respectively. After subtracting the responses in the control diet, the fruits-and-vegetables diet reduced systolic and diastolic BP by 7.2 and 2.8 mm Hg, respectively (P.001 and.013) and the combination diet reduced systolic BP by 11.4 mm Hg (P.001) and diastolic BP by 5.5 mm Hg (P.001). When compared with the fruits-andvegetables diet, the response in the combination diet was greater by 4.1 mm Hg for systolic BP (P.038) and 2.6 mm Hg for diastolic BP (P.031). In analyses that adjusted for clinical centers, gender, age, race, baseline BP, and alcohol use, the results were similar (Table 3). Mean changes from baseline in systolic and diastolic BP during the weeks of intervention feeding by diet assignment are shown in Figs. 2 and 3. Significant (P.01) between-diet differences were present by the second week of intervention feeding. DISCUSSION This detailed report on the hypertensive participants enrolled in the DASH clinical trial amplifies and extends previous reports from this study. Specifically, the DASH combination diet a diet that emphasizes fruits, vegetables, and low-fat dairy products; includes whole grains, poultry, fish, and nuts; and is reduced in fat, red meat, sweets, and sugar-containing beverages controlled hypertension in 70% of participants with Stage 1 systolic or diastolic hypertension at baseline. A diet rich in fruits and vegetables also lowered BP and controlled hypertension, but to a lesser extent. Within each diet group the onset of effect was within 2 weeks and sustained throughout the 8 weeks of intervention feeding. The BP response of each dietary intervention was also sustained through- TABLE 2. PREVALENCE OF HYPERTENSION AT END OF STUDY Randomized Diet Hypertension at End of Intervention (%) Relative Risk* (95% CI) P Value ISH at End of Intervention (%) Relative Risk* (95% CI) P Value Control 36/47 (77) /25 (76) 1.0 Fruits-and-Vegetables 27/49 (55) 0.72 (0.52, 0.97) /24 (54) 0.71 (0.46, 1.09).11 Combination 11/37 (30) 0.39 (0.23, 0.65).001 5/23 (22) 0.29 (0.13, 0.64).001 Hypertension average systolic blood pressure 140 mm Hg or diastolic blood pressure 90 mm Hg at the end of the intervention feeding period; CI confidence interval; ISH isolated systolic hypertension, average systolic blood pressure 140 mm Hg and diastolic blood pressure 90 at the end of the intervention feeding period. * Relative risk of hypertension by intervention diet as compared with the control diet.

5 AJH SEPTEMBER 2000 VOL. 13, NO. 9 DIETARY PATTERNS AND BP CONTROL 953 TABLE 3. MEAN BETWEEN-DIET DIFFERENCES IN BLOOD PRESSURE CHANGE IN DASH PARTICIPANTS WITH HYPERTENSION Category Change in Combination Group Minus Change in Control Group P Value Change in Combination Group Minus Change in Fruits/Veg Group P Value Change in Fruits/ Veg Group Minus Change in Control Group P Value Systolic blood pressure, Adjusted for clinical centers 11.4 ( 15.2, 7.4) ( 8.0, 0.2) ( 10.9, 3.6).001 Adjusted for clinical center, gender, race, age, ETOH, and baseline SBP 11.6 ( 15.5, 7.6) ( 8.4, 0.7) ( 10.7, 3.4).001 Diastolic blood pressure, Adjusted for clinical centers 5.5 ( 7.9, 3.1) ( 5.0, 0.2) ( 5.1, 0.6).013 Adjusted for clinical center, gender, race, age, ETOH, and baseline DBP 5.9 ( 8.3, 3.4) ( 5.3, 0.5) ( 5.3, 0.7).010 ETOH alcohol; SBP systolic blood pressure; DBP diastolic blood pressure. out the 24-h period, as measured by ambulatory BP monitoring. 6 Although subgroup analyses are vulnerable to maldistribution of confounding variables, it is reassuring that baseline characteristics of the hypertensive participants were similar in the three diet groups. In fact, the minor differences observed would tend to diminish an effect rather than augment it. For instance, there were fewer hypertensive blacks assigned to the combination diet. In a previous report, blacks tended to have a greater BP reduction than nonminority participants. 3 Likewise, mean baseline systolic and diastolic BPs were slightly less in the combination diet than corresponding values in the other two diets. After adjustment for these factors and other covariates, the DASH combination diet significantly reduced BP in hypertensives when compared with both the control diet and the fruits-and-vegetables diet. The DASH combination diet is consistent with other dietary recommendations. Its fat content (6% of calories from saturated fat) is similar to that of the AHA Step I diet. 7 The dairy content (approximately 3 servings/day) and calcium content (1200 mg/day/2100 kcal) are likewise similar to dietary recommendations designed to prevent osteoporosis. 8 The fruit and vegetable content (10 servings/day) also meets the current U.S. dietary guidelines designed to prevent cancer. 9 Hence, the DASH combination diet achieved BP reduction in the setting of an overall healthy diet that may also have other benefits in terms of preventing chronic disease. FIG. 2. Mean changes in systolic blood pressures from baseline during the 8 weeks of intervention feeding according to diet assignments. *P.001 v control diet; **P.001 v control diet and P.052 v fruits-and-vegetables diet. FIG. 3. Mean changes in diastolic blood pressures from baseline during the 8 weeks of intervention feeding according to diet assignments. *P.001 v control diet; **P.001 v control diet and P.033 v fruits-and-vegetables diet.

6 954 CONLIN ET AL AJH SEPTEMBER 2000 VOL. 13, NO. 9 The DASH combination diet produced its effects on BP while weight and salt intake were held constant. Although the salt intake of all three diets was similar, approximately 3 g/day, this amount still exceeds current recommendations of 2.3 g per day. 10 Hence, it is interesting to speculate on the additional effects of reducing salt and weight in addition to the combination diet. The effects of these established strategies in conjunction with the DASH intervention are currently under investigation. Even if the effects of these combined interventions are less than additive, the overall effect could still be quite marked, leading to improved control rates in hypertensive patients. The nutrients responsible for the BP reduction observed in DASH cannot be directly ascertained given the multiple differences between diets in nutrients, both known and unknown. Still, it is worthwhile to consider this issue in view of the evidence that certain specific dietary factors may have BP-lowering effects. One nutrient that likely contributed to the effect of the fruits-and-vegetables and combination diets is potassium. In DASH, the fruits-and-vegetables and combination diets were designed to provide approximately 75 mmol more potassium/day than the control diet (at 2100 kcal/day). In a recent metaanalysis, an increase of 60 mmol of potassium was associated with a 4.4-mm Hg reduction in SBP and 2.4-mm Hg reduction in DBP in hypertensive individuals. 11 Both diets are also enriched in fruits and vegetables and this has been associated with increased antioxidant activity. 12 Prior studies have shown that antioxidants can improve endothelium-dependent vasodilation. 13 Additionally, both diets are also increased in magnesium content. In population studies, dietary intake of magnesium was found to be inversely related to BP among men, 14 women, 15 and children, 16 and there was an inverse relationship between magnesium intake and risk of stroke. 17 However, direct supplementation of magnesium had no significant effect on BP in women with low daily intake. 18 The nutrients that might contribute to the BP reduction in the combination diet, compared with the fruitsand-vegetables diet, are less apparent. Compared with the fruits-and-vegetables diet, the combination diet is reduced in saturated fat, total fat, and cholesterol, and higher in calcium and protein content. Other nutrients certainly differed as well. Some may ascribe the BP reduction in the combination diet to its calcium content. Population studies have shown an inverse relationship between calcium intake and BP, and risk of stroke among women, 19 but not men. 17 However, as with magnesium, there does not appear to be a significant lowering of BP with supplementation. 18 Therefore, the available evidence from observational studies and clinical trials does not clarify that any one nutrient is responsible for the observed BP difference between the combination diet and the fruits-and-vegetables diet. As such, an interactive effect among nutrients is quite plausible. Other unanswered questions include the extent of BP reduction and hypertensive control in persons with higher levels of BP (Stage 2 hypertension or higher). For such individuals hypertension control may be more difficult to achieve with this dietary intervention alone. Thus, the effects of the DASH combination diet as an adjunct to antihypertensive therapy would also be of interest. Two studies that have attempted to evaluate this in treated hypertensives using low-fat/ high-fiber diets have suggested that the addition of moderate sodium restriction is necessary to achieve significant antihypertensive effect. 20,21 Also, adherence to the DASH dietary pattern among free-living persons is another critical issue, particularly if it is done in the context of achieving other dietary changes, ie, sodium reduction and weight loss. Lastly, the extent of adherence to the DASH diet that is necessary to reduce BP is not clear. In conclusion, a diet that emphasizes fruits, vegetables, and low-fat dairy products, includes whole grains, poultry, fish, and nuts, and is reduced in fat, red meats, sweets, and sugar-containing beverages led to significant hypertension control in persons with Stage 1 hypertension. ACKNOWLEDGMENTS In addition to the authors, the DASH Research Group includes the following institutions and individuals: Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, MD (sponsor): E. Obarzanek (project officer), J.A. Cutler, M.A. Proschan, D.G. Simons- Morton, M.A. Evans; Kaiser Permanente Center for Health Research, Portland, OR (coordinating center): T.M. Vogt (PI), W.M. Vollmer, N. Karanja, P. LaChance, R. Laws, C. Eddy, J. Rice, K. Pedula, L. Haworth, N. Adams, K. Pearson, L. Diller, J. Reinhardt; Brigham and Women s Hospital and Harvard Medical School, Boston, MA (clinical center): L. Jaffe, J. McKnight, M. MacDonald, K. Nauth, Y. Courtney; Duke University Medical Center, Durham, NC (clinical center): M. Drezner, C. Bales, L. Carter-Edwards, C. Plaisted, K. Hoben; S. Norris, P. Reams, K. Aicher, R. Fike; Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA (clinical center): G. Bray (PI), M.M. Windhauser, CM Champagne, PJ Wozniak, B. McGee, S. Crawford; Johns Hopkins University, Baltimore, MD (clinical center): B. Caballero, S. Kumanyika, S. Jee, J. Charleston, P. McCarron, S. Cappelli, B. Hamish, P. Coleman; Virginia Polytechnic Institute, Blacksburg, VA (food analysis coordinating center): K.K. Stewart, K. Phillips; Oregon Health Sciences University, Portland, OR ( central laboratory): D. McCarron, J.-B. Roulet, R. Illingworth; Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD (research kitchen for Johns Hopkins Clinical Center): S. Burns, E. Lashley, J.T. Spence. REFERENCES 1. Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, Bray GA, Vogt TM, Cutler JA,

7 AJH SEPTEMBER 2000 VOL. 13, NO. 9 DIETARY PATTERNS AND BP CONTROL 955 Windhauser MM, Lin PH, Karanja N: A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med 1997;336: Sacks F, Obarzanek E, Windhauser M, Svetkey LP, Vollmer WM, McCullough M, Karanja N, Lin PH, Steele P, Proschan MA, Evans MA, Appel LJ, Bray GA, Vogt TM, Moore TJ: Rationale and design of the dietary approaches to stop hypertension trial. Ann Epidemiol 1995;5: Svetkey LP, Simons-Morton D, Vollmer WM, Appel LJ, Conlin PR, Ryan DH, Ard J, Kennedy BM: Effects of dietary patterns on blood pressure: subgroup analysis of the Dietary Approaches to Stop Hypertension (DASH) randomized clinical trial. Arch Int Med 1999; 159: Appel LJ, Hebert PR, Cohen JD, Obarzanek E, Yamamoto M, Buring J, Stevens V, Kirchner K, Borhani NO: Baseline characteristics of participants in phase II of the Trials of Hypertension Prevention (TOHP II). Ann Epidemiol 1995;5: Blair SN, Haskell WL, Ho P, Paffenbarger RS Jr, Vranizan KM, Farquhar JW, Wood PD: Assessment of habitual physical activity by a seven-day recall in a community survey and controlled experiments. Am J Epidemiol 1985;122: Moore TJ, Vollmer WM, Appel LJ, Sacks FM, Svetkey LP, Vogt TM, Conlin PR, Simons-Morton D, Carter- Edwards L, Harsha DM: Effect of dietary patterns on ambulatory blood pressure: results from the DASH study. Hypertension 1999;34: National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the second report. (Adult Treatment Panel II). JAMA 1993; 269: National Institutes of Health. NIH Consensus Statement: Optimal calcium intake. 12(4), June, US Department of Agriculture/US Department of Health and Human Services. Dietary Guidelines for Americans. Fourth Edition. USDA Home and Garden Bulletin No 232, December The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of high blood pressure. Arch Intern Med 1997;157: Whelton P, He J, Cutler J, Brancati F, Appel LJ, Follmann D, Klag MJ: Effects of oral potassium on blood pressure. Meta-analysis of randomized controlled clinical trials. JAMA 1997;277: Miller ER, Appel LJ, Risby TH: Effect of dietary patterns on measures of lipid peroxidation. Results from a randomized clinical trial. Circulation 1998;98: Ting HH, Timini FK, Haley EA, Roddy MA, Ganz P, Creager MA: Vitamin C improves endothelium-dependent vasodilation in forearm resistance vessels of humans with hypercholesterolemia. Circulation 1997;95: Joffres MR, Reed DM, Yano K: Relationship of magnesium intake and other dietary factors to blood pressure: the Honolulu Heart Study. Am J Clin Nutr 1987;45: Ascherio A, Hennekens C, Willett WC, Sacks F, Rosner B, Manson J, Witteman J, Stampfer MJ: Prospective study of nutritional factors, blood pressure, and hypertension among US women. Hypertension 1996;27: Simons-Morton DG, Hunsberger SA, Horn LV, Barton BA, Robson AM, McMahon RP, Muhonen LE, Kwiterovich PO, Lasser NL, Kimm SYS, Greenlick MR: Nutrient intake and blood pressure in the Dietary Intervention Study in Children. Hypertension 1997;29: Ascherio A, Rimm EB, Hernan MA, Giovannucci EI, Kawachi I, Stampfer MJ, Willett WC: Intake of potassium, magnesium, calcium and fiber and risk of stroke among US men. Circulation 1998;98: Sacks FM, Willett WC, Smith A, Brown LE, Rosner B, Moore TM: Effect of blood pressure of potassium, calcium, and magnesium in women with low habitual intake. Hypertension 1998;31: Iso H, Stampfer MJ, Manson JE, Rexrode K, Hennekens CH, Colditz GA, Speizer FE, Willett WC: Prospective study of calcium, potassium, and magnesium intake and risk of stroke in women. Stroke 1999;30: Sciarrone SE, Beilin LJ, Rouse IL, Rogers PB: A factorial study of salt restriction and a low-fat/high-fibre diet in hypertensive subjects. J Hypertension 1992;10: Little P, Girling G, Hasler A, Trafford A, Craven A: A controlled trial of a low sodium, low fat, high fibre diet in treated hypertensive patients: the efficacy of multiple dietary intervention. Postgrad Med J 1990;66: