Comprehensive nutrition plan improves cardiovascular risk factors in essential hypertension

AJH

1998;11:31– 40

Comprehensive Nutrition Plan Improves Cardiovascular Risk Factors in Essential Hypertension David A. McCarron, Suzanne Oparil, Lawrence M. Resnick, Alan Chait, R. Brian Haynes, Penny Kris-Etherton, F. Xavier Pi-Sunyer, Judith S. Stern, Cynthia D. Morris, Sharon Clark, Daniel C. Hatton, Jill A. Metz, Margaret McMahon, Scott Holcomb, and Geoffrey W. Snyder

Increased arterial pressure is known to be influenced by a variety of nutrients. Compliance with dietary recommendations for risk reduction is often limited by the complexity of their implementation. In addition, how improvements in total diet, rather than single nutrients, influence concomitant cardiovascular risk factors has not been thoroughly explored. We assessed the effects of a nutritionally complete prepared meal program, the Campbell’s Center for Nutrition and Wellness plan (CCNW), compared with dietary therapy in which participants received a structured nutritional assessment and prescription and selected their own foods, in 101 women and men with mild-tomoderate hypertension. Outcome measures included blood pressure (BP), lipids and lipoproteins, glucose, glycosylated hemoglobin (HbA1c), insulin, homocysteine, nutrient intake, compliance, and quality of life. Both dietary interventions significantly lowered BP (P < .0001), while simultaneously improving the overall cardiovascular risk profile. Significantly greater

benefits were observed with the CCNW plan as compared with the participant selected diet in cholesterol and LDL levels (both P < .0001), LDL: HDL (P < .001), HbA1c (P < .05), homocysteine (P < .001), total nutrient intake (P < .0001), compliance (P < .0001), and quality of life (P < .001). This study demonstrates that improving the total diet to include the full array of recommended dietary guidelines, rather than focusing on single nutrients, has significant benefits for the cardiovascular risk profile of hypertensive persons beyond BP control. Compared with typical dietary therapy, the comprehensive CCNW meal plan has significantly greater effects on multiple cardiovascular risk factors while yielding greater compliance and improved quality of life. Am J Hypertens 1998;11:31– 40 © 1998 American Journal of Hypertension, Ltd.

Received April 16, 1997. Accepted September 15, 1997. From the Division of Nephrology, Hypertension, and Clinical Pharmacology (DAMcC, CDM, DCH, JAM, SH, GWS), Department of Medicine, Oregon Health Sciences University, Portland, Oregon; Hypertension Program (SO), University of Alabama at Birmingham, Birmingham, Alabama; Division of Endocrinology/Hypertension (LMR), Wayne State University Medical Center, Detroit, Michigan; Division of Metabolism, Endocrinology, and Nutrition (AC), Department of Medicine, University of Washington, Seattle, Washington; Department of Clinical Epidemiology and Biostatistics (BH), McMaster University, Hamilton, Ontario, Canada; Nutrition Department (PK-E), College of Health and Human Development,

Pennsylvania State University, University Park, Pennsylvania; Division of Endocrinology, Diabetes, and Nutrition (FXP-S), St. Luke’s/Roosevelt Hospital, Columbia University, New York, New York; Department of Nutrition and Metabolism (JSS), Division of Clinical Nutrition, University of California, Davis Medical Center, Davis, California; and Clinical Research Group of Oregon (SC, MMcM), Portland, Oregon. This study was supported by the Campbell’s Center for Nutrition and Wellness, Campbell’s Soup Company, Camden, New Jersey. Address correspondence and reprint requests to David A. McCarron, MD, Division of Nephrology, PP262, Oregon Health Sciences University, 3314 SW Veterans Hospital Road, Portland OR 97201.

© 1998 by the American Journal of Hypertension, Ltd. Published by Elsevier Science, Inc.

KEY WORDS:

Nutrition, blood pressure, hypertension, cardiovascular risk, lipids, quality of life, diet therapy, glycosylated hemoglobin (HbA1c).

0895-7061/98/$19.00 PII S0895-7061(97)00470-6

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McCARRON ET AL

A

rterial pressure regulation in humans has been linked to a variety of nutrients and nutritional issues.1,2 Current guidelines for the management of hypertension emphasize the importance of achieving several nutritional goals simultaneously.2 However, much of the evidence on which these recommendations are based derives from clinical trials assessing the effect of specific nutrients3–5 or the combination of single nutrients and lifestyle modifications.6 – 8 The effects on cardiovascular risk factors of improvements in the total diet alone, rather than single components and without other life style changes, have only recently been assessed in persons with mild-to-moderate hypertension, and have been shown to be beneficial.9,10 The Cardiovascular Risk Reduction Dietary Intervention Trial is a series of studies designed to assess the effects of total diet approaches to the management of hypertension, dyslipidemia, and non–insulin-dependent diabetes mellitus. In the first study in this series, reported previously,10 –13 we compared a comprehensive prepackaged meal program to a self-selected diet derived from the exchange list system in persons with one or more of these disorders, and found the former to be more effective in improving a variety of cardiovascular risk factors. However, in that study our participants were seen in the clinic every 2 weeks, a schedule that may well have contributed to the success of the study but that does not parallel the actual practice of dietary therapy for chronic disorders. Typically, recommendations to alter food intake as a therapeutic maneuver are not monitored between ‘‘medically related’’ clinic visits. In the second study in this series we evaluated two similar dietary approaches in 251 free living adults with any one of the above medical conditions, but scheduled their contact with study personnel at the frequency level that would occur with each of these regimens in the ‘‘real world.’’ Throughout the 10-week intervention, the group following the prepackaged meal program received the same amount of contact they would if practicing this plan independently (ordering meals biweekly), and the group selecting their own foods was seen in clinic on a schedule designed to mimic standard clinical management, or ‘‘usual care,’’ of patients placed on dietary therapy to the extent possible in a research study. In this article we report the effects of these interventions in the 101 persons in this study who met the hypertension criteria described below. DESIGN AND METHODS This study was conducted at six medical centers: Oregon Health Sciences University (coordinating center), Portland; Columbia-St. Luke’s/Roosevelt Hospital, New York; McMaster University and Hamilton Hos-

AJH–JANUARY 1998 –VOL. 11, NO. 1, PART 1

pital, Ontario, Canada; Pennsylvania State University, University Park; University of Alabama, Birmingham; and University of California, Davis. The protocol was approved by the institutional review board at each study site. Informed consent was obtained from each participant. Study Participants Adult men and women, 25 to 70 years of age, with essential hypertension were recruited through outpatient clinics and advertisements. Hypertension was defined as either untreated, with average sitting systolic blood pressure (SBP) of 140 to 180 mm Hg or sitting diastolic blood pressure (DBP) of 90 to 105 mm Hg, or treated, with no change in antihypertensive medication dosage at least 1 month before the study and average sitting SBP 135 to 180 mm Hg or DBP 85 to 100 mm Hg. Exclusion criteria included other chronic or life threatening diseases, body mass index (BMI) # 42 kg, insulin treatment, pregnancy, lactation, or not practicing birth control, substance or alcohol abuse, and refusal to discontinue vitamin/mineral supplements. Study Design A 4-week baseline period (24 through 0) preceded the 10-week treatment period. During baseline, participants were advised to maintain their usual diets, were seen weekly for blood pressure and weight measurements, and completed two 3-day food records and two sets of quality of life questionnaires. During this period, a physical examination was conducted and blood was collected for chemistry profile, CBC, plasma glucose, glycosylated hemoglobin (HbA1c), and lipid and lipoprotein determinations. Prior to randomization, a nutrition prescription was calculated for each patient using the Harris-Benedict equation14 to estimate the individual’s energy needs depending on her or his desire for weight maintenance or loss. Prescriptions targeted a 200 calorie range, the lowest being 1200 to 1399 kcal/day, calculated for weight loss up to 1 kg/week. Participants who did not desire weight loss were prescribed a caloric level to maintain their present weight. At week 22, participants were randomized by the coordinating center to either the CCNW meal plan or the usual care (UC) group, stratified by clinic site; they were advised of their randomization assignment and began the intervention at week 0. Persons randomized to the CCNW group discontinued any vitamin or mineral supplements at this time; those in the UC group were allowed to continue taking supplements during the study. The CCNW program requires participants to order their meals every 2 weeks. In keeping with this schedule, participants in the CCNW were seen in the clinic at weeks 2, 8, and 10, and received follow-up telephone calls from study personnel at weeks 4 and 6. Because patients for whom dietary therapy is recom-

AJH–JANUARY 1998 –VOL. 11, NO. 1, PART 1

mended are not generally seen on a regularly scheduled basis for diet assessment, follow-up of the UC group was limited to clinic visits on weeks 8 and 10. At each clinic visit, blood pressure and weight were measured and 3-day food records were collected. Blood was collected at week 0 for measurements of lipids and lipoproteins, plasma insulin, fructosamine, vitamins, and trace minerals; at week 8 for lipids and lipoproteins; and at week 10 for all of the above measures, glucose and HbA1c, and quality of life. Dietary Intervention Both interventions were intended to provide similar macronutrient compositions of approximately 20% kcal from fat, 55% to 60% kcal from carbohydrate, and 15% to 20% kcal from protein. The CCNW plan meets daily nutritional guidelines for sodium, total and saturated fat, cholesterol, fiber, and complex carbohydrates; and meals were vitamin/ mineral fortified to meet at least 100% of the RDA for adults1,15,16 for most nutrients, with the exceptions of vitamin D and copper (77% and 91% of recommended intakes, respectively). The meals included six breakfast, eight lunch, 10 dinner, and six snack selections produced by Campbell Soup Company (Camden, NJ) and developed in consultation with the American Heart Association and the American Diabetes Association. Participants ordered their choice of meals by means of telephone calls to a central distribution center every 2 weeks, and the foods were delivered to their homes. The CCNW group was instructed to consume one breakfast, lunch, and dinner; and one serving each of fruit, vegetables, and low fat dairy products. Prepared snacks or additional entre´es were used for caloric adjustment of the diet prescription. One selection daily was also allowed from a bonus list that included one alcoholic beverage or the calorie equivalent in fruits, vegetables, or dairy products. The UC group was advised to follow a macronutrient equivalent diet, composed primarily of breads and starches, fruits, low fat milk, vegetables, and lean meats; the number of servings was determined by the individual’s diet prescription. Participants could also select one serving daily from the bonus list. Their dietary counseling consisted of a discussion of the typical modifications recommended for risk reduction, including less fat, less salt, less sugar, and more high fiber, natural foods. They received a pamphlet entitled ‘‘Healthy Food Choices’’ published by the American Dietetic and American Diabetes associations that provides general information on healthy diets and the exchange list system. To offset the costs of food purchases and balance the effect of foods provided free of charge to the CCNW group, they received compensation of $125 at weeks 0 and 8. Par-

NUTRITIONAL MANAGEMENT OF HYPERTENSION

33

ticipants in both groups received travel compensation at study end. Measurements Blood pressure measurements were standardized across centers by a study-wide training session.17 Plasma lipoproteins were determined at Northwest Lipid Research Laboratories, University of Washington. Total cholesterol was measured by the Abbott Spectrum Analyzer (Abbott Laboratories, Abbott Park, IL). HDL cholesterol was analyzed by the heparin-manganese method.18 LDL cholesterol was calculated using the Friedewald algorithm.19 Insulin was measured using a solid phase radioimmunoassay (Coat-A-Countt, Diagnostic Products, Los Angeles, CA) at the Hormone and Mineral Laboratory, Oregon Health Sciences University. Glucose and blood chemistry were measured by SmithKline Beecham Clinical Laboratories, Seattle. Serum homocysteine levels were determined using a modification of the method of Smolin and Schneider20,21 at Oregon Regional Primate Research Center (Beaverton, OR). Food records were analyzed at the coordinating center with a licensed copy of the University of Minnesota Nutrition Coordinating Center (Minneapolis, MN) database supplemented by the product content of meals provided by Campbell Soup Company (Camden, NJ). Compliance was measured by %kcal from fat at the levels of #17% versus .17% and #25 versus .25. Quality of life was assessed using a battery of self-administered questionnaires that measured health and nutrition related quality of life. The health related instruments included the Mental Health Inventory, and the General Perceived Health, Daily Activities, Work Performance and Satisfaction, and Sexual Function scales. Nutrition related measures addressed nutritional health perception, hassles, affect, social function, and satisfaction. These instruments are described in detail elsewhere.11 Statistical Analysis The study was designed to detect differences between treatment groups of 3 mm Hg in BP, 10 mg/dL in plasma cholesterol, 20 mg/dL in triglycerides, 10 mg/dL in plasma glucose, and 1% difference in HbA1c. With a power of at least 80%, and a two-sided alpha of 0.05, these differences were detectable with a sample of 50 in each group, based on variation as defined in a preliminary study using a similar protocol. All data except weight were averaged over the baseline period when multiple measures were available. Because changes in weight could have occurred during the 4-week baseline period as a result of study participation, weight at week 0, the final visit in the baseline period, was considered baseline weight. For BP and lipoproteins, weeks 8 and 10 were averaged for computation of the diet effect. Data in text and tables are expressed as means 6 standard deviations.

34

McCARRON ET AL

A repeated measures analysis of variance model was used to analyze differences between baseline and treatment periods; this allowed computation of the effect of diet between periods and of the differential effect of the diets. To adjust for the effect of weight loss on endpoints, an analysis of covariance model was used to compare the two dietary therapies. For quality of life assessment, a responsiveness index was developed to facilitate the interpretation of the clinical importance of the data. The responsiveness index for each reported score was calculated by dividing the raw score by the between-participants standard deviation. Based on previous trials, a value of 0.2 responsiveness units was designated as a minimum criterion for clinical importance. Analysis of variance was used for responsiveness units to determine treatment differences. RESULTS Participants The study sample comprised 101 persons, 56 women and 45 men. A total of 29 women and 22 men (mean age, 55.0 6 9.1 years) were randomized to the UC group; the CCNW group included 27 women and 23 men (mean age, 53.4 6 9.9 years). The cohort was 86% white, 7% black, 4% Native American, and 3% Hispanic. There were no significant differences in the distribution of age, sex, or ethnicity between treatment groups. Antihypertensive medications were being taken by 38 (75%) of persons in the UC group and by 34 (68%) in the CCNW group. All participants completed the study. Nutrient Intake Table 1 summarizes the baseline and treatment values for all nutrients for both genders and interventions. Intake of all measured nutrients except for vitamin D (P 5 .24), vitamin E (P , .03), and thiamin (P , .04) changed significantly (P , .01) in both treatment groups. There were significant differences, however, in the nutrient impact of the two treatments. Although energy, protein, carbohydrate, total fat, saturated fat, and polyunsaturated fat intakes were improved in a similar fashion in both groups, monounsaturated fats tended (P , .07) to be improved more in the CCNW group. All other nutrient intakes improved to a greater degree (sodium P , .03, all others P , .01) in the CCNW group. Blood Pressure Baseline and treatment blood pressures for both groups are portrayed in Table 2. There was no statistical difference in blood pressure at baseline between the two groups. Average baseline pressures were high-normal, reflecting the fact that the majority of participants were taking antihypertensive medication. All measures of arterial pressure decreased significantly (P , .0001) in both treatment groups. As shown in Figure 1A and B, there was the anticipated regression to the mean during the baseline

AJH–JANUARY 1998 –VOL. 11, NO. 1, PART 1

period. Average decreases were comparable between groups in all blood pressure measures with the exception of sitting diastolic blood pressure, which was significantly greater in the CCNW group. Lipids and Lipoproteins The lipid and lipoprotein values for both treatment groups at baseline and end of treatment are shown in Table 3. There was no difference between groups at baseline in any of these parameters. The intervention produced significant reductions in both groups in all measures with the exception of HDL cholesterol, which was unchanged. However, there were important differences in responses between the two groups. For the CCNW group, cholesterol (P , .0001), HDL (P , .05), and LDL (P , .0001) decreased to a greater degree. Similarly, there was a significantly greater decrease in the LDL:HDL ratio (P , .001) in this group. Carbohydrate Metabolism The impact of the interventions on carbohydrate metabolism is shown in Table 4. Plasma glucose, fructosamine, and insulin decreased significantly (P , .0001) with both interventions. HbA1c decreased with the prepared meal program and increased minimally in the UC group; the difference in response between groups was significant (P , .05). Serum Homocysteine Serum homocysteine levels (mmol/L) were comparable at baseline (CCNW 11.9 6 5.5, UC 12.5 6 6.1). At week 10 the levels had decreased to 9.8 6 2.4 mmol/L in the CCNW group (P , .01), but increased slightly in the UC group to 13.0 6 6.6 mmol/L. This divergent response in the serum homocysteine was significant (P , .01). As shown in Figure 2, the higher the baseline homocysteine level, the greater the difference with the intervention. Thus, CCNW participants with highest homocysteine levels at baseline (highest quartile) experienced the greatest decrease. Body Weight As shown in Table 5, body weight at baseline was similar among men and women between the two treatment groups. Mean weight loss in men was 3.4 6 4.8 kg in the UC group and 8.6 6 3.5 kg in the CCNW group; weight loss in women was 3.1 6 3.2 kg and 4.9 6 3.3 kg, respectively. Both groups achieved significant reductions in body weight (P , .0001), although weight loss was greater in the CCNW group (women P , .05; men P , .001). Compliance Based on percentage of calories from fat as a measure of compliance, participants on the CCNW plan achieved significantly better compliance (P , .001) with their diet prescriptions. Using a definition of compliance of ,17% kcal from fat, 52% of the CCNW group was compliant as compared with 8% of the UC group. When ,25% kcal from fat was used as

Women Usual Care Diet*

CCNW Meal Plan*

Usual Care Diet*

CCNW Meal Plan*

Baseline (n 5 29)

Treatment (n 5 29)

Baseline (n 5 27)

Treatment (n 5 27)

Baseline (n 5 22)

Treatment (n 5 22)

Baseline (n 5 23)

Treatment (n 5 23)

1766 6 441 73 6 17 224 6 74 66 6 22 34 6 7 17 6 4 50 6 7 11.4 6 2.7 22 6 8 13 6 5 6.8 6 1.9 25 6 9 12.5 6 3.0 215 6 66 767 6 387 15.4 6 6.8 17.0 6 6.0 2753 6 981 2863 6 769 275 6 98 1168 6 373 11 6 4 1.3 6 0.4 1.8 6 0.7 4.3 6 2.5 106 6 49 3699 6 1995 24 6 12 191 6 130 269 6 114 23 6 7 4.7 6 2.3 1.8 6 0.7 1.6 6 0.5

1243 6 283 59 6 13 172 6 46 36 6 15 26 6 7 19 6 4 56 6 8 8.0 6 2.7 11 6 6 863 5.8 6 2.4 13 6 6 9.5 6 3.0 149 6 53 660 6 242 12.1 6 5.0 17.3 6 5.9 2516 6 805 2270 6 638 249 6 72 974 6 251 863 1.1 6 0.3 1.6 6 0.6 3.0 6 2.0 105 6 56 4009 6 2906 17 6 13 156 6 92 247 6 108 17 6 5 4.0 6 1.9 1.5 6 0.5 1.4 6 0.4

1811 6 469 72 6 21 232 6 64 67 6 24 33 6 7 16 6 3 51 6 7 11.5 6 3.2 24 6 10 13 6 5 6.4 6 1.7 25 6 9 12.4 6 2.8 244 6 112 783 6 355 14.7 6 4.5 17.6 6 6.4 2762 6 928 2872 6 663 283 6 96 1161 6 395 10 6 3 1.3 6 0.4 1.7 6 0.5 4.9 6 4.4 95 6 44 3442 6 1828 22 6 6 193 6 143 254 6 90 20 6 6 4.2 6 1.3 1.8 6 0.6 1.6 6 0.4

1406 6 392 70 6 12 212 6 60 32 6 16 20 6 6 20 6 2 60 6 6 6.7 6 2.1 11 6 6 863 5.1 6 1.6 11 6 6 7.0 6 2.6 110 6 45 1633 6 339 26.7 6 4.9 28.5 6 6.3 3792 6 738 2167 6 404 526 6 109 1724 6 314 22 6 5 3.3 6 0.8 3.5 6 0.7 10.4 6 2.4 260 6 83 11,060 6 3516 36 6 8 305 6 81 598 6 129 35 6 7 15.0 6 3.7 3.3 6 0.7 2.3 6 0.5

2406 6 617 100 6 26 303 6 84 86 6 38 31 6 8 17 6 4 51 6 9 10.4 6 3.3 29 6 15 16 6 6 5.9 6 1.4 34 6 16 12.1 6 3.7 290 6 104 886 6 428 17.9 6 4.4 21.9 6 8.0 3623 6 976 3711 6 1280 369 6 112 1513 6 504 13 6 4 1.6 6 0.5 2.3 6 0.5 8.1 6 11.0 150 6 79 3526 6 1741 29 6 10 316 6 208 328 6 119 30 6 6 5.6 6 1.6 2.2 6 0.8 2.1 6 0.6

1782 6 512 86 6 29 247 6 83 49 6 19 25 6 7 19 6 4 55 6 7 7.7 6 2.5 16 6 7 10 6 3 5.2 6 1.1 19 6 8 9.3 6 3.1 200 6 101 808 6 451 15.8 6 4.8 22.5 6 9.1 3190 6 1103 3106 6 1097 326 6 114 1276 6 514 11 6 4 1.4 6 0.5 2.1 6 0.6 5.9 6 6.7 124 6 69 3618 6 2414 22 6 7 238 6 191 294 6 116 25 6 7 4.8 6 2.0 1.9 6 0.7 1.8 6 0.6

2404 6 614 91 6 24 339 6 99 78 6 33 29 6 8 15 6 2 57 6 9 9.6 6 3.5 26 6 14 15 6 5 5.6 6 1.5 30 6 14 11.2 6 3.4 263 6 115 883 6 292 18.8 6 7.1 26.5 6 14.9 3548 6 1041 4006 6 935 385 6 135 1473 6 461 16 6 14 1.8 6 0.8 2.6 6 1.2 6.9 6 1.2 153 6 88 4660 6 4236 29 6 10 259 6 159 396 6 233 31 6 12 5.5 6 1.7 2.4 6 1.2 2.3 6 1.0

1608 6 365 74 6 13 261 6 64 29 6 8 16 6 2 19 6 2 65 6 4 5.2 6 1.1 963 863 4.6 6 0.7 10 6 3 5.6 6 1.2 94 6 33 1840 6 405 31.3 6 4.9 33.9 6 5.7 4308 6 730 2185 6 269 626 6 111 1962 6 392 25 6 5 3.9 6 0.7 4.1 6 0.7 11.9 6 2.8 310 6 88 12,384 6 3477 40 6 7 325 6 82 689 6 139 41 6 7 17.5 6 3.6 3.8 6 0.8 2.7 6 0.6

35

PFA, polyunsaturated fatty acids; MFA, monounsaturated fatty acids; CHO, sugars; CCNW, Campbell’s Center for Nutrition and Wellness plan. * Nutrient intake changes between diets: kcal, P 5 .80; protein, P 5 .35; carbohydrates, P 5 .73; total fat, P 5 .11; % kcal from protein, P , .02; % kcal from carbohydrate, P , .03; saturated fat, P 5 .25; PFA, P 5 .88; MFA, P 5 .07; sodium, P , .03; all others, P , .01.

NUTRITIONAL MANAGEMENT OF HYPERTENSION

Kcal Protein (g) CHO (g) Total fat (g) Percent Kcal from fat Percent Kcal from protein Percent Kcal from CHO Percent Kcal from sat. fat Saturated fat (g) PFA (g) Percent Kcal from PFA MFA (g) Percent Kcal from MFA Cholesterol (mg) Calcium (mg) Iron (mg) Fiber (g) Potassium (mg) Sodium (mg) Magnesium (mg) Phosphorus (mg) Zinc (mg) Copper (mg) Vitamin B6 (mg) Vitamin B12 (mg) Vitamin C (mg) Vitamin A (IU) Vitamin E (IU) Vitamin D (IU) Folate (mg) Niacin (mg) Pantothenic acid (mg) Riboflavin (mg) Thiamin (mg)

Men

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TABLE 1. CHANGES IN DAILY NUTRIENT INTAKE OVER 10-WEEK INTERVENTION

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McCARRON ET AL

TABLE 2. CHANGE IN BLOOD PRESSURE (mm Hg) Usual Care Diet (n 5 51)

Sitting systolic Sitting diastolic Supine systolic Supine diastolic

CCNW Meal Plan (n 5 50)

Baseline

Treatment

Change

Baseline

Treatment

Change

Change Between Diets

143.0 6 11.0 88.4 6 7.7 143.0 6 13.8 86.3 6 7.3

136.3 6 12.6 84.7 6 8.9 137.6 6 13.6 84.4 6 8.9

26.6 6 9.6 23.7 6 5.1 25.3 6 9.4 22.0 6 6.0

140.0 6 11.5 88.8 6 6.3 141.1 6 12.4 87.0 6 6.6

130.0 6 14.5 83.0 6 6.7 132.3 6 13.7 82.9 6 6.5

210.0 6 11.2 25.8 6 5.8 28.8 6 10.3 24.1 6 6.3

P 5 .11 P , .05 P 5 .08 P 5 .09

CCNW, Campbell’s Center for Nutrition and Wellness plan.

the definition of compliance, 90% of CCNW and 57% of UC participants were successful in achieving compliance. Quality of Life Figure 3 portrays the panel of quality of life outcomes. There were clinically important improvements in 7 of the 10 instruments in the CCNW group. The CCNW group experienced clinically important improvements for both of the primary measures of Quality of Life (Mental Health Inventory and General Perceived Health Scale). The UC group did improve on five of the 10 instruments; however, they did not achieve clinically important improvements on the primary measures of quality of life. Analysis of variance indicated that the improvements were significantly greater in the CCNW group for the Mental Health Inventory (P , .05), Nutritional Health Perceptions (P , .01), Nutrition and Mood (P , .01), and Nutrition Satisfaction (P , .01).

DISCUSSION Improving the overall diet, rather than altering intake of single nutrients, in persons with mild-to-moderate hypertension yields benefits far beyond improved arterial pressure control. Both the UC and CCNW interventions had clinically significant effects on blood pressure as well as on concomitant risk factors. The CCNW approach yielded substantially greater improvements in a number of cardiovascular risk factors and in compliance and quality of life. These more comprehensive effects of the CCNW meal plan likely reflect the improved intakes of micro- and macronutrients that were most easily accomplished with the total meal plan. The blood pressure reductions we observed are noteworthy, as approximately 70% of the participants were taking antihypertensive medication and their hypertension was generally considered well controlled.

FIGURE 1. A: Mean 6 SEM systolic BP in CCNW (solid line) and in UC (broken line) groups at baseline (weeks 24 to 0) and during intervention (weeks 8 and 10). B: Mean diastolic BP for same groups and time points.

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37

TABLE 3. CHANGE IN LIPIDS AND LIPOPROTEINS Usual Care Diet (n 5 51)

Cholesterol mmol/L mg/dL Triglycerides mmol/L mg/dL HDL cholesterol mmol/L mg/dL LDL cholesterol mmol/L mg/dL VLDL cholesterol mmol/L mg/dL LDL:HDL ratio

CCNW Meal Plan (n 5 50)

Baseline

Treatment

Change

Baseline

Treatment

5.62 6 0.85 217.5 6 32.7

5.48 6 0.86 211.8 6 33.3

20.15 6 0.52 25.7 6 20.0

5.58 6 0.82 215.8 6 31.6

4.99 6 0.93 193.0 6 36.0

20.59 6 0.56 P , .0001 222.8 6 21.7

2.29 6 1.30 203.2 6 115.6

1.93 6 1.14 171.5 6 101.4

20.36 6 0.77 231.6 6 68.7

2.08 6 1.15 184.9 6 101.7

1.72 6 1.04 152.2 6 92.6

20.37 6 0.59 P 5 .93 232.8 6 52.5

1.10 6 0.25 42.5 6 9.6

1.14 6 0.27 44.0 6 10.4

0.04 6 0.09 1.4 6 3.5

1.16 6 0.33 45.0 6 12.9

1.16 6 0.31 44.8 6 12.1

20.01 6 0.12 P , .05 20.2 6 4.5

3.49 6 0.76 134.9 6 29.3

3.45 6 0.73 133.4 6 28.1

20.04 6 0.41 21.5 6 16.0

3.46 6 0.91 133.9 6 35.0

3.05 6 0.88 117.8 6 34.2

0.42 6 0.51 P , .0001 216.1 6 19.7

1.02 6 0.51 39.3 6 19.8 3.3 6 1.0

0.87 6 0.46 33.5 6 17.7 3.2 6 1.0

20.15 6 0.33 25.8 6 12.9 20.1 6 0.4

0.94 6 0.49 36.4 6 18.8 3.2 6 1.3

0.77 6 0.45 29.7 6 17.3 2.8 6 1.1

20.17 6 0.32 P 5 .73 26.7 6 12.4 20.4 6 0.5 P , .001

Nevertheless, both interventions produced further, clinically important reductions in arterial pressure,2 suggesting that some component of blood pressure dysregulation is beyond the control of common antihypertensive agents, but is responsive to nutritional factors. The positive impact on blood pressure and other cardiovascular risk factors observed with the CCNW plan supports the recommendations of national health organizations and underscores the importance of assuring that the diets of high risk patients include the currently recommended levels of all micro- and macronutrients. Perhaps the best example of that principle is our finding regarding serum homocysteine. Observational data in recent years have demonstrated that elevated homocysteine levels in excess of 15 mmol/L are associated with significant increases in cardiovascular risk.22,23 The CCNW participants with the

Change

Change Between Diets

highest baseline homocysteine levels experienced more dramatic reductions in homocysteine than those observed in the UC group. To our knowledge, the potentially important benefit of reduced homocysteine achieved with comprehensive dietary improvements has not been previously reported in patients with mild-to-moderate hypertension. Increased levels of folate, vitamin B12, and vitamin B6 are known to ameliorate homocysteine levels,22 and likely account for the effect of the CCNW plan on homocysteine levels. The broad nature of the nutritional improvements that our participants experienced precludes ascribing the subsequent changes in blood pressure and other risk factors to alterations of any single factor. Although weight loss likely contributed to observed blood pressure reductions,24 changes in blood pressure were very similar between groups, whereas

TABLE 4. CHANGES IN MEASURES OF CARBOHYDRATE METABOLISM Usual Care Diet (n 5 51)

Glucose, mmol/L mg/dL HbA1c (%) Insulin (mIU/mL) Fructosamine (mmol/L)

CCNW Meal Plan (n 5 50)

Change Between Diets

Baseline

Treatment

Change

Baseline

Treatment

Change

5.6 6 0.8 101.2 6 14.1 5.7 6 0.6

5.3 6 0.8 95.9 6 13.9 5.7 6 0.6

20.3 6 0.6 25.3 6 11.6 0 6 0.5

5.5 6 1.0 99.6 6 17.2 5.7 6 0.7

5.1 6 1.0 91.9 6 13.0 5.5 6 0.5

20.4 6 0.6 27.7 6 10.5 20.2 6 0.4

P , .05

19.2 6 10.2

14.8 6 7.8

24.5 6 7.3

17.0 6 9.3

11.9 6 6.9

25.2 6 5.9

P 5 .60

234.5 6 35.6

217.9 6 20.5

216.4 6 33.7

231.0 6 32.0

220.4 6 20.5

210.7 6 28.6

P 5 .37

HbA1c, glycosylated hemoglobin.

P 5 .28

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FIGURE 2. Change (mean 6 SEM) in serum homocysteine for CCNW (solid line) and UC (broken line) groups from week 0 to week 10 by baseline quartiles (1 5 lowest; 4 5 highest) of serum homocysteine. CCNW participants with the highest levels at baseline experienced the greatest reduction. The difference between the response of the two groups was significant (P , .001).

weight reduction was significantly greater with the CCNW plan. Similarly, although blood pressure changes were similar between groups, sodium intake differed markedly at study end, as did both calcium and potassium intake. Thus, the reductions in blood pressure and improvements in other risk factors appear to occur independently, at least in part, of changes in any single nutrient. The retention of all 101 enrolled participants for the full duration of the trial is remarkable for an intervention in which individuals’ eating habits are considerably altered. This outcome in combination with the high compliance with diet prescriptions, particularly in the CCNW group in which 94% met the recommendations of the American Heart Association Step I diet, suggests that with a minimal level of support and a convenient means to consume a nutritionally-complete diet, motivated patients can improve their cardiovascular risk through dietary means. The results of the current study are remarkably

consistent with those observed in the previous study in this series involving 560 persons with hypertension, dyslipidemia, or non–insulin-dependent diabetes mellitus.10 In the latter study participants were seen biweekly, and it was speculated that the beneficial outcomes were likely influenced by frequent contact with study personnel. The current study was designed to more closely approximate the level of contact that patients would receive in a clinical rather than a research setting, but because closer monitoring is required to acquire accurate dietary data for research purposes, we acknowledge that, in practice, usual care diet therapy will differ from the protocol used here. Limitations of this study also include the unknown cost-effectiveness of such dietary interventions,25 which may restrict the usefulness of this approach in some patients, and the lack of information regarding long-term effects and compliance with these interventions. A 1-year study in this series is currently underway to resolve the latter issues.

TABLE 5. CHANGES IN BODY WEIGHT Usual Care Diet (n 5 51)

All (kg) Women (kg) Men (kg)

CCNW Meal Plan (n 5 50)

Baseline

Treatment

Baseline

Treatment

Change With Diets

Change Between Diets

94.1 6 15.5 89.7 6 15.5 99.9 6 13.8

90.8 6 15.4 86.6 6 15.4 96.4 6 13.8

93.4 6 17.7 88.4 6 14.3 99.4 6 19.6

86.8 6 16.5 83.4 6 14.9 90.8 6 17.7

P , .0001 P , .0001 P , .0001

P , .0001 P , .05 P , .001

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FIGURE 3. Quality of life measures for CCNW (open bars) and UC (solid bars) in responsiveness units. For seven of the 10 measures, clinically important improvements (.0.2 units) occurred in CCNW. For four measures, CCNW participants experienced significantly greater improvements (*P , .05; **P , .01).

In conclusion, this study documents that comprehensive adjustments in nutrition offer a number of clinically important benefits for patients with mild-to-moderate hypertension. The range of blood pressure reductions induced by the two dietary interventions assessed here easily surpassed those observed in studies involving manipulation of specific dietary nutrients, and the simultaneous improvements in multiple cardiovascular risk factors provide benefits not available with pharmaceutical treatment. Adherence to the full complement of dietary recommendations results in multiple cardiovascular benefits and is simplified by a comprehensive nutritional approach that offers additional benefits of improved compliance and quality of life.

5.

Luft FC, Miller JZ, Lyle RM, et al: The effect of dietary interventions to reduce blood pressure in normal man. J Am Coll Nutr 1989;8:495–503.

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Stamler R, Stamler J, Gosch FC, et al: Primary prevention of hypertension by nutritional-hygienic means— final report of a randomized, controlled trial. JAMA 1989;262:1801–1807.

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Applegate WB, Miller ST, Elam JT, et al: Nonpharmacologic intervention to reduce blood pressure in older patients with mild hypertension. Arch Intern Med 1992;152:1162–1166.

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Neaton JD, Grimm RH, Prineas RJ, et al: Treatment of Mild Hypertension Study—final results. JAMA 1993; 270:713–724.

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Appel LJ, Moore TJ, Obarzanek E, et al: A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med 1997;336:1117–1124.

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McCarron DA, Oparil S, Chait A, et al: Nutritional management of cardiovascular risk factors: a randomized clinical trial. Arch Intern Med 1997;175:169 –177.

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Hatton DC, Haynes RB, Oparil S, et al: Improved quality of life in patients with generalized cardiovascular metabolic disease on a prepared diet. Am J Clin Nutr 1996;64:935–943.

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Chait A, Malinow R, Resnick L, et al, on behalf of the Vanguard Study Group: A randomized control trial of the effects of a comprehensive risk reduction nutrition program on plasma homocysteine levels in hypertensives with associated cardiovascular risk factors. Am J Hypertens 1996;9:16A–17A.

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