Long-Term Weight Loss and Changes in Blood Pressure: Results of the Trials of Hypertension Prevention, Phase II

Approximately one fourth of the U.S. adult populationnearly 50 million peoplehas hypertension (1, 2). Taking a broader perspective, more than half of the adult population has higher than optimal blood pressure (1), defined as systolic blood pressure greater than 120 mm Hg and diastolic blood pressure greater than 80 mm Hg (2). These persons are at significantly increased risk for cardiovascular disease and stroke (3). Although pharmacologic treatment for hypertension significantly reduces morbidity and mortality from cardiovascular diseases (4, 5), long-term pharmacologic therapy can have undesirable side effects and requires the expense of continuing medical supervision. Furthermore, pharmacologic therapy is not usually initiated when blood pressure is higher than optimal yet below diagnostic thresholds for hypertension. Thus, lifestyle interventions for primary prevention and initial treatment of high blood pressure remain a vital strategy for controlling this highly prevalent condition (2). Weight loss has been shown to reduce blood pressure in overweight hypertensive patients (6-9) and in overweight persons with high-normal blood pressure (10-12). Two reviews of randomized trials of weight reduction to reduce blood pressure examined the results of nine studies (13, 14). Most of these trials were small, only one had more than 500 participants (11), and most had short-term follow-up (1 year or less). Only three studies had follow-up of 3 to 5 years (8, 10, 11). Compared with controls, weight loss averaged nearly 7 kg in the short-term trials and approximately 3 kg in the three longer-term trials. In almost all trials, systolic blood pressure and diastolic blood pressure were reduced in the intervention groups. Since these reviews were published, the Trials of Hypertension Prevention (TOHP) Phase I reported mean weight reduction of 3.9 kg at 18 months in 564 overweight participants with high-normal blood pressure, resulting in significant decreases in systolic blood pressure and diastolic blood pressure compared with a usual care control group (12, 15). To investigate whether nonpharmacologic interventions can prevent hypertension over the long term, TOHP II was initiated. This was a randomized, controlled trial examining the effects of weight loss and dietary sodium reduction, alone and in combination, in reducing blood pressure in overweight adults with high-normal diastolic blood pressure (16). This target population is at high risk for hypertension as they age. The primary outcome paper from this trial (17) provided only a brief overview of the effects of weight loss on blood pressure. Here, we provide more detailed analysis of weight loss and blood pressure in TOHP II. Of special interest are the long-term effects of weight loss on blood pressure, the magnitude of the doseresponse relationship at 36 months, the effect of patterns of weight loss on blood pressure, and the predictors of weight loss and blood pressure response. Methods Participants Participants in TOHP II were overweight adults with nonmedicated diastolic blood pressure of 83 to 89 mm Hg and systolic blood pressure less than 140 mm Hg. Other eligibility criteria included age 30 to 54 years and a body mass index of 26.1 to 37.4 kg/m2 for men and 24.4 to 37.4 kg/m2 for women, approximately 110% to 165% of ideal weight (18). Principal exclusion criteria were current treatment with medications that might affect blood pressure, clinical or laboratory evidence of cardiovascular disease, diabetes mellitus, renal insufficiency (serum creatinine concentration 150 mol/L [ 1.7 mg/dL] for men and 132 mol/L [ 1.5 mg/dL] for women), and current or planned pregnancy. Detailed descriptions of recruitment and participant characteristics have been published elsewhere (19, 20). The study was reviewed and approved by the institutional review boards at all nine TOHP centers and the coordinating center, and all participants signed informed consent forms. Design Eligible participants were randomly assigned with equal probability to one of four groups: weight loss only, sodium reduction only, combined weight loss and sodium reduction, or usual care (controls). Measurements Age, sex, ethnicity, and years of education were obtained by questionnaire. Baseline blood pressure measurements were taken at three screening visits, each separated by 7 to 45 days. At each visit, three readings of systolic blood pressure and diastolic blood pressure were obtained and averaged. Certified staff obtained measurements in seated participants by using a Hawksley random-zero sphygmomanometer (21). Body weight was measured to the nearest 0.2 kg (0.5 lb) by using a calibrated balance-beam scale; participants wore indoor clothing (without shoes). Blood pressure and weight were measured every 6 months after randomization to the end of follow-up at 36, 42, or 48 months, depending on randomization date. Clinic staff who were blinded to study group assignment made these assessments. Blood pressure measurements were obtained during a single visit at all follow-up points except for 18 and 36 months, when measurements were taken at a series of three visits approximately 1 week apart. Multiple measurements were taken at 18 and 36 months to provide a more precise assessment of average blood pressures at these primary outcome points. Dietary intake was assessed by 24-hour recall, and physical activity was assessed by questionnaire. Intervention Participants assigned to the weight loss intervention group sought to lose at least 4.5 kg (10 lb) during the first 6 months of the intervention and to maintain their weight loss for the remainder of the trial. A brief description of the intervention methods is presented here; a more detailed description has been published elsewhere (22). The intervention started with an individual counseling session, followed by 14 weekly group meetings led by dietitians or health educators. After this 14-week intensive phase, participants attended six biweekly group meetings and then monthly group meetings. Beginning in the 18th month, participants were offered a variety of options to keep them involved in the intervention, including individual counseling sessions and special group sessions focused on selected weight loss topics. The intervention focused on self-directed behavior change (behavioral self-management), nutrition education, information on physical activity, and social support for making and maintaining behavior changes. Specific behavior change techniques included self-monitoring (food diaries and graphs of minutes of physical activity per day), setting explicit short-term goals and developing specific action plans to achieve those objectives, and developing alternative strategies for situations that trigger problem eating. The dietary intervention focused on reducing caloric intake by decreasing consumption of excess fat, sugar, and alcohol. Keeping daily food diaries was emphasized for monitoring intake and assessing progress. With experience, the participants determined the caloric intake that produced moderate weight loss for them. It was suggested that men not consume less than 1500 kcal/d and women not less than 1200 kcal/d. Weight loss of more than 0.9 kg (2 lb) per week was discouraged. The physical activity goal was to gradually increase activity to 30 to 45 minutes per day, four to five days per week. Exercise intensity was moderate, approximately 40% to 55% of heart rate reserve, and consisted primarily of brisk walking. Statistical Analysis Baseline characteristics of the weight loss and usual care groups were compared overall and by sex by using t-tests for means and chi-square tests for proportions. Although weight and blood pressure data were collected every 6 months, special efforts were made to achieve high follow-up rates at 18 and 36 months; at each of these two time points, nine blood pressure readings were collected over three visits and were averaged. For participants prescribed antihypertensive medication, follow-up blood pressure for all subsequent visits was taken to be the last study blood pressure before therapy was started. Participants receiving medications that affect blood pressure for reasons other than hypertension or who became pregnant were treated as missing at that visit. We used two-sample t-tests to compare changes in weight and blood pressure from baseline in the weight loss intervention and usual care groups overall, by sex, by ethnicity, and by sex and ethnicity. The effects of the intervention in terms of changes in weight and blood pressure were examined overall and in subgroups defined by sex, ethnicity, and sex and ethnicity. Subgroup differences were tested by using terms for the interaction of treatment group with sex and with ethnicity in multiple linear regression models. Regression analyses were also used to analyze the doseresponse relationship between change in weight and change in blood pressure, overall and within sex and ethnicity subgroups. Differences in dose response were tested by using interaction terms in linear regression models. All regressions were adjusted for age and baseline weight. We also adjusted for baseline blood pressure in the blood pressure regression models. Change in blood pressure was also examined in relation to quintile of weight loss. Quintiles were computed by using the distribution of weight change in the weight loss intervention group. Additional multiple regression analyses were performed in which weight loss participants were categorized according to patterns of weight loss at 6 and 36 months. The PROC MIXED function of SAS software (SAS Institute, Inc., Cary, North Carolina) was used to perform repeated-measures analyses that tested differences over time by pattern of weight loss. Cox proportional-hazards models were used for survival analyses, with onset of hypertension as the outcome. Results Baseline Findings The baseline characteristics of participants assigned to th