James M. Raczynski

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

Ischemic, Hemodynamic, and Neurohormonal Responses to Mental and Exercise Stress Experience From the Psychophysiological Investigations of Myocardial Ischemia Study (PIMI)

BACKGROUND The pathophysiology of mental stress-induced myocardial ischemia, which occurs at lower heart rates than during physical stress, is not well understood. METHODS AND RESULTS The Psychophysiological Investigations of Myocardial Ischemia Study (PIMI) evaluated the physiological and neuroendocrine functioning in unmedicated patients with stable coronary artery disease and exercise-induced ischemia. Hemodynamic and neurohormonal responses to bicycle exercise, public speaking, and the Stroop test were measured by radionuclide ventriculography, ECG, and blood pressure and catecholamine monitoring. With mental stress, there were increases in heart rate, systolic blood pressure, cardiac output, and systemic vascular resistance that were correlated with increases in plasma epinephrine. During exercise, systemic vascular resistance fell, and there was no relationship between the hemodynamic changes and epinephrine levels. The fall in ejection fraction was greater with mental stress than exercise. During mental stress, the changes in ejection fraction were inversely correlated with the changes in systemic vascular resistance. Evidence for myocardial ischemia was present in 92% of patients during bicycle exercise and in 58% of patients during mental stress. Greater increases in plasma epinephrine and norepinephrine occurred with ischemia during exercise, and greater increases in systemic vascular resistance occurred with ischemia during mental stress. CONCLUSIONS Mental stress-induced myocardial ischemia is associated with a significant increase in systemic vascular resistance and a relatively minor increase in heart rate and rate-pressure product compared with ischemia induced by exercise. These hemodynamic responses to mental stress can be mediated by the adrenal secretion of epinephrine. The pathophysiological mechanism involved are important in the understanding of the etiology of myocardial ischemia and perhaps in the selection of appropriate anti-ischemic therapy.

Mental Stress-Induced Ischemia and All-Cause Mortality in Patients With Coronary Artery Disease Results From the Psychophysiological Investigations of Myocardial Ischemia Study

Background—Ischemia during laboratory mental stress tests has been linked to significantly higher rates of adverse cardiac events. Previous studies have not been designed to detect differences in mortality rates. Methods and Results—To determine whether mental stress–induced ischemia predicts death, we evaluated 196 patients from the Psychophysiological Investigations of Myocardial Ischemia (PIMI) study who had documented coronary artery disease and exercise-induced ischemia. Participants underwent bicycle exercise and psychological stress testing with radionuclide imaging. Cardiac function data and psychological test results were collected. Vital status was ascertained by telephone and by querying Social Security records 3.5±0.4 years and 5.2±0.4 years later. Of the 17 participants who had died, new or worsened wall motion abnormalities during the speech test were present in 40% compared with 19% of survivors (P =0.04) and significantly predicted death (rate ratio=3.0; 95% CI, 1.04 to 8.36;P =0.04). Ejection fraction changes during the speech test were similar in patients who died and in survivors (P =0.9) and did not predict death even after adjusting for resting ejection fraction (P =0.63), which was similar in both groups (mean, 56.4 versus 59.7;P =0.24). Other indicators of ischemia during the speech test (ST-segment depression, chest pain) did not predict death, nor did psychological traits, hemodynamic responses to the speech test, or markers of the presence and severity of ischemia during daily life and exercise. Conclusions—In patients with coronary artery disease and exercise-induced ischemia, the presence of mental stress–induced ischemia predicts subsequent death.

Cardiovascular reactivity to video game predicts subsequent blood pressure increases in young men: The CARDIA study:

Objective This study was undertaken to determine the relationship between heightened reactivity of blood pressure (BP) during stress and 5-year changes in blood pressure and hypertensive status, using the CARDIA study. Method A total of 3364 participants (910 white men, 909 white women, 678 black men, and 867 black women), initially 20 to 32 years old and normotensive, were included. Cardiovascular reactivity to psychological stressors (video game and star-tracing tasks for 3 minutes, cold pressor test for 1 minute) was measured in 1987-1988. We then examined reactivity as a predictor of significant BP change (>or=to8 mm Hg, thought to represent a clinically significant increase) over the next 5 years. Logistic regression models were used to control for potential covariates. Significant BP change and the development of hypertension (BP greater than 140/90 or taking medication for hypertension) over the 5-year follow-up were examined in separate analyses. Results Increased systolic blood pressure (SBP) reactivity to the video game was associated with a significant 5-year SBP increase among the entire cohort, independent of resting SBP (p < .0001). Subsequent analyses showed that this relationship held for men but not for women. Reactivity to the star-tracing task or the cold pressor test did not predict significant BP change. Among black men only, new hypertensives (N = 36) had greater diastolic blood pressure (DBP) reactivity to the video game (p = .01). Conclusions: Although BP reactivity to all physical and mental stressors used in this study did not consistently predict 5-year change in BP in this young cohort, the results indicate that reactivity to a video game stressor predicts 5-year change in BP and early hypertension among young adult men. These findings are consistent with other studies showing the usefulness of stressors producing a primarily beta-adrenergic response in predicting BP change and hypertension. The results may be limited by the shortened initial rest and recovery periods used in the CARDIA protocol.

Body image among men and women in a biracial cohort : The CARDIA study

OBJECTIVE To examine body image in a population-based, biracial cohort. METHOD Body image measures were obtained on 1,837 men (45% Black) and 1,895 women (51% Black) in the CARDIA study. Subscales of the Multidimensional Body Self-Relations Questionnaire (Appearance Evaluation and Appearance Orientation) and a measure of body size dissatisfaction were obtained. RESULTS Blacks were more invested in appearance than Whites and women were more invested than men. Women were more dissatisfied with size and overall appearance than men, and White men were more dissatisfied with appearance than Black men. Black and White women were similarly dissatisfied with size and appearance. However, after adjustment for age, body mass index, and education, Black women were more satisfied with both dimensions than White women. Obesity was strongly associated with body dissatisfaction across all gender-ethnicity groups. DISCUSSION Significant differences in body image were apparent by gender and ethnicity, and different patterns were evident depending on the dimension considered.

Alcohol intake and blood pressure in young adults: The CARDIA study

Associations between self-reported average daily alcohol intake and blood pressure were assessed in 5031 black and white men and women ages 18-30 from the Coronary Artery Risk Development in Young Adults Study (CARDIA). In general, intake was positively but weakly related to both systolic and diastolic blood pressure. Associations with systolic pressure were generally stronger than those with diastolic pressure. With average daily alcohol intake categorized as none, 0.1-9.9 ml, 10.0-19.9 ml, 20.0-29.9 ml, and 30.0+ ml, mean systolic pressure, adjusted for age, body mass index, education, smoking, and physical activity, increased progressively with increasing intake in black and white men and in white women. Mean diastolic pressure increased progressively with increasing intake only in white men and women, but was highest for those averaging 30.0+ ml per day in black women as well as white men and women. Mean pressures were also compared for those averaging 75.0+ ml per day (men) or 50.0+ ml per day (women) vs those reporting no intake. Differences in adjusted mean pressures for white men were 3.2 mmHg (95% confidence limits (CL) -0.3, 6.8) for systolic pressure and 1.7 mmHg (-1.6, 5.0) for diastolic pressure. In black men differences were 4.4 mmHg (1.4, 7.4) and 3.4 mmHg (0.6, 6.3), respectively. Differences in white women were 1.4 mmHg (-2.5, 5.3) for systolic pressure and 0.9 mmHg (-2.7, 4.5) for diastolic pressure and for black women, -0.2 mmHg (-4.3, 3.8) and 1.9 mmHg (-1.9, 5.8). Separate analyses in smokers and nonsmokers of the associations between alcohol intake and blood pressure suggested that associations may differ by smoking status in some sex-race groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The Depression Interview and Structured Hamilton (DISH): Rationale, development, characteristics, and clinical validity

Objective The Depression Interview and Structured Hamilton (DISH) is a semistructured interview developed for the Enhancing Recovery in Coronary Heart Disease (ENRICHD) study, a multicenter clinical trial of treatment for depression and low perceived social support after acute myocardial infarction. The DISH is designed to diagnose depression in medically ill patients and to assess its severity on an embedded version of Williams’ Structured Interview Guide for the Hamilton Depression scale (SIGH-D). This article describes the development and characteristics of the DISH and presents a validity study and data on its use in ENRICHD. Methods In the validity study, the DISH and the Structured Clinical Interview for DSM-IV (SCID) were administered in randomized order to 57 patients. Trained interviewers administered the DISH, and clinicians administered the SCID. In ENRICHD, trained research nurses administered the DISH and recorded a diagnosis. Clinicians reviewed 42% of the interviews and recorded their own diagnosis. The Beck Depression Inventory (BDI) was administered in both studies. Results In the validity study, the SCID diagnosis agreed with the DISH on 88% of the interviews (weighted &kgr; = 0.86). In ENRICHD, the clinicians agreed with 93% of the research nurses’ diagnoses. The BDI and the Hamilton depression scores derived from the DISH in the two studies correlated 0.76 (p < .0001) in the validity study and 0.64 (p < .0001) in ENRICHD. Conclusions These findings support the validity of the DISH as a semistructured interview to assess depression in medically ill patients. The DISH is efficient in yielding both a DSM-IV depression diagnosis and a 17-item Hamilton depression score.

Sufficient conditions for effective treatment of substance abusing homeless persons.

Treatment efficacy for homeless substance abusers (primarily crack cocaine) was studied in a randomized control design with subjects (n = 176) assigned to usual care (UC) or an enhanced day treatment program plus abstinent contingent work therapy and housing (EC). Subjects met DSM-III-R criteria for Substance Use Disorder and McKinny Act criteria for homelessness. UC involved weekly individual and group counseling. EC involved a day treatment program consisting of daily attendance, transportation, lunch, manualized psychoeducational groups, and individual counseling. A total of 131 (74.4%) subjects (62 UC and 69 EC) were treated and followed. UC subjects attended 28.5% and EC attended 48.4% of expected treatment during the first 2 months. After 2 months, EC subjects experienced up to 4 months of abstinent contingent work therapy (44.9% of EC subjects) and housing (37.7% of EC subjects), with day treatment available two afternoons per week. Longitudinal Wei-Lachin analyses of medians (reported alcohol use, days homeless and employed) and proportions (cocaine toxicologies) were conducted across 2-, 6-, and 12-month follow-up points. EC had 36% fewer positive cocaine toxicologies at 2-months and 18% fewer at 6-months than UC with regression toward baseline at 12-months. EC had 8 days fewer days of reported alcohol use in the past 30 days, 52 fewer days homeless in the past 60 days, and 10 more days employed in the past 30 days from baseline to the 12-months. UC showed no changes except a temporary increase in employment at 6-months. This is one of the first demonstrations that homeless cocaine abusers can be retained and effectively treated.

Psychosocial treatment within sex by ethnicity subgroups in the Enhancing Recovery in Coronary Heart Disease clinical trial.

Objective: Intervening in depression and/or low perceived social support within 28 days after myocardial infarction (MI) in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial did not increase event-free survival. The purpose of the present investigation was to conduct post hoc analyses on sex and ethnic minority subgroups to assess whether any treatment subgroup is at reduced or increased risk of greater morbidity/mortality. Methods: The 2481 patients with MI (973 white men, 424 minority men, 674 white women, 410 minority women) who had major or minor depression and/or low perceived social support were randomly allocated to usual medical care or cognitive behavior therapy. Total mortality or recurrent nonfatal MI (ENRICHD primary endpoint) and cardiac mortality or recurrent nonfatal MI (secondary endpoint) were analyzed as composite endpoints by group for time to first event using Cox proportional hazards regression. Results: There was a trend in the direction of treatment efficacy for white men for the primary endpoint (hazard ratio [HR], 0.80; 95% confidence interval, 0.61–1.05; p = .10) and a significant (p < .006, Bonferroni corrected) effect for the secondary endpoint (HR, 0.63; 95% CI, 0.46–0.87; p = .004). In contrast, the HRs for each of the other three subgroups were nonsignificant. The magnitude of differences in treatment effects between white men and the other subgroups remained significant for the secondary endpoint (p =.04) after adjustment for age, education, living alone, antidepressant use, comorbidity score, cardiac catheterization, ejection fraction, history of hypertension, and major depression. Conclusions: White men, but not other subgroups, may have benefited from the ENRICHD intervention, suggesting that future studies need to attend to issues of treatment design and delivery that may have prevented benefit among sex and ethnic subgroups other than white men.

Overweight children, weight-based teasing and academic performance

BACKGROUND School performance of overweight children has been found to be inferior to normal weight children; however, the reason(s) for this link between overweight and academic performance remain unclear. Psychosocial factors, such as weight-based teasing, have been proposed as having a possible mediating role, although they remain largely unexplored. METHODS Random parental telephone survey data (N=1 071) of public school students collected as part of the statewide evaluation of Arkansas Act 1220, a law to reduce childhood obesity, were used. Overweight status (body mass index > 85th percentile for gender and age) and weight-based teasing were examined as predictors of poorer school performance. RESULTS Overweight status was a significant predictor of poorer school performance (OR=1.51; 95% CI=1.01, 2.25), after adjustment for gender, school level, free and reduced lunch participation, and race. However, the addition of weight-based teasing to the model (with weight category and covariates) reduced the weight category parameter estimate by 24%, becoming non-significant (OR=1.40; 95% CI=0.93, 2.10) and indicating a possible mediating effect of weight-based teasing on the relationship between weight category and school performance. Weight-based teasing was significantly associated with school performance, with lower odds of strong school performance among weight-based teased children (OR=0.44; 95% CI=0.27, 0.74). CONCLUSION Psychosocial variables, such as weight-based teasing, should be considered in future research examining the impact of childhood obesity on school performance and in future intervention studies.