Vitamin E supplementation in the prevention of coronary heart disease.

Vitamin E consists of a number of compounds, tocopherols and tocotrienols, that function as lipid-soluble antioxidants. A hypothesis is that vitamin E may slow the progression of atherosclerosis by blocking the oxidative modification of low-density lipoprotein cholesterol and thus decrease its uptake into the arterial lumen. Basic science and animal studies have generally supported this hypothesis. Observational studies have primarily assessed patients with no established coronary heart disease (CHD), and results have generally supported a protective role of vitamin E in CHD. Early primary and secondary prevention clinical trials (Alpha-Tocopherol, Beta-Carotene Cancer Protection study and Cambridge Heart Antioxidant Study) showed mixed results. Despite years of encouraging evidence from basic science and observational studies, 3 large randomized clinical trials (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico, Heart Outcomes Prevention Evaluation, and Primary Prevention Project) with a combined total of more than 25,000 patients failed to show a significant benefit with vitamin E taken as a dietary supplement for the prevention of CHD. Four large randomized primary prevention trials currently under way should add to our knowledge. The American Heart Association has recommended consumption of a balanced diet with emphasis on antioxidant-rich fruits and vegetables but has made no recommendations regarding vitamin E supplementation for the general population. Although vitamin E supplementation seems to be safe for most people, recommendations from health care professionals should reflect the uncertainty of established benefit as demonstrated in clinical trials.

Dietary treatment and long-term weight loss and maintenance in type 2 diabetes.

Increasing body weight, particularly abdominal weight, is associated with increasing risk for type 2 diabetes, and 80% of people with type 2 diabetes are overweight or obese. Weight loss and maintenance are challenging in the obese population without diabetes, and data suggest that this may be more difficult in obese people with diabetes. Various weight-loss strategies with follow-up for at least 1 year have been evaluated in people with diabetes with mixed results. Diet is most effective in promoting initial weight loss. Energy restriction will improve glycemic control within days of initiation, independent of weight loss. There is deterioration of the effects of dietary therapy on glycemic control over time, even with partial weight maintenance, because of the relaxation of energy restriction. Diet composition has little effect on glycemic control independent of total calories. Very-low-calorie diets lead to better initial weight loss and glycemic control but yield no better long-term results than more moderate treatment. The initial results from studies using prepared meals and liquid meal replacements show that weight loss and glycemic control are comparable with conventional dietary treatment. Comprehensive lifestyle therapies, involving diet, exercise, and behavioral modification, can lead to weight losses of approximately 2 to 10 kg over 10 to 20 weeks, with regain over 1 year of one-third to one-half of weight initially lost. The net improvement on glycemic control is usually small 1 year after weight loss. Creative strategies using these and other modalities are needed to improve long-term weight loss, weight maintenance, and glycemic control in patients with type 2 diabetes. Greater efforts in primary prevention are also needed because of the increasing prevalence of obesity and type 2 diabetes.

Obesity is associated with premature occurrence of acute myocardial infarction.

BACKGROUND: The American Heart Association has classified obesity as a major modifiable risk factor for coronary artery disease, but its relationship with age at presentation with acute myocardial infarction (AMI) is poorly documented. HYPOTHESIS: The study was undertaken to evaluate the impact of obesity on age at presentation, and on in-hospital morbidity and mortality in patients with AMI. METHODS: Our analysis includes a consecutive series of 906 Olmsted County patients (mean age 67.7 years, 51% male) admitted with AMI to the Mayo Clinic Coronary Care Unit (CCU). The patients were entered into the Mayo CCU Database, a prospective registry of data pertaining to patients admitted to the Mayo Clinic CCU with AMI. Age at AMI occurrence and in-hospital morbidity and mortality were noted. RESULTS: Obese patients (body mass index [BMI] >30) with AMI were significantly younger than patients with AMI in the overweight (BMI 25-30) and normal-weight (BMI < 30) groups (62.3+/-13.1 vs. 66.9+/-13.2 and 72.9+/-13.4, respectively. p < 0.001). Obesity and overweight status were associated with male gender, diabetes mellitus, hypercholesterolemia, and smoking history; however, after multivariate adjustment for these risk factors, excess weight and premature AMI remained significantly associated. Compared with normal-weight patients, overweight patients presenting with AMI were 3.6 years younger (p < 0.001, confidence interval [CI] 1.9-5.4) and obese patients 8.2 years younger (p < 0.001, Cl 6.2-10.1). No significant increase in in-hospital morbidity and mortality was seen. CONCLUSION: In this population-based study, overweight and obese status are independently associated with the premature occurrence of AMI, but not with an increased incidence of in-hospital complications.

Do adaptive changes in metabolic rate favor weight regain in weight-reduced individuals? An examination of the set-point theory.

BACKGROUND: Obese persons generally regain lost weight, suggesting that adaptive metabolic changes favor return to a preset weight. OBJECTIVE: Our objective was to determine whether adaptive changes in resting metabolic rate (RMR) and thyroid hormones occur in weight-reduced persons, predisposing them to long-term weight gain. DESIGN: Twenty-four overweight, postmenopausal women were studied at a clinical research center in four 10-d study phases: the overweight state (phase 1, energy balance; phase 2, 3350 kJ/d) and after reduction to a normal-weight state (phase 3, 3350 kJ/d; phase 4, energy balance). Weight-reduced women were matched with 24 never-overweight control subjects. After each study phase, assessments included RMR (by indirect calorimetry), body composition (by hydrostatic weighing), serum triiodothyronine (T(3)), and reverse T(3) (rT(3)). Body weight was measured 4 y later, without intervention. RESULTS: Body composition-adjusted RMR and T(3):rT(3) fell during acute (phase 2) and chronic (phase 3) energy restriction (P: < 0.01), but returned to baseline in the normal-weight, energy-balanced state (phase 4; mean weight loss: 12.9 +/- 2.0 kg). RMR among weight-reduced women (4771 +/- 414 kJ/d) was not significantly different from that in control subjects (4955 +/- 414 kJ/d; P: = 0.14), and lower RMR did not predict greater 4-y weight regain (r = 0.27, NS). CONCLUSIONS: Energy restriction produces a transient hypothyroid-hypometabolic state that normalizes on return to energy-balanced conditions. Failure to establish energy balance after weight loss gives the misleading impression that weight-reduced persons are energy conservative and predisposed to weight regain. Our findings do not provide evidence in support of adaptive metabolic changes as an explanation for the tendency of weight-reduced persons to regain weight.

Body composition and resting energy expenditure in humans: role of fat, fat-free mass and extracellular fluid.

OBJECTIVE: The objective of this study was to determine whether there are independent effects of extracellular fluid volume (ECF) and fat mass (FM) on resting energy expenditure (REE) relative to fat-free mass (FFM) in adult men and women. METHODS: Multiple linear regression analysis was used to relate REE, as determined by indirect calorimetry, to FFM and FM (measured using dual energy X-ray absorptiometry) and ECF (measured using bromide space and/or the radiosulfate washout space) in 153 women and 100 men with varying amounts of body fat. RESULTS: REE correlated significantly with FFM and FM in women (r=0.65 and r=0.63, both P<0.001) and men (r=0.62 and r=0.48, both P<0.001, FFM and FM, respectively). In a multiple linear regression analysis FFM, FM and age significantly contributed to the ability to predict REE in both genders. The models that were derived were not significantly different between women and men. In women the contribution to REE from FM was easier to detect when FM was greater. Adjustment of FFM for ECF did not improve the relationship between FFM and REE. CONCLUSIONS: FFM, FM and age are significant, independent predictors of REE in both men and women. Adjustment of FFM for ECF does not improve the ability of FFM to predict REE, which suggests that ECF is a highly integrated component of FFM in healthy adults. Expressing REE relative to FFM alone will introduce errors when lean and obese populations are compared.

Prospective evaluation of Roux-en-Y gastric bypass as primary operation for medically complicated obesity.

OBJECTIVE: To determine prospectively the results of Roux-en-Y gastric bypass (RYGB) used as the primary weight-reducing operation in patients with medically complicated ("morbid") obesity. The RYGB procedure combines the advantages of a restrictive physiology (pouch of 10 mL) and a "dumping physiology" for high-energy liquids without requiring an externally reinforced (banded) stoma. PATIENTS AND METHODS: Between April 1987 and December 1998, a total of 191 consecutive patients with morbid obesity (median weight, 138 kg [range, 91-240 kg]; median body mass index, 49 kg/m2 [range, 36-74 kg/m2]), all of whom had directly weight-related morbidity, underwent RYGB and prospective follow-up. RESULTS: Hospital mortality was 0.5% (1/191), and hospital morbidity occurred in 10.5% (20/191). Good long-term weight loss was achieved, and patients adapted well to the required new eating habits. The mean +/- SD weight loss at 1 year after operation (113 patients) was 52 +/- 1 kg or 68% +/- 2% of initial excess body weight. By 3 years postoperatively (74 patients), weight loss was still 66% +/- 2% of excess body weight. Overall, 53 (72%) of 74 patients had achieved and maintained a weight loss of 50% or more of their preoperative excess body weight 3 years after the operation. In addition, only 1 (1%) of 98 patients had persistent postoperative vomiting 1 or more times per week. CONCLUSION: We believe that RYGB is a safe, effective procedure for most patients with morbid obesity and thus may be the current procedure of choice in patients requiring bariatrics++ surgery for morbid obesity.

Pharmacotherapy for obesity.

This article discusses former and current medications used to treat obesity, reviews efficacy and safety data for current medications, and suggests clinical guidelines for their use.

Clinical preventive medicine in primary care: background and practice: 3. Delivering preventive screening services.

The first article in this 3-part review on clinical preventive medicine described background information, supportive evidence, and current practices in preventive medicine. The second article discussed incorporating primary preventive activities including health promotion and immunizations into primary care practice. This third and final article in the series focuses on secondary prevention, i.e., screening, and examines the evidence and recommendations for various screening tests and procedures. Screening for hyperlipidemia and hypertension, 2 areas in which national programs are in place, are discussed. Wider incorporation of currently underutilized preventive services into primary care has a great potential to improve morbidity, mortality, and the quality of life in the general population.

Clinical preventive medicine in primary care: background and practice: 2. Delivering primary preventive services.

Strategies to incorporate preventive services into primary care settings have been underutilized. The first component of delivering preventive services in the primary care setting is the health risk assessment followed by establishment of practice guidelines and protocols for preventive services--who is eligible for what service (based on age, sex, and other clinical characteristics) and when. A computerized reminder system can be useful to track past and currently due preventive services for each patient and can also serve as a follow-up system for test results. Well-trained paramedical personnel can perform appropriate patient counseling and education. The goal of counseling and education is to change patient behavior. The first step in this difficult process is once again to ascertain health risks and then to determine the patient's stage of readiness--defined as precontemplation, contemplation, preparation, action, and maintenance. The counselor assists in identification of target behavior, advocates and commends behavior change, reinforces health benefits of behavior change, offers resources, strategies, and support, and creates a plan of action and monitoring mechanisms. Improved implementation of preventive services in primary care could have a major impact on the health of the population.

Clinical preventive medicine in primary care: background and practice: 1. Rationale and current preventive practices.

Impressive evidence supports the value of clinical preventive medicine, defined as the maintenance and promotion of health and the reduction of risk factors that result in injury and disease. Primary prevention activities deter the occurrence of a disease or adverse event, e.g., smoking cessation. Secondary prevention (screening) is early detection of a disease or condition in an asymptomatic stage so treatment delays or blocks occurrence of symptoms, e.g., mammographic detection of breast cancer. Tertiary prevention attempts to not allow adverse consequences of existing clinical disease, e.g., cardiac rehabilitation to prevent the recurrence of a myocardial infarction. Preventive services have decreased morbidity and mortality from both acute and chronic conditions. However, these services are underutilized for numerous reasons. Barriers to their use include physician, patient, and health system factors. The traditional disease/treatment model should be modified to incorporate more preventive services. The subsequent 2 parts of this review will discuss suggestions for integrating primary preventive services and screening into primary care practice.

Nutrition screening and assessment.

Both undernutrition and overnutrition contribute to increased risk of morbidity and mortality. Marasmus, kwashiorkor, and decreased micronutrient status are types of nutritional deficiencies, whereas obesity and problems resulting from dietary supplements are examples of overnutrition. Screening for malnutrition can be performed in the ambulatory, hospital, and institutional populations, each with methods appropriate for the target population. For patients determined to be at high risk, further nutrition assessment can be performed to help arrive at specific nutritional treatment goals. Identifying and treating malnutrition can potentially have an important impact on decreasing morbidity and mortality in the population.

Echocardiographic improvement over time after cessation of use of fenfluramine and phentermine.

OBJECTIVE: To determine the echocardiographic changes over time of valvular heart lesions in patients who took the weight loss drugs fenfluramine and phentermine. SUBJECTS AND METHODS: This prospective cohort study began at the termination of a randomized, double-blind, placebo-controlled weight loss trial of 18 obese women and 13 obese men (mean age, 42 years; mean body mass index, 33.4 kg/m2) who had been assigned randomly to treatment with fenfluramine and phentermine or to placebo. Echocardiograms were obtained at termination of the trial when fenfluramine was withdrawn from the market and 6 months later. They were interpreted independently by 3 cardiologists blinded to treatment assignment and temporal sequence of the echocardiograms. The main outcome measure was the change in drug-related valvular disease over time. RESULTS: One subject assigned to receive the drugs was lost to follow-up, and 3 subjects who did not meet a weight loss goal of 10 kg crossed over from placebo to drug treatment. Echocardiograms were obtained in 19 subjects who received the drugs and 11 subjects who received placebo, and 6-month follow-up echocardiograms were obtained in 15 subjects who received the drugs and 3 who received placebo. Subjects had taken fenfluramine and phentermine a mean of 41 weeks (range, 8-73 weeks). Five of 19 subjects who received the drugs (26%; 95% confidence interval, 7%-46%) and 1 of 11 who received placebo (9%) (odds ratio, 3.6; 95% confidence interval, 0.4-35.6) had findings that met criteria established for drug-related valvular disease. All 5 subjects (4 women and 1 man) receiving the drugs had mild aortic regurgitation, and 1 also had pulmonary hypertension (estimated pulmonary artery pressure, 59 mm Hg). Six months later, the echocardiographic findings had improved in all 5 subjects (P=.06), and 3 no longer met the criteria for drug-related valvular disease. Pulmonary artery pressures decreased to near normal in the subject with pulmonary hypertension (37 mm Hg). Overall, the echocardiographic valvular features improved in 8 of 15 subjects who received the drugs and had echocardiograms performed at both time periods (P=.008). CONCLUSIONS: Valvular heart disease did not appear to progress after cessation of use of fenfluramine and phentermine, and echocardiographic valvular features appeared to improve over time.