Abby G. Ershow

Report of the National Heart, Lung, and Blood Institute-National Institute of Diabetes and Digestive and Kidney Diseases Working Group on the Pathophysiology of Obesity-Associated Cardiovascular Disease

The ongoing obesity epidemic and its impending cardiovascular consequences represent a serious public health problem with worrisome implications for medical treatment. The urgency of providing new research directions recently led the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to convene a Working Group on the Pathophysiology of Obesity-Associated Cardiovascular Disease. Gathered at this meeting were researchers with substantial experience and expertise in either obesity-related sciences, including epidemiology, endocrinology, and metabolism, or cardiovascular sciences, including cardiology, neurobiology, hematology, renal function, and pediatrics. This report is the culmination of the blending of ideas during the 2-day meeting. The resulting research recommendations include the development of new models and synergistic approaches to basic studies of obesity-associated cardiovascular diseases. The adult US population, whose combined prevalence of overweight and obesity now exceeds 60%,1 is experiencing an unprecedented exposure to obesity-related cardiovascular risk factors and is expected to suffer the adverse clinical consequences in years to come. Also alarming are the ever-rising rates of overweight and obese children and adolescents, which have tripled over the last 30 years.2 Increased rates of co-morbidities such as dyslipidemia, hypertension, type 2 diabetes, and hepatic damage in overweight adolescents indicate that the young are not protected from the metabolic perturbations that accompany excess adipose tissue stores.3–5⇓⇓ We do not know what the consequences might be for the developing cardiovascular system if obesity is present during late stages of growth and maturation. Overweight or obese individuals experience greatly elevated morbidity and mortality from nearly all of the common cardiovascular diseases (stroke, coronary heart disease, congestive heart failure, cardiomyopathy, and possibly arrhythmia/sudden death).6,7⇓ Because primary treatment and prevention of obesity often fail or are only partially successful, it is anticipated that the …

Effects of Reducing Dietary Saturated Fatty Acids on Plasma Lipids and Lipoproteins in Healthy Subjects: The Delta Study, Protocol 1

Few well-controlled diet studies have investigated the effects of reducing dietary saturated fatty acid (SFA) intake in premenopausal and postmenopausal women or in blacks. We conducted a multicenter, randomized, crossover-design trial of the effects of reducing dietary SFA on plasma lipids and lipoproteins in 103 healthy adults 22 to 67 years old. There were 46 men and 57 women, of whom 26 were black, 18 were postmenopausal women, and 16 were men > or =40 years old. All meals and snacks, except Saturday dinner, were prepared and served by the research centers. The study was designed to compare three diets: an average American diet (AAD), a Step 1 diet, and a low-SFA (Low-Sat) diet. Dietary cholesterol was constant. Diet composition was validated and monitored by a central laboratory. Each diet was consumed for 8 weeks, and blood samples were obtained during weeks 5 through 8. The compositions of the three diets were as follows: AAD, 34.3% kcal fat and 15.0% kcal SFA; Step 1, 28.6% kcal fat and 9.0% kcal SFA; and Low-Sat, 25.3% kcal fat and 6.1% kcal SFA. Each diet provided approximately 275 mg cholesterol/d. Compared with AAD, plasma total cholesterol in the whole group fell 5% on Step 1 and 9% on Low-Sat. LDL cholesterol was 7% lower on Step 1 and 11% lower on Low-Sat than on the AAD (both P<.01). Similar responses were seen in each subgroup. HDL cholesterol fell 7% on Step 1 and 11% on Low-Sat (both P<.01). Reductions in HDL cholesterol were seen in all subgroups except blacks and older men. Plasma triglyceride levels increased approximately 9% between AAD and Step 1 but did not increase further from Step 1 to Low-Sat. Changes in triglyceride levels were not significant in most subgroups. Surprisingly, plasma Lp(a) concentrations increased in a stepwise fashion as SFA was reduced. In a well-controlled feeding study, stepwise reductions in SFA resulted in parallel reductions in plasma total and LDL cholesterol levels. Diet effects were remarkably similar in several subgroups of men and women and in blacks. The reductions in total and LDL cholesterol achieved in these different subgroups indicate that diet can have a significant impact on risk for atherosclerotic cardiovascular disease in the total population.

Update on prevention of cardiovascular disease in adults with type 2 diabetes mellitus in light of recent evidence: A scientific statement from the American Heart Association and the American Diabetes Association

Cardiovascular disease risk factor control as primary prevention in patients with type 2 diabetes mellitus has changed substantially in the past few years. The purpose of this scientific statement is to review the current literature and key clinical trials pertaining to blood pressure and blood glucose control, cholesterol management, aspirin therapy, and lifestyle modification. We present a synthesis of the recent literature, new guidelines, and clinical targets, including screening for kidney and subclinical cardiovascular disease for the contemporary management of patients with type 2 diabetes mellitus.

Accuracy of Energy Intake Data Estimated by a Multiplepass, 24-hour Dietary Recall Technique

OBJECTIVE This study examined the accuracy of a multiple-pass, 24-hour dietary recall method for estimating energy intakes of men and women by comparing it with energy intake required for weight maintenance. DESIGN Three-day, multiple-pass, 24-hour recalls were obtained on randomly selected days during a self-selected diet period when subjects were preparing their own meals and during a controlled diet period when all meals were provided by the study. During the dietary intervention, weight was maintained; body weight and dietary intake were monitored closely, thereby allowing estimation of the energy intake required for weight maintenance. SUBJECTS/SETTING Seventy-eight men and women (22 to 67 years old) from the Dietary Effects on Lipoprotein and Thrombogenic Activity (DELTA) study participated in this study. All 24-hour recalls were collected using a computer-assisted, interactive, multiple-pass telephone interview technique. Energy requirements for each individual were determined by the energy content of the DELTA study foods provided to maintain weight. STATISTICAL ANALYSIS Paired and independent t tests were conducted to examine differences among study variables. Agreement between recalled energy intake and weight maintenance energy intake was analyzed using the Bland-Altman technique. RESULTS Compared with weight maintenance energy intake, during the self-selected diet period men and women underestimated energy intake by 11% and 13%, respectively. During the controlled diet period, men underestimated energy intake by 13%, whereas women overestimated energy by 1.3%. APPLICATIONS/CONCLUSIONS Men had a tendency to under-estimate energy intake irrespective of the recording period. The accuracy of the recalled energy intake of women may be influenced by recording circumstances. Researchers should examine the factors influencing underreporting and overreporting by individuals and their impact on macronutrient and micronutrient intakes. Also, strategies need to be developed to minimize underreporting and overreporting.

Update on Prevention of Cardiovascular Disease in Adults With Type 2 Diabetes Mellitus in Light of Recent Evidence: A Scientific Statement From the American Heart Association and the American Diabetes Association

Cardiovascular disease risk factor control as primary prevention in patients with type 2 diabetes mellitus has changed substantially in the past few years. The purpose of this scientific statement is to review the current literature and key clinical trials pertaining to blood pressure and blood glucose control, cholesterol management, aspirin therapy, and lifestyle modification. We present a synthesis of the recent literature, new guidelines, and clinical targets, including screening for kidney and subclinical cardiovascular disease for the contemporary management of patients with type 2 diabetes mellitus.

Linxian nutrition intervention trials design, methods, participant characteristics, and compliance

Two nutrition intervention trials were conducted in Linxian, China, where the esophageal/gastric cardia cancer mortality rates are among the highest in the world and there is suspicion that the populations chronic deficiencies of multiple nutrients are etiologically involved. Both trials were randomized, double-blind, and placebo-controlled, and tested the effect of multiple-vitamin and multiple-mineral supplements in lowering the rates of cancer. In the first trial, the Dysplasia Trial, 3318 individuals with a cytologic diagnosis of esophageal dysplasia received daily vitamin and mineral supplements or placebos for 6 years. The second trial, the General Population Trial, involved 29,584 individuals and used a one-half replicate of a 2(4) fractional factorial design, which enabled the testing of daily supplementation of four different vitamin and mineral combinations and placebo for a period 5 1/4 years. This article describes the design and methods of these studies as well as the baseline characteristics and compliance behavior of the participants in these two trials, the largest cancer chemoprevention studies reported to date.

Estrogen receptor status and dietary intakes in breast cancer patients

We used data from a study of racial differences in cancer patient survival to examine the association between estrogen receptor status and the intake of nutrients and food groups among 689 black and white women, ages 20–79, with breast cancer newly diagnosed in 1985 and 1986. We reviewed medical records and collected interview data, including a 34-item food frequency questionnaire. Consistent with published reports, we found positive estrogen receptor status to be positively associated with age and inversely associated with parity and oral contraceptive use. Whites were more likely than blacks to have estrogen receptor-positive tumors. We examined eight nutrients and six food groups in multivariate analyses for association with estrogen receptor status. After adjusting for age, race, usual body mass index, and parity, a high percentage of calories from fat was associated with estrogen receptor-positive cancer, and a high percentage of calories from carbohydrates was associated with estrogen receptor-negative breast cancer. These findings indicate that women with breast cancer who are on diets with a high percentage of calories from fat may be more likely to develop estrogen receptor-positive cancers.

ApoE Genotype Does Not Predict Lipid Response to Changes in Dietary Saturated Fatty Acids in a Heterogeneous Normolipidemic Population

Recent studies have suggested that variations in apoE genotypes may influence the magnitude of plasma lipid changes in response to dietary interventions. We examined the ability of apoE genotype to predict plasma lipid response to reductions in percent of calories from total fat (TF) and saturated fat (SF) in a normolipidemic study population (n = 103) heterogeneous with respect to age, gender, race, and menopausal status. Three diets, an average American diet (34.3% TF, 15.0% SF), an AHA Step 1 diet (28.6% TF, 9.0% SF), and a low saturated fat (Low-Sat) diet (25.3% TF, 6.1% SF) were each fed for a period of 8 weeks in a three-way crossover design. Cholesterol was kept constant at 275 mg/d; monounsaturated and polyunsaturated fat were kept constant at approximately 13% and 6.5% of calories, respectively. Fasting lipid levels were measured during each of the final 4 weeks of each diet period. Participants were grouped by apoE genotype: E2 (E2/2, E2/3, E2/4); E3 (E3/3); E4 (E3/4, E4/4). Relative to the average American diet, both the Step 1 and Low-Sat diets significantly reduced total cholesterol, LDL cholesterol, and HDL cholesterol in all three apoE genotype groups. No evidence of a significant diet by genotype interaction, however, could be identified for any of the measured lipid and lipoprotein end points. Additional analysis of the data within individual population subgroup (men and women, blacks and whites) likewise provided no evidence of a significant diet by genotype interaction. Thus, in a heterogeneous, normolipidemic study population, apoE genotype does not predict the magnitude of lipid response to reductions in dietary saturated fat.

Environmental Influences on Development of Type 2 Diabetes and Obesity: Challenges in Personalizing Prevention and Management

Recent epidemic increases in the U.S. prevalence of obesity and diabetes are a consequence of widespread environmental changes affecting energy balance and its regulation. These environmental changes range from exposure to endocrine disrupting pollutants to shortened sleep duration to physical inactivity to excess caloric intake. Overall, we need a better understanding of the factors affecting individual susceptibility and resistance to adverse exposures and behaviors and of determinants of individual response to treatment. Obesity and diabetes prevention will require responding to two primary behavioral risk factors: excess energy intake and insufficient energy expenditure. Adverse food environments (external, nonphysiological influences on eating behaviors) contribute to excess caloric intake but can be countered through behavioral and economic approaches. Adverse built environments, which can be modified to foster more physical activity, are promising venues for community-level intervention. Techniques to help people to modulate energy intake and increase energy expenditure must address their personal situations: health literacy, psychological factors, and social relationships. Behaviorally oriented translational research can help in developing useful interventions and environmental modifications that are tailored to individual needs.

Dietary guidance in heart failure: a perspective on needs for prevention and management.

The role that dietary factors play in preventing heart failure (HF) and in improving prognosis is increasingly recognized, indicating a need for well-grounded guidelines that can provide recommendations for daily nutrient intakes. At present, however, the state of dietary guidance is more satisfactory for persons at risk of HF (Stages A and B) than for those with a diagnosis of HF (Stages C and D). For individuals at risk of HF, a good starting point is provided by governmental and professional society guidance directed at dietary management of cardiovascular risk factors such as hypertension, hyperlipidemia, and obesity. These dietary recommendations are consonant with epidemiologic research suggesting that improving risk factor profiles likely will lower the risk of developing HF. For patients with diagnosed HF, however, little information is available to define optimal nutrient intakes and optimal food patterns. Dietary services have been shown useful in improving clinical outcomes, but nutritional management must be individualized to the patient’s needs and must accommodate pharmacologic therapy, multiple co-morbidities, the possible need for nutritional supplements, repeated hospitalizations, salt and fluid retention, voluntary vs. involuntary weight loss, and other nutritional issues relevant to the aged population who comprise the majority of HF patients. Progress in the field will require well-designed clinical investigations addressing nutrient intake, nutrient metabolism, and nutritional status while mindful of the complex pathophysiology of HF.