Denise G. Simons-Morton

Effects of intensive glucose lowering in type 2 diabetes

BACKGROUND Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. METHODS In this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up. RESULTS At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P=0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard-therapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P=0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001). CONCLUSIONS As compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)

Effects on Blood Pressure of Reduced Dietary Sodium and the Dietary Approaches to Stop Hypertension (DASH) Diet

Background The effect of dietary composition on blood pressure is a subject of public health importance. We studied the effect of different levels of dietary sodium, in conjunction with the Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in vegetables, fruits, and low-fat dairy products, in persons with and in those without hypertension. Methods A total of 412 participants were randomly assigned to eat either a control diet typical of intake in the United States or the DASH diet. Within the assigned diet, participants ate foods with high, intermediate, and low levels of sodium for 30 consecutive days each, in random order. Results Reducing the sodium intake from the high to the intermediate level reduced the systolic blood pressure by 2.1 mm Hg (P<0.001) during the control diet and by 1.3 mm Hg (P=0.03) during the DASH diet. Reducing the sodium intake from the intermediate to the low level caused additional reductions of 4.6 mm Hg during the control diet (P<0.001) and 1.7 mm Hg during t...

Effects of intensive blood-pressure control in type 2 diabetes mellitus.

BACKGROUND There is no evidence from randomized trials to support a strategy of lowering systolic blood pressure below 135 to 140 mm Hg in persons with type 2 diabetes mellitus. We investigated whether therapy targeting normal systolic pressure (i.e., <120 mm Hg) reduces major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events. METHODS A total of 4733 participants with type 2 diabetes were randomly assigned to intensive therapy, targeting a systolic pressure of less than 120 mm Hg, or standard therapy, targeting a systolic pressure of less than 140 mm Hg. The primary composite outcome was nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years. RESULTS After 1 year, the mean systolic blood pressure was 119.3 mm Hg in the intensive-therapy group and 133.5 mm Hg in the standard-therapy group. The annual rate of the primary outcome was 1.87% in the intensive-therapy group and 2.09% in the standard-therapy group (hazard ratio with intensive therapy, 0.88; 95% confidence interval [CI], 0.73 to 1.06; P=0.20). The annual rates of death from any cause were 1.28% and 1.19% in the two groups, respectively (hazard ratio, 1.07; 95% CI, 0.85 to 1.35; P=0.55). The annual rates of stroke, a prespecified secondary outcome, were 0.32% and 0.53% in the two groups, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P=0.01). Serious adverse events attributed to antihypertensive treatment occurred in 77 of the 2362 participants in the intensive-therapy group (3.3%) and 30 of the 2371 participants in the standard-therapy group (1.3%) (P<0.001). CONCLUSIONS In patients with type 2 diabetes at high risk for cardiovascular events, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, did not reduce the rate of a composite outcome of fatal and nonfatal major cardiovascular events. (ClinicalTrials.gov number, NCT00000620.)

Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus

BACKGROUND We investigated whether combination therapy with a statin plus a fibrate, as compared with statin monotherapy, would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease. METHODS We randomly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo. The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years. RESULTS The annual rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group (hazard ratio in the fenofibrate group, 0.92; 95% confidence interval [CI], 0.79 to 1.08; P=0.32). There were also no significant differences between the two study groups with respect to any secondary outcome. Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (hazard ratio, 0.91; 95% CI, 0.75 to 1.10; P=0.33). Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women (P=0.01 for interaction), and a possible interaction according to lipid subgroup, with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol (P=0.057 for interaction). CONCLUSIONS The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone. These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)

Effects of comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18-month results of a randomized trial.

Context Can adults make sustained changes in unhealthy lifestyle behaviors? Content In this multicenter trial, 810 adult volunteers with prehypertension or stage 1 hypertension were randomly assigned to a multicomponent behavioral intervention group, a group combining the behavioral intervention plus the Dietary Approaches to Stop Hypertension (DASH) diet, or an advice only group. At 18 months, participants in both behavioral intervention groups had less hypertension, more weight loss, and better reduction in sodium and fat intake than those receiving advice only. The participants in the DASH diet group also increased their intake of fruits, vegetables, and fiber. Implications Motivated adults can sustain several lifestyle changes over 18 months, which might reduce their risk for cardiovascular disease. The Editors The public health burden of chronic diseases related to suboptimal diet and physical inactivity is enormous. It has been estimated that these lifestyle factors contribute to approximately 20% of deaths in the United States (1). Incidence of atherosclerotic cardiovascular disease, overweight and obesity, elevated blood pressure and lipid levels, diabetes, osteoporosis, and cancer is increased by unhealthy lifestyles (2-8). Multiple lifestyle factors, such as physical inactivity; excessive intake of calories, sodium, saturated fat, and cholesterol; and inadequate intake of fruits, vegetables, and low-fat dairy products, are etiologically related to the development of these diseases (4, 5, 8-10). To reduce the burden of chronic disease, increased physical activity and changes in diet are needed, yet few intervention studies have attempted to achieve many lifestyle changes simultaneously. The PREMIER randomized trial tested the effects of 2 multicomponent behavioral interventions on blood pressure (11). Both interventions promoted increased physical activity, weight loss, and reduced sodium intake, each of which is recommended by the 2005 Dietary Guidelines Scientific Advisory Committee (12). One intervention also added the Dietary Approaches to Stop Hypertension (DASH) diet (13). This diet, which is high in fruits, vegetables, and low-fat dairy products and low in saturated fat, total fat, and cholesterol, meets each of the major nutrient recommendations that were established by the Institute of Medicine (14-18). We report the effects of the PREMIER interventions on lifestyle changes and blood pressure status at 18 months. The main results of PREMIER, namely change in blood pressure at 6 months, were reported previously (11). Methods The PREMIER study design and rationale (19) and intervention methods (11) have been described previously. The institutional review boards at each clinical center; an external protocol review committee appointed by the National Heart, Lung, and Blood Institute (NHLBI); and the NHLBI reviewed and approved the protocol (available at www.kpchr.org/public/premier/intervention/default.asp). The NHLBI also appointed a data and safety monitoring board to monitor the trial. Each participant provided written informed consent. The trial was conducted from January 2000 through November 2002. Study Participants Participants were generally healthy adults, age 25 years or older, who had prehypertension or stage 1 hypertension and met the Joint National Committee VI (JNC VI) criteria for a 6-month trial of nonpharmacologic therapy (2). Targeted recruitment methods were used to ensure adequate representation of clinically important subgroups, in particular, African-American persons. Specific methods varied from site to site but included direct mailings, radio and newspaper advertisements, and networking within the local African-American communities. Eligibility criteria included not taking antihypertensive medication and having a systolic blood pressure of 120 to 159 mm Hg and a diastolic blood pressure of 80 to 95 mm Hg, based on the average of 3 screening visits. Persons with prehypertension (systolic blood pressure of 120 to 139 mm Hg or diastolic blood pressure of 80 to 89 mm Hg) were included because of the excess risk for cardiovascular disease in those with blood pressure within this range (20). Major exclusion criteria were a body mass index less than 18.5 kg/mg2 or greater than 45.0 kg/m2, use of antihypertensive drugs or other drugs that affect blood pressure, JNC VI risk category C (target organ damage or diabetes), use of prescription weight loss medications, previous cardiovascular event, congestive heart failure, angina, cancer, and consumption of more than 21 alcoholic drinks per week. Trial Conduct Eligible participants were randomly assigned, with equal probability, to 1 of 3 groups: an advice only comparison group (advice only); an intervention group that targeted established, guideline-recommended lifestyle recommendations (established) (2); or an intervention group targeting the established recommendations and adding the DASH dietary pattern (established plus DASH) (13). Computer-generated treatment assignments were stratified by clinic and hypertension status and were assigned in blocks of varying sizes to provide balance over time. The actual assignments were administered by using a password-protected, Web-based application developed by the coordinating center and accessible only by authorized individuals. All clinic measurement staff were blinded to treatment assignment, and all intervention staff were blinded to clinic measurements. Hypertension was defined by using the JNC VI criteria for hypertension treatment: an average systolic blood pressure of 140 mm Hg, a diastolic blood pressure greater than 90 mm Hg, or use of antihypertensive medication. Normal blood pressure was defined as systolic blood pressure less than 120 mm Hg, diastolic blood pressure less than 80 mm Hg, and no use of antihypertensive medication (21) (Figure). Intervention was provided by masters degreelevel counselors (dietitians and health educators trained in behavioral methods). The counselors were centrally trained before the start of the study, attended annual 3-day training sessions, and participated in monthly conference calls. Figure. Flow diagram of enrollment, measurements, and visit completion. Advice Only Group Participants in the advice group received advice to follow the National High Blood Pressure Education Program lifestyle recommendations for blood pressure control (2). Lifestyle recommendations included reducing weight (if overweight), following a reduced-sodium diet, engaging in regular moderate-intensity physical activity, and eating a heart-healthy diet, including the DASH diet. This advice was provided in two 30-minute individual sessions, 1 immediately after random assignment and 1 after the 6-month data collection visit. A PREMIER counselor reviewed the guidelines with the participant and provided printed educational materials and information about community resources. This intervention did not include advice to keep a food or exercise diary. Behavioral Interventions in the Established and Established plus DASH Groups Participant goals for the established and established plus DASH groups included weight loss of at least 6.8 kg (15 lb) for those with a body mass index of 25 kg/m2 or greater, at least 180 minutes per week of moderate-intensity physical activity, no more than 100 mmol per day of dietary sodium, and alcohol consumption of no more than 30 mL (1 oz) per day (2 drinks) for men and 15 mL (0.5) oz per day (1 drink) for women. Participants assigned to the established plus DASH group (but not those in the established group) also received counseling on the DASH diet, with goals for increased consumption of fruits and vegetables (9 to 12 servings/d) and low-fat dairy products (2 to 3 servings/d) and reduced consumption of saturated fat ( 7% of energy) and total fat ( 25% of energy). The intervention format, contact pattern, and behavior change strategies for the established and established plus DASH groups were identical. During the first 6 months, participants in both behavioral intervention groups attended 14 group sessions and 4 individual sessions; during months 7 to 18, they attended monthly group sessions supplemented with 3 individual counseling sessions. Throughout the trial, participants in the established and established plus DASH groups (but not those in the advice group) kept food diaries, monitored dietary calorie and sodium intakes, and recorded minutes of physical activity. Self-monitoring was used to provide individualized feedback, reinforcement, problem solving, and support. Social support for initial behavior changes and maintenance of change was provided during the group sessions. More detailed descriptions of the behavorial intervention methods are available (22). Measurements Blood pressure was assessed twice at each measurement, and systolic and diastolic blood pressures were calculated by using the mean of all available measurements (4 sets before random assignment, 3 sets at 6 and 18 months, and 1 set at 3 and 12 months). For 4 participants who were started on antihypertensive drug therapy between the 12- and 18-month visits, we obtained an official set of blood pressure measurements before initiation of therapy and used these as our 18-month blood pressure values for analysis. A similar procedure was used to obtain the 6-month blood pressure value for the 1 participant who began taking antihypertensive drugs between the 3- and 6-month visits. Two 24-hour dietary recalls, 1 obtained on a weekday and the other obtained on a weekend, were collected at baseline and at 6 and 18 months by telephone interview (23). Intakes of nutrients and food groups were calculated by using the Nutrition Data System for Research, version NDS-R 1998 (University of Minnesota, Minneapolis, Minnesota). Urinary excretion of sodium (reflecting salt intake) and potassium (reflecting fruit and vegetable intake) was obtained from 24-hour urinary collections at baseline a

Effects of Diet and Sodium Intake on Blood Pressure: Subgroup Analysis of the DASH-Sodium Trial

Although epidemiologic data show a direct relation between dietary sodium intake and blood pressure at the population level (1, 2), some experts question the universality of the findings and oppose public health recommendations to decrease sodium intake in the general population (3). Certainly, results from reports on the relationship between sodium and blood pressure among major subgroups vary considerably. Several studies suggest that African Americans and older adults have heightened salt sensitivity (greater blood pressure response to sodium intake) (4-6). Some evidence also indicates increased salt sensitivity in women (7), although other studies do not support this claim (4, 5). The association of sodium intake with cardiovascular morbidity and mortality varies by overweight status (8), perhaps reflecting a differential effect of sodium on blood pressure in overweight persons. Finally, higher dietary intakes of potassium and calcium have been shown to blunt the pressor effects of dietary sodium (9, 10). Dietary factors other than sodium also directly affect blood pressure, and these effects also appear to vary across subgroups. In the Dietary Approaches to Stop Hypertension (DASH) Trial, for example, a diet that had reduced total and saturated fat and was rich in fruits, vegetables, and low-fat dairy foods (the DASH diet) substantially decreased blood pressure compared with a more typical U.S. diet, in the absence of weight change and at sodium intakes approximating current U.S. consumption (11, 12). These effects persisted across all subgroups and were especially pronounced among hypertensive persons, African Americans, and persons who did not drink alcohol (13). The DASH-Sodium Trial examined the effects of reduced sodium intake in the context of the DASH diet and a more typical U.S. diet (14). In that study, highly significant decreases in blood pressure were observed with decreased sodium intake in participants following either diet, and the DASH diet decreased blood pressure at sodium intakes well below the current U.S. average. These results were observed overall and in subgroups defined by ethnicity, sex, and hypertension status (15). We report on more detailed subgroup analyses from the DASH-Sodium Trial, including results for subgroups defined by age, obesity, waist circumference, alcohol intake, and baseline sodium intake. We also report the results of multivariate analyses that demonstrate how these effects vary across subgroups defined jointly by age, ethnicity, sex, and hypertension status. Methods Study Design The DASH-Sodium Trial was a multicenter, randomized feeding trial comparing the effects on blood pressure of three levels of sodium intake and two dietary patterns. The 412 participants were 22 years of age or older and had systolic blood pressures of 120 to 159 mm Hg and diastolic blood pressures of 80 to 95 mm Hg (15). The three levels of sodium intake (lower, intermediate, and higher) varied according to energy intake in a ratio of 1:2:3; target intakes were 50, 100, and 150 mmol/d, respectively, for a 2100-kcal diet. The dietary patterns were a control diet, typical of what many Americans eat, and the DASH diet, which emphasizes fruits, vegetables, and low-fat dairy foods; includes whole grains, poultry, fish, and nuts; and is reduced in fats, red meat, sweets, and sugar-containing beverages (11, 14). Participants were recruited in four separate feeding cohorts and were randomly assigned to one of the two dietary patterns by using a parallel-group design. They then ate their assigned diet for three consecutive 30-day intervention feeding periods, during which sodium intake varied among the three levels by a randomly assigned sequence (Figure). Participants ate the control diet at the higher sodium intake during a 2-week run-in period. During the three intervention periods, participants received all their food in the context of the study and were asked not to eat any nonstudy food. Individual energy intake was adjusted to keep body weight stable. Figure. Design of the Dietary Approaches to Stop Hypertension (DASH)-Sodium Trial. Exclusion criteria were heart disease, renal insufficiency, poorly controlled hyperlipidemia or diabetes mellitus, diabetes requiring insulin, special dietary requirements, intake of more than 14 alcoholic drinks/wk, or use of antihypertensive drugs or other medications that would affect blood pressure or nutrient metabolism. The study was approved by the human subjects committees of the clinical centers and coordinating center, and participants gave informed consent. Measurement Protocol Trained staff measured blood pressure at each of three screening visits, on 2 days during the run-in period, and on 5 of the last 9 days of each intervention feeding period. Interim blood pressures were assessed once during each of the first 3 weeks of each intervention feeding period. During screening and the last week of each intervention feeding period, a 24-hour urine collection was obtained. Height and weight were measured, and body mass index was calculated. Baseline physical activity was measured by using a 7-day physical activity recall interview (16). Information on education level, income, alcohol consumption, and family history was obtained by using a questionnaire. Baseline blood pressure was defined as the average of the five preintervention blood pressures. End-of-feeding blood pressures were defined as the average of the five blood pressures at the end of each 30-day intervention feeding period. If no end-of-feeding blood pressure values were available (49 of 1236 possible cases), interim (n = 9) or screening (n = 40) blood pressures were used to impute end-of-feeding blood pressures. Definitions of Subgroups Ethnicity was categorized as African American versus other (primarily non-Hispanic white). Participants were considered hypertensive if their untreated baseline systolic blood pressure was 140 mm Hg or greater and their diastolic blood pressure was 90 mm Hg or greater. (Use of antihypertensive agents was an exclusion criterion [17].) Obesity was defined as body mass index of 30 kg/m2 or greater, and high-risk waist circumference was defined as greater than 102 cm in men and greater than 88 cm in women (18). Age, physical activity, baseline alcohol intake, baseline 24-hour urinary sodium level, and family income were dichotomized at the approximate median. Level of education was dichotomized as high school or less versus more than high school. Statistical Analysis The data were analyzed on an intention-to-treat basis. Given the differential effects of sodium on blood pressure observed in previous analyses among participants eating the DASH diet versus the control diet (15) and because power for subgroup analyses is more limited than for overall analysis, we focused our comparisons on the maximum contrasts (higher versus lower sodium intake with the control diet, DASH diet versus control diet at the higher sodium intake, and the combined effect of DASH diet and lower sodium intake versus control diet and higher sodium intake). We used generalized estimating equations (19) to fit linear models that predicted baseline and end-of-feeding blood pressures as a function of diet (DASH vs. control), sodium level, and subgroup indicators. Different ways of modeling the dietsodium effects and their interactions with the subgroup indicators were used to test specific hypotheses. In particular, two-way interactions of the various dietsodium effects with ethnicity, sex, hypertension status, and age were analyzed to determine the incremental effect on blood pressure in each of these subgroups while controlling for the main and incremental effects of the other subgroups. This model allowed us to estimate various diet-sodium contrasts for each of the 16 subgroups defined by hypertension status, ethnicity, sex, and age. A second set of models examined subgroup variables in a bivariate manner and did not assume simple additivity of subgroup effects. Finally, unadjusted subgroup analyses included main effects and interactions for a single subgroup indicator. All analyses were performed by using the xtgee procedure in Stata software, version 5 (Stata Corp., College Station, Texas) (20) and included adjustment for baseline blood pressure, site, feeding cohort, and carryover effects. An exchangeable covariance matrix was assumed for the repeated measurements for each participant. Unless otherwise stated, a P value less than 0.05 was significant, and all confidence intervals are 95% confidence intervals. Because subgroup analyses were planned to interpret and elucidate the overall study results, they are not adjusted for multiple comparisons. Results Of the 412 participants who underwent randomization, 390 (95%) completed the 12-week intervention feeding period. Adherence to the study diets seemed excellent, and body weight remained stable over time (15). Table 1 shows baseline characteristics of the 412 participants. Mean urinary sodium excretion at screening was 155 mmol/d, a value higher than that found while participants ate higher-sodium diets (142 mmol/d). Table 1. Characteristics of Study Sample Several key subgroups were highly interrelated. Women made up 70% of African-American participants but only 39% of non-African-American participants. Women were more likely to be hypertensive than were men. The percentage of both men and women with hypertension increased sharply with age among non-African-American participants (21% of those 45 years of age vs. 47% of those >45 years of age) but was equally high among older and younger African Americans (43% of those 45 years of age vs. 45% of those >45 years of age). These correlations highlight the potential for confounding in our results and, hence, the importance of the multivariate-adjusted analyses. Effects of the DASH Diet Table 2 shows the effect on systolic blood pressure of the DASH diet compared with the control diet du

Prehospital delay in patients hospitalized with heart attack symptoms in the United States: The REACT trial

BACKGROUND The use of thrombolytic therapy for patients with myocardial infarction has been limited by patient delay in seeking care. We sought to characterize prehospital delay in patients hospitalized for evaluation of heart attack symptoms. METHODS AND RESULTS The Rapid Early Action for Coronary Treatment (REACT) is a multicenter, randomized community trial designed to reduce patient delay. At baseline, data were abstracted from the medical records of 3783 patients hospitalized for evaluation of heart attack symptoms in 20 communities. The median prehospital delay was 2.0 hours; 25% of patients delayed longer than 5.2 hours. In a multivariable analysis, delay time was longer among non-Hispanic blacks than among non-Hispanic whites, longer at older ages, longer among Medicaid-only recipients and shorter among Medicare recipients than among privately insured patients, and shorter among patients who used an ambulance. CONCLUSIONS The observed pattern of differences is consistent with the contention that demographic, cultural, and/or socioeconomic barriers exist that impede rapid care seeking.

The Scientific Foundation for Personal Genomics: Recommendations from a National Institutes of Health–Centers for Disease Control and Prevention Multidisciplinary Workshop

The increasing availability of personal genomic tests has led to discussions about the validity and utility of such tests and the balance of benefits and harms. A multidisciplinary workshop was convened by the National Institutes of Health and the Centers for Disease Control and Prevention to review the scientific foundation for using personal genomics in risk assessment and disease prevention and to develop recommendations for targeted research. The clinical validity and utility of personal genomics is a moving target with rapidly developing discoveries but little translation research to close the gap between discoveries and health impact. Workshop participants made recommendations in five domains: (1) developing and applying scientific standards for assessing personal genomic tests; (2) developing and applying a multidisciplinary research agenda, including observational studies and clinical trials to fill knowledge gaps in clinical validity and utility; (3) enhancing credible knowledge synthesis and information dissemination to clinicians and consumers; (4) linking scientific findings to evidence-based recommendations for use of personal genomics; and (5) assessing how the concept of personal utility can affect health benefits, costs, and risks by developing appropriate metrics for evaluation. To fulfill the promise of personal genomics, a rigorous multidisciplinary research agenda is needed.

Effects of interventions in health care settings on physical activity or cardiorespiratory fitness

INTRODUCTION This paper reviews studies of physical activity interventions in health care settings to determine effects on physical activity and/or fitness and characteristics of successful interventions. METHODS Studies testing interventions to promote physical activity in health care settings for primary prevention (patients without disease) and secondary prevention (patients with cardiovascular disease [CVD]) were identified by computerized search methods and reference lists of reviews and articles. Inclusion criteria included assignment to intervention and control groups, physical activity or cardiorespiratory fitness outcome measures, and, for the secondary prevention studies, measurement 12 or more months after randomization. The number of studies with statistically significant effects was determined overall as well as for studies testing interventions with various characteristics. RESULTS Twelve studies of primary prevention were identified, seven of which were randomized. Three of four randomized studies with short-term measurement (4 weeks to 3 months after randomization), and two of five randomized studies with long-term measurement (6 months after randomization) achieved significant effect on physical activity. Twenty-four randomized studies of CVD secondary prevention were identified; 13 achieved significant effects on activity and/or fitness at twelve or more months. Studies with measurement at two time points showed decaying effects over time, particularly if the intervention were discontinued. Successful interventions contained multiple contacts, behavioral approaches, supervised exercise, provision of equipment, and/or continuing intervention. Many studies had methodologic problems such as low follow-up rates. CONCLUSION Interventions in health care settings can increase physical activity for both primary and secondary prevention. Long-term effects are more likely with continuing intervention and multiple intervention components such as supervised exercise, provision of equipment, and behavioral approaches. Recommendations for additional research are given.

Effect of Intensive Compared With Standard Glycemia Treatment Strategies on Mortality by Baseline Subgroup Characteristics: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial

OBJECTIVE To determine if baseline subgroups in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial can be identified for whom intensive compared with standard glycemia treatment had different effects on all-cause mortality. RESEARCH DESIGN AND METHODS Exploratory post hoc intention-to-treat comparisons were made between intensive and standard glycemia groups on all-cause mortality by subgroups defined by baseline characteristics. RESULTS There were few significant interactions between baseline characteristics and effects of intensive versus standard glycemia treatment on mortality: self-reported history of neuropathy (hazard ratio [HR] 1.95, 95% CI 1.41–2.69) versus no history of neuropathy (0.99, 0.79–1.26; P value for interaction 0.0008), higher A1C (A1C >8.5%: HR 1.64, 95% CI 1.22–2.22; A1C 7.5–8.4%: 1.00, 0.75–1.34; A1C <7.5%: 1.00, 0.67–1.50; P value for interaction 0.04), and aspirin use (HR 1.45, 95% CI 1.13–1.85, compared with 0.96, 0.72–1.27, in nonusers; P value for interaction 0.03). CONCLUSIONS We found a remarkable similarity of effect from intensive compared with standard glycemia treatment on mortality across most baseline subgroups. No differential effect was found in subgroups defined by variables anticipated to have an interaction: age, duration of diabetes, and previous history of cardiovascular disease. The three baseline characteristics that defined subgroups for which there was a differential effect on mortality may help identify patients with type 2 diabetes at higher risk of mortality from intensive regimens for glycemic control. Further research is warranted.