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While racial variation in ambulatory blood pressure (BP) is known, patterns of diurnal dipping in the context of diabetic kidney disease have not been well defined. The authors sought to determine the association of race with nocturnal dipping status among participants with diabetic kidney disease enrolled in the STOP-DKD (Simultaneous Risk Factor Control Using Telehealth to Slow Progression of Diabetic Kidney Disease) trial. The primary outcome was nocturnal dipping-percent decrease in average systolic BP from wake to sleep-with categories defined as reverse dippers (decrease <0%), nondippers (0%-<10%), and dippers (≥10%). Twenty-four-hour ambulatory BP monitoring was completed by 108 participants (54% were nondippers, 24% were dippers, and 22% were reverse dippers). In adjusted models, the common odds of reverse dippers vs nondippers/dippers and reverse dippers/nondippers vs dippers was 2.6 (95% confidence interval, 1.2-5.8) times higher in blacks than in whites. Without ambulatory BP monitoring data, interventions that target BP in black patients may be unable to improve outcomes in this high-risk group., (©2017 Wiley Periodicals, Inc.)

Background: Calorie restriction (CR) retards aging and increases longevity in many animal models. However, it is unclear whether CR can be implemented in humans without adverse effects on body composition. Objective: We evaluated the effect of a 2-y CR regimen on body composition including the influence of sex and body mass index (BMI; in kg/m 2 ) among participants enrolled in CALERIE-2 (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), a multicenter, randomized controlled trial. Design: Participants were 218 nonobese (BMI: 21.9-28.0) adults aged 21-51 y who were randomly assigned to 25% CR (CR, n = 143) or ad libitum control (AL, n = 75) in a 2:1 ratio. Measures at baseline and 12 and 24 mo included body weight, waist circumference, fat mass (FM), fat-free mass (FFM), and appendicular mass by dual-energy X-ray absorptiometry; activity-related energy expenditure (AREE) by doubly labeled water; and dietary protein intake by self-report. Values are expressed as means ± SDs. Results: The CR group achieved 11.9% ± 0.7% CR over 2-y and had significant decreases in weight (-7.6 ± 0.3 compared with 0.4 ± 0.5 kg), waist circumference (-6.2 ± 0.4 compared with 0.9 ± 0.5 cm), FM (-5.4 ± 0.3 compared with 0.5 ± 0.4 kg), and FFM (-2.0 ± 0.2 compared with -0.0 ± 0.2 kg) at 24 mo relative to the AL group (all between-group P < 0.001). Moreover, FFM as a percentage of body weight at 24 mo was higher, and percentage of FM was lower in the CR group than in the AL. AREE, but not protein intake, predicted preservation of FFM during CR ( P < 0.01). Men in the CR group lost significantly more trunk fat ( P = 0.03) and FFM expressed as a percentage of weight loss ( P < 0.001) than women in the CR group. Conclusions: Two years of CR had broadly favorable effects on both whole-body and regional adiposity that could facilitate health span in humans. The decrements in FFM were commensurate with the reduced body mass; although men in the CR group lost more FFM than the women did, the percentage of FFM in the men in the CR group was higher than at baseline. CALERIE was registered at clinicaltrials.gov as NCT00427193., (© 2017 American Society for Nutrition.)

The doubly labeled water (DLW) method is considered the reference method for the measurement of energy expenditure under free-living conditions. However, the reproducibility of the DLW method in longitudinal studies is not well documented. This study was designed to evaluate the longitudinal reproducibility of the DLW method using 2 protocols developed and implemented in a multicenter clinical trial-the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE). To document the longitudinal reproducibility of the DLW method, 2 protocols, 1 based on repeated analysis of dose dilutions over the course of the clinical trial (dose-dilution protocol) and 1 based on repeated but blinded analysis of randomly selected DLW studies (test-retest protocol), were carried out. The dose-dilution protocol showed that the theoretical fractional turnover rates for (2)H and (18)O and the difference between the 2 fractional turnover rates were reproducible to within 1% and 5%, respectively, over 4.5 y. The Bland-Altman pair-wise comparisons of the results generated from 50 test-retest DLW studies showed that the fractional turnover rates and isotope dilution spaces for (2)H and (18)O, and total energy expenditure, were highly reproducible over 2.4 y. Our results show that the DLW method is reproducible in longitudinal studies and confirm the validity of this method to measure energy expenditure, define energy intake prescriptions, and monitor adherence and body composition changes over the period of 2.5-4.4 y. The 2 protocols can be adopted by other laboratories to document the longitudinal reproducibility of their measurements to ensure the long-term outcomes of interest are meaningful biologically. This trial was registered at clinicaltrials.gov as NCT00427193.

Theoretical calculations suggest that small daily reductions in energy intake can cumulatively lead to substantial weight loss, but experimental data to support these calculations are lacking. We conducted a 1-year randomized controlled pilot study of low (10%) or moderate (30%) energy restriction (ER) with diets differing in glycemic load in 38 overweight adults (mean +/- s.d., age 35 +/- 6 years; BMI 27.6 +/- 1.4 kg/m(2)). Food was provided for 6 months and self-selected for 6 additional months. Measurements included body weight, resting metabolic rate (RMR), adherence to the ER prescription assessed using (2)H(2)(18)O, satiety, and eating behavior variables. The 10%ER group consumed significantly less energy (by (2)H(2)(18)O) than prescribed over 12 months (18.1 +/- 9.8%ER, P = 0.04), while the 30%ER group consumed significantly more (23.1 +/- 8.7%ER, P < 0.001). Changes in body weight, satiety, and other variables were not significantly different between groups. However, during self-selected eating (6-12 months) variability in % weight change was significantly greater in the 10%ER group (P < 0.001) and poorer weight outcome on 10%ER was predicted by higher baseline BMI and greater disinhibition (P < 0.0001; adj R(2) = 0.71). Weight loss at 12 months was not significantly different between groups prescribed 10 or 30%ER, supporting the efficacy of low ER recommendations. However, long-term weight change was more variable on 10%ER and weight change in this group was predicted by body size and eating behavior. These preliminary results indicate beneficial effects of low-level ER for some but not all individuals in a weight control program, and suggest testable approaches for optimizing dieting success based on individualizing prescribed level of ER.

Background: There remains no consensus about the optimal dietary composition for sustained weight loss., Objective: The objective was to examine the effects of 2 dietary macronutrient patterns with different glycemic loads on adherence to a prescribed regimen of calorie restriction (CR), weight and fat loss, and related variables., Design: A randomized controlled trial (RCT) of diets with a high glycemic load (HG) or a low glycemic load (LG) at 30% CR was conducted in 34 healthy overweight adults with a mean (+/-SD) age of 35 +/- 6 y and body mass index (kg/m(2)) of 27.6 +/- 1.4. All food was provided for 6 mo in diets controlled for confounding variables, and subjects self-administered the plans for 6 additional months. Primary and secondary outcomes included energy intake measured by doubly labeled water, body weight and fatness, hunger, satiety, and resting metabolic rate., Results: All groups consumed significantly less energy during CR than at baseline (P < 0.01), but changes in energy intake, body weight, body fat, and resting metabolic rate did not differ significantly between groups. Both groups ate more energy than provided (eg, 21% and 28% CR at 3 mo and 16% and 17% CR at 6 mo with HG and LG, respectively). Percentage weight change at 12 mo was -8.04 +/- 4.1% in the HG group and -7.81 +/- 5.0% in the LG group. There was no effect of dietary composition on changes in hunger, satiety, or satisfaction with the amount and type of provided food during CR., Conclusions: These findings provide more detailed evidence to suggest that diets differing substantially in glycemic load induce comparable long-term weight loss.

Aims: To explore variations in invasive care of the elderly with acute coronary syndromes across international practice., Methods and Results: Using combined populations from the SYMPHONY and 2nd SYMPHONY trials, we describe 30-day cardiac catheterization in elderly (> or = 75 years; n = 1794) vs. younger patients (< 75 years; n = 14,043) after multivariable adjustment and by region of enrolment. The use of cardiac catheterization and revascularization were not protocol-specified. Elderly patients (median age 78 years) were more often female and more frequently had hypertension, diabetes, prior myocardial infarction, and prior coronary bypass surgery. Overall, they underwent less cardiac catheterization than younger patients [53 vs. 63%; adjusted OR 0.53 (0.46, 0.60)]. The absolute rate of cardiac catheterization in the elderly varied from 77% (vs. 91% in younger patients) in the US cohort to 27% (vs. 41% in younger patients) in the non-US cohort. Revascularization of elderly who underwent cardiac catheterization was also higher in US than non-US cohorts (71.3 vs. 53.6%). There was a significant interaction between the patient age and the use of catheterization across US and non-US regions of enrolment, as well as differences in the predictors of catheterization in the elderly. Despite these findings, after adjustment, 90-day rates of death and death or myocardial infarction (MI) were not significantly different in elderly who underwent catheterization compared with those who did not., Conclusion: Although older age is universally predictive of lower use of cardiac catheterization, marked variation in catheterization of the elderly exists across international practice. Demonstrated differences in patterns of use suggest a lack of consensus regarding optimal use of an invasive strategy in the elderly.

Background: Chronic kidney disease (CKD) is highly prevalent in patients with cardiovascular disease. We explored the associations of CKD with outcomes using combined data from two large acute coronary syndrome (ACS) trials. We also explored the associations of CKD with prescription patterns for common cardiovascular medications and the association of these prescription patterns with clinical outcomes., Methods: Patients were stratified by CKD stage using creatinine clearance (CrCl, ml/min) estimated by the modified MDRD equation using baseline core laboratory creatinine measures. Serum creatinine > or =1.5 mg/dl was an exclusion criterion for the SYMPHONY trials. Baseline characteristics and outcomes across CKD categories were compared and Cox proportional hazards regression was used to assess the relationship of renal insufficiency with clinical outcomes after adjusting for previously identified outcome predictors. Interactions between the use of specific medications and calculated CrCl were tested in the final Cox proportional hazards model predicting time to mortality., Results: Of 13 707 patients analysed, 6840 had CKD stage I (CrCl > or =90 ml/min), 5909 stage II (CrCl 60-89 ml/min), 955 stage III (CrCl 30-59 ml/min) and three stage IV (CrCl <30 ml/min). Patients with more advanced CKD (III) were older, more often female, non-smokers and more likely to have co-morbid diseases including diabetes mellitus, hypertension and congestive heart failure. Cardiovascular medications were used less frequently in patients with CKD. Unadjusted survival was poorer in patients with CKD stages > or =II. In adjusted analyses, for those with CrCl < or =91, each 10 ml/min increase in CrCl was associated with a significantly decreased risk of mortality (hazards ratio 0.897, 95% confidence interval 0.815-0.986) (P = 0.024). The interaction between use of angiotensin-converting enzyme (ACE) inhibitors and CrCl was significantly associated with outcomes; the benefit of drug therapy was greater among patients with CKD., Conclusions: CKD is an independent predictor of risk among ACS patients, and is associated with less frequent use of proven medical therapies. More aggressive use of conventional cardiovascular therapies in patients with CKD and ACS may be warranted.

Aims: We investigated predictors of 90-day risk among patients surviving the early period after an acute coronary syndrome (ACS)., Methods and Results: The study population included 15 904 stabilized ST-segment elevation or non-ST-segment elevation ACS patients randomized in SYMPHONY and 2nd SYMPHONY. We developed risk models for death, death or myocardial infarction (MI), and death, MI, or severe recurrent ischaemia (SRI) using Cox proportional-hazards techniques. Demographic, history, and pre-randomization clinical and medication variables were tested. Validation techniques included development of individual trial models, backward elimination and bootstrapping. Of 118 variables, 17 independently predicted mortality. The strongest associations included greater age (chi(2)=31.1), higher randomization heart rate (chi(2)=27.4), and heart failure (HF) variables (HF between qualifying event and randomization, chi(2)=21.8; history of HF, chi(2)=12.2). Higher creatinine clearance (chi(2)=17.7) and percutaneous coronary intervention between qualifying event and randomization (chi(2)=11.1) most strongly predicted lower risk. Similar characteristics entered the double and triple composite models, but HF variables and age less strongly predicted these end-points., Conclusions: In patients stabilized after ACS, those at highest risk over the next 90 days can be identified. Typical clinical markers are better at identifying risk of death than non-fatal MI or SRI. Novel risk markers are needed for these outcomes.