Uric acid as a predictor of weight gain and cardiometabolic health in the Study of Novel Approaches to Weight Gain Prevention (SNAP) study.

Young adulthood is often a period of substantial weight gain increasing risk for obesity and cardiometabolic disease. Uric acid (UA), a clinical marker of oxidative stress, is associated with cardiometabolic dysfunction in established CVD, type 2 diabetes, and CKD. Yet, few trials have examined UA as a predictor of cardiometabolic risk in young, healthy populations, particularly in the context of weight gain prevention intervention. The purpose of this ancillary study was to examine UA in the Study of Novel Approaches to Weight Gain Prevention (SNAP), a randomized, controlled trial of weight gain prevention strategies in young healthy adults. UA was examined as a predictor of weight and cardiometabolic outcomes over 6 years; the impact of weight gain prevention interventions on UA was also examined. We found that higher baseline UA was a significant predictor of less favorable BMI, triglycerides, HDL, glucose, insulin, and HOMA, independent of age, sex, baseline weight, baseline level of the outcome variable, and weight gain prevention intervention. Additionally, ≥1% weight loss was associated with lower UA. UA is a promising biomarker for future weight gain and cardiometabolic risk in young adults that may respond to weight gain prevention.Clinical trial registration: clinicaltrials.gov identifier NCT01183689.

Genetic Predictors of Change in Waist Circumference and Waist-to-Hip Ratio With Lifestyle Intervention: The Trans-NIH Consortium for Genetics of Weight Loss Response to Lifestyle Intervention.

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with waist circumference (WC) and waist-to-hip ratio (WHR) adjusted for BMI (WCadjBMI and WHRadjBMI), but it remains unclear whether these SNPs relate to change in WCadjBMI or WHRadjBMI with lifestyle intervention for weight loss. We hypothesized that polygenic scores (PS) comprised of 59 SNPs previously associated with central adiposity would predict less of a reduction in WCadjBMI or WHRadjBMI at 8-10 weeks in two lifestyle intervention trials, NUGENOB and DiOGenes, and at 1 year in five lifestyle intervention trials, Look AHEAD, Diabetes Prevention Program, Diabetes Prevention Study, DIETFITS, and PREDIMED-Plus. One-SD higher PS related to a smaller 1-year change in WCadjBMI in the lifestyle intervention arms at year 1 and thus predicted poorer response (ß = 0.007; SE = 0.003; P = 0.03) among White participants overall and in White men (ß = 0.01; SE = 0.004; P = 0.01). At average weight loss, this amounted to 0.20-0.28 cm per SD. No significant findings emerged in White women or African American men for the 8-10-week outcomes or for WHRadjBMI. Findings were heterogeneous in African American women. These results indicate that polygenic risk estimated from these 59 SNPs relates to change in WCadjBMI with lifestyle intervention, but the effects are small and not of sufficient magnitude to be clinically significant.

Food Liking-Based Diet Quality Indexes (DQI) Generated by Conceptual and Machine Learning Explained Variability in Cardiometabolic Risk Factors in Young Adults.

The overall pattern of a diet (diet quality) is recognized as more important to health and chronic disease risk than single foods or food groups. Indexes of diet quality can be derived theoretically from evidence-based recommendations, empirically from existing datasets, or a combination of the two. We used these methods to derive diet quality indexes (DQI), generated from a novel dietary assessment, and to evaluate relationships with cardiometabolic risk factors in young adults with (n = 106) or without (n = 106) diagnosed depression (62% female, mean age = 21). Participants completed a liking survey (proxy for usual dietary consumption). Principle component analysis of plasma (insulin, glucose, lipids) and adiposity (BMI, Waist-to-Hip ratio) measures formed a continuous cardiometabolic risk factor score (CRFS). DQIs were created: theoretically (food/beverages grouped, weighted conceptually), empirically (grouping by factor analysis, weights empirically-derived by ridge regression analysis of CRFS), and hybrid (food/beverages conceptually-grouped, weights empirically-derived). The out-of-sample CRFS predictability for the DQI was assessed by two-fold and five-fold cross validations. While moderate consistencies between theoretically- and empirically-generated weights existed, the hybrid outperformed theoretical and empirical DQIs in cross validations (five-fold showed DQI explained 2.6% theoretical, 2.7% empirical, and 6.5% hybrid of CRFS variance). These pilot data support a liking survey that can generate reliable/valid DQIs that are significantly associated with cardiometabolic risk factors, especially theoretically- plus empirically-derived DQI.

Deep-targeted sequencing of endothelial nitric oxide synthase gene exons uncovers exercise intensity and ethnicity-dependent associations with post-exercise hypotension.

In previous studies, we found an endothelial nitric oxide synthase gene (NOS3) variant rs2070744 associated with the ambulatory blood pressure (BP) response following bouts of moderate and vigorous intensity acute exercise, termed post-exercise hypotension (PEH). In a validation cohort, we sequenced NOS3 exons for associations with PEH Obese (30.9 ± 3.6 kg.m-2) African American (n = 14) [AF] and Caucasian (n = 9) adults 42.0 ± 9.8 years with hypertension (139.8 ± 10.4/84.6 ± 6.2 mmHg) performed three random experiments: bouts of vigorous and moderate intensity cycling and control. Subjects were attached to an ambulatory BP monitor for 19 h. We performed deep-targeted exon sequencing with the Illumina TruSeq Custom Amplicon kit. Variant genotypes were coded as number of minor alleles (#MA) and selected for additional statistical analysis based upon Bonferonni or Benjamini-Yekutieli multiple testing-corrected P-values under time-adjusted linear models for 19 hourly BP measurements for each subject. After vigorous intensity over 19 h, among NOS3 variants passing multiple testing thresholds, as the #MA increased in rs891512 (P = 6.4E-04), rs867225 (P = 6.5E-04), rs743507 (P = 2.6E-06), and rs41483644 (P = 2.4E-04), systolic (SBP) decreased from 17.5 to 33.7 mmHg; and in rs891512 (P = 9.7E-05), rs867225 (P = 2.6E-05), rs41483644 (P = 1.6E-03), rs3730009 (P = 2.6E-04), and rs77325852 (P = 5.6E-04), diastolic BP decreased from 11.1 mmHg to 20.3 mmHg among AF only. In contrast, after moderate intensity over 19 h in NOS3 rs3918164, as the #MA increased, SBP increased by 16.6 mmHg (P = 2.4E-04) among AF only. NOS3 variants exhibited associations with PEH after vigorous, but not moderate intensity exercise among AF only. NOS3 should be studied further for its effects on PEH in a large, ethnically diverse sample of adults with hypertension to confirm our findings.

Small Sample Sizes Confound Understanding of Cardiometabolic Responses to Exercise.

Considerable variability exists in the cardiometabolic disease biomarker response to exercise. We propose that a major contributor to this heterogeneity is underpowered studies due to small sample sizes. To test our hypothesis, we conducted a systematic review to identify meta-analyses/reviews of randomized controlled trials (RCT) and RCT that examined the cardiometabolic disease biomarker response to aerobic and resistance exercise.

Is Concurrent Training Efficacious Antihypertensive Therapy? A Meta-analysis.

: Aerobic exercise training and, to a lesser degree, dynamic resistance training, are recommended to lower blood pressure (BP) among adults with hypertension. Yet the combined influence of these exercise modalities, termed concurrent exercise training (CET), on resting BP is unclear. PURPOSE: This study aimed to meta-analyze the literature to determine the efficacy of CET as antihypertensive therapy. METHODS: Electronic databases were searched for trials that included the following: adults (>19 yr), controlled CET interventions, and BP measured pre- and postintervention. Study quality was assessed with a modified Downs and Black Checklist. Analyses incorporated random-effects assumptions. RESULTS: Sixty-eight trials yielded 76 interventions. Subjects (N = 4110) were middle- to older-age (55.8 ± 14.4 yr), were overweight (28.0 ± 3.6 kg·m), and had prehypertension (systolic BP [SBP]/diastolic BP [DBP] = 134.6 ± 10.9/80.7 ± 7.5 mm Hg). CET was performed at moderate intensity (aerobic = 55% maximal oxygen consumption, resistance = 60% one-repetition maximum), 2.9 ± 0.7 d·wk for 58.3 ± 20.1 min per session for 19.7 ± 17.8 wk. Studies were of moderate quality, satisfying 60.7% ± 9.4% of quality items. Overall, CET moderately reduced SBP (db = -0.32, 95% confidence interval [CI] = -0.44 to -0.20, -3.2 mm Hg) and DBP (db = -0.35, 95% CI = -0.47 to -0.22, -2.5 mm Hg) versus control (P < 0.01). However, greater SBP/DBP reductions were observed among samples with hypertension in trials of higher study quality that also examined BP as the primary outcome (-9.2 mm Hg [95% CI = -12.0 to -8.0]/-7.7 mm Hg [95% CI = -14.0 to -8.0]). CONCLUSIONS: Among samples with hypertension in trials of higher study quality, CET rivals aerobic exercise training as antihypertensive therapy. Because of the moderate quality of this literature, additional randomized controlled CET trials that examine BP as a primary outcome among samples with hypertension are warranted to confirm our promising findings.