Short term e-bicycle riding results in favorable cardiometabolic shifts in moderately active adults.

PURPOSE: Electric bikes (EB) are a form of active transportation with demonstrated health benefits. The purpose of this study was to determine the influence of riding an EB for one week on indices of cardiometabolic health in middle-aged adults. METHODS: Adults (n = 22; age = 57.1 ± 11.3 year; BMI = 27.7 ± 4.9) participated in a 2 week study. During Week 1, participants were instructed to continue regular activities. Starting Week 2 participants were provided an EB to ride at least 3 days for a minimum of 30 min·day-1. Physical activity (PA) and glucose were measured continuously. Body composition, blood lipids, glucose, insulin, hemoglobin A1c (HbA1c), plasma endothelin-1 (ET-1), and carotid-femoral pulse wave velocity (cf-PWV) were measured on days 1 and 14.Data and Statistical analyses or Statistics. Each participant served as their own control. Paired t-tests compared dependent variables between week 1 (without EB) and week 2 (with EB). RESULTS: When provided an EB for one week, moderate to vigorous PA increased by 6-9 min·day-1 (P < 0.05) and sedentary time decreased by ~ 77 min·day-1 (P < 0.05). Data from 24 h continuous glucose monitoring showed the percentage of time in healthy range (70-120 mg·dl-1 glucose) increased (P < 0.05) from week 1 to week 2. Compared to day 1, cf-PWV was lower at day 14 (P < 0.05) following one week of riding an EB. CONCLUSION: Moderately-active, middleaged adults showed improved continuous glucose regulation and lower central arterial stiffness following one week of riding an EB.

Influence of time of day and intermittent aerobic exercise on vascular endothelial function and plasma endothelin-1 in healthy adults.

Reduced flow-mediated dilation (FMD) and elevated plasma endothelin-1 (ET-1) levels may contribute to the higher incidence of adverse cardiovascular events observed in the morning hours. A single bout of intermittent exercise abolishes the diurnal variation in FMD. Studies examining the effects of exercise on vascular and plasma ET-1 responses at different times of day are lacking. We determined the effects of time of day and intermittent aerobic exercise on brachial artery FMD and plasma ET-1 levels in healthy adults. We hypothesized that lower brachial artery FMD in the morning (compared to the afternoon) will be accompanied by higher plasma ET-1 levels. Additionally, we hypothesized that the diurnal variation in brachial artery FMD and plasma ET-1 will be abolished by performing a single bout of intermittent aerobic exercise. Utilizing a randomized, cross-over design, healthy adults [n = 12; 22 ± 4 y; 25.2 ± 2.7 kg/m2] completed two separate trials: morning (08:00 h) and afternoon (16:00 h). Brachial artery FMD and plasma ET-1 were measured prior to and immediately following a bout of intermittent cycling performed at 70% peak Watts. Brachial artery FMD was lower (P < .05) at 08:00 h (4.4 ± 3.4%) compared to 16:00 h (6.3 ± 3.7%), but was unaffected by exercise (4.8 ± 3.9% and 5.7 ± 2.2% for 08:00 h and 16:00 h, respectively). Plasma ET-1 was unaffected by time of day. Compared to pre-exercise, plasma ET-1 decreased (P < .01) at both times of day. Our data indicate that circulating ET-1 levels do not explain the lower morning FMD in healthy adults. Further, a bout of intermittent exercise did not affect brachial artery FMD but decreased plasma ET-1 levels.

Associations Among Physical Activity Level and Skeletal Muscle Antioxidants in Older Adults.

BACKGROUND: Endogenous antioxidants are critical to limiting cellular oxidative damage. METHODS: The authors determined if habitual physical activity (PA) and cardiorespiratory fitness were associated with skeletal muscle expression of endogenous antioxidants (superoxide dismutase, catalase, and glutathione peroxidase) and circulating oxidative stress markers (serum 8-hydroxy-2'-deoxyguanosine [8-OHdG]; oxidized low-density lipoprotein [LDL]) in older adults. Moderate to vigorous PA (MVPA) was estimated using a validated PA questionnaire in 26 older adults (mean [SD]; M/F = 9/17, age = 68 [4] y, body mass index = 26 [3] kg·m-2). Maximal oxygen consumption was estimated using the YMCA submaximal cycle test. Skeletal muscle endogenous antioxidants and serum 8-OHdG and oxidized LDL were measured. Bivariate and partial correlations (controlling for body mass index) were utilized to determine associations among variables. RESULTS: MVPA (1640 [1176] kcal·wk-1) was correlated with superoxide dismutase 2 (r = .55), catalase (r = .55), glutathione peroxidase 1 (r = .48), and 8-OHdG (r = -.41) (all Ps < .05), but not oxidized LDL. MVPA and 8-OHdG were not significantly correlated when controlling for body mass index (r = -.29). Estimated maximal oxygen consumption was correlated with glutathione peroxidase 1 (r = .48; P < .05). CONCLUSIONS: These data show that skeletal muscle endogenous antioxidant expression and circulating oxidative damage are associated with habitual MVPA in older adults. Thus, MVPA in older adults may be protective against reactive oxygen species damage due to higher expression of endogenous antioxidants.

Aerobic or resistance exercise performed the previous day does not attenuate postprandial hyperglycemia-induced endothelial dysfunction in overweight/obese adults.

INTRODUCTION: Postprandial hyperglycemia (PPH) impairs vascular endothelial function (VEF). A single bout of aerobic exercise (AE) attenuates PPH-induced decreases in brachial artery flow-mediated dilation (FMD), a non-invasive measure of VEF, in healthy adults for up to 17 h post-exercise. Studies examining the effects of resistance exercise (RE) on postprandial FMD responses are lacking. PURPOSE: We hypothesized that a single bout of exercise performed the prior evening would attenuate PPH-induced decreases in FMD, independent of exercise modality. METHODS: In a randomized, cross-over design, overweight/obese adults [n = 11 (8 women); 22 ± 4 years; 32.3 ± 5.8 kg m-2] completed 3 separate trials: control (seated rest), AE (30 min at ~ 60% VO2max), or whole-body RE (30 min, 6 exercises, 3 × 10-repetition maximum). Each trial occurred 14-17 h prior to an oral glucose tolerance test (OGTT). Brachial artery FMD and plasma glucose and insulin were measured prior to and at 30-min intervals for 2 h following the OGTT. Repeated-measures ANOVA and Bonferroni post hoc tests were used to evaluate differences within and between trials. RESULTS: Trials occurred 15.3 ± 1.0 h prior to the OGTT. Relative to baseline, FMD transiently decreased (P < 0.05) at 30-60 min post-ingestion, plasma glucose increased (P < 0.01) at 30-90 min post-ingestion, and plasma insulin increased (P < 0.01) at 30-120 min post-ingestion. No between trial differences were observed for FMD, glucose, or insulin. CONCLUSIONS: Aerobic or resistance exercise performed the evening prior to an OGTT does not attenuate postprandial decreases in brachial artery FMD in overweight/obese adults.

The Influence of Compression Socks During a Marathon on Exercise-Associated Muscle Damage.

CONTEXT: Compression socks have become increasingly popular with athletes due to perceived enhancement of exercise performance and recovery. However, research examining the efficacy of compression socks to reduce exercise-associated muscle damage has been equivocal, with few direct measurements of markers of muscle damage. OBJECTIVE: To examine the influence of compression socks worn during a marathon on creatine kinase (CK) levels. DESIGN: A randomized controlled trial. SETTING: 2013 Hartford Marathon, Hartford, CT. PARTICIPANTS: Adults (n = 20) randomized to control (CONTROL; n = 10) or compression sock (SOCK; n = 10) groups. MAIN OUTCOME MEASURES: Blood samples were collected 24 hours before, immediately after, and 24 hours following the marathon for the analysis of CK, a marker of muscle damage. RESULTS: Baseline CK levels did not differ between CONTROL (89.3 [41.2] U/L) and SOCK (100.0 [56.2] U/L) (P = .63). Immediately following the marathon (≤1 h), CK increased 273% from baseline (P < .001 for time), with no difference in exercise-induced changes in CK from baseline between CONTROL (+293.9 [278.2] U/L) and SOCK (+233.1 [225.3] U/L; P = .60 for time × group). The day following the marathon (≤24 h), CK further increased 1094% from baseline (P < .001 for time), with no difference in changes in CK from baseline between CONTROL (+ 1191.9 [1194.8] U/L) and SOCK (+889.1 [760.2] U/L; P = .53 for time × group). These similar trends persisted despite controlling for potential covariates such as age, body mass index, and race finishing time (Ps > .29). CONCLUSIONS: Compression socks worn during a marathon do not appear to mitigate objectively measured markers of muscle damage immediately following and 24 hours after a marathon.

Altering Physical Activity Influences Insulin Responses to Glucose Ingestion in Healthy Adults.

This study determined if varying physical activity (PA) the day prior to an oral glucose tolerance test (OGTT) differentially influenced postprandial glucose and insulin kinetics. Fifteen healthy, young adults participated in three OGTT trials the morning after performing 50% (LOW), 100% (HABITUAL), or 150% (HIGH) of their habitual PA (determined by 7-day pedometry). Trials were randomized and separated by at least 1-wk. For each OGTT trial, blood glucose and insulin were measured after an overnight fast and at 30-min intervals for 2 h following ingestion of the glucose beverage. Between-trial differences were analyzed using a general linear model with repeated measures. Subjects successfully achieved the desired percentage of habitual steps prior to each trial: LOW: 51±5%, HABITUAL: 99±6%, and HIGH: 149±9%. Fasting blood glucose and glucose total area under the curve (AUC) did not differ between trials. Serum insulin AUC was lower (p<0.05) following the HIGH (34,158±8,786 pmol·min·L-1) compared to the LOW (40,738±9,276 pmol·min·L-1) trial. No differences were observed when the LOW and HIGH trials were compared to HABITUAL. These data suggest that varying the PA level (from 50 to 150% of habitual PA) the day prior to an OGTT influences the insulin (but not blood glucose) response to an OGTT.

Age-related macular degeneration and progression of coronary artery calcium: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Age-related macular degeneration (AMD) shares many similarities with cardiovascular disease (CVD) pathophysiology. We sought to determine the relationship of AMD to the progression of coronary artery calcium (CAC) using data from the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: Our cohort consisted of 5803 adults aged 45 to 84 years free of known cardiovascular disease (CVD). Retinal photographs were taken during visit 2 (Aug 2002-Jan 2004). CAC was measured with computed tomography at visit 1 (July 2000-Aug 2002) and visit 5 (April 2010-Dec 2011) and changes between visits were determined. RESULTS: Participants were categorized as with (n = 244) and without AMD (n = 5559) at visit 2. At visit 5, 92 participants with and 2684 without AMD had CAC scores. Among those with detectable CAC at baseline (>0 at visit 1), CAC progression was greater in persons with compared to those without AMD after multivariable adjustment (530 ± 537 vs. 339 ± 426 Agatston units, P<0.01). CONCLUSIONS: The presence of AMD in a diverse population without known clinical CVD independently predicted higher 10-year CAC progression in participants with baseline CAC >0. The retinal exam might be a useful tool for pre-clinical assessment and prevention of CVD events.

Comparative Metabolomics Elucidates Postprandial Metabolic Modifications in Plasma of Obese Individuals with Metabolic Syndrome.

Although higher intakes of dairy milk are associated with a lower risk of metabolic syndrome (MetS), the underlying protective mechanism remains unclear. This study investigated the dynamic metabolic profile shift following the ingestion of low-fat milk or an isocaloric volume of rice milk in obese individuals with metabolic syndrome (MetS). In a randomized, double-blind, crossover study, postprandial plasma samples ( n = 266) were collected from 19 MetS participants. Plasma samples were analyzed by a targeted metabolomics platform which specifically detects 117 metabolites from 25 metabolic pathways. The comprehensive time-course metabolic profiling in MetS participants indicated that the postprandial metabolic profiles distinguish low-fat milk and rice milk consumption in a time-dependent manner. Metabolic biomarkers, such as orotate, leucine/isoleucine and adenine, showed significantly different trends in the two test beverages. Bayesian statistics identified 12 metabolites associated with clinical characteristics of postprandial vascular endothelial function, such as flow-mediated dilation (FMD), postprandial plasma markers of oxidative stress and NO status. Furthermore, metabolic pathway analysis based on these metabolite data indicated the potential utility of metabolomics to provide mechanistic insights of dietary interventions to regulate postprandial metabolic excursions.

Creatine supplementation does not alter the creatine kinase response to eccentric exercise in healthy adults on atorvastatin.

BACKGROUND: Serum creatine kinase (CK) levels are higher after eccentric, muscle-damaging exercise in statin-treated patients. This could contribute to the increased statin-associated muscle symptoms reported in physically active individuals. OBJECTIVE: We tested the hypothesis in this pilot study that creatine (Cr) monohydrate supplementation would reduce the CK response to eccentric exercise in patients using statins to determine if Cr supplementation could be a strategy to mitigate statin-associated muscle symptoms in physically active individuals. METHODS: Healthy, nonsmoking men (n = 5) and women (n = 14) were randomized to Cr monohydrate = atorvastatin 80 mg + 10 g Cr monohydrate (n = 10, age = 60 ± 7 years) or to placebo (PL) = atorvastatin 80 mg + PL (n = 9, age = 52 ± 6 years). After 4 weeks of treatment, subjects performed 45 minutes of eccentric exercise (downhill walking at a -15% grade). Serum CK levels, muscle soreness (visual analog scale after two squats), and muscle pain severity and interference (using the brief pain inventory) were measured before and after 4 weeks of treatment, and then for 4 consecutive days after downhill walking. Vitamin D, or serum 25(OH)D, was also measured at baseline. RESULTS: The PL group was younger (P = .01) but not otherwise different in blood lipids, vitamin D, CK, muscle visual analog scale, and pain scores before (all P > .21) or after (all P > .12) treatment. CK increased in all subjects after downhill walking (P < .01), but neither the relative peak change (expressed as group mean difference with 95% confidence intervals: 43.52% [-196.41, 283.45]) nor the absolute peak change (67.38 U/L [-121.55, 256.31]) relative to baseline was different between groups (P = .46 and .71, respectively). A similar lack of treatment effect was observed for muscle soreness (11.03 mm [-9.49, 31.55]), pain severity (0.77 pts [-0.95, 2.50]), and pain interference (1.02 pts [-1.25, 3.29]) with P-values for group comparisons = 0.27, 0.36, and 0.35, respectively. However, subjects with "insufficient" Vitamin D < 30 ng/mL (n = 10) had an ∼2-fold greater CK increase with eccentric exercise (nominal P-value = .04) than subjects with higher vitamin D levels. CONCLUSION: Cr monohydrate did not reduce CK increases after exercise in statin-treated subjects. We did observe that low vitamin D levels are associated with a greater CK response to eccentric exercise in statin-treated subjects.

Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death among adults with type 2 diabetes mellitus (T2D). We recently reported that glycemic control in patients with T2D can be significantly improved through a continuous care intervention (CCI) including nutritional ketosis. The purpose of this study was to examine CVD risk factors in this cohort. METHODS: We investigated CVD risk factors in patients with T2D who participated in a 1 year open label, non-randomized, controlled study. The CCI group (n = 262) received treatment from a health coach and medical provider. A usual care (UC) group (n = 87) was independently recruited to track customary T2D progression. Circulating biomarkers of cholesterol metabolism and inflammation, blood pressure (BP), carotid intima media thickness (cIMT), multi-factorial risk scores and medication use were examined. A significance level of P < 0.0019 ensured two-tailed significance at the 5% level when Bonferroni adjusted for multiple comparisons. RESULTS: The CCI group consisted of 262 participants (baseline mean (SD): age 54 (8) year, BMI 40.4 (8.8) kg m-2). Intention-to-treat analysis (% change) revealed the following at 1-year: total LDL-particles (LDL-P) (- 4.9%, P = 0.02), small LDL-P (- 20.8%, P = 1.2 × 10-12), LDL-P size (+ 1.1%, P = 6.0 × 10-10), ApoB (- 1.6%, P = 0.37), ApoA1 (+ 9.8%, P < 10-16), ApoB/ApoA1 ratio (- 9.5%, P = 1.9 × 10-7), triglyceride/HDL-C ratio (- 29.1%, P < 10-16), large VLDL-P (- 38.9%, P = 4.2 × 10-15), and LDL-C (+ 9.9%, P = 4.9 × 10-5). Additional effects were reductions in blood pressure, high sensitivity C-reactive protein, and white blood cell count (all P < 1 × 10-7) while cIMT was unchanged. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score decreased - 11.9% (P = 4.9 × 10-5). Antihypertensive medication use was discontinued in 11.4% of CCI participants (P = 5.3 × 10-5). The UC group of 87 participants [baseline mean (SD): age 52 (10) year, BMI 36.7 (7.2) kg m-2] showed no significant changes. After adjusting for baseline differences when comparing CCI and UC groups, significant improvements for the CCI group included small LDL-P, ApoA1, triglyceride/HDL-C ratio, HDL-C, hsCRP, and LP-IR score in addition to other biomarkers that were previously reported. The CCI group showed a greater rise in LDL-C. CONCLUSIONS: A continuous care treatment including nutritional ketosis in patients with T2D improved most biomarkers of CVD risk after 1 year. The increase in LDL-cholesterol appeared limited to the large LDL subfraction. LDL particle size increased, total LDL-P and ApoB were unchanged, and inflammation and blood pressure decreased. Trial registration Clinicaltrials.gov: NCT02519309. Registered 10 August 2015.

Replacing carbohydrate during a glucose challenge with the egg white portion or whole eggs protects against postprandial impairments in vascular endothelial function in prediabetic men by limiting increases in glycaemia and lipid peroxidation.

Eggs attenuate postprandial hyperglycaemia (PPH), which transiently impairs vascular endothelial function (VEF). We hypothesised that co-ingestion of a glucose challenge with egg-based meals would protect against glucose-induced impairments in VEF by attenuating PPH and oxidative stress. A randomised, cross-over study was conducted in prediabetic men (n 20) who ingested isoenegertic meals (1674 kJ (400 kcal)) containing 100 g glucose (GLU), or 75 g glucose with 1·5 whole eggs (EGG), seven egg whites (WHITE) or two egg yolks (YOLK). At 30 min intervals for 3 h, brachial artery flow-mediated dilation (FMD), plasma glucose, insulin, cholecystokinin (CCK), lipids (total, LDL- and HDL-cholesterol; TAG), F2-isoprostanes normalised to arachidonic acid (F2-IsoPs/AA), and methylglyoxal were assessed. In GLU, FMD decreased at 30-60 min and returned to baseline levels by 90 min. GLU-mediated decreases in FMD were attenuated at 30-60 min in EGG and WHITE. Compared with GLU, FMDAUC was higher in EGG and WHITE only. Relative to baseline, glucose increased at 30-120 min in GLU and YOLK but only at 30-90 min in EGG and WHITE. GlucoseAUC and insulinAUC were also lower in EGG and WHITE only. However, CCKAUC was higher in EGG and WHITE compared with GLU. Compared with GLU, F2-IsoPs/AAAUC was lower in EGG and WHITE but unaffected by YOLK. Postprandial lipids and methylglyoxal did not differ between treatments. Thus, replacing a portion of a glucose challenge with whole eggs or egg whites, but not yolks, limits postprandial impairments in VEF by attenuating increases in glycaemia and lipid peroxidation.

Compression Socks Worn During Flight and Hemostatic Balance in Boston Marathon Runners on Oral Contraceptives.

OBJECTIVE: To investigate the effect of oral contraceptive (OC) use and compression socks on hemostatic activation in women flying cross-country to and from a marathon. DESIGN: Prospective study. SETTING: 2015 Boston Marathon. PARTICIPANTS: Women were divided into non-OC using (CONTROL; n = 12), OC-using (OC; n = 15), and OC-using plus compression sock (OC + SOCK; n = 14) groups. INTERVENTION: Women in OC + SOCK wore compression socks during flights to and from the marathon. MAIN OUTCOME MEASURES: Venous blood samples were collected within 24 hours of arriving in Boston (EXPO), immediately after the marathon (RUN), and within 24 hours after a return flight home (Post-Flight) for analysis of thrombin-antithrombin complex (TAT), d-dimer, and tissue plasminogen activator (t-PA). RESULTS: TAT did not increase with exercise (P = 0.48) and was not affected by group (P = 0.08) or the interaction between these 2 factors (P = 0.80). Group, time, and their interaction were significant for d-dimer (all P < 0.05) such that d-dimer increased with acute exercise to a greater extent (Δ d-dimer from expo to postrace = 909.5 ± 1021.9 ng/mL) in the OC + SOCK group relative to OC (Δ d-dimer = 240.0 ± 178.5 ng/mL; P = 0.02) and CONTROL (Δ d-dimer = 230.3 ± 120.3 ng/mL; P = 0.02). There was a significant effect of time, group, and the interaction on t-PA (all P < 0.01) such that t-PA increased with acute exercise to a greater extent (Δ t-PA from expo to postrace = 19.6 ± 10.0 ng/mL) in the CONTROL group relative to OC (Δ t-PA = 4.0 ± 1.8 ng/mL; P < 0.01) and OC + SOCK (Δ t-PA = 3.3 ± 1.2 ng/mL; P < 0.01). CONCLUSIONS: Female runners using OCs did not exhibit disproportionately increased coagulation. The use of compression socks in women on OCs, surprisingly, resulted in a greater increase in d-dimer after exercise.

Effects of prior aerobic exercise on sitting-induced vascular dysfunction in healthy men.

INTRODUCTION: Acute aerobic exercise prevents sitting-induced impairment of flow-mediated dilation (FMD). Further, evidence suggests that sitting-induced impairment of FMD occurs via an oxidative stress-dependent mechanism that disrupts endothelial function. PURPOSE: We hypothesized that acute aerobic exercise would prevent impairment of femoral artery FMD by limiting oxidative stress responses that increase endothelin-1 (ET-1) levels and disrupt nitric oxide (NO) status. METHODS: In a randomized, cross-over study, healthy men (n = 11; 21.2 ± 1.9 years) completed two 3 h sitting trials that were preceded by 45 min of either quiet rest (REST) or a single bout of continuous treadmill exercise (65% maximal oxygen consumption) (EX). Superficial femoral artery FMD, plasma glucose, malondialdehyde (MDA), ET-1, arginine (ARG) and its related metabolites [homoarginine (HA), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA)] were assessed at baseline, 1 h following EX (or REST) (0 h), and at 1 h intervals during 3 h of uninterrupted sitting. Data were analyzed using repeated measures ANOVA. RESULTS: During REST, femoral artery FMD declined from baseline (2.6 ± 1.8%) at 1, 2, and 3 h of sitting and resting shear rate decreased at 3 h. In contrast, when sitting was preceded by EX, femoral artery FMD (2.7 ± 2.0%) and resting shear rate responses were unaffected. No between trial differences were detected for plasma glucose, MDA, ET-1, ARG, HA, ADMA, or SDMA. CONCLUSION: Prior aerobic exercise prevented the decline in femoral artery FMD that is otherwise induced by prolonged sitting independent of changes in oxidative stress, ET-1, and NO status.

Targeted High Performance Liquid Chromatography Tandem Mass Spectrometry-based Metabolomics differentiates metabolic syndrome from obesity.

Both obesity and the metabolic syndrome are risk factors for type 2 diabetes and cardiovascular disease. Identification of novel biomarkers are needed to distinguish metabolic syndrome from equally obese individuals in order to direct them to early interventions that reduce their risk of developing further health problems. We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to evaluate the associations between metabolite profiles and established metabolic syndrome criteria (i.e. elevated waist circumference, hypertension, elevated fasting glucose, elevated triglycerides, and low high-density lipoprotein cholesterol) in plasma samples from obese men ( n = 29; BMI = 35.5 ± 5.2 kg/m2) and women ( n = 40; 34.9 ± 6.7 kg/m2), of which 26 met the criteria for metabolic syndrome (17 men and 9 women). Compared to obese individuals without metabolic syndrome, univariate statistical analysis and partial least squares discriminant analysis showed that a specific group of metabolites from multiple metabolic pathways (i.e. purine metabolism, valine, leucine and isoleucine degradation, and tryptophan metabolism) were associated with the presence of metabolic syndrome. Receiver operating characteristic curves generated based on the PLS-DA models showed excellent areas under the curve (0.85 and 0.96, for metabolites only model and enhanced metabolites model, respectively), high specificities (0.86 and 0.93), and good sensitivities (0.71 and 0.91). Moreover, principal component analysis revealed that metabolic profiles can be used to further differentiate metabolic syndrome with 3 versus 4-5 metabolic syndrome criteria. Collectively, these findings support targeted metabolomics approaches to distinguish metabolic syndrome from obesity alone, and to stratify metabolic syndrome status based on the number of criteria met. Impact statement We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to evaluate the associations between metabolite profiles and established MetS criteria. To our best knowledge, the findings of this study provide the first evidence that metabolic profiles can be used to differentiate participants with MetS from similarly obese individuals who do not meet established criteria of MetS. Furthermore, the study demonstrated that within MetS participants, their unique metabolic profiles correlated to the number of criteria used for MetS determination. Taken together, this metabolic profiling approach can potentially serve as a novel tool for MetS detection and monitoring, and provide useful metabolic information for future interventions targeting obesity and MetS.

The antihypertensive effects of aerobic versus isometric handgrip resistance exercise.

BACKGROUND: Aerobic exercise reduces blood pressure (BP) on average 5-7 mmHg among those with hypertension; limited evidence suggests similar or even greater BP benefits may result from isometric handgrip (IHG) resistance exercise. METHOD: We conducted a randomized controlled trial investigating the antihypertensive effects of an acute bout of aerobic compared with IHG exercise in the same individuals. Middle-aged adults (n = 27) with prehypertension and obesity randomly completed three experiments: aerobic (60% peak oxygen uptake, 30 min); IHG (30% maximum voluntary contraction, 4 × 2 min bilateral); and nonexercise control. Study participants were assessed for carotid-femoral pulse wave velocity pre and post exercise, and left the laboratory wearing an ambulatory BP monitor. RESULTS: SBP and DBP were lower after aerobic versus IHG (4.8 ±â€Š1.8/3.1 ±â€Š1.3 mmHg, P = 0.01/0.04) and control (5.6 ±â€Š1.8/3.6 ±â€Š1.3 mmHg, P = 0.02/0.04) over the awake hours, with no difference between IHG versus control (P = 0.80/0.83). Pulse wave velocity changes following acute exercise did not differ by modality (aerobic increased 0.01 ±â€Š0.21 ms, IHG decreased 0.06 ±â€Š0.15 ms, control increased 0.25 ±â€Š0.17 ms, P > 0.05). A subset of participants then completed either 8 weeks of aerobic or IHG training. Awake SBP was lower after versus before aerobic training (7.6 ±â€Š3.1 mmHg, P = 0.02), whereas sleep DBP was higher after IHG training (7.7 ±â€Š2.3 mmHg, P = 0.02). CONCLUSION: Our findings did not support IHG as antihypertensive therapy but that aerobic exercise should continue to be recommended as the primary exercise modality for its immediate and sustained BP benefits.

Single Low-Density Lipoprotein Apheresis Does Not Improve Vascular Endothelial Function in Chronically Treated Hypercholesterolemic Patients.

Objective. To investigate vascular endothelial function (VEF) responses to a single low-density lipoprotein (LDL) apheresis session in hypercholesterolemic patients undergoing chronic treatment. Methods. We measured brachial artery flow-mediated dilation (FMD), plasma lipids, vitamin E (α- and γ-tocopherol), markers of oxidative/nitrative stress (malondialdehyde (MDA) and nitro-γ-tocopherol (NGT)), and regulators of NO metabolism (arginine (ARG) and asymmetric dimethylarginine (ADMA)) prior to (Pre) and immediately following (Post) LDL apheresis and at 1, 3, 7, and 14 d Post in 5 hypercholesterolemic patients (52 ± 11 y). Results. Relative to Pre, total cholesterol (7.8 ± 1.5 mmol/L) and LDL-cholesterol (6.2 ± 1.2 mmol/L) were 61% and 70% lower (P < 0.01), respectively, at Post and returned to Pre levels at 14 d. Brachial FMD responses (6.9 ± 3.6%) and plasma MDA, ARG, and ADMA concentrations were unaffected by LDL apheresis. Plasma α-tocopherol, γ-tocopherol, and NGT concentrations were 52-69% lower at Post (P < 0.01), and α-tocopherol remained 36% lower at 1 d whereas NGT remained 41% lower at d 3. Conclusions. Acute cholesterol reduction by LDL apheresis does not alter VEF, oxidative stress, or NO homeostasis in patients treated chronically for hypercholesterolemia.

Short-term cessation of statin therapy does not alter aerobic exercise performance in physically active middle-aged adults.

OBJECTIVES: Physically active adults may be especially vulnerable to the adverse muscular side effects of statins. We determined if short-term cessation of statin therapy would improve aerobic exercise performance in middle-aged adults engaged in regular aerobic exercise training. METHODS: Physically active middle-aged adults on statin therapy ≥6 mo (n = 16; 58 ± 10 y) or not taking lipid-lowering medications (controls) (n = 19; 51 ± 9 y) completed a peak oxygen consumption (VO2peak) and time to exhaustion test on a cycle ergometer 2-7 d apart. Tests were repeated following 1 mo of statin cessation or a 1 mo period for controls. Questionnaires were administered to assess exercise history and muscle complaints. RESULTS: Statin users reported little or no muscle complaints and participation in aerobic exercise was similar between groups (p≥0.13). The lower VO2peak (37.3 ± 9.0 vs. 43.1 ± 4.9 ml/kg/min; p = 0.02) and time to exhaustion (21.9 ± 4.4 vs. 26.0 ± 6.3 min; p = 0.04) in statin users versus controls did not persist after controlling for age (p≥0.08). Aerobic exercise performance did not change with 1 mo of statin cessation (p≥0.54). No changes were observed in controls when tests were repeated 1 mo later (p≥0.38). CONCLUSION: Short-term cessation of statin therapy does not alter maximal aerobic capacity or aerobic endurance in physically active middle-aged adults with few or no statin muscle complaints.

Effect of Simvastatin on Arterial Stiffness in Patients with Statin Myalgia.

Statins reduce arterial stiffness but are also associated with mild muscle complaints. It is unclear whether individuals with muscle symptoms experience the same vascular benefit or whether statins affect striated and smooth muscle cells differently. We examined the effect of simvastatin treatment on arterial stiffness in patients who did versus those who did not exhibit muscle symptoms. Patients with a history of statin-related muscle complaints (n = 115) completed an 8 wk randomized, double-blind, cross-over trial of daily simvastatin 20 mg and placebo. Serum lipids and pulse wave velocity (PWV) were assessed before and after each treatment. Muscle symptoms with daily simvastatin treatment were reported by 38 patients (33%). Compared to baseline, central PWV decreased (P = 0.01) following simvastatin treatment but not placebo (drug ∗ time interaction: P = 0.047). Changes in central PWV with simvastatin treatment were not influenced by myalgia status or time on simvastatin (P ≥ 0.15). Change in central PWV after simvastatin treatment was inversely correlated with age (r = -0.207, P = 0.030), suggesting that advancing age is associated with enhanced statin-mediated arterial destiffening. In patients with a history of statin-related muscle complaints, the development of myalgia with short-term simvastatin treatment did not attenuate the improvement in arterial stiffness.

The effect of compression socks worn during a marathon on hemostatic balance.

INTRODUCTION: Marathon running evokes parallel increases in markers of coagulation and fibrinolysis (i.e. hemostatic activation) immediately following strenuous, endurance exercise such that hemostatic balance is maintained. However, other factors incident to marathon running (i.e. dehydration, travel) may disproportionately activate the coagulatory system, increasing blood clot risk after an endurance event in otherwise healthy individuals. We investigated the effect of compression socks on exercise-induced hemostatic activation and balance in endurance athletes running the 2013 Hartford Marathon. METHODS: Adults (n = 20) were divided into compression sock (SOCK; n = 10) and control (CONTROL; n = 10) groups. Age, anthropometrics, vital signs, training mileage and finishing time were collected. Venous blood samples were collected 1 day before, immediately after and 1 day following the marathon for analysis of coagulatory (i.e. thrombin-antithrombin complex [TAT] and D-dimer) and fibrinolytic (i.e. tissue plasminogen activator [t-PA]) factors. RESULTS: Plasma D-dimer, TAT and t-PA did not differ between groups at baseline (p > 0.16). There were no significant group · time interactions (all p ≥ 0.17), however, average t-PA was lower in SOCK (8.9 ± 0.7 ng/mL) than CONTROL (11.2 ± 0.7 ng/mL) (p = 0.04). Average TAT also tended to be lower in SOCK (2.8 ± 0.2 µg/L) than CONTROL (3.4 ± 0.2 µg/L) (p = 0.07). CONCLUSIONS: Our results suggest that overall hemostatic activation (both coagulation and fibrinolysis) following a marathon tended to be lower with compression socks. Thus, compression socks do not adversely influence markers of hemostasis, appear safe for overall use in runners and may reduce exercise-associated hemostatic activation in individuals at risk for deep vein thrombosis.

Protective role of dairy and its constituents on vascular function independent of blood pressure-lowering activities.

Greater intakes of dairy are frequently associated with reduced risk of cardiovascular disease. These observational studies have served as the basis for controlled interventions aimed at defining the cardioprotective mechanisms of dairy. Understanding these relationships is of public health importance because most of the US population fails to meet dietary recommendations for dairy, suggesting that many individuals could lower their cardiovascular disease risk by relatively simple dietary modification. Clinical studies investigating the acute ingestion of dairy or its constituents, including short-term (≤2 week) supplementation studies or those assessing postprandial responses, have largely shown benefits on vascular function without concomitant improvements in blood pressure. Chronic interventions have been less conclusive, with some showing benefits and others indicating a lack of improvement in vascular function regardless of blood pressure changes. Vasoprotective activities of dairy are likely mediated through improvements in nitric oxide bioavailability, oxidative stress, inflammation, and insulin resistance. Future controlled studies are needed to determine if these health benefits are mediated directly by dairy or indirectly by displacing other dietary components that otherwise impair vascular health.