A Preliminary Investigation into the Frequency Dose Effects of High-Intensity Functional Training on Cardiometabolic Health.

The objective of this study was to explore the effects of three weekly frequency doses of high-intensity functional training (HIFT) on an array of cardiometabolic markers in adults with metabolic syndrome (MetS). Twenty-one men and women, randomized into one (HIFT1), two (HIFT2), or three (HIFT3) days per week of HIFT, completed 3-weeks of familiarization plus a 12-week progressive training program. Pre- and post-intervention, several cardiometabolic, body composition, oxygen consumption, metabolic syndrome severity, and perceptions of fitness measurements were assessed. Additionally, an exercise enjoyment survey was administered post-intervention. A Cohen's d was used to demonstrate within-group change effect size. Although this study was not fully powered, a one-way and two-way ANOVA were used to compare the dose groups to provide provisional insights. No differences were found when frequency dose groups were compared. Many cardiometabolic, body composition, and fitness improvements were seen within each group, with clinically meaningful improvements in the metabolic syndrome severity score (MSSS) (HIFT1: -0.105, d = 0.28; HIFT2: -0.382, d = 1.20; HIFT3: -0.467, d = 1.07), waist circumference (HIFT1: -4.1cm, d = 3.33; HIFT2: -5.4cm, d = 0.89; HIFT3: -0.7cm, d = 0.20), and blood glucose (HIFT1: -9.5mg/dL, d = 0.98; HIFT2: -4.9mg/dL, d = 1.00; HIFT3: -1.7mg/dL, d = 0.23). All three groups similarly reported high exercise enjoyment and likeliness to continue after the intervention. In conclusion, HIFT performed once, twice, or thrice a week elicits improvements in MetS and is considered enjoyable. HIFT, even at a low weekly dose, therefore represents a potential strategy to reduce the global MetS burden.

The Effects of a Single Session of High Intensity Functional Training on Energy Expenditure, VO2, and Blood Lactate.

High intensity functional training (HIFT) provides a potential option to meet public exercise recommendations for both cardiorespiratory and strength outcomes in a time efficient manner. To better understand the potential for HIFT as an exercise approach, energy expenditure (EE) and relative intensity need quantifying. In thirteen sedentary men and women with metabolic syndrome (MetS), we used both indirect calorimetry and blood lactate levels to calculate EE of a single session of HIFT. The HIFT session included four, 6-minute sets of consecutive functional exercises. Examples of the exercises involved were squats, deadlifts, suspension rows, suspension chest press, and planks. Intensity is described relative to individual ventilatory thresholds. The total group EE was 270.3 ± 77.3 kcal with approximately 5% attributed anaerobic energy production. VO2 ranged between 88.8 ± 12.3% and 99 ± 12% of the second ventilatory threshold (VT2), indicating a vigorous effort. After each work interval, peak blood lactate ranged between 7.9 ± 1.9 and 9.3 ± 2.9 mmol, and rate of perceived exertion between 6.9 ± 1.0 and 8.7 ± 0.8 arbitrary units from 1-10. These were achieved in approximately 46 minutes of exercise per participant. In conclusion, HIFT elicits the energy expenditure and effort requisite to result in the adaptive responses to produce the known suite of benefits of exercise for individuals with MetS.

Impacts of circulating microRNAs in exercise-induced vascular remodeling.

Cardiovascular adaptation underlies all athletic training modalities, with a variety of factors contributing to overall response during exercise-induced stimulation. In this regard the role of circulating biomarkers is a well-established and invaluable tool for monitoring cardiovascular function. Specifically, novel biomarkers such as circulating cell free DNA and RNA are now becoming attractive tools for monitoring cardiovascular function with the advent of next generation technologies that can provide unprecedented precision and resolution of these molecular signatures, paving the way for novel diagnostic and prognostic avenues to better understand physiological remodeling that occurs in trained versus untrained states. In particular, microRNAs are a species of regulatory RNAs with pleiotropic effects on multiple pathways in tissue-specific manners. Furthermore, the identification of cell free microRNAs within peripheral circulation represents a distal signaling mechanism that is just beginning to be explored via a diversity of molecular and bioinformatic approaches. This article provides an overview of the emerging field of sports/performance genomics with a focus on the role of microRNAs as novel functional diagnostic and prognostic tools, and discusses present knowledge in the context of athletic vascular remodeling. This review concludes with current advantages and limitations, touching upon future directions and implications for applying contemporary systems biology knowledge of exercise-induced physiology to better understand how disruption can lead to pathology.

Endothelial Vasodilation After a High-Volume Training Load and Tapered Training in Collegiate Female Swimmers.

ABSTRACT: Weihl, FM and Van Guilder, GP. Endothelial vasodilation after a high-volume training load and tapered training in collegiate female swimmers. J Strength Cond Res 35(3): 811-818, 2021-High-volume endurance training loads have been linked to adverse remodeling of the heart and large arteries; yet, data on the vascular endothelial function are unclear. Moreover, although collegiate-level endurance athletes often perform high-volumes of vigorous endurance training and resistance training as part of their strength and conditioning programs, it is unknown whether they also experience vascular abnormalities, particularly changes in endothelial function. The aim of this study was to verify the impact of a high-volume training load phase followed by low-volume tapered training on endothelial vasodilator function in National Collegiate Athletic Association (NCAA) Division I competitive female swimmers. Microvascular endothelial vasodilation was assessed by pulse arterial tonometry that provides a reactive hyperemia index in 10 female NCAA Division 1 swimmers after 4 weeks of a high-volume training load, and subsequently, after 3 weeks of low-volume tapered training as part of preparation for annual conference championships. The reactive hyperemia index was calculated as the ratio of the pulse volume amplitude after 5 minutes of left-arm brachial artery ischemia to the baseline amplitude, divided by same ratio in the contralateral arm. The high-volume training load included a 4-week block of dual-day sessions (120 minutes per practice) consisting of vigorous intensity endurance and high-intensity interval/sprint swim training, coupled with 5K running, resistance training, and Olympic weightlifting. Tapered training consisted of 3 weeks of 3-5 swims per week at ∼50% V̇o2max for 60 minutes per practice (∼4,000 minutes per practice). The reactive hyperemia index (1.73 ± 0.50) was low in athletes after the high-volume training load with 8 athletes demonstrating endothelial dysfunction. However, after tapered training, the reactive hyperemia index was ∼33% higher (2.29 ± 0.43; 95% confidence interval [CI]: 1.98-2.60, p = 0.0223 vs. the high-volume training load). Effect size, as expressed by the partial eta2 (0.46) and Cohen's dz (1.1923; 95% CI: 0.1687-2.4643) with tapered training, was large. These results demonstrate distinct differences in endothelial vasodilation after 4 weeks of a high-volume training load compared with a 3-week taper in NCAA Division I female swimmers.

Correction to: Association of HIV-infection, antiretroviral treatment and metabolic syndrome with large artery stiffness: a cross-sectional study.

Following publication of the original article [1], the authors reported that they have provided the wrong caption.

Association of HIV-infection, antiretroviral treatment and metabolic syndrome with large artery stiffness: a cross-sectional study.

BACKGROUND: Effective combined antiretroviral therapy (cART) has improved life expectancy among people living with HIV-1 infection. Treated HIV-1infection increases the prevalence of metabolic syndrome (MS). Despite sub-Saharan Africa having among the highest rates of HIV-1 infection, the effects of MS in HIV-1-infected individuals on cardiovascular risk is poorly explored. The aim of the study was to assess whether MS and/or HIV-1 treatment correlates with large elastic artery stiffness in HIV-1-infected patients treated with first-line cART. METHODS: The study sample comprised of 102 subjects free of cardiovascular disease and major risk factors divided into two groups based on HIV-1 infection, treatment, and MS status: HIV-1+/cART+/MS+ (n = 12); HIV-1+/cART-/MS+ (n = 16); HIV-1-/ MS+ (n = 10); HIV-1+/cART+/MS- (n = 42); HIV-1+/cART-/MS- (n = 32); HIV-1-/ MS- (n = 39). MS was established according the International Diabetes Federation definition. Large artery stiffness was measured using applanation tonometry to assess aortic pulse wave velocity (aPWV) and aortic augmentation index at heart rate of 75 bpm (AIx@HR75). cART included lamivudine/zidovudine and nevirapine or efavirenz. RESULTS: The prevalence of MS in the HIV-1-infected patients was 28%. There were no significant differences in aPWV in the non-MS groups. However, in subjects with MS, aPWV was significantly higher in the HIV-1 cART patients (9.0 ± 1.9 m/s) compared with both controls (7.5 ± 1.8 m/s; P = 0.018) and untreated HIV-1 patients (7.7 ± 1.3 m/s; P = 0.023), and these differences remained after adjustment for blood pressure and sex. Aortic PWV was significantly elevated (P = 0.009) in HIV-1 cART patients with MS compared to their counterparts without MS. Untreated HIV-1 patients with MS also demonstrated increased aPWV compared to their counterparts without MS (P = 0.05). Aortic AIx@HR75 was, on average, ~ 5% higher in HIV-1 cART patients with MS (28.3 ± 62% compared with untreated HIV-1 patients with MS (23.5 ± 9%; P = 0.075). Sub-group multivariate analysis identified MS as an independent predictor of increased aPWV in HIV-1 cART patients. CONCLUSIONS: Our study established that presence of MS in HIV-1 patients on treatment was associated with increased aPWV and hence increased arterial stiffness in sub-Saharan African HIV-1 patients on first-line cART.

No influence of ischemic preconditioning on running economy.

PURPOSE: Many of the potential performance-enhancing properties of ischemic preconditioning suggest that the oxygen cost for a given endurance exercise workload will be reduced, thereby improving the economy of locomotion. The aim of this study was to identify whether ischemic preconditioning improves exercise economy in recreational runners. METHODS: A randomized sham-controlled crossover study was employed in which 18 adults (age 27 ± 7 years; BMI 24.6 ± 3 kg/m2) completed two, incremental submaximal (65-85% VO2max) treadmill running protocols (3 × 5 min stages from 7.2-14.5 km/h) coupled with indirect calorimetry to assess running economy following ischemic preconditioning (3 × 5 min bilateral upper thigh ischemia) and sham control. Running economy was expressed as mlO2/kg/km and as the energy in kilocalories required to cover 1 km of horizontal distance (kcal/kg/km). RESULTS: Ischemic preconditioning did not influence steady-state heart rate, oxygen consumption, minute ventilation, respiratory exchange ratio, energy expenditure, and blood lactate. Likewise, running economy was similar (P = 0.647) between the sham (from 201.6 ± 17.7 to 204.0 ± 16.1 mlO2/kg/km) and ischemic preconditioning trials (from 202.8 ± 16.2 to 203.1 ± 15.6 mlO2/kg/km). There was no influence (P = 0.21) of ischemic preconditioning on running economy expressed as the caloric unit cost (from 0.96 ± 0.12 to 1.01 ± 0.11 kcal/kg/km) compared with sham (from 1.00 ± 0.10 to 1.00 ± 0.08 kcal/kg/km). CONCLUSIONS: The properties of ischemic preconditioning thought to affect exercise performance at vigorous to severe exercise intensities, which generate more extensive physiological challenge, are ineffective at submaximal workloads and, therefore, do not change running economy.

Menstrual Cycle and the Protective Effects of Ischemic Preconditioning Against Endothelial Ischemia/Reperfusion Injury: Comparison with Postmenopausal Women.

The aim of this study was to determine whether the capacity of remote ischemic preconditioning (IPC) against endothelial ischemia/reperfusion (I/R) injury changes across the menstrual cycle in premenopausal women, and to compare IPC responses to postmenopausal women. Thirty-five women were studied (22 premenopausal/13 postmenopausal). Changes in endothelial function were determined during the early follicular versus the late follicular phase (after positive urine ovulation test; Study 1); versus the mid-luteal phase (after positive urine progesterone test; Study 2); and versus estrogen-deficient postmenopausal women; Study 3). Endothelium-dependent vasodilation was assessed by the forearm blood flow (FBF) to reactive hyperemia with/without I/R injury with remote IPC (3×5 min cycles of upper arm ischemia). In the premenopausal women, peak FBF responses during the early follicular phase were blunted 20% (P<0.0001) with I/R injury (from baseline: 23.4±6.2 to 19.5±4.9 ml/100 ml tissue/min) compared with the late follicular/mid-luteal phases despite IPC. In postmenopausal women, peak FBF was diminished (from: 21.1±5.1 to 17.2±4.4 ml/100 ml tissue/min), and total FBF (area under the curve) was decreased a third (-32%; P<0.001) with I/R injury. Protection from I/R injury was preserved during the late follicular (from baseline: 21.7±5.3 to 24.8±5.9 ml/100 ml tissue/min; P=0.109), and mid-luteal phases (from: 25.1±3.9 to 27.2±5.7 ml/100 ml tissue/min; P=0.267). Reduced estrogen during the early follicular phase, and the rise in estrogen associated with ovulation and the mid-luteal phase, may contribute to changes in IPC-mediated protection in premenopausal women, and sheds light about how cardioprotection may change with ovarian hormone deficiency with the menopause transition.

Primary prevention of metabolic syndrome in the community using an evidence-based exercise program.

OBJECTIVES: The purpose of the present study was to examine the effectiveness of a community-based exercise program to lower metabolic syndrome (MetS) risk factors. METHODS: MetS components were retrospectively analyzed in 332 adults (190 women, 142 men) before and after a 14-week supervised community exercise program between January 2007 and May 2012 at the University of Wisconsin-Eau Claire. RESULTS: Except for total cholesterol, all health outcome variables, including the 5 MetS components, improved following community exercise. Individuals having MetS decreased from 22.3% before participation to 13.5% at end (p<0.05), while prevalence of participants with no MetS components increased 56% (from 65 to 102; p<0.05). Compared to the lowest quartile of relative energy expenditure, participants with the highest quartile were 6.4 (95% CI 1.8-23.2; p<0.05), 7 (95% CI 2.5-20.0; p<0.05) and 9.3 (95% CI 2.6-34.0; p<0.05) times more likely to eliminate low-HDL cholesterol, impaired fasting glucose, and low cardiorespiratory fitness as MetS risk factors, respectively. CONCLUSION: A community exercise program is an effective method to reduce cardiovascular risk in adults by substantially decreasing the prevalence of MetS and its components. Greater volumes of exercise may increase the likelihood of MetS risk factor elimination.

Changes in Choline Metabolites and Ceramides in Response to a DASH-Style Diet in Older Adults.

This feeding trial evaluated the impact of the Dietary Approaches to Stop Hypertension diet on changes in plasma choline, choline metabolites, and ceramides in obese older adults; 28 adults consumed 3oz (n = 15) or 6oz (n = 13) of beef within a standardized DASH diet for 12 weeks. Plasma choline, betaine, methionine, dimethylglycine (DMG), phosphatidylcholine (PC), lysophosphotidylcholine (LPC), sphingomyelin, trimethylamine-N-oxide (TMAO), L-carnitine, ceramide, and triglycerides were measured in fasted blood samples. Plasma LPC, sphingomyelin, and ceramide species were also quantified. In response to the study diet, with beef intake groups combined, plasma choline decreased by 9.6% (p = 0.012); DMG decreased by 10% (p = 0.042); PC decreased by 51% (p < 0.001); total LPC increased by 281% (p < 0.001); TMAO increased by 26.5% (p < 0.001); total ceramide decreased by 22.1% (p < 0.001); and triglycerides decreased by 18% (p = 0.021). All 20 LPC species measured increased (p < 0.01) with LPC 16:0 having the greatest response. Sphingomyelin 16:0, 18:0, and 18:1 increased (all p < 0.001) by 10.4%, 22.5%, and 24%, respectively. In contrast, we observed that sphingomyelin 24:0 significantly decreased by 10%. Ceramide 22:0 and 24:0 decreased by 27.6% and 10.9% (p < 0.001), respectively, and ceramide 24:1 increased by 36.8% (p = 0.013). Changes in choline and choline metabolites were in association with anthropometric and cardiometabolic outcomes. These findings show the impact of the DASH diet on choline metabolism in older adults and demonstrate the influence of diet to modify circulating LPC, sphingomyelin, and ceramide species.

The Effect of Acetaminophen on Running Economy and Performance in Collegiate Distance Runners.

Acetaminophen (ACT) may decrease perception of pain during exercise, which could allow runners to improve running economy (RE) and performance. The aim of this study was to determine the effects of ACT on RE and 3 km time trial (TT) performance in collegiate distance runners. A randomized, double blind, crossover study was employed in which 11 track athletes (9M/2F; age: 18.8 ± 0.6 years; VO2 max: 60.6 ± 7.7 mL/kg/min) completed three intervention sessions. Participants ingested either nothing (baseline, BSL), three gelatin capsules (placebo, PLA), or three 500 mg ACT caplets (ACT). One hour after ingestion, participants completed a graded exercise test consisting of 4 × 5 min steady-state stages at ~55-75% of VO2 max followed by a 3 km TT. There was no influence of ACT on RE in any stage. Similarly, ACT did not favorably modify 3 km TT performance [mean ± SD: BSL = 613 ± 71 s; PLA = 617 ± 70 s; ACT = 618 ± 70 s; p = 0.076]. The results indicate that ACT does not improve RE or TT performance in collegiate runners at the 3 km distance. Those wanting to utilize ACT for performance must understand that ACT's benefits have yet to be significant amongst well-trained runners. Future studies should examine the effects of ACT on well-trained runners over longer trial distances and under more controlled conditions with appropriate medical oversight.

Decreased myostatin in response to a controlled DASH diet is associated with improved body composition and cardiometabolic biomarkers in older adults: results from a controlled-feeding diet intervention study.

BACKGROUND: Elevated concentrations of myostatin inhibit muscle growth, function and strength. Myostatin is a mediator of sarcopenia and is associated with insulin resistance. For this study we tested the response of a calorie-restricted Dietary Approaches to Stop Hypertension (DASH) diet on changes in myostatin, follistatin, and mystatin:follistatin ratio levels after 12 weeks in comparison to basline in adults aged 65 years and older. Furthermore we evaluated correlations between changes in myostatin, body composition and cardiometabolic biomarkers in this cohort of older adults. METHODS: This was a controlled-feeding diet intervention study in which females (n = 17) and males (n = 11) aged 65 years and older consumed either 85 g (n = 15) or 170 g (n = 13) of fresh lean beef within a standardized DASH diet for 12-weeks. Myostatin and follistatin concentrations were measured from fasted blood samples collected at 5 timepoints throughout the 12-week feeding intervention period. Correlations were assessed between changes in myostatin and follistatin levels and measures of body composition and cardiometabolic biomarkers. RESULTS: There were no differences (p > 0.05) in circulating myostatin or follistatin levels between the beef intake groups. However, with beef groups combined myostatin decreased by 17.6% (p = 0.006) and the myostatin-to-follistatin ratio decreased by 16.5% (p < 0.001) in response to the study diet. Decreased myostatin was positively correlated with reductions in waist circumference (R2 = 0.163; p = 0.033) and fat mass (R2 = 0.233; p = 0.009). There was an inverse relationship between decreased myostatin and increased strength-to-weight ratio (R2 = 0.162; p = 0.034). The change in myostatin-to-follistatin ratio was associated with the change in skeletal muscle mass-to-fat mass ratio (R2 = 0.176; p = 0.026). Decreased myostatin was positively correlated with reductions in total cholesterol (R2 = 0.193; p = 0.012), LDL-C (R2 = 0.163; p = 0.031), insulin (R2 = 0.234; p = 0.009), and HOMA-IR (R2 = 0.248; P = 0.007). There was no change (p > 0.05) in circulating follistatin concentrations in response to the diet intervention. CONCLUSIONS: The outcomes from this study suggest that a calorie-restricted DASH diet has the potential to reduce myostatin concentrations in older adults. Furthermore these outcomes support interrelationships between myostatin, body composition and cardiometabolic health in adults aged 65 years and older. TRIAL REGISTRATION: ClinicalTrials.gov; Identifier: NCT04127240 ; Registration Date: 15/10/ 2019.

Plasma fatty acid responses to a calorie-restricted, DASH-style diet with lean beef.

BACKGROUND: Plasma fatty acid (FA) levels are used as biomarkers of health outcomes and nutritional intake. METHODS: This was an exploratory analysis of the plasma FA profile from a parallel-designed, controlled-feeding study in older, obese adults (females, n = 17; males, n = 11) consuming a DASH-based diet with two levels of lean beef (3oz and 6oz per day). Plasma FA levels (as percent composition) were measured by gas chromatography from five timepoints over the 12-week intervention. The primary plasma FA change patterns modeled were sustained (initial change to 'new normal') or homeostatic (initial change, then return toward original baseline). RESULTS: The study diet was low in fat (< 60 g/d), especially polyunsaturated FAs (PUFAs; < 5 g/d), compared to the average American diet of obese individuals as described by a nationally representative sample. Participants lost ∼6% of body mass and lowered plasma fasting triglyceride levels by ∼9% over the course of the study. With strong to very strong strength of evidence, the individual FAs displaying a sustained response were C16:1n7t, C18:1n9, C20:1n9, and C18:2n6, and homeostatic response, C18:0, 24:0, C24:1n9, C18:3n6, C20:4n6, and C22:6n3 (Ps < 0.0021, Bonferroni-adjusted). The data suggested that systematic changes in both the PUFA and de novo lipogenesis pathways occurred. CONCLUSIONS: Diet can affect plasma FA changes both due to nutritional composition and by affecting metabolic processes.

Is the Tyme Wear Smart Shirt Reliable and Valid at Detecting Personalized Ventilatory Thresholds in Recreationally Active Individuals?

The aim of this study was to determine the extent to which the Tyme Wear smart shirt is as reliable and valid in detecting personalized ventilatory thresholds when compared to the Parvo Medics TrueOne 2400. In this validation study, 19 subjects were recruited to conduct two graded exercise test (GXT) trials. Each GXT trial was separated by 7 to 10 days of rest. During the GXT, gas exchange and heart rate data were collected by the TrueOne 2400 (TRUE) in addition to the ventilation data collected by the Tyme Wear smart shirt (S-PRED). Gas exchange data from TRUE were used to detect ventilatory threshold 1 (VT1) and ventilatory threshold 2 (VT2). TRUE and S-PRED VT1 and VT2 were compared to determine the reliability and validity of the smart shirt. Of the 19 subjects, data from 15 subjects were used during analysis. S-PRED exhibited excellent (intraclass correlation coefficient-CC > 0.90) reliability for detection of VT1 and VT2 utilizing time point and workload and moderate (0.90 > ICC > 0.75) reliability utilizing heart rate. TRUE exhibited excellent reliability for detection of VT1 and VT2 utilizing time point, workload, and heart rate. When compared to TRUE, S-PRED appears to underestimate the VT1 workload (p > 0.05) across both trials and heart rate (p < 0.05) for trial 1. However, S-PRED appears to underestimate VT2 workload (p < 0.05) and heart rate (p < 0.05) across both trials. The result from this study suggests that the Tyme Wear smart shirt is less valid but is comparable in reliability when compared to the gold standard. Moreover, despite the underestimation of S-PRED VT1 and VT2, the S-PRED-detected personalized ventilatory thresholds provide an adequate training workload for most individuals. In conclusion, the Tyme Wear smart shirt provides easily accessible testing to establish threshold-guided training zones but does not devalue the long-standing laboratory equivalent.

Enhanced endothelin-1 system activity with overweight and obesity.

Endothelin (ET)-1-mediated vasoconstrictor tone contributes to the development and progression of several adiposity-related conditions, including hypertension and atherosclerotic vascular disease. The aims of the present study were to determine 1) whether endogenous ET-1 vasoconstrictor activity is elevated in overweight and obese adults, and, if so, 2) whether increased ET-1-mediated vasoconstriction contributes to the adiposity-related impairment in endothelium-dependent vasodilation. Seventy-nine adults were studied: 34 normal weight [body mass index (BMI) < 25 kg/m(2)], 22 overweight (BMI ≥ 25 and < 30 kg/m(2)), and 23 obese (BMI ≥ 30 kg/m(2)). Forearm blood flow (FBF) responses to intra-arterial infusion of ET-1 (5 pmol/min for 20 min) and selective ET-1 receptor blockade (BQ-123, 100 nmol/min for 60 min) were determined. In a subset of the study population, FBF responses to ACh (4.0, 8.0, and 16.0 µg·100 ml tissue(-1)·min(-1)) were measured in the absence and presence of selective ET-1 receptor blockade. The vasoconstrictor response to ET-1 was significantly blunted in overweight and obese adults (∼ 70%) compared with normal weight adults. Selective ET-1 receptor blockade elicited a significant vasodilator response (∼ 20%) in overweight and obese adults but did not alter FBF in normal weight adults. Coinfusion of BQ-123 did not affect FBF responses to ACh in normal weight adults but resulted in an ∼ 20% increase (P < 0.05) in ACh-induced vasodilation in overweight and obese adults. These results demonstrate that overweight and obesity are associated with enhanced ET-1-mediated vasoconstriction that contributes to endothelial vasodilator dysfunction and may play a role in the increased prevalence of hypertension with increased adiposity.

Cardiometabolic Changes in Response to a Calorie-Restricted DASH Diet in Obese Older Adults.

Objective: To examine the response of a calorie-restricted Dietary Approaches to Stop Hypertension diet on indicators of cardiometabolic health in a cohort of sedentary obese older adults. Design: This was a controlled-feeding trial with a parallel design. Each participant consumed either 3 oz (85 g; n = 15) or 6 oz (170.1 g; n = 13) of lean fresh beef within a standardized calorie-restricted DASH-like diet for 12-weeks. Fasted blood samples were collected and used to measure conventional biomarkers of cardiovascular, metabolic and inflammatory health. Participants: Caucasian older (70.8 years), obese (BMI: 32 ± 6.9 kg/m2; WC: 101 ± 16.4 cm) females (n = 17) and males (n = 11) from the rural community of Brookings, South Dakota. Results: 28 participants completed the 12-week feeding trial, with no differences (p > 0.05) among the biomarkers of cardiometabolic health between the 3 and 6 oz beef intake groups. However, when the beef intake groups were combined, all biomarkers changed concentration in response to the intervention diet. Total cholesterol (p < 0.001), LDL-C (p = 0.004), HDL-C (p < 0.0001), insulin (p = 0.014), glucose (p = 0.008), HOMA-IR (p < 0.05), IL-12 (p < 0.001), and CRP (p = 0.006) all decreased in response to the study diet. IGF-1 (p < 0.001) and IL-8 (p = 0.005) increased in response to the intervention. Correlations among cardiometabolic biomarkers and body composition measures were observed. By study end, the decrease in insulin (R 2 = 0.22; P = 0.012) and HOMA-IR (R 2 = 0.22; P = 0.01) was positively correlated with the decrease in waist circumference. The increase in IGF-1 was significantly correlated with the decrease in waist circumference (R 2 = 0.21; p = 0.014). The increase in IGF-1 was significantly correlated with the increase in sit-to-stand (R 2 = 0.21; p = 0.016). The increase in IL-8 was significantly correlated with decreases in total cholesterol (R 2 = 0.24; P = 0.008), LDL-C (R 2 = 0.17; P = 0.031) and glucose (R 2 = 0.44; P = 0.0001). Conclusions: These findings suggest that a DASH-like diet with restricted calories may potentially improve biomarkers of cardiometabolic health in sedentary obese older adults. These results also point to interrelationships between body composition changes and changes in cardiometabolic biomarkers. Lastly, regardless of meat intake amount, positive impacts on cardiometabolic biomarkers were observed in this cohort of older adults with an obese phenotype.

Reduced effect of ischemic preconditioning against endothelial ischemia-reperfusion injury with cardiovascular risk factors in humans.

The extent that clustered CVD risk factors interfere with ischemic preconditioning (IPC) to protect against microvascular endothelial dysfunction with ischemia-reperfusion (I/R) injury in humans is unclear. We hypothesized that adults with a clustered burden of ≥3 CVD risk factors would demonstrate a reduced capacity of IPC to protect endothelial function with I/R injury. Twenty-two (age: 45 ± 14 year) adults [12 healthy controls; 10 raised risk (10-year FRS risk score ~3%)] were studied using a 2 × 2 randomized cross-over design. Pulse arterial tonometry was used to assess microvascular endothelium-dependent vasodilation during reactive hyperemia in response to endothelial I/R injury (20 min brachial artery occlusion/45 min reperfusion) that was preceded by remote IPC (3 × 5 min ischemia/reperfusion) or mock IPC. In both groups, microvascular reactive hyperemia was reduced ~20% (both P < 0.01) after endothelial I/R injury without remote IPC. However, in control subjects remote IPC prevented endothelial I/R injury (from baseline reactive hyperemic ratio: 2.1 ± 0.4 AU to post I/R injury: 2.5 ± 0.5 AU; P = 0.09). In contrast, the reactive hyperemia ratio in raised risk subjects was significantly reduced from 2.2 ± 0.6 AU to 1.9 ± 0.5 AU (P = 0.0087) despite attempts to induce protection by remote IPC, with the magnitude of reduction similar to their mock IPC trial. The magnitude of remote IPC-mediated endothelial protection against I/R injury was inversely related to the number of risk factors. CVD risk factors diminish the effect of IPC to protect the microvasculature from I/R injury in humans. Translating IPC to clinical practice for vasculoprotection will continue to be challenging in patients with increased CVD risk.

CD31+ T cells represent a functionally distinct vascular T cell phenotype.

In contrast to CD3(+)/CD31(-) cells, CD3(+)/CD31(+) cells aid in endothelial repair and revascularization. There are limited data regarding the functional differences between circulating CD3(+)/CD31(+) and CD3(+)/CD31(-) cells that may contribute to their divergent cardiovascular effects. The aim of the present study was to characterize functional differences between CD3(+)/CD31(+) and CD3(+)/CD31(-) cells. To address this aim, migratory capacity, proangiogenic cytokine release and apoptotic susceptibility of CD3(+)/CD31(+) and CD3(+)/CD31(-) cells were determined. Human CD3(+)/CD31(+) and CD3(+)/CD31(-)cells from peripheral blood were isolated using magnetic-activated cell sorting. CD3(+)/CD31(+) cells demonstrated significantly higher ( approximately 60%) migratory capacity to the chemokines SDF-1alpha (655+/-99 vs. 273+/-54 AU) and VEGF (618+/-99 vs. 259+/-57 AU) vs. CD3(+)/CD31(-) cells. Release of angiogenic cytokines G-CSF, interleukin-8 and matrix metallopeptidase-9 were all approximately 100% higher (P<0.05) in CD3(+)/CD31(+) than CD3(+)/CD31(-) cells. CD3(+)/CD31(+) cells exhibited significantly higher intracellular concentrations of active caspase-3 (2.61+/-0.60 vs. 0.34+/-0.09 ng/mL) and cytochrome-c (21.8+/-1.4 vs. 13.7+/-1.0 ng/mL). In summary, CD3(+)/CD31(+) cells have greater migratory and angiogenic cytokine release capacity, but are more susceptible to apoptosis compared with CD3(+)/CD31(-) cells. Enhanced migratory capacity and angiogenic cytokine release may contribute to the vasculogenic properties of this unique T cell subpopulation.

Sex differences in endothelin-1-mediated vasoconstrictor tone in middle-aged and older adults.

The prevalence of cardiovascular disease is lower in middle-aged and older women than men. Increased endothelin-1-mediated vasoconstriction has been linked to the etiology of a number of cardiovascular diseases, including atherosclerosis, heart failure, and hypertension. It is unknown whether a sex difference in endothelin-1-mediated vasoconstrictor tone exists in middle-aged and older adults. Therefore, we tested the hypothesis that middle-aged and older men would demonstrate greater ET-1-mediated vasoconstrictor tone than age-matched women. Forearm blood flow in response to intra-arterial infusions of endothelin (ET)-1, BQ-123 (a selective ET(A) receptor antagonist), and BQ-788 (a selective ET(B) receptor antagonist) was assessed by venous occlusion plethysmography in 21 women (age: 58 + or - 1 yr; body mass index: 26.0 + or - 1.0 kg/m(2)) and 25 men (age: 57 + or - 2 yr; body mass index: 26.8 + or - 0.7 kg/m(2)). In response to BQ-123, the increase in forearm blood flow from baseline was significantly higher in the men than the women (24 + or - 5% vs. 9 + or - 5%; P < 0.05). In contrast, the increase in forearm blood flow in response to BQ-123 coinfused with BQ-788 was greater in the women than the men, such that the maximum vasodilation to dual endothelin receptor blockade was similar between men and women (approximately 25%). There was no difference in the vasoconstrictor response to ET-1 between the sexes. These results indicate that middle-aged and older men are under greater ET(A) receptor-mediated vasoconstrictor tone than age-matched women. Since the ET(A) receptor is the predominant receptor subtype in the coronary vasculature, this sex difference in vasoconstrictor tone may be a mechanism contributing to the sex difference in the prevalence of coronary heart disease in middle-aged and older adults.