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Blood pressure (BP) and arterial stiffness are important predictors of cardiovascular health with aging. Nutraceuticals are an easy-to-implement lifestyle strategy demonstrating promise to effectively lower BP and arterial stiffness with aging and ultimately cardiovascular disease risk. We demonstrate that coconut sap powder (CSP), a traditional Asian sweetener, lowers brachial systolic BP and carotid artery mechanical stiffness in middle-aged and older (MA/O) adults. These findings provide initial evidence for the CSP-related cardioprotective effects in MA/O adults.

Aortic perivascular adipose tissue (aPVAT) promotes age-related aortic stiffening in preclinical animal models, but the relation between aPVAT density and cardiovascular function in adults is unknown. We demonstrate that aPVAT, but not abdominal visceral adipose tissue density, is positively associated with aging, aortic stiffness, and higher resting aortic blood pressure in apparently healthy adults. These findings provide novel evidence for aPVAT as a viable therapeutic target for improving cardiovascular function in humans.

Brittany E Smith,1 James E Peterman,2 Matthew P Harber,3 Mary T Imboden,4 Bradley S Fleenor,3 Leonard A Kaminsky,2 Mitchell H Whaley3 1Exercise Science and Exercise Physiology, Kent State University, Kent, OH, 44240, USA; 2Fisher Institute of Health and Wellbeing, Ball State University, Muncie, IN, 47306, USA; 3School of Kinesiology, Ball State University, Muncie, IN, 47306, USA; 4Department of Exercise Science, George Fox University, Portland, OR, 97132, USACorrespondence: Mitchell H Whaley, Email mwhaley@bsu.eduPurpose: To evaluate how the changes in directly measured cardiorespiratory fitness (CRF) relate to the changes in metabolic syndrome (MetS) status following 4– 6 months of exercise training.Methods: Maximal cardiopulmonary exercise (CPX) tests and MetS risk factors were analyzed prospectively from 336 adults (46% women) aged 45.8 ± 10.9 years. MetS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III criteria, as updated by the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI). Pearson correlations, chi-squares, and dependent 2-tail t-tests were used to assess the relationship between the change in CRF and the change in MetS risk factors, overall number of MetS risk factors, and a MetS severity score following 4– 6 months of participation in a self-referred, community-based exercise program.Results: Overall prevalence of MetS decreased from 23% to 14% following the exercise program (P < 0.05), while CRF improved 15% (4.7 ± 8.4 mL/kg/min, P < 0.05). Following exercise training, the number of positive risk factors declined from 1.4 ± 1.3 to 1.2 ± 1.2 in the overall cohort (P < 0.05). The change in CRF was inversely related to the change in the overall number of MetS risk factors (r = − 0.22; P < 0.05) and the MetS severity score (r = − 0.28; p < 0.05).Conclusion: This observational cohort study indicates an inverse relationship between the change in CRF and the change in MetS severity following exercise training. These results suggest that participation in a community-based exercise program yields significant improvements in CRF, MetS risk factors, the prevalence of the binary MetS, and the MetS severity score. Improvement in CRF through exercise training should be a primary prevention strategy for MetS.Keywords: cardiorespiratory fitness, metabolic syndrome, exercise training, abdominal obesity

Purpose: Nutrition has been increasingly recognized as a key component to optimal sports performance. Though several botanical agents have been reported to possess ergogenic potential, there exists a great interest for tasty and safe natural substances as performance boosters. In the present contribution, the ergogenic potential of a novel powder form of coconut inflorescence sap (CSP) was investigated for the first time. Method: Out of the fourteen participants recruited, twelve recreationally active men completed the single-blinded, placebo-controlled, crossover study for 8 weeks. Running based anaerobic sprint test (RAST) and 2.4 km running test were performed as anaerobic and aerobic tests, respectively. In arm 1, the participants were received with either placebo (200 mL water containing 400 mg aspartame/day) or CSP (3 g in 200 mL water/day) for 21 days. After the washout period, arm 2 was performed with a reversed treatment regime. VO2 max was estimated using a predictive formula. Results: The primary outcome showed a significant enhancement in peak power and mean power (peak power from 3.67 W/kg b. wt. to 5.38 W/kg b. wt.; mean power from 3.47 W/kg b. wt. to 5.06 W/kg b. wt.). A significant (p 0.05) in safety parameters. Conclusion: It was concluded that CSP possesses significant ergogenic effect and may find wide application as a natural ingredient for sports nutrition and energy drinks. Trail Registration: The study was registered in Clinical Trial Registry of India (Reg No.: CTRI/2018/03/012551 dated 13/03/2018).

The goal of this study is twofold: i) identification of features associated with three cardiovascular disease (CVD) risk factors, and (ii) identification of subgroups with differential treatment effects. Multivariate analysis is performed to identify the features associated with the CVD risk factors: hypertension, diabetes, and dyslipidemia. For subgroup identification, we applied model-based recursive partitioning approach. This method fits a local model in each subgroup of the population rather than fitting one global model for the whole population. The method starts with a model for the overall effect of treatment and checks whether this effect is equally applicable for all individuals under the study based on parameter instability of M fluctuation test over a set of partitioning variables. The procedure produces a segmented model with a differential effect of cardio-respiratory fitness (CRF) corresponding to each subgroup. The subgroups are linked to predictive factors learned by the recursive partitioning approach. This approach is applied to the data from the Ball State Adult Fitness Program Longitudinal Lifestyle Study (BALL ST), where we considered the level of CRF as a treatment variable. The overall results indicate that CRF is inversely associated with hypertension, diabetes and dyslipidemia. The partitioning factors that are selected are related to these risk factors. The subgroup-specific results indicate that for each subgroup, the chance of hypertension, diabetes and dyslipidemia increases with low CRF.

Equations are often used to predict cardiorespiratory fitness (CRF) from submaximal or maximal exercise tests. However, no study has comprehensively compared these exercise-based equations with directly measured CRF using data from a single, large cohort. PURPOSE This study aimed to compare the accuracy of exercise-based prediction equations with directly measured CRF and evaluate their ability to classify an individual's CRF. METHODS The sample included 4871 tests from apparently healthy adults (38% female, age 44.4 ± 12.3 yr (mean ± SD)). Estimated CRF (eCRF) was determined from 2 nonexercise equations, 3 submaximal exercise equations, and 10 maximal exercise equations; all eCRF calculations were then compared with directly measured CRF, determined from a cardiopulmonary exercise test. Analysis included Pearson product-moment correlations, standard error of estimate values, intraclass correlation coefficients, Cohen κ coefficients, and the Benjamini-Hochberg procedure to compare eCRF with directly measured CRF. RESULTS All eCRF values from the prediction equations were associated with directly measured CRF (P < 0.01), with intraclass correlation coefficient estimates ranging from 0.07 to 0.89. Although significant agreement was found when using eCRF to categorize participants into fitness tertiles, submaximal exercise equations correctly classified an average of only 51% (range, 37%-58%) and maximal exercise equations correctly classified an average of only 59% (range, 43%-76%). CONCLUSIONS Despite significant associations between exercise-based prediction equations and directly measured CRF, the equations had a low degree of accuracy in categorizing participants into fitness tertiles, a key requirement when stratifying risk within a clinical setting. The present analysis highlights the limited accuracy of exercise-based determinations of eCRF and suggests the need to include cardiopulmonary measures with maximal exercise to accurately assess CRF within a clinical setting.

Background: Compare arterial stiffness among law enforcement officers (LEOs) versus general population normative values and identify predictors of arterial stiffness in LEOs. Methods: Seventy male LEOs (age: 24–54 years) completed body composition, blood pressures, physical activity level, and carotid-femoral pulse wave velocity (cfPWV) measurements. T-tests and regression analyses were utilized to compare LEO data to normative data and predict cfPWV, respectively. Results: Compared to similar age strata within the general population, cfPWV was lower among LEO’s under 30-years (mean difference = −0.6 m·s−1), but higher among LEOs 50–55-years (mean difference = 1.1 m·s−1). Utilizing regression, age, relative body fat, and diastolic blood pressure explained the greatest variance in LEO’s cfPWV (adj. R2 = 0.56, p &lt, 0.001). Conclusion: This investigation demonstrated that arterial stiffness may progress more rapidly in LEOs and LEOs’ relative body fat and blood pressure may primarily affect arterial stiffness and risk of CVD.

PURPOSE Cardiorespiratory fitness (CRF) is known to be directly related to fat-free mass (FFM), therefore, it has been suggested that normalizing CRF to FFM (V˙O2peakFFM) may be the most accurate expression of CRF as related to exercise performance and cardiorespiratory function. However, the influence of V˙O2peakFFM (mL·kg FFM·min) on predicting mortality has been largely unexplored. This study aimed to primarily assess the relationship between V˙O2peakFFM and all-cause and disease-specific mortality risk in apparently healthy adults. Further, this study sought to compare the predictive ability of V˙O2peakFFM to V˙O2peak normalized to total body weight (V˙O2peakTBW) for mortality outcomes. METHODS Participants included 2905 adults (1555 men, 1350 women) who completed a cardiopulmonary exercise test between 1970 and 2016 to determine CRF. Body composition was assessed using the skinfold method to estimate FFM. Cardiorespiratory fitness was expressed as V˙O2peakTBW and V˙O2peakFFM. Participants were followed for 19.0 ± 11.7 yr after their cardiopulmonary exercise test for mortality outcomes. Cox-proportional hazard models were performed to determine the relationship of V˙O2peakFFM with mortality outcomes. Parameter estimates were assessed to compare the predictive ability of CRF expressed as V˙O2peakTBW and V˙O2peakFFM. RESULTS Overall, V˙O2peakFFM was inversely related to all-cause, cardiovascular disease, and cancer mortality, with a 16.2%, 8.4%, and 8.0% lower risk per 1 mL·kg FFM·min improvement, respectively (P < 0.01). Further, assessment of the parameter estimates showed V˙O2peakFFM to be a significantly stronger predictor of all-cause mortality than V˙O2peakTBW (parameter estimates, -0.49 vs -0.16). CONCLUSIONS Body composition is an important factor when considering the relationship between CRF and mortality risk. Clinicians should consider normalizing CRF to FFM when feasible, because it will strengthen the predictive power of the measure.

Aims A recent scientific statement suggests clinicians should routinely assess cardiorespiratory fitness using at least non-exercise prediction equations. However, no study has comprehensively compared the many non-exercise cardiorespiratory fitness prediction equations to directly-measured cardiorespiratory fitness using data from a single cohort. Our purpose was to compare the accuracy of non-exercise prediction equations to directly-measured cardiorespiratory fitness and evaluate their ability to classify an individual's cardiorespiratory fitness. Methods The sample included 2529 tests from apparently healthy adults (42% female, aged 45.4 ± 13.1 years (mean±standard deviation). Estimated cardiorespiratory fitness from 28 distinct non-exercise prediction equations was compared with directly-measured cardiorespiratory fitness, determined from a cardiopulmonary exercise test. Analysis included the Benjamini–Hochberg procedure to compare estimated cardiorespiratory fitness with directly-measured cardiorespiratory fitness, Pearson product moment correlations, standard error of estimate values, and the percentage of participants correctly placed into three fitness categories. Results All of the estimated cardiorespiratory fitness values from the equations were correlated to directly measured cardiorespiratory fitness (p Conclusion Differences exist between non-exercise prediction equations, which influences the accuracy of estimated cardiorespiratory fitness. The present analysis can assist researchers and clinicians with choosing a non-exercise prediction equation appropriate for epidemiological or population research. However, the error and misclassification associated with estimated cardiorespiratory fitness suggests future research is needed on the clinical utility of estimated cardiorespiratory fitness.

Heart failure (HF) is associated with increased large conduit artery stiffness and afterload resulting in stiffening of the coronary arteries. Perivascular adipose tissue (PVAT) and advanced glycation end products (AGE) both promote arterial stiffness, yet the mechanisms by which coronary PVAT promotes arterial stiffness and the efficacy of exercise to prevent coronary stiffness are unknown. We hypothesized that both chronic continuous and interval exercise training would prevent coronary PVAT-mediated AGE secretion and arterial stiffness. Yucatan miniature swine were divided into four groups: control-sedentary (CON), aortic banded sedentary-heart failure (HF), aortic banded HF-continuous exercise trained (HF+CONT), and aortic banded HF-interval exercise trained (HF+IT). The left circumflex and right coronary arteries underwent ex vivo mechanical testing, and arterial AGE, elastin, and collagen were assessed. Coronary elastin elastic modulus (EEM) and elastin protein were lower and AGE was increased with HF compared with CON, which was prevented by both HF+CONT and HF+IT. Mouse aortic segments treated with swine coronary PVAT conditioned medium had lower EEM and elastin content and greater AGE secretion and arterial AGE accumulation in HF compared with CON, which was prevented by both HF+CONT and HF+IT. Aminoguanidine (AMG), an AGE inhibitor, prevented the reduction in EEM, arterial elastin content, and AGE accumulation in mouse aortic segments treated with PVAT conditioned medium in the HF group. Our data demonstrate efficacy for chronic continuous and interval exercise to prevent coronary artery stiffness via inhibition of PVAT-derived AGE secretion in a preclinical miniswine model of pressure overload-induced HF. NEW & NOTEWORTHY Our findings show that chronic continuous and interval exercise training regimens prevent coronary artery stiffness associated with inhibition of perivascular adipose tissue-derived advanced glycation end products in a translational pressure overload-induced heart failure model potentially providing an effective therapeutic option for heart failure patients.

To assess the influence of changes in cardiorespiratory fitness (CRF) after exercise training on mortality risk in a cohort of self-referred, apparently healthy adults.A total of 683 participants (404 men, 279 women; mean age: 42.7±11.0 y) underwent two maximal cardiopulmonary exercise tests (CPX) between March 20, 1970, and December 11, 2012, to assess CRF at baseline (CPX1) and post-exercise training (CPX2). Participants were followed for an average of 29.8±10.7 years after their CPX2. Cox proportional hazards models were performed to determine the relationship of CRF change with mortality, with change in CRF as a continuous variable, as well as a categorical variable. A Wald chi-square test was used to compare the coefficients estimating the relationship of peak oxygen consumption (VODuring the follow-up period there were 180 deaths. When assessed independently, there were 20% (95% CI, 10-49%) and 38% (95% CI, 7-66%) lower mortality risks per 1 metabolic equivalent improvement in CRF (P.01) in men and women, respectively, after multivariable adjustment. Those that remained unfit had ∼2-fold higher risk for all-cause mortality compared with those that remained fit and CRF at CPX2 was a stronger predictor of all-cause mortality than at CPX1 (P=.02).Improving CRF through exercise training lowers mortality risk. Clinicians should encourage individuals to participate in exercise training to improve CRF to lower risk of mortality.

Background The relationship between cardiorespiratory fitness (CRF) and mortality risk has typically been assessed using a single measurement, though some evidence suggests the change in CRF over time influences risk. This evidence is predominantly based on studies using estimated CRF (CRFe). The strength of this relationship using change in directly measured CRF over time in apparently healthy men and women is not well understood. Purpose To examine the association of change in CRF over time, measured using cardiopulmonary exercise testing (CPX), with all-cause and disease-specific mortality and to compare baseline and subsequent CRF measurements as predictors of all-cause mortality. Methods Participants included 833 apparently healthy men and women (42.9 ± 10.8 years) who underwent two maximal CPXs, the second CPX being ≥1 year following the baseline assessment (mean 8.6 years, range 1.0 to 40.3 years). Participants were followed for up to 17.7 (SD 11.8) years for all-cause-, cardiovascular disease- (CVD), and cancer mortality. Cox-proportional hazard models were performed to determine the association between the change in CRF, computed as visit 1 (CPX1) peak oxygen consumption (VO2peak [mL·kg−1·min−1]) – visit 2 (CPX2) VO2peak, and mortality outcomes. A Wald-Chi square test of equality was used to compare the strength of CPX1 to CPX2 VO2peak in predicting mortality. Results During follow-up, 172 participants died. Overall, the change in CPX-CRF was inversely related to all-cause, CVD, and cancer mortality (p Conclusion The change in CRF over time was inversely related to mortality outcomes, and mortality was better predicted by CRF measured at subsequent test than CPX1 CRF. These findings emphasize the importance of adopting lifestyle behaviors that promote CRF, as well as support the need for routine assessment of CRF in clinical practice to better assess risk.

Heart failure (HF) patients with deteriorating right ventricular (RV) structure and function have a nearly twofold increased risk of death compared with those without. Despite the well-established clinical risk, few studies have examined the molecular signature associated with this HF condition. The purpose of this study was to integrate morphological, molecular, and functional data with the transcriptome data set in the RV of a preclinical model of cardiometabolic HF. Ossabaw swine were fed either normal diet without surgery (lean control, n = 5) or Western diet and aortic-banding (WD-AB; n = 4). Postmortem RV weight was increased and positively correlated with lung weight in the WD-AB group compared with CON. Total RNA-seq was performed and gene expression profiles were compared and analyzed using principal component analysis, weighted gene co-expression network analysis, module enrichment analysis, and ingenuity pathway analysis. Gene networks specifically associated with RV hypertrophic remodeling identified a hub gene in MAPK8 (or JNK1) that was associated with the selective induction of the extracellular matrix (ECM) component fibronectin. JNK1 and fibronectin protein were increased in the right coronary artery (RCA) of WD-AB animals and associated with a decrease in matrix metalloproteinase 14 protein, which specifically degrades fibronectin. RCA fibronectin content was correlated with increased vascular stiffness evident as a decreased elastin elastic modulus in WD-AB animals. In conclusion, this study establishes a molecular and transcriptome signature in the RV using Ossabaw swine with cardiometabolic HF. This signature was associated with altered ECM regulation and increased vascular stiffness in the RCA, with selective dysregulation of fibronectin.

Herrick, LP, Goh, J, Menke, W, Campbell, MS, Fleenor, BS, Abel, MG, and Bergstrom, HC. Effects of curcumin and fenugreek soluble fiber on the physical working capacity at the fatigue threshold, peak oxygen consumption, and time to exhaustion. J Strength Cond Res 34(12): 3346-3355, 2020-The purpose of this study was to examine the effects of curcumin in combination with fenugreek soluble fiber (CUR + FEN) or fenugreek soluble fiber alone (FEN) on the neuromuscular fatigue threshold (PWCFT), peak oxygen consumption (V˙o2peak), and time to exhaustion (Tlim) on a graded exercise test (GXT), in untrained subjects. The PWCFT estimates the highest power output that can be maintained without evidence of neuromuscular fatigue. Forty-seven untrained, college-aged subjects were randomly assigned to one of 3 supplementation groups; placebo (PLA, n = 15), CUR + FEN (500 mg·d, n = 18), or FEN (300 mg·d, n = 14). The subjects completed a maximal GXT on a cycle ergometer to determine the PWCFT, V˙o2peak, and Tlim before (PRE) and after (POST) 28 days of daily supplementation. Surface electromyographic signals were recorded from a bipolar electrode arrangement on the vastus lateralis of the right leg during each test. Separate one-way analysis of covariances were used to determine if there were between-group differences for adjusted POST-PWCFT, POST-V˙o2peak, and POST-Tlim values, covaried for the respective PRE-test scores. The adjusted POST-PWCFT for the CUR + FEN group (mean ± SD: 196 ± 58 W) was greater (p = 0.016) than the PLA group (168 ± 49 W) but the FEN group (185 ± 32 W) was not different from the CUR + FEN or PLA groups (p > 0.05). There were no differences for adjusted POST-V˙o2peak (p = 0.612) or POST-Tlim (p = 0.508) among the groups. These findings suggested curcumin combined with fenugreek soluble fiber might delay neuromuscular fatigue.

Aortic stiffening, assessed as pulse-wave velocity (PWV), increases with age and is an important antecedent to, and independent predictor of, cardiovascular diseases (CVD) and other clinical disorders of aging. Aerobic exercise promotes lower levels of aortic stiffness in older adults, but the underlying mechanisms are incompletely understood, largely due to inherent challenges of mechanistic studies of large elastic arteries in humans. Voluntary wheel running (VWR) is distinct among experimental animal exercise paradigms in that it allows investigation of the physiologic effects of aerobic training without potential confounding influences of aversive molecular signaling related to forced exercise. In this study, we investigated whether VWR in mice may be a suitable model for mechanistic studies (i.e., “reverse translation”) of the beneficial effects of exercise on arterial stiffness in humans. We found that 10 weeks of VWR in old mice (~ 28 months) reversed age-related elevations in aortic PWV assessed in vivo (Old VWR: 369 ± 19 vs. old sedentary: 439 ± 20 cm/s, P

Background Repeated assessment of cardiorespiratory fitness ( CRF ) improves mortality risk predictions in apparently healthy adults. Accordingly, the American Heart Association suggests routine clinical assessment of CRF using, at a minimum, nonexercise prediction equations. However, the accuracy of nonexercise prediction equations over time is unknown. Therefore, we compared the ability of nonexercise prediction equations to detect changes in directly measured CRF . Methods and Results The sample included 987 apparently healthy adults from the BALL ST (Ball State Adult Fitness Longitudinal Lifestyle Study) cohort (33% women; average age, 43.1±10.4 years) who completed 2 cardiopulmonary exercise tests ≥3 months apart (3.2±5.4 years of follow‐up). The change in estimated CRF ( eCRF ) from 27 distinct nonexercise prediction equations was compared with the change in directly measured CRF . Analysis included Pearson product moment correlations, SEE values, intraclass correlation coefficient values, Cohen's κ coefficients, γ coefficients, and the Benjamini‐Hochberg procedure to compare eCRF with directly measured CRF . The change in eCRF from 26 of 27 equations was significantly associated to the change in directly measured CRF ( P eCRF was significantly different from the change in directly measured CRF . The median percentage of participants correctly classified as having increased, decreased, or no change in CRF was 56% (range, 39%–61%). Conclusions Variability was observed in the accuracy between nonexercise prediction equations and the ability of equations to detect changes in CRF . Considering the appreciable error that prediction equations had with detecting even directional changes in CRF , these results suggest eCRF may have limited clinical utility.

The renin-angiotensin system (RAS) precursor angiotensinogen (AGT) has been implicated in the functional and mechanical alterations of the vascular wall in response to high-fat diet (HFD). Previously, we showed that HFD exacerbates angiotensin II-induced constriction in isolated aortic rings from male rats exposed to maternal separation (MatSep), a model of early-life stress. Thus, the aim of this study was to investigate whether MatSep increases AGT secretion promoting vascular stiffness in rats fed a HFD. Male Wistar-Kyoto MatSep offspring were separated (3 h/day, postnatal days 2–14), and undisturbed littermates were used as controls. At weaning, rats were fed for 17 wk a normal diet (ND) or a HFD, 18% or 60% kcal from fat, respectively. In plasma, there was a main effect of MatSep reducing AGT concentration (P < 0.05) but no effect due to diet. In urine, ND-fed MatSep rats displayed higher AGT concentrations that were further increased by HFD (P < 0.05 vs. control). AGT mRNA abundance and protein expression were increased in adipose tissue from HFD-fed MatSep rats compared with control rats (P < 0.05). No significant differences in liver and kidney AGT levels were found between groups. In addition, MatSep augmented vascular stiffness assessed on freshly isolated aortic rings from ND-fed rats (P < 0.05), yet HFD did not worsen vascular stiffness in either MatSep or control rats. There was no correlation between plasma AGT and vascular stiffness in ND-fed rats; however, this relationship was negative in HFD-fed MatSep rats only (P < 0.05). Therefore, this study shows that MatSep-induced increases in vascular stiffness are independent of diet or plasma AGT. NEW & NOTEWORTHY This study demonstrates that there was no correlation between circulating levels of angiotensinogen (AGT) and the development of vascular stiffness in rats exposed to early-life stress and fed a normal diet. This study also shows that early-life stress-induced hypersensitive vascular contractility to angiotensin II in rats fed a high-fat diet is independent of circulating levels of AGT and occurs without further progression of vascular stiffness. Our data show that early-life stress primes the adipose tissue to secrete AGT in a sex- and species-independent fashion.

Introduction: Mortality risk predictions are improved with routine assessment of cardiorespiratory fitness (CRF). Accordingly, an American Heart Association Scientific Statement suggests routine clinical assessment of CRF in apparently healthy adults minimally using non-exercise prediction equations, which can be calculated from common health metrics. However, no study has assessed the ability of non-exercise CRF prediction equations to accurately detect longitudinal changes. Hypothesis: Changes in estimated CRF (eCRF) would be related to directly-measured changes, yet appreciable misclassification would occur at the individual level. Methods: The sample included 987 apparently healthy adults (324 females; mean±SD age 43.1±10.4 years) who completed 2 cardiopulmonary exercise tests (CPX) at least 3 months apart (3.2±5.4 years follow-up). The change in eCRF from 27 distinct non-exercise prediction equations was compared to the change in directly-measured CRF determined from CPX. A change of ≥5% was used to classify participants as having a directional increase or decrease in CRF. Analysis included Pearson product moment correlations, standard error of estimate (SEE) values, the Benjamini-Hochberg procedure to compare eCRF with directly-measured CRF, and chi-squared tests to examine the impact of follow-up time on the percentage of participants correctly identified as having a directional increase or decrease in CRF. Results: The change in eCRF from each equation was correlated to the change in directly-measured CRF ( P 2 values ranging from 0.06-0.43 and SEE values ranging from 0.9-5.9 ml·kg -1 ·min -1 . For 16 of the 27 equations, the change in eCRF was significantly different from the change in directly-measured CRF. When classifying directional changes, the prediction equations correctly categorized an average of 54% of individuals as having increased, decreased, or no change in CRF. When examining the influence of follow-up time, the average percentage of individuals correctly classified as having a directional increase in CRF was greater when the time between tests was ≤8months (54%) compared to ≥2years (28%). In contrast, the average percentage correctly classified as having a directional decrease in CRF was lower with tests ≤8months apart (8%) compared to ≥2years (73%). Conclusions: As hypothesized, discernible variability was found in the accuracy between non-exercise prediction equations and the ability of equations to accurately assess changes in directly-measured CRF over time. Considering the appreciable error that prediction equations had with detecting even directional changes in CRF, these results suggest eCRF may have limited clinical utility.

Increased peripheral conduit artery stiffness has been shown in patients with heart failure (HF) with preserved ejection fraction. However, it is unknown whether this phenomenon extends to the coronary vasculature. HF with preserved ejection fraction may be driven, in part, by coronary inflammation, and inhibition of the enzyme DPP-4 (dipeptidyl-peptidase 4) reduces inflammation and oxidative stress. The purpose of this study was to determine the effect of saxagliptin—a DPP-4 inhibitor—on coronary stiffness in aortic-banded mini swine. We hypothesized saxagliptin would prevent increased coronary artery stiffness in a translational swine model with cardiac features of HF with preserved ejection fraction by inhibiting perivascular adipose tissue inflammation. Yucatan mini swine were divided into 3 groups: control, aortic-banded untreated HF, and aortic-banded saxagliptin-treated HF. Ex vivo mechanical testing was performed on the left circumflex and right coronary arteries, and advanced glycation end product, NF-κB (nuclear factor-κB), and nitrotyrosine levels were measured. An increase in the coronary elastic modulus of HF animals was associated with increased vascular advanced glycation end products, NF-κB, and nitrotyrosine levels compared with control and prevented by saxagliptin treatment. Aortas from healthy mice were treated with media from swine perivascular adipose tissue culture to assess its role on vascular stiffening. Conditioned media from HF and saxagliptin-treated HF animals increased mouse aortic stiffness; however, only perivascular adipose tissue from the HF group showed increased advanced glycation end products and NF-κB levels. In conclusion, our data show increased coronary conduit vascular stiffness was prevented by saxagliptin and associated with decreased advanced glycation end products, NF-κB, and nitrotyrosine levels in a swine model with potential relevance to HF with preserved ejection fraction.

Objective— Aortic pathologies exhibit sexual dimorphism, with aneurysms in both the thoracic and abdominal aorta (ie, abdominal aortic aneurysm [AAA]) exhibiting higher male prevalence. Women have lower prevalence of aneurysms, but when they occur, aneurysms progress rapidly. To define mechanisms for these sex differences, we determined the role of sex chromosome complement and testosterone on the location and progression of angiotensin II (AngII)–induced aortic pathologies. Approach and Results— We used transgenic male mice expressing Sry (sex-determining region Y) on an autosome to create Ldlr (low-density lipoprotein receptor)–deficient male mice with an XY or XX sex chromosome complement. Transcriptional profiling was performed on abdominal aortas from XY or XX males, demonstrating 1746 genes influenced by sex chromosomes or sex hormones. Males (XY or XX) were either sham-operated or orchiectomized before AngII infusions. Diffuse aortic aneurysm pathology developed in XY AngII-infused males, whereas XX males developed focal AAAs. Castration reduced all AngII-induced aortic pathologies in XY and XX males. Thoracic aortas from AngII-infused XY males exhibited adventitial thickening that was not present in XX males. We infused male XY and XX mice with either saline or AngII and quantified mRNA abundance of key genes in both thoracic and abdominal aortas. Regional differences in mRNA abundance existed before AngII infusions, which were differentially influenced by AngII between genotypes. Prolonged AngII infusions resulted in aortic wall thickening of AAAs from XY males, whereas XX males had dilated focal AAAs. Conclusions— An XY sex chromosome complement mediates diffuse aortic pathology, whereas an XX sex chromosome complement contributes to focal AngII-induced AAAs.

Obesity results in greater aortic stiffness assessed by carotid-femoral Pulse Wave Velocity (cfPWV), which is an independent predictor of cardiovascular (CV) events. We hypothesized that a novel curcumin formulation with enhanced bioavailability, CurQfen®, would reduce cfPWV and inflammation in young, obese men. In the present placebo-controlled pilot study, 22 obese subjects (BMI ⩾ 30.0 kg/m2) were randomized into placebo (n = 11, BMI = 33.18 ± 3.38 kg/m2) and curcumin (n = 11, BMI = 33.29 ± 3.69 kg/m2) supplemented groups. When CurQfen® was supplemented at 500 mg/day for 12 weeks, it was found that individuals who did respond to the treatment (n = 6) entered the study with higher baseline cfPWV versus those who did not respond (n = 5) (6.81 ± 0.83 m/s v. 5.84 ± 0.41 m/s, p = 0.045, group by time interaction). The curcumin responders also had increased plasma IL-13 concentrations (p = 0.018, 12 weeks v. baseline). These findings suggest CurQfen curcumin has potential to de-stiffen arteries in young, obese men with greater aortic stiffness.

This study examined the effects of curcumin and fenugreek soluble fiber supplementation on the ventilatory threshold (VT) and peak oxygen consumption (VO2 peak). Methods: Forty-five untrained men and women were randomly assigned to one of three supplementation groups: placebo (PLA, n = 13), 500 mg·day−1 CurQfen® (CUR, n = 14), or 300 mg·day−1 fenugreek soluble fiber (FEN, n = 18). Participants completed a maximal graded exercise test on a cycle ergometer to determine the VT and VO2 peak before (PRE) and after (POST) 28 days of daily supplementation. Separate, one-way analyses of covariance (ANCOVAs) were used to examine the between-group differences for adjusted POST VT and VO2 peak values, covaried for the respective PRE-test values. Results: The adjusted POST VT VO2 values for the CUR (mean SD = 1.593 0.157 L·min−1) and FEN (1.597 0.157 L·min−1) groups were greater than (p = 0.039 and p = 0.025, respectively) the PLA (1.465 0.155 L·min−1) group, but the FEN and CUR groups were not different (p = 0.943). There were no differences in the adjusted VO2 peak values (F = 0.613, p = 0.547) among groups. Conclusion: These findings indicated that fenugreek soluble fiber was responsible for the improvements in the submaximal performance index for both CUR and FEN groups.

We tested the hypothesis that aortic perivascular adipose tissue (PVAT) from young low-density lipoprotein receptor-deficient (LDLr−/−) mice promotes aortic stiffness and remodeling, which would be mediated by greater PVAT-derived IL-6 secretion. Arterial stiffness was assessed by aortic pulse wave velocity and with ex vivo intrinsic mechanical properties testing in young (4–6 mo old) wild-type (WT) and LDLr−/− chow-fed mice. Compared with WT mice, LDLr−/− mice had increased aortic pulse wave velocity (407 ± 18 vs. 353 ± 13 cm/s) and intrinsic mechanical stiffness (5,308 ± 623 vs. 3,355 ± 330 kPa) that was associated with greater aortic protein expression of collagen type I and advanced glycation end products (all P < 0.05 vs. WT mice). Aortic segments from LDLr−/− compared with WT mice cultured in the presence of PVAT had greater intrinsic mechanical stiffness (6,092 ± 480 vs. 3,710 ± 316 kPa), and this was reversed in LDLr−/− mouse arteries cultured without PVAT (3,473 ± 577 kPa, both P < 0.05). Collagen type I and advanced glycation end products were increased in LDLr−/− mouse arteries cultured with PVAT ( P < 0.05 vs. WT mouse arteries), which was attenuated when arteries were cultured in the absence of PVAT ( P < 0.05). PVAT from LDLr−/− mice secreted larger amounts of IL-6 (3.4 ± 0.1 vs. 2.3 ± 0.7 ng/ml, P < 0.05), and IL-6 neutralizing antibody decreased intrinsic mechanical stiffness in LDLr−/− aortic segments cultured with PVAT ( P < 0.05). Collectively, these data provide evidence for a role of PVAT-derived IL-6 in the pathogenesis of aortic stiffness and remodeling in chow-fed LDLr−/− mice.

We tested the hypothesis that hesperidin would reverse age-related aortic stiffness, perivascular adipose (PVAT) mediated-arterial stiffening and PVAT advanced glycation end-products (AGE) accumulation. Aortic pulse wave velocity (aPWV) and intrinsic mechanical stiffness, two measures of arterial stiffness, were assessed in C57BL/6 mice that were young (6 months), old (27–29 months), or old treated with hesperidin for 4 weeks. Old compared with young mice had increased aPWV (444 ± 10 vs. 358 ± 8 cm/s, P < 0.05) and mechanical stiffness (6506 ± 369 vs. 3664 ± 414 kPa, P < 0.05). In old mice hesperidin reduced both aPWV (331 ± 38 cm/s) and mechanical stiffness (4445 ± 667 kPa) to levels not different from young. Aortic segments from old animals cultured with (+) PVAT had greater mechanical stiffness compared to young (+) PVAT (6454 ± 323 vs. 3575 ± 440 kPa, P < 0.05) that was ameliorated in arteries from old hesperidin treated cultured (+) PVAT (2639 ± 258 kPa). Hesperidin also reversed the aging-related PVAT AGE accumulation (all, P < 0.05). A 4-week treatment with the AGE inhibitor aminoguanidine reversed both the age-related increase in aPWV (390 ± 7 cm/s) and mechanical stiffness (3396 ± 1072 kPa), as well as mechanical stiffness in arteries cultured (+) PVAT (3292 ± 716 kPa) (all, P < 0.05) to values not different from young. In conclusion, hesperidin ameliorates the age-related increase in aortic stiffness and the PVAT-mediated effects on arterial stiffening. Hesperidin also reversed PVAT AGE accumulation, where PVAT AGE were shown to promote aortic stiffness with aging.