Cardiac hemodynamics phenotypes and individual responses to training in coronary heart disease patients.

BACKGROUND: In patients with coronary heart disease (CHD), individualized exercise training (ET) programs are strongly recommended to optimize peak oxygen uptake ( V ̇ $$ \dot{\mathrm{V}} $$ O2peak) improvement and prognosis. However, the cardiac hemodynamic factors responsible for a positive response to training remain unclear. The aim of this study was to compare cardiac hemodynamic changes after an ET program in responder (R) versus non-responder (NR) CHD patients. METHODS: A total of 72 CHD patients completed a 3-month ET program and were assessed by cycle ergometer cardiopulmonary exercise test (CPET: V ̇ $$ \dot{\mathrm{V}} $$ O2peak assessment) with impedance cardiography (ICG) for hemodynamic measurements before and after training. Cardiac hemodynamics (e.g., CO, CI, SV, ESV, EDV, and SVR) were measured by ICG during CPET. The R and NR groups were classified using the median change in V ̇ $$ \dot{\mathrm{V}} $$ O2peak (>the median for R and ≤the median for NR). RESULTS: In the R group, V ̇ $$ \dot{\mathrm{V}} $$ O2peak (+17%, p < 0.001), CO, CI, SV, and HR increased by 17%, 17%, 13%, and 5%, respectively (p < 0.05) after the training program. In the NR group, V ̇ $$ \dot{\mathrm{V}} $$ O2peak, CO, CI, and SV increased by 0.5%, 5%, 8%, and 6%, respectively (p < 0.01). The SVR decreased in both groups (-19% in R and -11% in NR, p < 0.001). CONCLUSION: Among CHD patients, the R group showed a better improvement in peak cardiac output via an increase in peak stroke volume and heart rate and a reduced systemic vascular resistance than the NR group. Different cardiac phenotype adaptations and clinical individual responses were identified in CHD patients according to the aerobic fitness responder's status.

Determinants of V̇+O2peak Changes After Aerobic Training in Coronary Heart Disease Patients.

This study aimed to highlight the ventilatory and circulatory determinants of changes in ˙VO2peak after exercise-based cardiac rehabilitation (ECR) in patients with coronary heart disease (CHD). Eighty-two CHD patients performed, before and after a 3-month ECR, a cardiopulmonary exercise testing (CPET) on a bike with gas exchanges measurements (˙VO2peak, minute ventilation, i. e., ˙VE), and cardiac output (Q˙c). The arteriovenous difference in O2 (C(a-v¯)O2) and the alveolar capillary gradient in O2 (PAi-aO2) were calculated using Fick's laws. Oxygen uptake efficiency slope (OUES) was calculated. A 5.0% cut off was applied for differentiating non- (NR: ˙VO2<0.0%), low (LR: 0.0≤ ∆˙VO2<5.0%), moderate (MR: 5.0≤∆˙VO2 < 10.0%), and high responders (HR: ∆˙VO2≥10.0%) to ECR. A total of 44% of patients were HR (n=36), 20% MR (n=16), 23% LR (n=19), and 13% NR (n=11). For HR, the ˙VO2peak increase (p<0.01) was associated with increases in ˙VE (+12.8±13.0 L/min, p<0.01), (+1.0±0.9 L/min, p<0.01), and C(a-v¯)O2 (+2.3±2.5 mLO2/100 mL, p<0.01). MR patients were characterized by+6.7±19.7 L/min increase in ˙VE (p=0.04) and+0.7±1.0 L/min of Q˙c (p<0.01). ECR induced decreases in ˙VE (p=0.04) and C(a-v¯)O2 (p<0.01) and a Q˙c increase in LR and NR patients (p<0.01). Peripheral and ventilatory responses more than central adaptations could be responsible for the ˙VO2peak change with ECR in CHD patients.

The Presence of Wind Worsens the Effect of Cold Temperature on Time to Ischemia in Patients with Stable Angina.

PURPOSE: This study tested the hypothesis that the combination of cold temperature and wind further reduces time to ischemia during treadmill stress testing compared with cold temperature alone. METHODS: Eighteen participants (56 ± 9 yr) with stable angina performed four treadmill stress tests in a randomized crossover design at +20°C and -8°C, with and without a 24-km·h -1 headwind. Time to ischemia (≥1-mm ST-segment depression) and angina, rate pressure product, and total exercise duration were determined. RESULTS: At -8°C, time to ischemia was reduced by 22% (-58 s (-85 to -31 s), P < 0.01) compared with +20°C. The addition of wind at -8°C reduced time to ischemia by a further 15% (-31 s (-58 to -4 s) vs -8°C without wind, P = 0.02). The addition of wind did not affect time to ischemia at +20°C ( P = 0.38). Cold temperature and wind did not affect time to angina ( P = 0.46 and P = 0.61) or rate pressure product ( P = 0.46 and P = 0.09). Total exercise time was reduced in the presence of wind at -8°C (-29 s (-51 to -7 s), P = 0.01), but not at +20°C ( P = 0.09). CONCLUSIONS: The presence of wind reduces time to ischemia when exercise stress testing is performed in a cold environment. These results suggest that wind should be considered when evaluating the risks posed by cold weather in patients with coronary artery disease and exercise-induced ischemia.

Impact of aerobic training periodisation on global and regional right ventricular strain in coronary heart disease.

Linear aerobic training periodisation (LP) is recommended for patients with coronary heart disease (CHD). However, the effects of training periodisation on the right heart mechanics in patients with CHD have never been examined. This study aimed to explore the effects of LP and non-linear periodisation (NLP) on right heart mechanics. We prospectively randomised CHD patients to 12 weeks of aerobic training with LP or NLP. While there was a weekly increase in energy expenditure with LP, there was a steeper increase during the first 3 weeks, followed by a decrease in the fourth week with NLP. Echocardiography was performed at baseline and after the training period to assess the right ventricular free wall (RVFW) and right atrial strain. Thirty patients with CHD were included (NLP, n = 16; LP, n = 14). The traditional right and left heart parameters showed no significant time effects. There was a decrease of RVFW strain with time in both groups (+1.3 ± 0.9% with NLP, and +1.5 ± 0.8% with LP; p = 0.033). Mid-ventricular RVFW strain changed significantly with time (+2.0 ± 1.3% with NLP, and from +2.3 ± 1.2% with LP; p = 0.025). There was no time effect on the right atrial strain. In stable CHD patients, LP and NLP resulted in right ventricular strain decrements with a segment-specific pattern. This study was registered at ClinicalTrials.gov (identifier number: NCT03414996). Novelty: In stable coronary heart disease patients, both linear and non-linear aerobic training periodisation programs result in right ventricular strain decrements with time, particularly in the mid-ventricular segment. Traditional right and left heart parameters and right atrial strain showed no significant time effect in both 12 weeks aerobic training periodisation programs.

High-intensity interval training vs. hydrochlorothiazide on blood pressure, cardiovascular health and cognition: Protocol of a non-inferiority trial.

BACKGROUND: While the number of people with hypertension (HBP) continues to increase, the therapeutic target for optimal blood pressure (BP) has been revised to a lower level. Studies have suggested that High-Intensity Interval Training (HIIT) could be as efficient as BP-lowering drugs, but no study has compared their efficacy in a randomized trial. The aim of this protocol is to determine if HIIT is as efficient as Hydrochlorothiazide (HCTZ) in lowering 24 h ambulatory BP in prehypertensive older adults. Moreover, the secondary aim is to determine if HIIT is associated with greater cardiovascular and cognitive benefits than HCTZ. METHODS: This study is an interventional, single-center, non-inferiority trial, with two randomized parallel groups of prehypertensive participants aged 60 years or more. One group will be prescribed daily doses of 12.5 mg of HCTZ for 12 weeks, and the other group will follow thrice-weekly HIIT for 12 weeks. Each group will be composed of 30 participants. The primary outcome is 24 h ambulatory BP. Secondary outcomes are scores on neuropsychological assessments, balance and gait performances, maximal oxygen uptake, peripheral endothelial function, and arterial stiffness. Non-inferiority tests will be performed on the primary outcome, and secondary outcomes will be compared using independent t-tests. CONCLUSION: This study will determine if HIIT is at least as efficient as HCTZ in lowering BP in prehypertensive older adults. This study will also determine if HIIT provides greater benefits in terms of cardiovascular and cognitive status (NCT04103411).

Impact of 2 different aerobic periodization training protocols on left ventricular function in patients with stable coronary artery disease: an exploratory study.

We compared the impacts of linear (LP) and nonlinear (NLP) aerobic training periodizations on left ventricular (LV) function and geometry in coronary artery disease (CAD) patients. Thirty-nine CAD patients were randomized to either a 3-month isoenergetic supervised LP or NLP. All underwent standard echocardiography with assessment of 3D LV ejection fraction (LVEF), diastolic function, strain (global longitudinal, radial, and circumferential), and strain rate at baseline and study end. Training was performed 3 times/week and included high-intensity interval and moderate-intensity continuous training sessions. Training load was progressively increased in the LP group, while it was deeply increased and intercepted with a recovery week each fourth week in the NLP group. For the 34 analyzed patients, we found similar improvements for 3D LVEF (effect size (ES): LP, 0.29; NLP, 0.77), radial strain (ES: LP, 0.58; NLP, 0.48), and radial strain rate (ES: LP, 0.87; NLP, 0.17) in both groups (time for all: p ≤ 0.01). All other parameters of cardiac function remained similar. In conclusion, NLP and LP led to similar improvements in 3D LVEF and radial strain, suggesting a favourable positive cardiac remodelling through myofibers reorganization. These findings must be investigated in patients with more severe cardiac dysfunction. The study was registered on ClinicalTrials.gov (NCT03443193). Novelty: Linear and nonlinear periodization programs improved radial strain, accompanied by improvement of ejection fraction. Both aerobic periodization programs did not negatively impact cardiac function in coronary artery disease patients.

Women and men with coronary heart disease respond similarly to different aerobic exercise training modalities: a pooled analysis of prospective randomized trials.

We aimed to compare cardiopulmonary exercise test (CPET) parameters, cardiac adaptations, and proportion of responders after different aerobic training programs amongst women and men with coronary heart disease (CHD). Patients with CHD were evaluated with a CPET and echocardiography before and after 3 months of aerobic exercise training. Peak oxygen uptake exercise training response was assessed according to the median peak oxygen uptake change for post- versus pretraining in the whole cohort (stratification non/low responders (NLR) vs. high-responders) and normalized for lean body mass (LBM). Eighty-three CHD patients were included (19 women, 64 men; 27 patients with interval, 19 with continuous, and 37 with combination exercises). Peak oxygen uptake, peak workload normalized for LBM, pulmonary variables (i.e., ventilation and oxygen uptake efficiency slope), and O2 pulse were significantly lower in women versus men. These parameters improved similarly with training in both sexes (p < 0.05). There were no differences in the proportion of NLR among women and men with CHD (7/19 (37%) vs. 35/64 (55%), p = 0.1719). Left ventricular ejection fraction and mean peak early diastolic mitral annulus velocity improved similarly with training in both sexes (p < 0.05). Women and men with CHD have a similar exercise training response regarding key CPET and echocardiographic parameters. The proportion of responders is similar. ClinicalTrials.gov: NCT03414996, NCT02048696, NCT03443193. Novelty: Cardiopulmonary adaptations to exercise training are similar among CHD men and women. Proportion of peak oxygen uptake for non/low/high responders is similar in CHD men and women. Left ventricular systolic and diastolic function improved similarly after exercise training in CHD men and women.

El ejercicio continuo de moderada intensidad es superior al ejercicio interválico de alta intensidad en mejorar el VO2 pico en pacientes tras SCA / Moderate-intensity continuous exercise is superior to high-intensity interval training in the proportion of VO2peak responders after ACS

INTRODUCCIÓN Y OBJETIVOS: Se comparó los efectos de 12 semanas de ejercicio interválico de alta intensidad y de bajo volumen (EIAI-BV) frente a un ejercicio continuo de intensidad moderada (ECIM), sobre los parámetros de la prueba de esfuerzo cardiopulmonar y la proporción de no respondedores o con baja respuesta (NBR) al ejercicio físico en pacientes que sufrieron un síndrome coronario agudo (SCA). MÉTODOS: Se aleatorizó a pacientes con un SCA reciente a EIAI-BV, ECIM y a cuidados habituales. EIAI-BV constó de 2 a 3 sesiones de 6-10 minutos con periodos de repetición de 15 a 30 s al 100% de la carga de trabajo alternados con 15-30 segundos de recuperación pasiva. Los parámetros de la prueba de ejercicio cardiopulmonar se evaluaron y se calcularon las variables claves. La respuesta al ejercicio se evaluó con la mediana de VO2 pico de cambio (post- frente a preejercicio) en toda la cohorte estratificada en NBR al ejercicio frente a alta respuesta. RESULTADOS: Se incluyó a 50 pacientes en el análisis (EIAI-BV, n=23; ECIM, n=18; cuidados habituales, n=9), el 74% eran varones. La proporción de NBR fue mayor en el EIAI-BV en comparación con el grupo ECIM y el grupo de cuidados habituales (el 61 frente al 21 y el 80%, respectivamente; p = 0,0040). Las variables dependientes del VO2 (VO2 pico y porcentaje VO2 pico predicho) mejoraron en ambos grupos de entrenamiento (p = 0,002 y p <0,0001 para EIAI-BV y ECIM, respectivamente), pero la mejora fue más pronunciada con ECIM (p = 0,004 y p = 0,001 para la interacción, respectivamente). El ΔVO2 /Δ pendiente de la carga de trabajo ha mejorado únicamente con ECIM (p = 0,021). CONCLUSIONES: En pacientes con un SCA reciente, varias variables pronósticas dependientes del VO2 pico mejoraron después de EIAI-BV, pero la mejora fue más pronunciada o bien mejoró únicamente después de ECIM. El EIAI-BV resultó en una mayor proporción de NBR en comparación con el ECIM isocalórico

INTRODUCTION AND OBJECTIVES: We compared the effects of 12 weeks of low-volume high-intensity interval training (LV-HIIT) vs moderate-intensity continuous exercise training (MICET) on cardiopulmonary exercise test parameters and the proportion of non/low responders (NLR) to exercise training in post-acute coronary syndrome (ACS) patients. METHODS: Patients with a recent ACS were randomized to LV-HIIT, MICET, or a usual care group. LV-HIIT consisted of 2 to 3 sets of 6 to 10minutes with repeated bouts of 15 to 30seconds at 100% of peak workload alternating with 15 to 30seconds of passive recovery. Cardiopulmonary exercise test parameters were assessed, and key exercise variables were calculated. Training response was assessed according to the median VO2peak change post vs pretraining in the whole cohort (stratification NLR vs high response). RESULTS: Fifty patients were included in the analysis (LV-HIIT, n=23; MICET, n=18; usual care, n=9) and 74% were male. The proportion of NLR was higher in the LV-HIIT group than in the MICET group (LV-HIIT 61%, MICET 21%, and usual care 80%; P=.0040). VO2peak-dependent variables (VO2peak, percent-predicted VO2peak) improved in both training groups (P=.002 and P <.0001 for time with LV-HIIT and MICET, respectively), but the improvement was more pronounced with MICET (P=.004 and P=.001 for interaction, respectively). The ΔVO2/Δworkload slope improved only with MICET (P=.021). CONCLUSIONS: In patients with a recent ACS, several prognostic VO2peak-dependent variables were improved after LV-HIIT, but the improvement was more pronounced or only found after MICET. Low-volume HIIT resulted in a higher proportion of NLR than isocaloric MICET

Obese but Fit: The Benefits of Fitness on Cognition in Obese Older Adults.

BACKGROUND: Obesity is associated with an accelerated cognitive decline. Aerobic fitness has a protective effect on cognition in older adults, but no study has investigated this effect in obese individuals. The present study aimed to 1) compare cognitive function in lower-fit (LoFit) and higher-fit (HiFit) obese individuals compared with nonobese individuals, and 2) examine the association between exercise variables (including hemodynamic variables) and cognitive function in obese individuals. METHODS: Fifty-four obese and 16 nonobese individuals performed a maximal cardiopulmonary exercise test (with gas exchange analysis and noninvasive hemodynamic measurement) and cognitive tests assessing short-term and working memory, processing speed, executive function, and long-term verbal memory. Obese individuals were divided into 2 groups according to their median aerobic fitness divided by lean body mass to form a group of LoFit obese (n = 27) and a group of HiFit obese (n = 27) individuals. RESULTS: A total of 14 nonobese individuals and 49 obese individuals were included in the final analysis (HiFit: n = 26, LoFit: n = 23). Compared with LoFit obese, HiFit obese participants had greater performances in executive function (P = 0.002) and short-term memory (P = 0.02). Nonobese and HiFit obese participants showed equivalent performances in all domains of cognition. In obese individuals, aerobic fitness was the only independent predictor for short-term memory (R2 = 0.24; P < 0.001), working memory (R2 = 0.16; P = 0.02), processing speed (R2 = 0.22; P = 0.01), and executive function (R2 = 0.49; P = 0.003), but not for long-term verbal memory (R2 = 0.15; P = 0.26). CONCLUSIONS: HiFit obese individuals showed greater short-term memory and executive function performances compared with LoFit obese individuals, suggesting that aerobic fitness could help preserve cognitive function despite the presence of obesity.

Moderate-intensity continuous exercise is superior to high-intensity interval training in the proportion of VO2peak responders after ACS.

INTRODUCTION AND OBJECTIVES: We compared the effects of 12 weeks of low-volume high-intensity interval training (LV-HIIT) vs moderate-intensity continuous exercise training (MICET) on cardiopulmonary exercise test parameters and the proportion of non/low responders (NLR) to exercise training in post-acute coronary syndrome (ACS) patients. METHODS: Patients with a recent ACS were randomized to LV-HIIT, MICET, or a usual care group. LV-HIIT consisted of 2 to 3 sets of 6 to 10minutes with repeated bouts of 15 to 30seconds at 100% of peak workload alternating with 15 to 30seconds of passive recovery. Cardiopulmonary exercise test parameters were assessed, and key exercise variables were calculated. Training response was assessed according to the median VO2peak change post vs pretraining in the whole cohort (stratification NLR vs high response). RESULTS: Fifty patients were included in the analysis (LV-HIIT, n=23; MICET, n=18; usual care, n=9) and 74% were male. The proportion of NLR was higher in the LV-HIIT group than in the MICET group (LV-HIIT 61%, MICET 21%, and usual care 80%; P=.0040). VO2peak-dependent variables (VO2peak, percent-predicted VO2peak) improved in both training groups (P=.002 and P <.0001 for time with LV-HIIT and MICET, respectively), but the improvement was more pronounced with MICET (P=.004 and P=.001 for interaction, respectively). The ΔVO2/Δworkload slope improved only with MICET (P=.021). CONCLUSIONS: In patients with a recent ACS, several prognostic VO2peak-dependent variables were improved after LV-HIIT, but the improvement was more pronounced or only found after MICET. Low-volume HIIT resulted in a higher proportion of NLR than isocaloric MICET. Clinical trialsregistered at ClinicalTrials.gov (Identifiers: NCT03414996 and NCT02048696).

The impact of high-intensity interval training on ventricular remodeling in patients with a recent acute myocardial infarction-A randomized training intervention pilot study.

BACKGROUND: Aerobic exercise training is associated with beneficial ventricular remodeling and an improvement in cardiac biomarkers in chronic stable heart failure. High-intensity interval training (HIIT) is a time-efficient method to improve V ˙ O 2 peak in stable coronary heart disease patients. This pilot study aimed to compare the effect of HIIT on ventricular remodeling in patients with a recent acute myocardial infarction (AMI). METHODS: Nineteen post-AMI patients were randomized to either HIIT (n = 9) or usual care (n = 10). A cardiopulmonary exercise test (CPET), transthoracic echocardiography, and cardiac biomarker assessment (ie, N-terminal pro B-type natriuretic peptide levels and G protein-coupled receptor kinase 2 expression) were performed before and after a 12-week training intervention. CPET parameters including oxygen uptake efficiency slope (OUES) and V ˙ O 2 at the first ventilatory threshold ( V ˙ O 2 VT1) were calculated. left ventricular (LV) structural and functional echocardiographic parameters including myocardial strain imaging were assessed. RESULTS: V ˙ O 2 peak and OUES improved solely in the HIIT group (P < .05 for group/time, respectively). There was a significant training effect for the improvement of peak work load in both groups (P < .05). O2 pulse and V ˙ O 2 at VT1 both improved only in the HIIT group (P < .05 for time, no interaction). HIIT improved radial strain and pulsed-wave tissue Doppler imaging derived e' (P < .05 for time, no interaction). Cardiac biomarkers did not change in either group. CONCLUSIONS: In post-AMI patients, HIIT lead to significant improvements in prognostic CPET parameters compared to usual care. HIIT was associated with favorable ventricular remodeling regarding certain echocardiographic parameters of LV function.

Ambulatory blood pressure reduction following 2 weeks of high-intensity interval training on an immersed ergocycle.

BACKGROUND: Hypertension guidelines recommend moderate-intensity continuous training (MICT) for the primary or secondary prevention of hypertension. However, alternative modalities, such as high-intensity interval training (HIIT) on dry land or in water, have been studied less widely. AIM: To assess chronic blood pressure (BP) response to a 2-week training programme involving six sessions of either MICT or HIIT performed on dry land or HIIT performed in an immersed condition, in participants with baseline office systolic/diastolic BP (SBP/DBP)≥130/85mmHg. METHODS: We randomly assigned 42 individuals (mean age 65±7 years; 52% men) with baseline office SBP/DBP≥130/85mmHg to perform six 24-minute sessions on an ergocycle (three times a week for 2 weeks) of either MICT on dry land, HIIT on dry land or HIIT in a swimming pool, and assessed BP responses using 24-hour ambulatory BP monitoring. RESULTS: While 2-week MICT and HIIT on dry land modified none of the 24-hour average haemodynamic variables significantly, immersed HIIT induced a significant decrease in 24-hour BP (SBP -5.1±7.3 [P=0.02]; DBP -2.9±4.1mmHg [P=0.02]) and daytime BP (SBP -6.2±8.3 [P=0.015]; DBP -3.4±4.0mmHg [P=0.008]), and slightly improved 24-hour and daytime pulse wave velocity (PWV) (24-hour PWV -0.17±0.23m/s [P=0.015]; daytime PWV -0.18±0.24m/s [P=0.02]). CONCLUSION: HIIT on an immersed stationary ergocycle is an innovative method that should be considered as an efficient non-pharmacological treatment of hypertension. As such, it should now be implemented in a larger cohort to study its long-term effects on the cardiovascular system.

Effects of interval training on risk markers for arrhythmic death: a randomized controlled trial.

OBJECTIVE: To compare the effects of high-intensity interval training versus moderate-intensity continuous training on risk markers of arrhythmic death in patients who recently suffered from an acute coronary syndrome. DESIGN: Double-blind (patient and evaluator) randomized controlled trial. SETTING: Cardiovascular Prevention and Rehabilitation Centre (EPIC Centre) of the Montreal Heart Institute, Montreal, Canada. SUBJECTS: A total of 43 patients were randomized following an acute coronary syndrome. INTERVENTIONS: Patients were assigned to either high-intensity interval training (n = 18) or isocaloric moderate-intensity continuous training (n = 19), three times a week for a total of 36 sessions. MAIN MEASURES: Heart rate recovery for 5 minutes, heart rate variability for 24 hours, occurrence of ventricular arrhythmias, and QT dispersion were measured before and after the 36 sessions of training. RESULTS: Among the 43 patients randomized, 6 participants in the high-intensity interval training group stopped training for reasons unrelated to exercise training and were excluded from the analyses. Heart rate recovery improved solely in the high-intensity interval training group, particularly at the end of recovery period (p < 0.05). There were no differences in heart rate variability, occurrence of ventricular arrhythmias, or QT dispersion parameters between the groups at study end. CONCLUSION: Despite the lack of power to detect any large difference between the two interventions with respect to risk markers of arrhythmic death, high-intensity interval training appears safe and may be more effective at improving heart rate recovery relative to moderate-intensity continuous training in our patients following acute coronary syndrome.

Exercise Lowers Plasma Angiopoietin-Like 2 in Men with Post-Acute Coronary Syndrome.

Pro-inflammatory angiopoietin-like 2 (angptl2) promotes endothelial dysfunction in mice and circulating angptl2 is higher in patients with cardiovascular diseases. We previously reported that a single bout of physical exercise was able to reduce angptl2 levels in coronary patients. We hypothesized that chronic exercise would reduce angptl2 in patients with post-acute coronary syndrome (ACS) and endothelial dysfunction. Post-ACS patients (n = 40, 10 women) were enrolled in a 3-month exercise-based prevention program. Plasma angptl2, hs-CRP, and endothelial function assessed by scintigraphic forearm blood flow, were measured before and at the end of the study. Exercise increased VO2peak by 10% (p<0.05), but did not significantly affect endothelial function, in both men and women. In contrast, exercise reduced angptl2 levels only in men (-26±7%, p<0.05), but unexpectedly not in women (+30±16%), despite similar initial levels in both groups. Exercise reduced hs-CRP levels in men but not in women. In men, levels of angptl2, but not of hs-CRP, reached at the end of the training program were negatively correlated with VO2peak (r = -0.462, p = 0.012) and with endothelial function (r = -0.419, p = 0.033) measured at baseline: better initial cardiopulmonary fitness and endothelial function correlated with lower angptl2 levels after exercise. Pre-exercise angptl2 levels were lower if left ventricular ejection time was long (p<0.05) and the drop in angptl2 induced by exercise was greater if the cardiac output was high (p<0.05). In conclusion, in post-ACS men, angptl2 levels are sensitive to chronic exercise training. Low circulating angptl2 reached after training may reflect good endothelial and cardiopulmonary functions.

Lower Methylation of the ANGPTL2 Gene in Leukocytes from Post-Acute Coronary Syndrome Patients.

DNA methylation is believed to regulate gene expression during adulthood in response to the constant changes in environment. The methylome is therefore proposed to be a biomarker of health through age. ANGPTL2 is a circulating pro-inflammatory protein that increases with age and prematurely in patients with coronary artery diseases; integrating the methylation pattern of the promoter may help differentiate age- vs. disease-related change in its expression. We believe that in a pro-inflammatory environment, ANGPTL2 is differentially methylated, regulating ANGPTL2 expression. To test this hypothesis we investigated the changes in promoter methylation of ANGPTL2 gene in leukocytes from patients suffering from post-acute coronary syndrome (ACS). DNA was extracted from circulating leukocytes of post-ACS patients with cardiovascular risk factors and from healthy young and age-matched controls. Methylation sites (CpGs) found in the ANGPTL2 gene were targeted for specific DNA methylation quantification. The functionality of ANGPTL2 methylation was assessed by an in vitro luciferase assay. In post-ACS patients, C-reactive protein and ANGPTL2 circulating levels increased significantly when compared to healthy controls. Decreased methylation of specific CpGs were found in the promoter of ANGPTL2 and allowed to discriminate age vs. disease associated methylation. In vitro DNA methylation of specific CpG lead to inhibition of ANGPTL2 promoter activity. Reduced leukocyte DNA methylation in the promoter region of ANGPTL2 is associated with the pro-inflammatory environment that characterizes patients with post-ACS differently from age-matched healthy controls. Methylation of different CpGs in ANGPTL2 gene may prove to be a reliable biomarker of coronary disease.

Ambulatory blood pressure reduction following high-intensity interval exercise performed in water or dryland condition.

We aimed to compare blood pressure (BP) responses following moderate-intensity continuous exercise (MICE), high-intensity interval exercise (HIIE) in dry land or HIIE in immersed condition, using 24-hour ambulatory BP monitoring. Forty-two individuals (65 ± 7 years, 52% men) with a baseline BP ≥ 130/85 mm Hg (systolic/diastolic blood pressures [SBP/DBP]) were randomly assigned to perform one of the three following exercises on a stationary cycle: MICE (24 minutes at 50% peak power output) or HIIE in dry land (two sets of 10 minutes with phases of 15 seconds 100% peak power output interspersed by 15 seconds of passive recovery) or HIIE in up-to-the-chest immersed condition. While MICE modified none of the 24-hour average hemodynamic variables, dryland HIIE induced a 24-hour BP decrease (SBP: -3.6 ± 5.7/DBP: -2.8 ± 3.0 mm Hg, P < .05) and, to a much greater extent, immersed HIIE (SBP: -6.8 ± 9.5/DBP: -3.0 ± 4.5 mm Hg, P < .05). The one condition that modified 24-hour pulse-wave velocity was immersed HIIE (-0.21 ± 0.30 m/s, P < .05).

Acute High-Intensity Intermittent Aerobic Exercise Reduces Plasma Angiopoietin-Like 2 in Patients With Coronary Artery Disease.

BACKGROUND: Circulating levels of angiopoietin-like 2 (ANGPTL2), a proinflammatory and proatherogenic protein, are elevated in patients with coronary artery disease (CAD). We hypothesized that high-intensity intermittent exercise (HIIE), known to be beneficial in patients with CAD, would reduce circulating ANGPTL2 levels. METHODS: Plasma levels of ANGPTL2 were measured before and 20 minutes, 24 hours, and 72 hours after an acute exercise session in a crossover study comparing HIIE to moderate-intensity continuous exercise (MICE) in 14 patients with CAD and 20 age-matched and 20 young healthy controls. RESULTS: Pre-exercise ANGPTL2 levels were 3-fold higher in patients with CAD than in age-matched controls (P < 0.05) and correlated negatively with Vo2max/lean body mass (P < 0.0001). In healthy controls, ANGPTL2 levels were low and not affected by HIIE or MICE. In patients with CAD, ANGPTL2 levels decreased significantly by 41% after 20 minutes of HIIE, a reduction that was maintained after 24 and 72 hours (P < 0.05). In contrast, although ANGPTL2 levels decreased by 47% after 20 minutes of MICE, they increased by 104% after 24 hours and returned to baseline values after 72 hours (P < 0.05). A negative correlation was observed between this increase in ANGPTL2 levels and the mean rate-pressure product (heart rate × systolic blood pressure; index of myocardial O2 consumption) measured during MICE, suggesting that subclinical ischemia might promote ANGPTL2 expression. CONCLUSIONS: In patients with CAD, circulating ANGPTL2 levels are acutely reduced after HIIE and transiently increased after MICE. A sustained reduction in circulating ANGPTL2 levels could contribute to the chronic beneficial cardiometabolic effects of HIIE in patients with CAD.

Forearm reactive hyperemic blood flow and arm-cranking exercise capacity in healthy and heart failure subjects.

BACKGROUND: The relationship between lower limbs maximal vasodilatory capacity and exercise capacity in congestive heart failure (CHF) and healthy subjects has been well-documented. However, the relationship between upper limbs maximal vasodilatory capacity and exercise is less well-established. METHODS AND RESULTS: Twelve patients with CHF, 16 age-matched normal subjects, and 11 very fit individuals underwent an arm-cranking exercise test using maximal oxygen uptake (arm VO(2max)) and measurements of peak forearm reactive hyperemic blood flow. Despite similar forearm strength, arm VO(2max) was significantly reduced in patients with CHF when compared to normal and very fit individuals (13.9 +/- 2.9, 23.5 +/- 4.8, and 36.4 +/- 8.5 mL/kg/min, respectively, P <.05). Similarly, peak reactive hyperemia was lower in CHF patients as compared to normal and very fit individuals (18.6 +/- 5.9, 24.3 +/- 5.8, and 41.1 +/- 8.1 mL/100 mL/min, respectively, P <.05). There was a strong relationship between peak reactive hyperemic blood flow and arm VO(2max) (r =.75; P <.001) in all subjects. CONCLUSIONS: These results suggest a significant relationship between forearm vasodilatory capacity and arm-cranking VO(2max) in CHF patients, sedentary, and very fit individuals.