Cardio-Oncology Rehabilitation for Cancer Survivors With High Cardiovascular Risk: A Randomized Clinical Trial.

Importance: Cardiovascular disease is a leading cause of morbidity in cancer survivors, which makes strategies aimed at mitigating cardiovascular risk a subject of major contemporary importance. Objective: To assess whether a center-based cardiac rehabilitation (CBCR) framework compared with usual care encompassing community-based exercise training (CBET) is superior for cardiorespiratory fitness improvement and cardiovascular risk factor control among cancer survivors with high cardiovascular risk. Design, Setting, and Participants: This prospective, single-center, randomized clinical trial (CORE trial) included adult cancer survivors who had exposure to cardiotoxic cancer treatment and/or previous cardiovascular disease. Enrollment took place from March 1, 2021, to March 31, 2022. End points were assessed at baseline and after the 8-week intervention. Interventions: Participants were randomly assigned in a 1:1 ratio to 8 weeks of CBCR or CBET. The combined aerobic and resistance exercise sessions were performed twice a week. Main Outcomes and Measures: The powered primary efficacy measure was change in peak oxygen consumption (V̇o2) at 2 months. Secondary outcomes included handgrip maximal strength, functional performance, blood pressure (BP), body composition, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), lipid profile, plasma biomarker levels, physical activity (PA) levels, psychological distress, quality of life (QOL), and health literacy. Results: A total of 75 participants completed the study (mean [SD] age, 53.6 [12.3] years; 58 [77.3%] female), with 38 in the CBCR group and 37 in the CBET group. Participants in CBCR achieved a greater mean (SD) increase in peak V̇o2 than those in CBET (2.1 [2.8] mL/kg/min vs 0.8 [2.5] mL/kg/min), with a between-group mean difference of 1.3 mL/kg/min (95% CI, 0.1-2.6 mL/kg/min; P = .03). Compared with the CBET group, the CBCR group also attained a greater mean (SD) reduction in systolic BP (-12.3 [11.8] mm Hg vs -1.9 [12.9] mm Hg; P < .001), diastolic BP (-5.0 [5.7] mm Hg vs -0.5 [7.0] mm Hg; P = .003), and BMI (-1.2 [0.9] vs 0.2 [0.7]; P < .001) and greater mean (SD) improvements in PA levels (1035.2 [735.7] metabolic equivalents [METs]/min/wk vs 34.1 [424.4] METs/min/wk; P < .001), QOL (14.0 [10.0] points vs 0.4 [12.9] points; P < .001), and health literacy scores (2.7 [1.6] points vs 0.1 [1.4] points; P < .001). Exercise adherence was significantly higher in the CBCR group than in the CBET group (mean [SD] sessions completed, 90.3% [11.8%] vs 68.4% [22.1%]; P < .001). Conclusion and Relevance: The CORE trial showed that a cardio-oncology rehabilitation model among cancer survivors with high cardiovascular risk was associated with greater improvements in peak V̇o2 compared with usual care encompassing an exercise intervention in a community setting. The CBCR also showed superior results in exercise adherence, cardiovascular risk factor control, QOL, and health literacy. Trial Registration: ClinicalTrials.gov Identifier: NCT05132998.

"What do we think?": a qualitative exploratory study of acceptability and experiences of individuals with resistant hypertension after completing a physical exercise program (the EnRICH trial).

Purpose: Aerobic exercise training programs decrease blood pressure in individuals with resistant hypertension. However, participants' experiences regarding exercise training participation are unknown and often undervalued. Therefore, participant's experiences and program acceptability of the exercise arm of the EnRicH trial, a randomized clinical trial investigating the effect of a 12-week aerobic exercise training program in individuals with resistant hypertension were analysed.Methods: An exploratory qualitative study was conducted with twenty individuals with resistant hypertension (11 males, mean age 58.9 ± 8.9 years), after the exercise program. Four focus group interviews were performed to explore participants' perspectives. The interviews were digitally audio-recorded, transcribed verbatim, and subjected to thematic analysis.Results: Five themes emerged from the data analyses: 1) main impacts of participating in the exercise program; 2) facilitators of adherence; 3) perceived barriers; 4) perception of the program structure; and 5) global satisfaction with the program. Positive physical and emotional changes were reported, associated with reduced perceived stress and irritability, and decreased blood pressure. Adherence to the exercise program was facilitated by personalized supervision and feedback, the personal commitment to attend the training sessions, and different schedule options. Lack of motivation, peer support, physical health limitations, and difficulty in conciliating schedules were identified as barriers to the maintenance of exercise training after the program.Conclusion: The qualitative analysis demonstrates the acceptability of the program. Peer and health professional's support, commitment to health professionals, and boosting individual-perceived advantages are key-points to promote participants adherence.Implications for RehabilitationExercising in small groups seems to provide peer support, facilitating maintenance of exercise trainingProviding feedback on the health gains achieved by participants is important to increase adherence to exerciseEstablishing good and empathic communication between health professionals and participants facilitates adherence to exercise trainingProviding personal nutritional counselling may improve patient satisfactionIndividually tailored exercise programs may facilitate exercising for participants with physical limitationsProviding different training schedules may increase adherence and maintenance of exercise training.

Wearable Devices for Physical Activity and Healthcare Monitoring in Elderly People: A Critical Review.

The availability of wearable devices (WDs) to collect biometric information and their use during activities of daily living is significantly increasing in the general population. These small electronic devices, which record fitness and health-related outcomes, have been broadly utilized in industries such as medicine, healthcare, and fitness. Since they are simple to use and progressively cheaper, they have also been used for numerous research purposes. However, despite their increasing popularity, most of these WDs do not accurately measure the proclaimed outcomes. In fact, research is equivocal about whether they are valid and reliable methods to specifically evaluate physical activity and health-related outcomes in older adults, since they are mostly designed and produced considering younger subjects' physical and mental characteristics. Additionally, their constant evolution through continuous upgrades and redesigned versions, suggests the need for constant up-to-date reviews and research. Accordingly, this article aims to scrutinize the state-of-the-art scientific evidence about the usefulness of WDs, specifically on older adults, to monitor physical activity and health-related outcomes. This critical review not only aims to inform older consumers but also aid researchers in study design when selecting physical activity and healthcare monitoring devices for elderly people.

Low- and moderate-intensity aerobic exercise acutely reduce blood pressure in adults with high-normal/grade I hypertension.

The aim of the study is to compare the acute effects of low- and moderate-intensity aerobic exercise on post-exercise blood pressure in active adults with high-normal/grade I hypertension. Thirteen physically active adults (67.0 ± 8.7 years) randomly completed two aerobic exercise sessions of 30 minutes at low (30% heart rate reserve [HRres]) and moderate (60% HRres) intensity. Blood pressure was assessed pre-session and every hour until 3 hours after. Systolic blood pressure decreased after both exercise intensities without significant differences between sessions at 1 hour after the session (30%: -10.0 ± 12.6% vs 60%: -11.4 ± 12.7 mm Hg, P > .05). Three hours after the 60% session, the systolic blood pressure remained significantly lower than baseline (139.9 ± 12.9 to 129.3 ± 11.9 mm Hg, P < .05), but without significant differences between sessions. No relevant changes were observed in diastolic and mean blood pressure. In conclusion, a single session of aerobic exercise acutely reduces systolic blood pressure in active adults with high-normal/grade I hypertension.

Arterial Stiffness is Associated With Moderate to Vigorous Physical Activity Levels in Post-Myocardial Infarction Patients.

PURPOSE: Arterial stiffness has shown independent predictive value for all-cause and cardiovascular mortalities, as well as fatal and nonfatal coronary events. Physical activity (PA) is associated with reduced cardiovascular morbidity and mortality. The study aims to analyze the cross-sectional association of arterial stiffness with objectively measured PA in patients following acute myocardial infarction. METHODS: One hundred patients were consecutively recruited after experiencing an acute myocardial infarction. Central arterial stiffness was measured through carotid-femoral pulse wave velocity (cf-PWV) and daily PA was assessed objectively during 7 consecutive days with accelerometers. To be valid, data required recordings of at least 8 hr/d on 5 d. RESULTS: The cf-PWV showed a negative and significant association with total weekly time spent in moderate to vigorous PA (MVPA) (r = -0.416, P < .001). Patients classified as having higher risk according to arterial stiffness values (cf-PWV ≥10 m/sec) showed significantly lower time spent in MVPA than those below that threshold. The cf-PWV was significantly lower in patients performing >300 min of MVPA/wk than in those performing <150 min/wk (8.53 ± 2.08 vs 10.3 ± 2.44 m/sec, P = .021). Differences remained significant after adjustment for several confounders. CONCLUSIONS: Moderate to vigorous PA was inversely associated with arterial stiffness and time spent in MVPA was lower in patients after acute myocardial infarction, with cf-PWV above the risk threshold value (≥10 m/sec). These results seem to reinforce the importance of PA as a nonpharmacological tool for secondary cardiovascular prevention.

Arterial Stiffness is Related to Impaired Exercise Capacity in Patients With Coronary Artery Disease and History of Myocardial Infarction.

BACKGROUND: Augmented arterial stiffness and reduced cardiorespiratory fitness are associated with increased morbidity and mortality from coronary artery disease (CAD). The relationship between exercise capacity and arterial stiffness is independent of known influencing variables in CAD. This study aimed to analyse the interaction between exercise capacity, arterial stiffness and early vascular ageing in patients with CAD. METHODS: This cross-sectional study included 96 CAD patients with myocardial infarction (55.9±10.9years, 81 men) referred to cardiac rehabilitation. Arterial stiffness was assessed using carotid-femoral pulse wave velocity (cf-PWV). Cardiopulmonary exercise test was performed to measure VO2peak. Comparisons of VO2peak across cf-PWV risk threshold values (high-risk cf-PWV≥10m/s) and tertile groups, and across cf-PWV threshold values and age groups (younger group<60 years) were performed. Correlation tests were used to study the association between pair of variables. RESULTS: Patients with high-risk cf-PWV had lower VO2peak than those with low-risk cf-PWV (p<0.001). VO2peak decreased across tertiles of cf-PWV, showing significantly lower values in the third tertile (p<0.001). There were no differences in the VO2peak between younger patients with high-risk cf-PWV and older patients irrespective of their cf-PWV values. VO2peak showed an upward trend in younger patients with low-risk cf-PWV compared to their age-mates with high-risk cf-PWV (p=0.09). VO2peak was strongly and inversely correlated with cf-PWV (r=-0.502, p<0.001). CONCLUSIONS: Arterial stiffening is associated with lower cardiorespiratory fitness in CAD patients with myocardial infarction. When its values are above risk threshold, exercise capacity is impaired regardless of the relationship between age and arterial stiffness.

Effect of exercise-based cardiac rehabilitation on arterial stiffness and inflammatory and endothelial dysfunction biomarkers: a randomized controlled trial of myocardial infarction patients.

BACKGROUND: Arterial stiffness have shown an independent predictive value for cardiovascular and all-cause mortality. OBJECTIVE: This study sought to evaluate the effects of an 8-week exercise-based cardiac rehabilitation program (ECR) on arterial stiffness, and on inflammatory and endothelial dysfunction biomarkers. Additionally, it was assessed two potential confounding variables, daily physical activity and dietary intake. METHODS: In this parallel-group trial, 96 patients (56 ± 10 years) were randomized to either the exercise group (EG) or control group (CG) 4 weeks after suffering acute myocardial infarction (MI). ECR consisted of 8 weeks of aerobic exercise at 70-85% of maximal heart rate during 3 sessions weekly, plus usual care. CG participants received only usual care. Baseline and final assessments included arterial stiffness through carotid-femoral pulse wave velocity (cf-PWV), inflammatory and endothelial dysfunction biomarkers, daily physical activity, and dietary intake. (ClinicalTrials.gov: NCT01432639). RESULTS: After 8 weeks, no significant changes were found between groups in cf-PWV, inflammatory and endothelial dysfunction biomarkers, daily physical activity, or dietary intake. Excluding those patients (n = 7) who did not attend, at least 80% of the exercise sessions provided similar results, excepting a significant reduction in cf-PWV in the EG compared to the CG. CONCLUSIONS: A short-term ECR does not seem to reduce arterial stiffness and inflammatory and endothelial dysfunction biomarkers of post-MI patients under optimized medication. Nevertheless, the decrease of cf-PWV observed in the EG, when considering only those patients who attended at least 80% of exercise sessions, warrants further investigation.

Effect of 8-week exercise-based cardiac rehabilitation on cardiac autonomic function: A randomized controlled trial in myocardial infarction patients.

PURPOSE: The purpose of this study is to evaluate the effects of an 8-week exercise-based cardiac rehabilitation program on traditional and nonlinear heart rate variability (HRV) indexes, assessing the potential confounding influences of habitual physical activity (PA) and dietary intake. METHODS: In this parallel-group trial, 96 patients (56 ± 10 years old) were randomized to the exercise group (EG) or to the control group (CG) 4 weeks after an acute myocardial infarction. Exercise-based cardiac rehabilitation program consisted of aerobic exercise at 70% to 85% of maximal heart rate for 3 sessions per week plus usual care. The CG received only usual care. The baseline and final assessments comprised resting short-term HRV (primary outcome) by a Polar R-R recorder under controlled breathing (12 breaths per minute), habitual PA by accelerometers, and dietary intake by a 4-day food diary. RESULTS: Two patients in each group dropped out and were not included in the intention-to-treat analysis. In the remaining 92 patients (EG = 47 and CG = 45), at baseline, only a difference in the proportion of nitrate medication use was significant between groups. After 8 weeks, no significant changes were found between groups on traditional and nonlinear HRV indexes (eg, ln HF, EG from 5.7 ± 1.5 to 5.9 ± 1.3 and CG from 5.5 ± 1.6 to 5.5 ± 1.5), habitual PA, and dietary intake. CONCLUSION: Eight weeks of exercise-based cardiac rehabilitation program is an insufficient stimulus to improve cardiac autonomic function in post-myocardial infarction patients under optimal medication and with high levels of traditional and nonlinear HRV indexes at baseline.

The effects of exercise training on arterial stiffness in coronary artery disease patients: a state-of-the-art review.

The purpose of this state-of-the-art review was to examine the effects of exercise training on arterial stiffness (AS) in patients with coronary artery disease (CAD). A PubMed and SCOPUS literature search was conducted up to March of 2013. Two authors performed the selection of the studies and the subsequent data extraction (e.g. information on study design, exercise programme characteristics and outcome measures). Of 34 papers identified, only five studies met the inclusion criteria, with no one being a randomized controlled trial. Within the selected studies, the sample size varied between 28 and 119 patients, with mean ages ranging from 48 to 67 years old in patients with CAD after an acute myocardial infarction, coronary artery bypass graft or percutaneous transluminal coronary angioplasty. Although all studies utilized the aerobic exercise mode, the other characteristics of the exercise programmes varied largely between the studies: programme length (from 6 to 20 weeks), exercise duration (15-20 to 50 min) and exercise intensity, which was based on heart rate reserve (40 to 85%) or heart rate at anaerobic threshold or ventilatory threshold. All the three studies evaluating pulse wave velocity, as well as one of two studies that assessed the augmentation index, reported significant reductions on those variables after exercise training. Results indicated that the majority of the AS and related measures improved after the different exercise training programmes. However, these results need to be confirmed in future randomized clinical studies controlling potential confounders.

Heart rate variability in myocardial infarction patients: effects of exercise training.

Heart rate variability (HRV) is a simple and noninvasive measure that estimates cardiac autonomic modulation, mainly the parasympathetic contribution. Increased sympathetic and/or decreased parasympathetic nervous activity is seen in post-myocardial infarction (MI) patients. Consequently, these patients present reduced HRV, which has been associated with increased risk of adverse events and mortality. Exercise training, recommended as a complementary therapy for patients with cardiovascular disease, has shown numerous beneficial effects. The main aim of the present manuscript was to provide a critical review of studies investigating the effects of exercise training on cardiac autonomic modulation, through HRV, in MI patients and the possible mechanisms involved. Despite conflicting evidence, exercise training appears to be a useful therapeutic intervention to improve the unbalanced autonomic function of MI patients. Finally, the mechanisms involved are not yet well understood, but nitric oxide bioavailability and angiotensin II levels seem to play an important role.

Exercise training enhances autonomic function after acute myocardial infarction: a randomized controlled study.

INTRODUCTION: Heart rate recovery, defined as the fall in heart rate during the first minute after exercise, is an indicator of autonomic function, and has been found to be an independent predictor of mortality after acute myocardial infarction. Exercise training has several well-known benefits in terms of cardiorespiratory fitness, modifiable cardiovascular risk factors and prognosis after acute coronary events. However, there are no randomized controlled studies in the literature evaluating the effects of exercise training per se, controlling for changes in medication and diet, on heart rate recovery. Thus, this study aims to assess the effects of exercise training on autonomic function in coronary artery disease patients recovering from acute myocardial infarction. METHODS: Thirty-eight patients following a first acute myocardial infarction participated in this prospective randomized clinical trial. Patients were randomized into two groups: exercise training or control. The exercise group participated in an 8-week aerobic exercise program, while the control received standard medical care and follow-up. Changes in hemodynamics at rest and at peak exercise (heart rate, systolic and diastolic blood pressure, and rate pressure product), dietary intake, cardiorespiratory fitness, and heart rate recovery were assessed. RESULTS: Medication and diet remained unchanged in both groups during the study period. The exercise-training group improved resting hemodynamics, particularly resting heart rate (from 68.0 ± 9.2 to 62.6 ± 8.7 bpm, p=0.030) and systolic blood pressure (from 135 ± 7.1 to 125.6 ± 11.3 mm Hg, p=0.012), cardiorespiratory fitness (from 30.8 ± 7.8 to 33.9 ± 8.3 ml/min/kg, p=0.016), and heart rate recovery (from 20 ± 6 to 24 ± 5 bpm, p=0.007). No significant changes were observed in the control group. CONCLUSIONS: Exercise training improved autonomic function, assessed by heart rate recovery, resting heart rate and systolic blood pressure, in the absence of changes in diet or medication.

Exercise training improves diastolic function in heart failure patients.

PURPOSE: The study's purpose was to analyze the effects of exercise training on exercise tolerance and left ventricular systolic function and structure in heart failure patients with preserved, mild, and moderate to severe reduction of left ventricular ejection fraction (LVEF). METHODS: Ninety-eight patients with moderate to severe (n = 34), mild (n = 33), and preserved (n = 31) LVEF were randomly assigned to exercise training plus usual care (n = 65) or usual care alone (n = 33) in a randomization ratio of 2:1. Left ventricular function, left ventricular dimensions, and exercise tolerance were assessed before and after each intervention. RESULTS: Exercise tolerance and LVEF increased with exercise training in all patient groups, whereas they remained unchanged after usual care alone. Exercise training increased the mean ratio of early to late mitral inflow velocities (E/A ratio) and decreased deceleration time (DT) of early filling in patients with mild and preserved LVEF. In patients with moderate to severe systolic dysfunction and advanced diastolic dysfunction (DT < 160 ms), exercise training decreased E/A ratio and increased DT, both of which were unchanged after usual care alone. In the remaining patients (DT > 160 ms), exercise training also improved mitral inflow patterns. Exercise training decreased left ventricular dimensions in patients with mild and moderate to severe reduction of LVEF but not in patients with preserved LVEF. CONCLUSIONS: These results indicate that exercise training can improve the course of heart failure independent of the degree of baseline left ventricular dysfunction.

Is the interaction between HIF1A P582S and ACTN3 R577X determinant for power/sprint performance?

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates gene expression in response to hypoxia and has been associated with athletic performance. The aims of this study were (1) to determine the frequency distribution of HIF1A Pro582Ser (rs11549465) polymorphism among 155 Israeli athletes (sprinters and endurance athletes) and 240 healthy controls and (2) to analyze the influence of the interaction between HIF1A Pro582Ser and ACTN3 R577X (rs1815739) genotypes on sprint performance. There were no differences across the HIF1A genotype and allele frequencies among endurance athletes, sprinters, and controls. Similarly, no differences were found between the subgroups of top-level and national-level endurance athletes, or between top-level and national-level sprinters. Conversely, interaction effects were found between HIF1A Pro582Ser and ACTN3 R577X polymorphisms and sprinters. The proportion of HIF1A Pro/Pro + ACTN3 R/R genotypes was significantly higher in sprinters than in endurance athletes and healthy controls (P = .002). In addition, the odds ratio for HIF1A Pro/Pro + ACTN3 R/R genotype carriers being a sprinter was 2.25 (95% confidence interval, 1.24-4.1); and that for HIF1A Pro/Pro + ACTN3 R/R genotype carriers being an endurance athlete was 0.5 (95% confidence interval, 0.2-1.24). We conclude that HIF1A Pro582Ser polymorphism by itself is not critical in determining sprint performance. However, sprinter performance is determined by the interaction between the wild-type HIF1A Pro/Pro genotype and ACTN3 RR genotype.

Interaction between SNPs in the NRF2 gene and elite endurance performance.

Nuclear respiratory factor 2 (NRF2), a member of the Cap-N-Collar family of transcription factors, plays an important role in the mitochondrial biogenesis, and variants of NRF2 gene have been associated with endurance performance. The aims of the present study were 1) to compare NRF2 A/C (rs12594956) and NRF2 C/T (rs8031031) genotype and allele frequencies between athletes of sports with different demands (endurance vs. sprinters) as well as between competitive levels (elite level vs. national level) and 2) to analyze the interaction of these two polymorphisms and its influence on the level of endurance performance. One hundred and fifty-five track and field athletes (74 endurance athletes and 81 sprinters) and 240 nonathletic healthy individuals participated in this study. Endurance athletes presented a higher frequency of the AA (rs12594956) and CT (rs8031031) genotypes than sprinters and the control group, as well as higher A and T alleles, respectively. These differences did not appear between the sprinters and control subjects. The odds ratio for harboring the "optimal genotype" (NRF2 AA+ NRF2 CT) was 4.53 (95% confidence interval 1.23-16.6) in the whole cohort of endurance athletes and 6.55 (95% confidence interval 1.12-38.25) in elite-level endurance athletes, compared with control subjects and both levels of sprinters. In conclusion, our data indicate that the NRF2 A/C and NRF2 C/T single nucleotide polymorphisms (SNPs) are associated, separately and in combination, with elite endurance athletes, which supports the notion that these specific gene variants might belong to a growing group of SNPs that are associated with endurance performance.

Is exercise training an effective therapy targeting endothelial dysfunction and vascular wall inflammation?

There is an increasing evidence that endothelial dysfunction and vascular wall inflammation are present in all stages of atherosclerosis. Atherosclerosis does not have to necessarily progress to an acute clinical event. Several therapeutic strategies exist, such as exercise training, which mitigates endothelial dysfunction and inflammation. Exercise training consistently improves the nitric oxide bioavailability, and the number of endothelial progenitor cells, and also diminishes the level of inflammatory markers, namely pro-inflammatory cytokines and C-reactive protein. However, the mechanisms by which exercise improves endothelial function in coronary artery disease patients are not fully clarified. Several mechanisms have been proposed to explain the positive effect of exercise on the disease progression. They include the decrease in cytokine production by the adipose tissue, skeletal muscles, endothelial cells, and blood mononuclear cells, and also, the increase in the bioavailability of nitric oxide, antioxidant defences, and regenerative capacity of endothelium. This study aims to provide a critical review of the literature linking exercise, inflammation, and endothelial dysfunction in coronary artery patients, and to discuss the potential mechanisms behind the exercise-training improvement of endothelial function and inflammatory status.

The effect of cardiac rehabilitation with relaxation therapy on psychological, hemodynamic, and hospital admission outcome variables.

PURPOSE: To examine the effect of a cardiac rehabilitation program with relaxation therapy (CPRT) in comparison with cardiac rehabilitation alone on psychological stress, hemodynamic variables, cardiac risk factors, and cardiac-related hospital admissions in patients with coronary artery disease. METHODS: Patients (N = 81) were randomly assigned to either a 12-week cardiac rehabilitation program alone (CPA) or a CPRT. Perceived stress, blood pressure, heart rate, rate-pressure product value, total cholesterol level, body mass index, smoking status, and physical activity were recorded at baseline and following the 12-week intervention. Cardiac-related hospital admissions were analyzed in a 2-year follow-up. RESULTS: Perceived stress declined in both groups, although this improvement was significantly superior in the CPRT (31.5 +/- 4.9 vs 23.4 +/- 4.1; P

Is there an interaction between PPARD T294C and PPARGC1A Gly482Ser polymorphisms and human endurance performance?

Functional Gly482Ser (rs8192678) and T294C (rs2016520) polymorphisms in the peroxisome proliferator-activated receptor gamma coactivator-1 (PPARGC1A) and peroxisome proliferator-activated receptor delta (PPARD) genes, respectively, have been associated with mRNA and/or protein activity. The aim of this study was to determine their frequency distribution among 155 Israeli athletes (endurance athletes and sprinters) and 240 healthy control subjects. There were no differences between the endurance athletes, the sprinters and the control group across the PPARD T294C genotypes (P = 0.62). Similarly, no statistical differences were found between the subgroups of elite-level endurance athletes (those who had represented Israel in a world track and field championship or in the Olympic Games) and national-level endurance athletes (P = 0.3), or between elite-level and national-level sprinters (P = 0.9). However, a combined influence of these two polymorphisms on endurance performance was found. The PPARD CC + PPARGC1A Gly/Gly genotypes were more frequently found in the elite endurance athletes than in national-level endurance athletes (P < 0.000). In the cohort of endurance athletes, the odds ratio of the 'optimal genotype' for endurance athletes (PPARD CC + PPARGC1A Gly/Gly + PPARGC1A Gly/Ser) being an elite-level athlete was 8.32 (95% confidence interval 2.2-31.4). In conclusion, the present study suggests that PPARD T294C is not associated with endurance performance. However, a higher frequency of the PPARGC1A Gly/Gly + PPARD CC genotype is associated with elite-level endurance athletes.

NRF2 intron 3 A/G polymorphism is associated with endurance athletes' status.

The aim of this study was to determine the frequency distribution of nuclear respiratory factor 2 (NRF2) intron 3 A/G polymorphism (rs7181866) among 155 Israeli athletes (endurance athletes and sprinters) and 240 healthy controls. Results showed that there was a significantly higher proportion of the AG genotype, rather than the AA genotype, in the group of endurance athletes compared with the sprinters (P = 0.014) and controls (P = 0.0008). However, the sprinters' genotype and allele frequencies were similar to those of the control group (P = 0.62 for genotype distribution percentage). These results were even more pronounced when we compared between the subgroups of 20 elite endurance athletes (those who had represented Israel in a world track-and-field championship or in the Olympic Games) and 54 national-level endurance athletes. In the group of elite endurance athletes the G allele was more frequent than in the national-level endurance athletes (P = 0.047). We conclude that 1) in Israeli athletes the NRF2 AG genotype is more frequent in elite endurance athletes than in sprinters, and 2) within the endurance group the NRF2 AG genotype and the G allele are more frequent in elite athletes, suggesting a positive association between the AG genotype, and possibly the G allele, and the likelihood of being an elite endurance athlete.