Exercise and Coronary Atherosclerosis: Observations, Explanations, Relevance, and Clinical Management.

Physical activity and exercise training are effective strategies for reducing the risk of cardiovascular events, but multiple studies have reported an increased prevalence of coronary atherosclerosis, usually measured as coronary artery calcification, among athletes who are middle-aged and older. Our review of the medical literature demonstrates that the prevalence of coronary artery calcification and atherosclerotic plaques, which are strong predictors for future cardiovascular morbidity and mortality, was higher in athletes compared with controls, and was higher in the most active athletes compared with less active athletes. However, analysis of plaque morphology revealed fewer mixed plaques and more often only calcified plaques among athletes, suggesting a more benign composition of atherosclerotic plaques. This review describes the effects of physical activity and exercise training on coronary atherosclerosis in athletes who are middle-aged and older and aims to contribute to the understanding of the potential adverse effects of the highest doses of exercise training on the coronary arteries. For this purpose, we will review the association between exercise and coronary atherosclerosis measured using computed tomography, discuss the potential underlying mechanisms for exercise-induced coronary atherosclerosis, determine the clinical relevance of coronary atherosclerosis in middle-aged athletes and describe strategies for the clinical management of athletes with coronary atherosclerosis to guide physicians in clinical decision making and treatment of athletes with elevated coronary artery calcification scores

Endurance exercise-induced changes in BNP concentrations in cardiovascular patients versus healthy controls.

BACKGROUND: Healthy athletes demonstrated increased B-type natriuretic peptide (BNP) concentrations following exercise, but it is unknown whether these responses are exaggerated in individuals with cardiovascular risk factors (CVRF) or disease (CVD). We compared exercise-induced increases in BNP between healthy controls (CON) and individuals with CVRF or CVD. Furthermore, we aimed to identify predictors for BNP responses. METHODS: Serum BNP concentrations were measured in 191 participants (60±12yrs) of the Nijmegen Marches before (baseline) and immediately after 4 consecutive days of walking exercise (30-50km/day). CVRF (n=54) was defined as hypertension, hypercholesterolemia, obesity or smoking and CVD (n=55) was defined as a history of myocardial infarction, heart failure, atrial fibrillation or angina pectoris. RESULTS: Individuals walked 487±79min/day at 65±10% of their maximum heart rate. Baseline BNP concentrations were higher for CVD (median: 28.1pg/ml; interquartile range: 13-50, p0.05). Predictors for post-exercise BNP (R(2)=0.77) were baseline BNP, beta-blocker use and age. CONCLUSION: Prolonged moderate-intensity walking exercise increases BNP concentrations in CVD participants, but not in CVRF and CON. BNP increases were small, and did not accumulate across consecutive days of exercise. These findings suggest that prolonged walking exercise for multiple consecutive days is feasible with minimal effect on myocardial stretch, even for participants with CVD

The Relationship Between Lifelong Exercise Volume and Coronary Atherosclerosis in Athletes.

Background -Higher levels of physical activity are associated with a lower risk of cardiovascular events. Nevertheless, there is debate on the dose-response relationship of exercise and CVD outcomes and whether high volumes of exercise may accelerate coronary atherosclerosis. We aimed to determine the relationship between lifelong exercise volumes and coronary atherosclerosis. Methods -Middle aged men engaged in competitive or recreational leisure sports underwent a non-contrast and contrast-enhanced computed tomography scan to assess coronary artery calcification (CAC) and plaque characteristics. Participants reported lifelong exercise history patterns. Exercise volumes were multiplied by Metabolic Equivalent of Task (MET) scores to calculate MET-min/week. Participants were categorized as 2000 MET-min/week. Results -284 men (55±7 years) were included. CAC was present in 150/284 (53%) participants with a median CAC score of 35.8 [9.3-145.8). Athletes with a lifelong exercise volume >2000 MET-min/week (n=75) had a significantly higher CAC score (9.4 [0-60.9] versus 0 [0-43.5], p=.02) and prevalence of CAC (68%,ORadjusted=3.2 (95%CI: 1.6-6.6)) and plaque (77%, ORadjusted=3.3 (95%CI: 1.6-7.1)) compared to 0, there was no difference in CAC score (p=.20), area (p=.21), density (p=.25) and regions of interest (p=.20) across exercise volume groups. Among participants with plaque, the most active group (>2000 MET-min/week) had a lower prevalence of mixed plaques (48% versus 69%, ORadjusted=0.35 (95%CI: 0.15-0.85) and more often had only calcified plaques (38% versus 16%, ORadjusted=3.57 (95%CI: 1.28-9.97)) compared to the least active group (2000 MET-min/week group had a higher prevalence of CAC and atherosclerotic plaques. The most active group did however have a more benign composition of plaques, with fewer mixed plaques and more often only calcified plaques. These observations may explain the increased longevity typical of endurance athletes despite the presence of more coronary atherosclerotic plaque in the most active participants

A comparison of dicarbonyl stress and advanced glycation endproducts in lifelong endurance athletes vs. sedentary controls

Objectives: Dicarbonyl stress and high concentrations of advanced glycation endproducts (AGEs) relate to an elevated risk for cardiovascular diseases (CVD). Exercise training lowers the risk for future CVD. We tested the hypothesis that lifelong endurance athletes have lower dicarbonyl stress and AGEs compared to sedentary controls and that these differences relate to a better cardiovascular health profile. Design: Cross-sectional study. Methods: We included 18 lifelong endurance athletes (ATH, 61±7years) and 18 sedentary controls (SED, 58±7years) and measured circulating glyoxal (GO), methylglyoxal (MGO) and 3-deoxyglucosone (3DG) as markers of dicarbonyl stress. Furthermore, we measured serum levels of protein-bound AGEs NE(open)-(carboxymethyl)lysine (CML), NE(open)-(carboxyethyl)lysine (CEL), methylglyoxal-derived hydroimidazolone-1 (MG-H1), and pentosidine. Additionally, we measured cardiorespiratory fitness (VO2peak) and cardiovascular health markers. Results: ATH had lower concentrations of MGO (196 [180-246] vs. 242 [207-292] nmol/mmol lysine, p=0.043) and 3DG (927 [868-972] vs. 1061 [982-1114] nmol/mmol lysine, p<0.01), but no GO compared to SED. ATH demonstrated higher concentrations CML and CEL compared to SED. Pentosidine did not differ across groups and MG-H1 was significantly lower in ATH compared to SED. Concentrations of MGO en 3DG were inversely correlated with cardiovascular health markers, whereas CML and CEL were positively correlated with VO2peak and cardiovascular health markers. Conclusion: Lifelong exercise training relates to lower dicarbonyl stress (MGO and 3DG) and the AGE MG-H1. The underlying mechanism and (clinical) relevance of higher CML and CEL concentrations among lifelong athletes warrants future research, since it conflicts with the idea that higher AGE concentrations relate to poor cardiovascular health outcomes. © 2017 Sports Medicine Australia

Exercise-Induced Cardiac Troponin I Increase and Incident Mortality and Cardiovascular Events.

BACKGROUND: Blood concentrations of cardiac troponin above the 99th percentile are a key criterion for the diagnosis of acute myocardial injury and infarction. Troponin concentrations, even below the 99th percentile, predict adverse outcomes in patients and the general population. Elevated troponin concentrations are commonly observed after endurance exercise, but the clinical significance of this increase is unknown. We examined the association between postexercise troponin I concentrations and clinical outcomes in longdistance walkers. METHODS: We measured cardiac troponin I concentrations in 725 participants (61 [54–69] yrs) before and immediately after 30 to 55 km of walking. We tested for an association between postexercise troponin I concentrations above the 99th percentile (>0.040 µg/L) and a composite end point of all-cause mortality and major adverse cardiovascular events (myocardial infarction, stroke, heart failure, revascularization, or sudden cardiac arrest). Continuous variables were reported as mean ± standard deviation when normally distributed or median [interquartile range] when not normally distributed. RESULTS: Participants walked 8.3 [7.3–9.3] hours at 68±10% of their maximum heart rate. Baseline troponin I concentrations were >0.040 µg/L in 9 participants (1%). Troponin I concentrations increased after walking (P0.040 µg/L. During 43 [23–77] months of follow-up, 62 participants (9%) experienced an end point; 29 died and 33 had major adverse cardiovascular events. Compared with 7% with postexercise troponin I ≤0.040 µg/L (log-rank P0.040 µg/L experienced an end point. The hazard ratio was 2.48 (95% CI, 1.29–4.78) after adjusting for age, sex, cardiovascular risk factors (hypertension, hypercholesterolemia or diabetes mellitus), cardiovascular diseases (myocardial infarction, stroke, or heart failure), and baseline troponin I concentrations. CONCLUSIONS: Exercise-induced troponin I elevations above the 99th percentile after 30 to 55 km of walking independently predicted higher mortality and cardiovascular events in a cohort of older long-distance walkers. Exercise-induced increases in troponin may not be a benign physiological response to exercise, but an early marker of future mortality and AQ3 cardiovascular events

Exercise Volume Versus Intensity and the Progression of Coronary Atherosclerosis in Middle-Aged and Older Athletes: Findings From the MARC-2 Study.

BACKGROUND: Physical activity and exercise training are associated with a lower risk for coronary events. However, cross-sectional studies in middle-aged and older male athletes revealed increased coronary artery calcification (CAC) and atherosclerotic plaques, which were related to the amount and intensity of lifelong exercise. We examined the longitudinal relationship between exercise training characteristics and coronary atherosclerosis. METHODS: Middle-aged and older men from the MARC-1 (Measuring Athlete's Risk of Cardiovascular Events 1) study were invited for follow-up in MARC-2 (Measuring Athlete's Risk of Cardiovascular Events 2) study. The prevalence and severity of CAC and plaques were determined by coronary computed tomography angiography. The volume (metabolic equivalent of task [MET] hours/week) and intensity (moderate [3 to 6 MET hours/week]; vigorous [6 to 9 MET hours/week]; and very vigorous [≥9 MET hours/week]) of exercise training were quantified during follow-up. Linear and logistic regression analyses were performed to determine the association between exercise volume/intensity and markers of coronary atherosclerosis. RESULTS: We included 289 (age, 54 [50 to 60] years [median (Q1 to Q3)]) of the original 318 MARC-1 participants with a follow-up of 6.3±0.5 years (mean±SD). Participants exercised for 41 (25 to 57) MET hours/week during follow-up, of which 0% (0 to 19%) was at moderate intensity, 44% (0 to 84%) was at vigorous intensity, and 34% (0 to 80%) was at very vigorous intensity. Prevalence of CAC and the median CAC score increased from 52% to 71% and 1 (0 to 32) to 31 (0 to 132), respectively. Exercise volume during follow-up was not associated with changes in CAC or plaque. Vigorous intensity exercise (per 10% increase) was associated with a lesser increase in CAC score (β, -0.05 [-0.09 to -0.01]; P=0.02), whereas very vigorous intensity exercise was associated with a greater increase in CAC score (β, 0.05 [0.01 to 0.09] per 10%; P=0.01). Very vigorous exercise was also associated with increased odds of dichotomized plaque progression (adjusted odds ratio [aOR], 1.09 [1.01 to 1.18] per 10% vs 2.04 [0.93 to 4.15] for highest vs lowest very vigorous intensity tertiles, respectively), and specifically with increased calcified plaques (aOR, 1.07 [1.00 to 1.15] per 10% vs 2.09 [1.09 to 4.00] for highest vs lowest tertile, respectively). CONCLUSIONS: Exercise intensity but not volume was associated with progression of coronary atherosclerosis during 6-year follow-up. It is intriguing that very vigorous intensity exercise was associated with greater CAC and calcified plaque progression, whereas vigorous intensity exercise was associated with less CAC progression

Exercise-Induced Cardiac Troponin Elevations: From Underlying Mechanisms to Clinical Relevance.

Serological assessment of cardiac troponins (cTn) is the gold standard to assess myocardial injury in clinical practice. A greater magnitude of acutely or chronically elevated cTn concentrations is associated with lower event-free survival in patients and the general population. Exercise training is known to improve cardiovascular function and promote longevity, but exercise can produce an acute rise in cTn concentrations, which may exceed the upper reference limit in a substantial number of individuals. Whether exercise-induced cTn elevations are attributable to a physiological or pathological response and if they are clinically relevant has been debated for decades. Thus far, exercise-induced cTn elevations have been viewed as the only benign form of cTn elevations. However, recent studies report intriguing findings that shed new light on the underlying mechanisms and clinical relevance of exercise-induced cTn elevations. We will review the biochemical characteristics of cTn assays, key factors determining the magnitude of postexercise cTn concentrations, the release kinetics, underlying mechanisms causing and contributing to exercise-induced cTn release, and the clinical relevance of exercise-induced cTn elevations. We will also explain the association with cardiac function, correlates with (subclinical) cardiovascular diseases and exercise-induced cTn elevations predictive value for future cardiovascular events. Last, we will provide recommendations for interpretation of these findings and provide direction for future research in this field

Myocardial Fibrosis in Athletes.

Myocardial fibrosis (MF) is a common phenomenon in the late stages of diverse cardiac diseases and is a predictive factor for sudden cardiac death. Myocardial fibrosis detected by magnetic resonance imaging has also been reported in athletes. Regular exercise improves cardiovascular health, but there may be a limit of benefit in the exercise dose-response relationship. Intense exercise training could induce pathologic cardiac remodeling, ultimately leading to MF, but the clinical implications of MF in athletes are unknown. For this comprehensive review, we performed a systematic search of the PubMed and MEDLINE databases up to June 2016. Key Medical Subject Headings terms and keywords pertaining to MF and exercise (training) were included. Articles were included if they represented primary MF data in athletes. We identified 65 athletes with MF from 19 case studies/series and 14 athletic population studies. Myocardial fibrosis in athletes was predominantly identified in the intraventricular septum and where the right ventricle joins the septum. Although the underlying mechanisms are unknown, we summarize the evidence for genetic predisposition, silent myocarditis, pulmonary artery pressure overload, and prolonged exercise-induced repetitive micro-injury as contributors to the development of MF in athletes. We also discuss the clinical implications and potential treatment strategies of MF in athletes

The Female Athlete's Heart: Facts and Fallacies.

Purpose of the review For many years, competitive sport has been dominated by men. Recent times have witnessed a significant increase in women participating in elite sports. As most studies investigated male athletes, with few reports on female counterparts, it is crucial to have a better understanding on physiological cardiac adaptation to exercise in female athletes, to distinguish normal phenotypes from potentially fatal cardiac diseases. This review reports on cardiac adaptation to exercise in females. Recent findings Recent studies show that electrical, structural, and functional cardiac changes due to physiological adaptation to exercise differ in male and female athletes. Women tend to exhibit eccentric hypertrophy, and while concentric hypertrophy or concentric remodeling may be a normal finding in male athletes, it should be evaluated carefully in female athletes as it may be a sign of pathology. Although few studies on veteran female athletes are available, women seem to be affected by atrial fibrillation, coronary atherosclerosis, and myocardial fibrosis less than male counterparts. Summary Males and females exhibit many biological, anatomical, and hormonal differences, and cardiac adaptation to exercise is no exception. The increasing participation of women in sports should stimulate the scientific community to develop large, longitudinal studies aimed at a better understanding of cardiac adaptation to exercise in female athletes