Vincent L. Aengevaeren

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.

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 cardiovascular disease 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 noncontrast 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-minutes per week. Participants’ activity was categorized as <1000, 1000 to 2000, or >2000 MET-min/wk. Results: A total of 284 men (age, 55±7 years) were included. CAC was present in 150 of 284 participants (53%) with a median CAC score of 35.8 (interquartile range, 9.3–145.8). Athletes with a lifelong exercise volume >2000 MET-min/wk (n=75) had a significantly higher CAC score (9.4 [interquartile range, 0–60.9] versus 0 [interquartile range, 0–43.5]; P=0.02) and prevalence of CAC (68%; adjusted odds ratio [ORadjusted]=3.2; 95% confidence interval [CI], 1.6–6.6) and plaque (77%; ORadjusted=3.3; 95% CI, 1.6–7.1) compared with <1000 MET-min/wk (n=88; 43% and 56%, respectively). Very vigorous intensity exercise (≥9 MET) was associated with CAC (ORadjusted=1.47; 95% CI, 1.14–1.91) and plaque (ORadjusted=1.56; 95% CI, 1.17–2.08). Among participants with CAC>0, there was no difference in CAC score (P=0.20), area (P=0.21), density (P=0.25), and regions of interest (P=0.20) across exercise volume groups. Among participants with plaque, the most active group (>2000 MET-min/wk) 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 with the least active group (<1000 MET-min/wk). Conclusions: Participants in the >2000 MET-min/wk group had a higher prevalence of CAC and atherosclerotic plaques. The most active group, however, had 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.

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 cardiovascular disease 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 noncontrast 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-minutes per week. Participants’ activity was categorized as <1000, 1000 to 2000, or >2000 MET-min/wk. Results: A total of 284 men (age, 55±7 years) were included. CAC was present in 150 of 284 participants (53%) with a median CAC score of 35.8 (interquartile range, 9.3–145.8). Athletes with a lifelong exercise volume >2000 MET-min/wk (n=75) had a significantly higher CAC score (9.4 [interquartile range, 0–60.9] versus 0 [interquartile range, 0–43.5]; P=0.02) and prevalence of CAC (68%; adjusted odds ratio [ORadjusted]=3.2; 95% confidence interval [CI], 1.6–6.6) and plaque (77%; ORadjusted=3.3; 95% CI, 1.6–7.1) compared with <1000 MET-min/wk (n=88; 43% and 56%, respectively). Very vigorous intensity exercise (≥9 MET) was associated with CAC (ORadjusted=1.47; 95% CI, 1.14–1.91) and plaque (ORadjusted=1.56; 95% CI, 1.17–2.08). Among participants with CAC>0, there was no difference in CAC score (P=0.20), area (P=0.21), density (P=0.25), and regions of interest (P=0.20) across exercise volume groups. Among participants with plaque, the most active group (>2000 MET-min/wk) 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 with the least active group (<1000 MET-min/wk). Conclusions: Participants in the >2000 MET-min/wk group had a higher prevalence of CAC and atherosclerotic plaques. The most active group, however, had 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.

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, p<0.001) compared to CVRF (3.9pg/ml; 0-14) and CON (5.5pg/ml; 0-14). Post-exercise BNP concentrations were elevated in CVD (35.7pg/ml, 17-67, p=0.01), but not in CVRF participants (p=0.11) or CON (p=0.07). No cumulative effect in BNP concentrations was observed across the consecutive walking days (p>0.05). Predictors for post-exercise BNP (R2=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.

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 NƐ-(carboxymethyl)lysine (CML), NƐ-(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.