Thijs L. Braber

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.

Occult coronary artery disease in middle-aged sportsmen with a low cardiovascular risk score: The Measuring Athlete's Risk of Cardiovascular Events (MARC) study.

Background Most exercise-related cardiac arrests in men aged ≥45 years are due to coronary artery disease (CAD). The current sports medical evaluation (SME) of middle-aged sportsmen includes medical history, physical examination and resting and exercise electrocardiography (ECG). We investigated the added value of low-dose cardiac computed tomography (CCT) – both non-contrast CT for coronary artery calcium scoring (CACS) and contrast-enhanced coronary CT angiography (CCTA) – in order to detect occult CAD in asymptomatic recreational sportsmen aged ≥45 years without known cardiovascular disease. Methods Following a normal SME (with resting and bicycle exercise ECG), 318 asymptomatic sportsmen underwent CCT and 300 (94%) had a low European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE) risk. Occult CAD was defined as a CACS ≥100 Agatston units (AU) or obstructive (≥50%) luminal stenosis on CCTA. The number needed to screen (NNS) in order to prevent one cardiovascular event within 5 years with statin treatment was estimated. Results Fifty-two (16.4%, 95% confidence interval (CI): 12.7–20.8%) of 318 participants had a CACS ≥100 AU. The CCTA identified an additional eight participants with luminal narrowing ≥50% (and a CACS <100 AU). Taken together, CCT identified CAD in 60 (18.9%, 95% CI: 14.9–23.5%) of 318 participants. The 5-year estimated NNS was 183 (95% CI: 144–236) for CACS and 159 (95% CI: 128–201) for CACS combined with CCTA. Conclusions Coronary CT detects occult CAD in almost one in five asymptomatic sportsmen aged ≥45 years after a normal SME that included resting and bicycle exercise ECG. CACS reveals most of the relevant CAD with limited additional value of contrast-enhanced CCTA. The NNS in order to prevent one cardiovascular event compares favourably to that of other screening tests.

Identifying Coronary Artery Disease in Asymptomatic Middle-Aged Sportsmen: The Additional Value of Pulse Wave Velocity

Background Cardiovascular screening may benefit middle-aged sportsmen, as coronary artery disease (CAD) is the main cause of exercise-related sudden cardiac death. Arterial stiffness, as measured by pulse wave velocity (PWV), may help identify sportsmen with subclinical CAD. We examined the additional value of PWV measurements to traditional CAD risk factors for identifying CAD. Methods From the Measuring Athlete’s Risk of Cardiovascular events (MARC) cohort of asymptomatic, middle-aged sportsmen who underwent low-dose Cardiac CT (CCT) after routine sports medical examination (SME), 193 consecutive sportsmen (aged 55±6.6 years) were included with additional PWV measurements before CCT. Sensitivity, specificity and predictive values of PWV values (>8.3 and >7.5m/s) assessed by Arteriograph were used to identify CAD (coronary artery calcium scoring ≥100 Agatston Units or coronary CT angiography luminal stenosis ≥50%) and to assess the additional diagnostic value of PWV to established cardiovascular risk factors. Results Forty-seven sportsmen (24%) had CAD on CCT. They were older (58.9 vs. 53.8 years, p<0.001), had more hypertension (17 vs. 4%, p=0.003), higher cholesterol levels (5.7 vs. 5.4mmol/l) p=0.048), and more often were (ever) smokers (55 vs. 34%, p=0.008). Mean PWV was higher in those with CAD (8.9 vs. 8.0 m/s, p=0.017). For PWV >8.3m/s respectively >7.5m/s sensitivity to detect CAD on CT was 43% and 74%, specificity 69% and 45%, positive predictive value 31% and 30%, and negative predictive value 79% and 84%. Adding PWV to traditional risk factor models did not change the area under the curve (from 0.78 (95% CI = 0.709-0.848)) to AUC 0.78 (95% CI 0.710-0.848, p = 0.99)) for prediction of CAD on CCT. Conclusions Limited additional value was found for PWV on top of established risk factors to identify CAD. PWV might still have a role to identify CAD in middle-aged sportsmen if risk factors such as cholesterol are unknown.

Cardiac imaging to detect coronary artery disease in athletes aged 35 years and older. A scoping review

Sudden cardiac death (SCD) is a devastating event in athletes. Screening efforts that were first directed at athletes younger than 35 years are now focusing on the rapidly growing group of older sportspersons. Athletes aged ≥35 years have a 10‐fold increased risk of exercise‐related cardiac arrest, mostly due to coronary artery disease (CAD). Although cardiac imaging is pivotal in identifying CAD, the role of imaging modalities in screening asymptomatic older sportspersons remains unclear. We performed a scoping review to identify the role of cardiac imaging to detect CAD in older sportspersons and to identify gaps in the existing literature. We searched MEDLINE, EMBASE and the Cochrane library for studies reporting data on cardiac imaging of CAD in sportspersons ≥35 years. The systematic search yielded 1737 articles, and 14 were included in this scoping review. Imaging modalities included two echocardiography, one unenhanced computed tomography (CT) for coronary artery calcium scoring (CACS), three CACS and contrast‐enhanced CT angiography (CCTA), two CACS and cardiac magnetic resonance (CMR), one CCTA with CMR and echocardiography, two CCTA, two CMR, and one myocardial perfusion imaging article. The low number of relevant articles and the selection bias introduced by studying specific groups, like veteran marathon runners, indicate the need for future research. Cardiac CT (CACS and CCTA) probably has the highest potential for pre‐participation screening, with high diagnostic value to detect CAD and low radiation dose. However, currently there is insufficient evidence for incorporating routine cardiac imaging in the pre‐participation screening of asymptomatic sportspersons over 35 years.

Assessment of Coronary Artery Calcium on Low-Dose Coronary Computed Tomography Angiography With Iterative Reconstruction

Objective This study aims to evaluate whether coronary calcium scoring (CCS) is also feasible using low-radiation-dose coronary computed tomography angiography (CCTA) in combination with iterative reconstruction. Methods Forty-three individuals without known coronary artery disease underwent both noncontrast CCS (±1 mSv) for reference Agatston scores and low-dose CCTA (±3 mSv). Raw CCTA data were reconstructed with filtered back projection (FBP), hybrid iterative reconstruction (HIR), and model-based iterative reconstruction (MIR). Calcification volumes were derived with thresholds of >351 and >600 Hounsfield units (HU) and converted to proxy Agatston scores with linear regression analysis. Results Intraclass correlation coefficients for Agatston scores versus CCTA volumes with FBP and iterative reconstruction were excellent (ranges 0.94–0.99 and 0.96–0.99 for >351 HU and >600 HU thresholds, respectively). The >351 HU threshold resulted in higher CCTA volume scores ranging from 65.9 (15.1–347.0) for HIR to 94.8 (42.0–423.0) for MIR (P = 0.001 and <0.001, respectively). The >600 HU threshold scores ranged from 14.1 (0.0–159.3) for HIR to 28.6 (0.0–215.6) for MIR (P = 0.003 and 0.027, respectively). At >351 HU, reclassification occurred in 21 individuals (49%) for FBP and HIR and 25 individuals (58%) for MIR. Reclassifications decreased with >600 HU to 10 (HIR, 23%), 8 (FBP, 19%), and 4 (MIR, 9%). Conclusions The CCS is feasible using iteratively reconstructed low-dose CCTA with a calcium threshold of >600 HU. Using MIR, only 9% of individuals were reclassified.

Reproducibility and Impact of CT-Scanning on Pulse Wave VelocityMeasurement for Cardiovascular Risk Stratification in an AsymptomaticPopulation

Objective: Pulse wave velocity (PWV) measurements for aortic arterial stiffness and coronary CT angiography (CCTA) may help improve cardiovascular risk assessment in asymptomatic people. On the CT-table PWV measurement is an efficient addition to the CT workflow. This study evaluated if on CT-table PWV measurements are influenced by CT anticipation stress and if the PWV measurements are reproducible. Methods: Aortic PWV measurement reproducibility was assessed in 41 asymptomatic male sportsmen (aged 56.5 ± 6.7 years) who underwent CCTA as part of a sports medical evaluation. Three consecutive measurements were performed, two outside the CT-room for intra-observer variability followed by one on the CT-table. Pearson correlation coefficients were assessed for agreement between measurements outside the CT-room and on the CT-table. Bland-Altman analysis of limits of agreement was assessed to evaluate intra-observer variability outside the CT-room. Results: Aortic PWV and systolic blood pressure (SBP) on the CT-table were significantly higher (+0.61 m/s, P = 0.004 and + 7 mmHg, P = 0.003 respectively), with acceptable correlation (Pearson’s correlation 0.8, R² 0.6). The Pearson’s correlation coefficients of PWV measurements outside the CT-room showed good intra-observer agreement, (Pearson’s correlation 0.9, R² 0.8) The mean re-test difference and the 95% limits of agreement outside the CT-room were fair: 0.25 m/s, 95%CI -0.99–1.51 m/s. Conclusion: On the CT-table PWV measurements, although higher due to anticipation stress causing higher SBP, are comparable to off-table measurements at rest. The reproducibility of PWV measurements is good when done prior to a coronary CT-scan and the limits of agreement are acceptable.