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 (ß, -0.05 [-0.09 to -0.01]; P=0.02), whereas very vigorous intensity exercise was associated with a greater increase in CAC score (ß, 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%; aOR, 2.04 [0.93 to 4.15] for highest versus lowest very vigorous intensity tertiles, respectively), and specifically with increased calcified plaques (aOR, 1.07 [1.00 to 1.15] per 10%; aOR, 2.09 [1.09 to 4.00] for highest versus 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.

ULTrasound-guided TRAnsfemoral puncture in COmplex Large bORe PCI: study protocol of the UltraCOLOR trial.

INTRODUCTION: Although recently published evidence favours transradial access (TRA) when using large-bore guiding catheters for percutaneous coronary intervention (PCI) of complex coronary lesions, the femoral artery will still be used in a considerate proportion of patients undergoing complex PCI, especially in PCI of chronic total occlusions (CTO). Ultrasound-guided puncture of the femoral artery may reduce clinically relevant access site complications, but robust evidence is lacking up to date. METHODS AND ANALYSIS: A total of 542 patients undergoing complex PCI, defined as PCI of CTO, complex bifurcation, heavy calcified lesion or left main, in which the 7-F or 8-F transfemoral access is required, will be randomised to ultrasound-guided puncture or fluoroscopy-guided puncture. The primary outcome is the incidence of the composite end-point of clinically relevant access site related bleeding and/or vascular complications requiring intervention. Access site complications and major adverse cardiovascular events up to 1 month will also be compared between both groups. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the local Ethics Committee ('Medisch Ethische Toetsing Commissie Isala Zwolle') for all Dutch sites, 'Comité Medische Ethiek Ziekenhuis Oost-Limburg' for Hospital Oost-Limburg, 'Comité d'éthique CHU-Charleroi-ISPPC' for Centre Hospilatier Universitaire de Charleroi and 'Ethik Kommission de Ärztekammer Nordrhein' for Elisabeth-Krankenhaus). The trial outcomes will be published in peer-reviewed journals of the concerned literature. The ultrasound guided transfemoral access in complex large bore PCI trial has been administered in the ClinicalTrials.gov database, reference number: NCT03846752. REGISTRATION DETAILS: ClinicalTrials.gov identifier: NCT03846752.

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.

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.

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 >7.5 m/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. 5.4 mmol/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 >7.5 m/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.

Prasugrel as alternative treatment strategy in a case with a hypersensitivity reaction to clopidogrel.

We report a case with a hypersensitivity reaction to clopidogrel that resolved after clopidogrel discontinuation and recurred on rechallenge. The reaction included fever, tachycardia, rash and mild angioedema. As an alternative to clopidogrel, the more potent thienopyridine prasugrel was administered without any signs of an allergic reaction in the hours, days and weeks following administration.