Endurance exercise and the risk of cardiovascular pathology in men: a comparison between lifelong and late-onset endurance training and a non-athletic lifestyle - rationale and design of the Master@Heart study, a prospective cohort trial

Abstract

Introduction: Low and moderate endurance exercise is associated with better control of cardiovascular risk factors, a decreased risk of coronary artery disease and atrial fibrillation (AF). There is, however, a growing proportion of individuals regularly performing strenuous and prolonged endurance exercise in which the health benefits have been challenged. Higher doses of endurance exercise have been associated with a greater coronary atherosclerotic plaque burden, risk of AF and myocardial fibrosis (MF).

Methods and analysis: Master@Heart is a multicentre prospective cohort study aiming to assess the incidence of coronary atherosclerosis, AF and MF in lifelong endurance athletes compared to late-onset endurance athletes (initiation of regular endurance exercise after the age of 30 years) and healthy non-athletes.The primary endpoint is the incidence of mixed coronary plaques. Secondary endpoints include coronary calcium scores, coronary stenosis >50%, the prevalence of calcified and soft plaques and AF and MF presence. Tertiary endpoints include ventricular arrhythmias, left and right ventricular function at rest and during exercise, arterial stiffness and carotid artery intima media thickness.Two hundred male lifelong athletes, 200 late-onset athletes and 200 healthy non-athletes aged 45-70 will undergo comprehensive cardiovascular phenotyping using CT, coronary angiography, echocardiography, cardiac MRI, 12-lead ECG, exercise ECG and 24-hour Holter monitoring at baseline. Follow-up will include online tracking of sports activities, telephone calls to assess clinical events and a 7-day ECG recording after 1 year.

Ethics and dissemination: Local ethics committees approved the Master@Heart study. The trial was launched on 18 October 2018, recruitment is complete and inclusions are ongoing.

Trial registration number: NCT03711539.

Keywords: athlete; cardiology; exercise; heart disease; male.

Figure 1

Study design and flow chart of the Master@Heart study. From an online screening questionnaire eligible individuals will be sampled and stratified in three groups (lifelong athletes, late-onset athletes, non-athletic controls) of 200 individuals. Baseline evaluation includes an overview of medical history, review of medication and supplements, physical examination, blood sampling, resting 12-lead ECG, two-dimensional and three-dimensional resting echocardiogram (TTE), carotid artery ultrasound, pulse wave velocity for arterial stiffness and non-invasive central blood pressure measurements using a Sphygmocor device, cardiopulmonary exercise testing including 12-lead exercise ECG and maximal oxygen consumption measurement, dual-energy X-ray absorptiometry, CT coronary angiography scan and a 24-hour Holter monitoring. Two hundred and ten subjects, 70 from each group, will undergo cardiac magnetic resonance (CMR) imaging. The latter subjects will also undergo cardiac imaging during exercise, using two-dimensional TTE (Antwerp and Hasselt) or CMR (Leuven). Follow-up consists of a 6-monthly telephone call for clinical events and a 7-day ECG monitoring at 1 year. y, years.

Figure 2

Study hypothesis of the Master@Heart study. The primary hypothesis is that lifelong endurance exercise, more than late-onset training, is associated with more calcified plaques and less mixed/and or soft plaques as compared with non-athletic controls. The secondary hypothesis is that prolonged exposure to endurance exercise is associated with a higher risk for atrial fibrillation and myocardial fibrosis.

Figure 3

Sampling stratification of the Master@Heart study by current age (45–53 years, 54–62 years and 63–70 years) and age at which endurance training was started (lifelong: <20 years and 20–30 years; late-onset: 31–40 years and >40 years; non-athletic controls: N/A). For current age a proportion of 3/7 : 3/7 : 1/7 of individuals aged 45–53 years, 54–62 years and 63–70 years, respectively, was applied.

Figure 4

Bar graph of the registrations per month on the Master@Heart website.

Figure 5

Flow chart of cohort selection. Step-by-step flowchart representing the inclusion of the three cohorts. Numbers represent the remaining eligible participants after application of the inclusion and exclusion criteria. BMI, body mass index, y, years.

Figure 6

Distribution of endurance, cycling and running training hours. Panel (A) depicts the distribution of endurance exercise hours per participant who filled in the screening questionnaire including the average training hours for controls and athletes as per the inclusion criteria. Panels (B) and (C) show the distribution of running hours per week (B) and cycling hours per week (C) of participants who filled in the screening questionnaire. The black frames indicate the participants that fulfil the criteria for athletes as per the study inclusion criteria.