Masters athlete screening study (MASS): incidence of cardiovascular disease and major adverse cardiac events and efficacy of screening over five years

Abstract

Background

The efficacy of cardiovascular screening in Masters athletes (MAs) (≥35 y), and whether screening decreases their risk of major adverse cardiac events (MACEs) is unknown.

Purpose

To evaluate the effectiveness of yearly cardiovascular screening, and the incidence of cardiovascular disease (CVD) and MACE over five years.

Methods and results

MAs (≥35 y) without previous history of CVD underwent yearly cardiovascular screening. Participants with an abnormal screen underwent further evaluations. In the initial year, 798 MAs (62.7% male, 55 ± 10 y) were screened; 11.4% (n = 91) were diagnosed with CVD. Coronary artery disease (CAD) was the most common diagnosis (n = 64; 53%). During follow-up, there were an additional 89 CVD diagnoses with an incidence rate of 3.58/100, 4.14/100, 3.74/100, 1.19/100, for years one to four, respectively. The most common diagnoses during follow-up were arrhythmias (n = 33; 37%). Increasing age (OR = 1.047, 95% confidence interval (CI): 1.003–1.094; P = 0.0379), Framingham Risk Score (FRS) (OR = 1.092, 95% CI: 1.031–1.158; P = 0.003), and LDL cholesterol (OR = 1.709, 95% CI: 1.223–2.401; P = 0.002) were predictive of CAD, whereas moderate intensity activity (min/wk) (OR = 0.997, 95% CI: 0.996–0.999; P = 0.002) was protective. Ten MACE (2.8/1000 athlete-years) occurred. All of these MAs were male, and 90% had ≥10% FRS. All underwent further evaluations with only two identified to have obstructive CAD.

Conclusion

MACE occurred despite yearly screening. All MAs who had an event had an abnormal screen; however, cardiac functional tests failed to detect underlying CAD in most cases. It may be appropriate to offer computed coronary tomography angiography in MAs with ≥10% FRS to overcome the limitations of functional testing, and to assist with lifestyle and treatment modifications.

See the editorial comment for this article ‘Cardiovascular screening of master athletes: insights from the Master Athletes Screening Study’, by E. Cavarretta et al ., https://doi.org/10.1093/eurjpc/zwad115.

Introduction

Masters athletes (MAs) (≥35 y) are a rapidly growing population that participate in a variety of sports at a competitive level or for leisure activity. Regular physical activity has tremendous health benefits, including primary and secondary prevention in several medical conditions [i.e. coronary artery disease (CAD), diabetes, hypertension, obesity, and premature death].¹ Although regular physical activity reduces ones risk of developing such medical conditions, studies have shown that those with a lifelong exercise history have increased coronary artery calcium (CAC) and atrial fibrillation compared to the general population.^2–7 Male athletes have a higher prevalence of coronary plaques and higher prevalence of a high atherosclerotic burden (≥50% luminal stenosis) compared to sedentary males (44% vs. 22% and 7.5% vs. 0%, respectively).⁴ The prevalence of CAD between female athletes and sedentary females does not differ.⁴ Additionally, the odds of having atrial fibrillation is doubled in endurance athletes compared to the general population (OR = 2.34, 95% CI: 1.04–5.28).³

The incidence rates of sports-related sudden cardiac death (SCD) is reported to be 4.6 cases per million per year, with recreational MAs comprising the majority (>90%) of them.⁸ This incidence rate does not include non-fatal events such non-fatal myocardial infarctions (MIs) and stroke. Cardiovascular screening aims to identify cardiovascular risk factors and underlying cardiovascular disease (CVD) that may precipitate a major adverse cardiac event (MACE) [sudden cardiac arrest (SCA), SCD, fatal or non-fatal MI, stroke]. The American Heart Association and European Society of Cardiology agree that screening is justifiable and compelling on ethical, legal, and medical grounds to identify underlying CVD. However, the optimal screening protocol and frequency of screening remains in question, and has not been systematically evaluated.^9–13

Current guidelines for CVD screening in MAs recommend consideration of an electrocardiogram (ECG) (rest and exercise), cardiovascular physical examination (i.e. cardiac auscultation, blood pressure), personal symptom assessment, family history, sport history, and comprehensive cardiovascular risk assessment including risk scoring [i.e. Framingham Risk Score (FRS), Systematic Coronary Risk Evaluation (SCORE)].^10,11,13,14 The FRS estimates a patient’s 10-year risk of experiencing a MACE based on age, sex, total cholesterol, high-density lipoprotein cholesterol, blood pressure, smoking history, presence of diabetes, and family history of premature CVD.¹⁴ Routine use of more advanced imaging investigations such as computed coronary tomography angiography (CCTA) in asymptomatic MAs with a normal exercise stress test (EST) is not recommended. However, in asymptomatic MAs with a high cardiovascular risk, a functional imaging test or CCTA may be considered.¹³ The higher prevalence of CAD in the MA population raises the question on whether non-invasive cardiovascular imaging techniques, such as CCTA and/or CAC score (CACS) should be included in the screening process to add diagnostic and prognostic value in those with no known CVD by improving long-term risk stratification.^12,15–18

The current study aimed to evaluate the efficacy of yearly cardiovascular evaluations and report the incidence of CVD and MACE over a 5-year period.

Methods

Study population and design

This observational longitudinal study builds on an initial dataset (‘initial year’) obtained from the cross-sectional study, with the addition of four years of follow-up (‘follow-up years’).¹⁹ The study occurred between April 2015 and February 2021 throughout British Columbia, Canada. Participants volunteered to participate in the study. From the initial population (n = 798), 726 MAs participated in the present follow-up study with yearly attrition as outlined in Figure 1. The study design and population has been previously described.¹⁹ Briefly, eligible participants had to engage in moderate to vigorous intensity physical activity at least three days per week during the preceding three months. Those with known CVD at baseline were excluded.

Figure 1.

Study overview. CAD, coronary artery disease; CVD, cardiovascular disease; MACE, major adverse cardiac event; SCA, sudden cardiac arrest.

Participants underwent cardiovascular screening on a yearly basis and included a tiered three-stage process (Figure 2): Stage 1) baseline assessments (questionnaire to ascertain cardiac-related symptoms and family history, new CVD (diagnosed ‘outside of the study’) and MACE, medications, and physical activity (type of activities, frequency, intensity and duration); resting 12-lead ECG; resting blood pressure; anthropometrics (height, weight, waist circumference); FRS (initial year, follow-up years one and two only); Stage 2) EST; and Stage 3) clinical evaluation including consultation with sports cardiologist and clinically indicated testing. MAs with an abnormal baseline assessment (see Supplementary Material online S1) progressed to Stage 2 and and/or Stage 3. Those with an abnormal EST also progressed to Stage 3. Sports cardiologists determined if subsequent evaluations were necessary based on their clinical discretion in a shared decision-making approach with the participant-athlete. The final decision to undergo further examination [i.e. CCTA, CACS, echocardiography, stress echocardiography, myocardial perfusion imaging (MIBI), cardiac magnetic resonance imaging, cardiac catheterization, Holter monitor, ambulatory blood pressure] was based on the shared decision between the cardiologist and participant. MAs diagnosed with CVD at any timepoint continued in the study with yearly assessments and were followed clinically (additional evaluations performed at the discretion of the cardiologist). All ECGs (Mortara Instrument, Milwaukee, WI) were interpreted using the ‘International Recommendations for Electrocardiographic Interpretation in Athletes’.²⁰ In the fourth year, due to COVID-19, all MAs completed the questionnaire; however, only a portion completed the ECG (n = 131), blood pressure (n = 444), weight (n = 637), and waist circumference (n = 613) measurements. MAs that withdrew at any timepoint during the study received the lost to follow-up questionnaire to determine MACE and vital status. There was a total of 136 MAs that received the lost to follow-up questionnaire. Of those, 74.3% completed it resulting in 4.4% patients in whom we do not know cardiac events or vital status (Figure 1).

Figure 2.

Yearly screening procedures. BP, blood pressure; CACS, coronary artery calcium score; CCTA, coronary computer tomography angiography; MIBI, myocardial perfusion imaging; ECG: electrocardiogram; Echo, echocardiogram; FRS, Framingham Risk Score. *Abnormal exercise stress test included: equivocal ST-changes (upsloping ST-depression >1 mm), positive ST-changes (horizontal or down sloping ST depression >1 mm), complex ventricular arrhythmias [i.e. ventricular run > 3 beats, non-sustained ventricular tachycardia, polymorphic PVCs, accelerated idioventricular rhythm (with left bundle branch morphology)], > 7 PVCs/min at peak or during recovery, angina or marked shortness of breath. *The Bruce protocol performed on a treadmill was utilized in the majority of the cases. A bike was used if an injury prohibited the participant from using the treadmill or if the MAs strongly preferred using the bike as it was their primary sport and therefore was better suited to elicit their reported symptoms.

Outcome measures

The primary outcomes were incidence of MACE (SCA/SCD, MI, stroke), and new diagnoses of CVD divided into five sub-groups ‘CAD’, ‘arrhythmias’ [high premature ventricular contractions (PVC) burden, atrial fibrillation/flutter, supraventricular tachycardia], ‘aortic dilatation’, ‘valvular heart disease’ and ‘other CVD’ [hypertrophic cardiomyopathy, dilated cardiomyopathy, coronary artery anomalies, myocarditis, and inherited electrical abnormalities (e.g. long QT syndrome)] (see Supplementary Material online S2). MAs were included in the four-year incidence for CVD if they were diagnosed with CVD through the screening process and subsequent tests ordered by study physicians. MAs that were diagnosed outside of the screening protocol (i.e. their primary care physician ordered the test and a CVD diagnosis resulted or CVD was discovered incidentally when diagnostic tests were ordered for other reasons were not included in the four-year incidence, but reported separately as ‘false-negatives’.

Statistical analysis

All parameters were checked for normality visually and tested using Shapiro–Wilk test. Continuous variables were expressed as means and standard deviations when normally distributed or as median (interquartile range) when not normally distributed. Frequency tables were generated for all categorical data and reported as number of participants (n) and percentage (%). Chi-square test was used to compare differences between categorical variables. Group differences were tested with an independent sample t-test or Mann–Witney U test for normally and non-normally distributed continuous variables, respectively. Analysis of variance and the Kruskal–Wallis tests were used to compare means between more than one group for normally and non-normally distributed variables, respectively. Bonferroni was performed as a post-hoc to evaluate differences between more than two groups. A binary logistic regression analysis was performed to calculate odds ratios of risk factors associated with the presence CAD and arrhythmias. The variables of interest that were included in the modelling are included in Supplementary Material online S3. The dataset was aggregated over the entire time period (including the initial year) depending on whether they were diagnosed with CAD or arrhythmias (including those detected outside of the study (‘false-negatives’) and those that had a MACE), or not. These aggregations involve aggregating all variables of interest across all timepoints pre-diagnosis up to the first diagnosis for those that were diagnosed (or had a MACE).

Statistical analysis was performed using SPSS software Version 27.0.1.0 (IBM Corp. Armonk, NY) or Excel Version 16.49 (Microsoft Corp. Redmond, WA). R statistical software²¹ was used for regression analysis. Those with missing data were not included in the sample size for the associated variable and the mean, median or percentage was adjusted accordingly.

Ethics approval was granted by the University of British Columbia’s Clinical Research Ethics Board (H15–00009) in accordance with the declaration of Helsinki. All participants provided written informed consent prior to enrolment.

Results

Study population

The study population (55 ± 10 y; 62.7% male; 88% Caucasian) is described in detail in our initial publication.¹⁹ Over the mean follow-up time of 4.82 ± 0.76y, there were a total of 3594 athlete-years (Figure 1). Participant characteristics over the entire study are displayed in Table 1. The number of participants taking lipid-lowering and anti-hypertensives increased each year, however, some participants who met the criteria for medication declined to initiate therapy. Expectantly, systolic and diastolic blood pressure decreased and lipid profiles significantly improved. There were eight non-cardiac adverse events, and three non-cardiac related deaths; two from cancer and one from a brain aneurysm (see Supplementary Material online S4).

Table 1.

Participant demographics over entire study period

Variable	Initial year	Year 1	Year 2	Year 3	Year 4a	P-value
Number of athletes, n (%)	798	726	700	696	674	—
Sex						0.993
Male	501 (62.7)	462 (63.6)	445 (63.6)	444 (63.8)	428 (63.5)	—
Female	298 (37.3)	264 (36.4)	255 (36.4)	252 (36.2)	246 (36.5)	—
Age, y (SD)	54.6 (9.5)b,c,d,e	56.5 (9.4)a	57.7 (9.4)a	58.7 (9.4)c	60.1 (9.4)d	<0.001**
Height, cm (SD)	173.2 (9.6)	172.9 (11.5)	175 (11.5)	172.0 (10.1)	173.1 (9.9)	0.999
Weight, kg (SD)	75.0 (14.4)	75.3 (15.1)	75.5 (14.7)	75.2 (15.0)	74.3 (14.8)	0.700
Body mass index, kg/m2 (SD)	24.8 (3.4)	24.5 (3.7)	25.0 (3.7)	25.0 (4.0)	24.7 (4.5)	0.218
Waist circumference, cm (SD)	86.6 (10.4)c,d	88.1 (11.9)	88.6 (11.1)c	88.5 (11.5)c	87.9 (10.3)	<0.001**
Systolic blood pressure, mm Hg (SD)	124 (15.3)b,c,d,e	121 (15.9)a	120 (14.9)b	120 (15.0)c	120 (14.9)e	<0.001**
Diastolic blood pressure, mm Hg (SD)	76.0 (8.3)a,b,c	74.3 (8.8)a	73.9 (8.5)b	74.0 (8.3)c	74.7 (9.1)	<0.001**
Resting heart rate, bpm (SD)	57.9 (9.4)	58.1 (10.0)	58.6 (10.9)	57.8 (10.2)	58.5 (9.4)	0.465
Framingham Risk Score, % (SD)	8.7 (7.0)	9.0 (6.8)	9.2 (6.9)	n/a	n/a	0.164
Low FRS, n (%)	535 (67)	473 (65)	449 (64)	n/a	n/a	—
Intermediate FRS, n (%)	197 (25)	191 (26)	191 (27)	n/a	n/a	—
High FRS, n (%)	67 (8)	60 (8)	59 (8)	n/a	n/a	—
Total cholesterol, mmol/L (SD)	5.20 (0.93)	5.21 (0.97)	5.13 (0.95)	n/a	n/a	0.583
HDL-C, mmol/L (SD)	1.75 (0.49)c	1.8 (0.54)	1.8 (0.53)c	n/a	n/a	0.045*
LDL-C, mmol/L (SD)	3.00 (0.80)c	2.97 (0.84)	2.85 (0.83)b	n/a	n/a	0.004*
Triglycerides, mmol/L (SD)	0.97 (0.50)	0.99 (0.49)	0.99 (0.53)	n/a	n/a	0.463
HDL-TC ratio	3.16 (0.92)c	3.11 (0.97)	3.00 (0.92)c	n/a	n/a	<0.001**
Fasting blood glucose, mmol/L (SD)	5.2 (0.5)	5.5 (6.2)	5.2 (0.6)	n/a	n/a	0.080
Taking lipid-lowering medication, n (%)	22 (3)	58 (8)	97 (14)	108 (16)	119 (18)	—
Taking hypertensive medication, n (%)	68 (9)	77 (11)	89 (13)	97 (14)	104 (15)	—
Declined lipid-lowering medication, n (%)	37 (7)	28 (4)	18 (3)	n/a	n/a	—
Declined hypertensive medication, n (%)	47 (6)	3 (0.4)	8 (1)	3 (0.4)	n/a	—
Level of competition, n (%)						<0.001**
Recreational	535 (67)	508 (70)	528 (76)	492 (72)	490 (73)	—
Competitive	185 (23)	166 (23)	154 (22)	122 (18)	85 (13)	—
Elite (professional, provincial, national)	78 (10)	49 (7)	11 (2)	40 (6)	37 (5)	—
Currently do not participate at any of these levels	n/a	n/a	n/a	41 (6)	62 (9)	—
Weekly training volume, MET-hour/week, mean (SD)	71 (49-102)	71 (47–102)b	75 (51–103)	79 (52–110)b	77 (49–112)	0.018

Continuous variables presented as mean (SD) if normally distributed and median (IQR) for non-normally distributed; Categorical variables presented as n (%).

Follow-up year 4: due to the COVID-19 pandemic, 131 participants completed the full screen (prior to the start of the pandemic) and the remaining 543 completed the screen remotely. A total of 637, 613, and 444 completed their weight, waist circumference, and resting blood pressure/heart rate, respectively. All of the participants that completed the screen remotely, completed the yearly questionnaire.

denotes statistical significance between initial year and follow-up year 1.

denotes statistical significance between initial year and follow-up year 2.

denotes statistical significance between initial year and follow-up year 3.

denotes statistical significance between initial year and follow-up year 4; e denotes statistical significance between follow-up years 1 and 4

*denotes statistical significance P < 0.05; **denotes statistical significance P < 0.001

Major adverse cardiac events

Ten MACE occurred over the study period with an incidence of 2.8 MACE per 1000 athlete years (Table 2). Five MIs with subsequent percutaneous coronary intervention, three strokes (one athlete had two strokes), one exertional SCD, and one presumed non-exertional SCD. The mean age of those that experienced a MACE was 63.6 ± 12.5y; 100% male. All exhibited high fitness classification on EST (mean maximal METs was 13.4 ± 3.4). Seven MAs had an intermediate FRS, one had a high FRS, and one had a low FRS (40 y, father had coronary artery bypass grafting at 55 y). Out of the five MAs who had an MI, two were on lipid-lowering therapy due to positive secondary tests (one had a positive MIBI and the other underwent CCTA secondary to a positive EST to assist in the decision-making process and discovered obstructive CAD). The three MAs who did not initiate lipid-lowering therapy, two had a negative EST and one had a positive EST but negative MIBI. In the two MAs who died, both had a negative EST, with one of the MAs also having a negative stress echocardiogram. Neither of these MAs had initiated lipid-lowering therapy. In the two MAs who had a stroke, one had initiated lipid-lowering therapy after obstructive CAD was discovered on CCTA, and one did not undergo further testing after a negative EST.

Table 2.

Characteristics of masters athletes who had a major adverse cardiac event

Athlete No.	Year of event	Age, sex	FRS (%)	Primary sport	Volume of PA (MET-hrs/week)	Type of MACE	Previous diagnosis through study (year)	Medication status	Screening indicators prior to the event	Previous EST results (year completed)	Further tests conducted through study prior to MACE
Myocardial infarction
1	1	65, M	13	Track and field (throwing)	38	NSTEMI with PCIx3 (RCA, LAD, LCx)	Obstructive CAD (initial)	On lipid-lowering	Int FRS	11 METs, positive for ischemia (initial)	MIBI—no ischemia, normal LVEF (63%) CCTA: Left main <25%; mLAD 50% to 69%; RCA <25%; LCx no significant disease.
2	1	59, M	15	Running	65	NSTEMI with PCI × 2 (LAD)	None	None	Int FRS	15 METs, no ischemia (initial)	None
3	1	40, M	5	Dance	45	NSTEMI with PCIx2 (dLAD and LCx)	Obstructive CAD (initial)	Initiated lipid-lowering and beta-blocker after positive MIBI in yr 1	Syncope, 3/6 systolic murmur; midsystolic click FH (dad CABG at 55) Right before the event: DYS, angina	12 METs, positive for ischemia (initial)	MIBI—positive, mildly reversible apical defect, normal LVEF (61%)
4	2	62, M	16	Basketball	40	STEMI with PCIx1 (mLAD)	None	Declined lipid-lowering	Int FRS	14 METs, positive for ischemia (initial)	MIBI—no defect to suggest myocardial ischemia
5	3	47, M	11	Orienteering	87	STEMI with PCIx1 (mLCx)	None	None	Int FRS FH—father CABG at 52	18 METs, no ischemia (initial)	None
Stroke
6 and 7	1 and 4	77, 81 M	30	Rugby	69	Stroke	Obstructive CAD (initial)	Initiated statin and blood pressure medication after diagnosis in year 1	High FRS, diabetic, > 65 years	7 METs, positive for ischemia (initial)	MIBI (no ischemia, LVEF 46%) ECHO CATH: LAD 60%; 1st DIAG 70%; RAMUS 50%; OM2 90%; RCA 40 AND 50%; PDA 40% (no stent; no LV dysfunction or ischemia)
8	4	66, M	9	Cross-country ski	218	Stroke	None	None	Int FRS, DYS	18 METs, no ischemia (2)	None
Cardiac mortality
9	3	70, M	11	Cycling	135	Presumed non-exertional SCD	None	None	Initial: > 65 years Year 3: Int FRS, angina (only once, thought was a muscle cramp)	13 METs, no ischemic changes (initial) 13 METs, no ischemic changes, 93% THR (2)	None
10	4	69, M	13	Swimming	52	SCD while exercising	None	None	ECG (Q waves), Int FRS	18 METs, no ischemic changes (initial)	Stress echo—no wall motion abnormalities

CABG, coronary artery bypass graft; CAD, coronary artery disease; CATH, invasive coronary angiography; CCTA, computed coronary tomography angiography; CVA, cerebrovascular accident; DYS, dyspnea; FH, family history; FRS, Framingham Risk Score; Int: intermediate; LAD, left anterior artery; LCx, left circumflex artery; LM, left main artery; LVEF, left ventricular ejection fraction; M, male; PCI, percutaneous intervention; METs, Metabolic Equivalent Tasks; MIBI, myocardial perfusion imaging; OM1, 1st obtuse marginal artery; OM2, 2nd obtuse marginal artery; PDA, posterior descending artery; RCA, right coronary artery; SCA, sudden cardiac arrest

Detection of cardiovascular disease

Over the entire study period, there were a total of 207 (61.2 ± 8.2y; 79% male) CVD diagnoses occurring in 165 MAs (35 MAs diagnosed with >1 form of CVD) (Figure 3). Fifty-eight percent (n = 120) of diagnoses occurred in the initial screening year with CAD as the predominant diagnosis (53%). There were 87 CVD diagnoses (63.3 ± 8.0y, 69% male) made on subsequent screening during the four years of follow-up (26, 28, 25, and 5 in years one to four, respectively). The overall incidence of CVD diagnoses was 3.58, 4.00, 3.59, and 1.19 per 100-athete years, for years one to four, respectively. Arrhythmias were the most common diagnoses during the follow-up years (n = 32; 37%).

Figure 3.

Incidence of cardiovascular disease. Valvular heart disease: mitral valve prolapse (n = 18), bicuspid aortic valve (n = 4); aortic insufficiency (n = 5), aortic stenosis (n = 3); Arrhythmias: atrial fibrillation/flutter (n = 19), high PVC burden (n = 17), supraventricular tachycardia (n = 7), conduction system disease (n = 4); Other: myocarditis (n = 2), myocardial bridging (n = 3), cerebrovascular disease (n = 1), dilated cardiomyopathy (n = 1), probable Long QT syndrome (n = 1), papillary fibroelastoma (n = 1).

Male MAs were approximately four times more likely to be diagnosed with CVD compared to female MAs. Specifically, males were more likely to be diagnosed with CAD (85.2% vs. 14.8%), arrhythmias (83.0% vs. 17.0%), aortic dilatation (74.3% vs. 25.7%), valvular heart disease (76.7% vs. 23.3%), and other CVD (53.8% vs. 46.2%) compared to females. When females were examined for the influence of menopause on the presence of CAD, there was no statistical differences in the presence of CAD based on menopause status (P = 0.361). However, there were only 13 females diagnosed with CAD during the study. Out of these 13 female MAs that were diagnosed with CAD, 6 (46.2%) had started menopause less than 10 years ago, 5 (38.5%) had started menopause more than 10 years ago, and 2 (7.7%) had a hysterectomy. CAD in females was predominately non-obstructive (n = 11; 84.6%).

The first stage of the screening process was abnormal in 513 (63.4%), 190 (26.2%), 173 (24.7%), 153 (21.2%), and 103 (15.3%) MAs in the initial year to follow-up year four, respectively (Figure 1). These MAs progressed to stage two of the screening process where an EST was performed in 498 (62.3%), 84 (11.6%), 100 (14.3%), 76 (10.9%), and 37 (5.5%) MAs in the initial year to follow-up year four, respectively. A total of 347 (43.4%), 166 (22.9%), 146 (20.9%), 134 (19.3%), and 100 (14.9%) MAs progressed to stage three of the screening process (cardiologist follow-up) in the initial year to follow-up year four, respectively. Overall, there were 1132 abnormal screens resulting in 207 CVD diagnoses over the entire study period, an abnormal screen resulted in a diagnosis 18.3% of the time.

The most common screening indicators that warranted a follow-up were a high cardiovascular risk (27%), symptoms (angina, dyspnea, syncope, or exertional fatigue) (17%), and an abnormal ECG (13%) (Figure 4A). The screening indicators that were the most prevalent in those diagnosed with CAD was a high cardiovascular risk (37%), an abnormal ECG (14%), and age (>65 y) (13%) (Figure 4B). The screening indicator that was the most prevalent in those diagnosed with an arrhythmia was high cardiovascular risk (24%), an abnormal ECG (20%) and palpitations (13%) (Figure 4C), and those diagnosed with valvular heart disease, high cardiovascular risk (24%), palpitations (15%) and a heart murmur (14%) were the most prevalent (Figure 4D).

Figure 4.

(A) screening indicators that elicited follow-up, (B) screening indicators present in those with CAD, (C) screening indicators present in those with arrhythmias, (D) screening indicators present in those with valvular heart disease. *high CV risk: includes those with an intermediate or high Framingham Risk Score, diabetes, high cholesterol (≥8 mmol/L), high blood pressure (>180/110 mmHg); CVD, cardiovascular disease; ECG, electrocardiogram; Fhx: Family history; HR, Heart rate; SCD, sudden cardiac death.

Twenty-one MAs (86% male) were diagnosed outside of the screening protocol with CVD (four with obstructive CAD, four with non-obstructive CAD, three with unknown CAD severity, one with cerebrovascular disease, five with atrial fibrillation, three with atrial flutter, one genotype positive/phenotype negative hypertrophic cardiomyopathy) (see Supplementary Material online S5). Most (75%) of these MAs with CAD (obstructive and non-obstructive) had an intermediate FRS and a negative EST.

Exercise stress test

The mean maximal METs achieved for all ESTs performed was 14.1 ± 2.8. A summary of the diagnostic utility of the EST in those diagnosed with CAD, coronary artery anomalies and myocardial bridging is presented in Supplementary Material online S6. Eleven (41%) MAs with obstructive CAD had a negative EST. A CCTA was ordered in these MAs due to a high FRS or a strong family history as it was believed that identification of CAD would result in behaviour modification (see Supplementary Material online S7). After identification of CAD in these MAs, all except one MA initiated lipid-lowering therapy. There were 13 MAs that had a positive EST, who were not diagnosed with CAD. Of these, five (27.8%) did not undergo further testing (i.e. initiated medication or declined testing), six (33.3%) underwent MIBI (all negative), one (5.6%) had a stress echocardiogram (negative), and one (5.6%) had a CCTA (negative).

Determinants of CAD and arrhythmias

Risk factors for CAD were increasing age (y) (OR = 1.047, 95% CI: 1.003–1.094; P = 0.0379), FRS (%) (OR = 1.092, 95% CI: 1.031–1.158; P = 0.003), and LDL cholesterol (mmol/L) (OR = 1.709, 95% CI: 1.223–2.401; P = 0.002). Moderate intensity activity (min/wk) (OR = 0.997, 95% CI: 0.996–0.999; P = 0.002) was protective (see Supplementary material online, Table S8). Lifetime hours were not predictive for CAD. None of the traditional risk factors were predictive of arrhythmias; however, light and vigorous intensity physical activity (1.003, 95% CI: 1.001–1.004; P = 0.002 and 1.003, 95% CI: 1.001–1.005; P = 0.007, respectively) were predictive for arrhythmias in binary regression analysis (see Supplementary material online, Table S9). Additionally, in a bivariate comparison, those with arrhythmias had greater lifetime training hours (P = 0.038) and had spent more time being physically active (P < 0.001) compared to those not diagnosed with an arrhythmia.

Cost of the program

The cost of the program reflects the cost of screening up to a MAs’ first CVD diagnosis to the third year of follow-up (see Supplementary Material online S10). For each participant, the calculated cost included their yearly screening cost and all further examinations performed to their first CVD or hypertension diagnosis, and removed from the analysis thereafter. Participants that had a MACE were also removed from the cost analysis in subsequent years. The cost of the evaluations were calculated according to the current British Columbia Medical Service Plan payment schedule.²² There were 181 (22.6%) MAs who did not undergo any additional testing and therefore no further cost implications. The cost of the remaining MAs who had additional testing varied depending on additional investigations performed. The highest cost was attributed to the eight MAs that underwent a cardiac catheterization.

The first year of screening was the most expensive, compared to years one to three follow-up study years ($334.702 vs. $101 923 vs. $90 826 vs. $70 677) due to the higher cost of the baseline examination, the greatest number of additional investigations performed and the greatest number of participants that underwent the baseline screen. However, the first year had the highest number of diagnoses detected (120 vs. 21 vs. 28 vs. 17), thereby had the lowest cost per diagnosis ($2789 vs. $4853 vs. $3244 vs. $4157). The cost of the overall screening program was $605 205 or $3072 per diagnosis.

Discussion

This is the first study to report the incidence of MACE and CVD over five years in a cohort of MAs participating in a yearly screening programme. The main findings were: (i) 10 MACE (seven cardiac events and three CVAs) (2.8 MACE per 1000 athlete-years) occurred in exclusively male athletes, (ii) 207 (26%) MAs were identified with CVD, (iii) the abnormal initial evaluation was associated with a high number of secondary tests and associated increased cost implications that did not result in identification of CVD most of the time, and (iv) increasing age, FRS, LDL cholesterol is predictive of CAD identification, whereas increasing amounts of moderate intensity activity was protective.

The male predominance for MACE is consistent with previous literature.⁸ One previous study reported four MACE in 108 male marathon runners; however, the follow-up duration was only 21.3 ± 2.8 months.⁵ In the Canadian general population, the prevalence of a MI in 40–54y is 0.3% and 1.3%, and increases to 1.2% and 4.3% in 55–64 y in women and men, respectively.²³ While a direct comparison cannot be made with the present population, there were five MIs over the five-year study period, providing an annual incidence of (1.4 per 1000 athlete-years). Potential reasons for this lower rate in athletes may include: yearly screening resulting in risk factor identification and modification, higher cardiorespiratory fitness, and potential improved metabolic profiles.

Screening tools and risk factors in the prediction of coronary artery disease and arrhythmias

Over the course of five years, 207 CVD diagnoses were identified. The majority of diagnoses were made during the first year of the study (n = 120), and 87 diagnoses were made over the four follow-up years. CAD was the most prevalent diagnosis in the initial year (64; 53%). Arrhythmias (32; 37%) were the most common diagnosis during follow-up. However, despite the detection of CVD in some cases, yearly screening produced a high number of secondary testing without the identification of underlying CVD diagnoses in 82% of cases. Increasing age and presence of risk factors are known to increase the likelihood of developing CAD, which is supported by the present findings. The risk of CAD increased with increasing age, LDL cholesterol, FRS, and decreased with increasing amounts of moderate intensity activity. Aengevaeren et al. similarly reported that in a group of competitive and recreational male athletes, those with CAC were older, and more likely to have traditional risk factors compared to those without CAD.² Additionally, high lifetime exercise volumes (>2000 MET-min/wk) and increased time spent doing very vigorous intensity exercise (>9 METs) was associated with increased CAC presence.² Conversely, in a study of 152 MAs (70% male), all with a low FRS, the male athletes had a higher prevalence of atherosclerotic plaques (44.3% vs. 22.3%) compared to controls, and only male athletes had a CAC >300 and luminal stenosis >50%. These findings suggest that those with a lifelong exercise may be more susceptible to the development of CAC, despite the absence of traditional risk factors.⁴ Age and years of training were the only risk factors that predicted significant CAD in these men.⁴ Neither increasing levels of physical activity volume, vigorous intensity exercise, nor lifetime training hours were predictive of CAD in the present study. Potential reasons for this include: (i) the prevalence of CAD was underestimated due to a limited proportion of participants undergoing gold standard evaluations to diagnose CAD (i.e. CCTA), particularly in those with a low FRS as few MAs with low FRS underwent CCTA; and (ii) cardioprotective benefits of moderate intensity exercise may outweigh the potential deleterious effects associated with vigorous intensity exercise.

Studies that found increased CAC in MAs with a low cardiovascular risk score compared to healthy controls did not follow the athletes longitudinally, therefore, it is possible that even though MAs with a low cardiovascular risk score may have a higher CACS than healthy controls, it may not translate to an increase risk of mortality, due to the predominately calcific stable nature of the plaques found in these athletes.^2,4 In the Cooper Center Longitudinal Study of 21 758 men, it was demonstrated that although the adjusted risk of CACS of ≥100 AU was 11% greater among individuals with high physical activity compared to those with lower levels, there was not a concomitant increase in all-cause or cardiovascular mortality after a decade of follow-up.²⁴ Additionally, elite athletes have been shown to live longer (5–6 y) than the general population and have a lower risk of cardiovascular and all-cause mortality.^25,26

The EST had modest diagnostic accuracy to detect CAD at risk of a MI. While it would be expected that the EST would detect those with obstructive CAD, it would not be expected that the EST would detect non-obstructive/non flow-limiting CAD. Non-obstructive CAD lesions are a significant source of MIs.²⁷ In the seven MAs who had a cardiac event, three (43%) had a positive EST. Of those, two initiated a lipid-lowering medication after either a positive MIBI or CCTA. The third did not initiate cholesterol-lowering medication after a negative MIBI. Ten MAs who had a negative EST, but underwent a CCTA due to a high FRS and/or a strong family history of CAD that were identified with obstructive CAD. After identification of CAD on CCTA, all of these MAs, except one, initiated lipid-lowering medication. There were four MAs that were identified with obstructive CAD outside of the study, all of whom had an intermediate FRS and/or strong family history, and a negative EST conducted through the study. Therefore, it may be reasonable to include a CCTA to confirm or refute the presence of CAD in those with a ≥10% FRS to assist in positive behaviour change and intensification of risk factor reduction.

An increased prevalence of atrial fibrillation has been seen in endurance MAs who train at high-intensity, and have a large volume of endurance exercise even in the absence of structured heart disease.^3,28 Arrhythmias, particularly atrial fibrillation, was common in the present cohort, and time spent performing high-intensity exercise was predictive in the development of arrhythmias. Additionally, increasing time spent in light intensity physical activity was predictive for arrhythmias. These findings suggest a curvilinear response similar to that seen in the Cardiovascular Health Study where those exercising at the highest intensity had a risk of atrial fibrillation similar to exercising at low intensity, whereas moderate intensity physical activity had the greatest reduction in atrial fibrillation.²⁹ In contrast to previous research, lifetime training hours was not predictive of arrhythmias in the logistic regression models; however, in a bivariate comparison those with arrhythmias had significantly greater lifetime training hours and years spent being physically active compared to those that were not diagnosed with an arrhythmia.

Feasibility and cost of the programme

The initial year of screening was the most expensive due to the higher cost of the baseline examination that included cardiac auscultation, a greater number of MAs that underwent the baseline screen, and the greatest number of additional investigations performed. The cardiac auscultation was removed from subsequent years as a cost-effective strategy as serial cardiac auscultations (which requires a qualified physician to perform) had limited utility in detecting clinically relevant valvular heart disease at the expense of a high cost.¹⁹ Concomitantly, the initial year had the highest number of diagnoses detected (120 vs. 21 vs. 28 vs. 17), thereby had the lowest cost per diagnosis ($2779 vs. $4853 vs. $3244 vs. $4157). Only one previous study of MAs, reported the cost of their programme. The cost after one year of screening was US$5052 (∼$6290 CAD) per new CVD finding which is double than the cost of the initial screen in the present study (CAN $3072).³⁰ While the cost of some examinations is more expensive in the United States, the higher cost is also attributed to fewer diagnoses (3% vs. 15%). Studies that included a CCTA in all athletes found a prevalence of 34–71% of athletes with CAD.^2,4,5 The prevalence of CAD is therefore expected to be higher due to all athletes undergoing CCTA or coronary angiography. While the cost of performing a CCTA in MAs with a ≥10% FRS would be high, the early identification of CAD and earlier initiation of prevention therapies and positive behaviour change could lead to less MACE in the long-term. Additionally, there were significant cost implications associated with yearly screenings and high numbers of secondary testing which did not result in the identification of CVD most of the time. This high cost could likely be reduced if a more sensitive test such as a CCTA was performed in those with ≥10% FRS in the initial year without subsequent yearly screenings.

The overall higher cost may also be justifiable if the cost of hospitalizations, invasive interventions, emergency transportation and on the individual level (i.e. years of life lost, lost wages, decreased productivity, decreased quality of life, psychological impact, burden on the family) is reduced. The potential benefits alongside all costs (i.e. initial of medications) requires further study. Additional risk and logistical factors (i.e. radiation exposure, risk of adverse reactions, accessibility, availability of skilled personnel and insurance implications in the event of a diagnosis) of performing a CCTA in those with FRS ≥10% also need to be taken into consideration and may vary between cities and countries.

Proposed screening algorithm

A predictive model for MACE was unable to be developed due to limited events. The descriptive analysis of MACE and the screening indicators, alongside the logistic regression model allowed for a theoretical model to be suggested (Figure 5). Master athletes should undergo an initial screen that includes FRS (or an equivalent cardiovascular risk stratification tool such as SCORE), ECG, and a family history and symptom questionnaire. A CCTA may be reasonable in MAs with FRS ≥10% and/or a strong family history of premature CAD to assist in behaviour modification (i.e. initiation of cholesterol-lowering treatment if CAD is identified on CCTA). In the presence of an abnormal ECG, an echocardiogram, Holter, and/or a CCTA may be recommended depending on the abnormality identified. If the CCTA has uncertain functional significance or is non-diagnostic, a stress echocardiogram or MIBI may be suggested. In the event of a CVD diagnosis, the European Association of Preventative Cardiology guidelines on exercise intensity assessment and prescription can be followed.³¹ After the initial screening, yearly screening is probably not warranted due to a lower yield of CVD diagnoses. Subsequent screenings should be on a symptom driven basis and as per local guidelines, serial reassessment of lipids, blood pressure and glycaemic control should be performed. Findings from our previous work provides additional management guidance in the event a CVD diagnosis is made.³²

Figure 5.

Theoretical screening algorithm for Masters athletes to detect cardiovascular disease. *inclusion based on clinical likelihood of CVD, availability of tests and local expertise. **Equivocal or positive ST-depression; complex ventricular arrhythmias; > 7 PVCs/min at peak or during recovery; angina or marked shortness of breath; HRE. CCTA, coronary computed tomography angiography; CV, cardiovascular; Echo: echocardiogram; ECG, electrocardiogram; EST, exercise stress test; LAD, left axis deviation; LAE: left atrial enlargement MIBI, myocardial perfusion imaging; PVC, premature ventricular contractions; RAE: right atrial enlargement; RBBB, right bundle branch block.

Limitations

The incidence of CVD is underestimated as not all MAs underwent the complete battery of gold standard tests (e.g. CCTA, echocardiogram) to accurately delineate the presence or absence of CAD or structural heart disease. Previous studies that performed a CCTA in all MAs have demonstrated that 34–71% of MAs possess CAD with 19–36% possessing a high atherosclerotic burden^4,5,7,12,33 which is higher than that reported in the present study. Conducting all of these tests in all of the MAs was not clinically justified at the time of study conception. As such, sensitivity and specificity could not be determined. Additionally, in the shared decision-making model, concern regarding the identification of CAD and the resulting impact on insurance, one’s self-identity, and sport eligibility were reasons for not wanting to pursue a definitive diagnosis with CCTA. Furthermore, there was no control population to determine whether screening decreased the incidence of MACE amongst MAs. While we did not find a difference in the presence of CAD based on menopause status in our female MA, further research in female MAs is needed to confirm the present findings. Lastly, the sample size of MAs (798) and follow-up (5 years) limits a more robust measure/estimate of MACE in this population.

There are some limitations related to the logistic regression models. Firstly, they were conducted to predict the presence of CVD by CVD sub-group, however, since the modelling used a diagnosis-based aggregation, the results can only infer (and not strongly conclude) that certain variables may be important to use in diagnosis prediction models and in more focused research. Secondly, they may have underestimated the odds of having CVD, as they only included MAs that were flagged as high risk or had symptoms and underwent subsequent testing. Previous research has indicated that MAs with low cardiovascular risk may have CAD, particularly those with high physical activity volumes and intensity, therefore, the group that was deemed low risk in the current study may indeed have CVD and thereby, limited the odds of predicting CVD in this group.

Lastly, 4.4% MAs that withdrew at some point in the study, did not respond to our correspondence (emails, phone calls, and/or contact by family physician) in the last year of the study despite numerous attempts, therefore, we do not know cardiac events or vital status in these MAs.

Conclusion

Major adverse coronary events occurred in MAs despite yearly screening. All MAs who experienced a MACE had an abnormal screen; however, a negative functional stress test (i.e. EST, stress echocardiogram, MIBI) did not ensure event-free survival over five years of the study period. The inclusion of CCTA may be reasonable in MAs with an intermediate FRS or greater to assist with positive behaviour change to prevent MACE. CAD and atrial fibrillation were the most common diagnoses with moderate physical activity being protective against their development. The inclusion of the FRS to predict the presence of CAD is supported. Further study is warranted to refine the screening strategy to reduce false-positive screens, decrease costs, and improve accuracy.

Authors’ contributions

Barbara Nicole Morrison (conception, design, acquisition of data, analysis, interpretation of data, wrote the manuscript), Saul Isserow (conception, design, acquisition of data, interpretation of data, critically revised the document), Jack Taunton (conception, design, acquisition of data, interpretation of data, critically revised the document), Nathaniel Moulson and David Oxborough (analysis and interpretation of data, critically revised the document), James McKinney (conception, design, acquisition of data, interpretation of data, critically revised the document), and Darren E. R. Warburton (conception, design, analysis and interpretation of data, critically revised the document).

Supplementary material

Supplementary material is available at European Journal of Preventive Cardiology.

Funding

This work was supported by the Vancouver General Hospital and University of British Columbia Hospital Foundation, MITACs to B.M., the Canadian Institute of Health Research (grant number: 157930) to B.M. and the Natural Sciences and Engineering Research Council of Canada (grant number NSERC RGPIN-2018–04613) to D.W.

Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.