Introduction: The optimal pre-participation screening strategy to identify athletes at risk for exercise-induced cardiovascular events is unknown. We therefore aimed to compare the American College of Sports Medicine (ACSM) and European Society of Cardiology (ESC) pre-participation screening strategies against extensive cardiovascular evaluations in identifying high-risk individuals among 35–50-year-old apparently healthy men. Methods: We applied ACSM and ESC pre-participation screenings to 25 men participating in a study on first-time marathon running. We compared screening outcomes against medical history, physical examination, electrocardiography, blood tests, echocardiography, cardiopulmonary exercise testing, and magnetic resonance imaging. Results: ACSM screening classified all participants as “medical clearance not necessary.” ESC screening classified two participants as “high-risk.” Extensive cardiovascular evaluations revealed ≥1 minor abnormality and/or cardiovascular condition in 17 participants, including three subjects with mitral regurgitation and one with a small atrial septal defect. Eleven participants had dyslipidaemia, six had hypertension, and two had premature atherosclerosis. Ultimately, three (12%) subjects had a serious cardiovascular condition warranting sports restrictions: aortic aneurysm, hypertrophic cardiomyopathy (HCM), and myocardial fibrosis post-myocarditis. Of these three participants, only one had been identified as “high-risk” by the ESC screening (for dyslipidaemia, not HCM) and none by the ACSM screening. Conclusion: Numerous occult cardiovascular conditions are missed when applying current ACSM/ESC screening strategies to apparently healthy middle-aged men engaging in their first high-intensity endurance sports event.

The cardiovascular health benefits of moderate-intensity exercise have been extensively documented [1]. However, detrimental cardiovascular effects of endurance exercise are increasingly being recognized [2]. In particular, popular events such as marathon running [3] have been associated with increased levels of circulating cardiac biomarkers and transient dysfunction of the right ventricle [4‒6]. Furthermore, prolonged elevation of cardiac troponins following strenuous exercise has been shown to be associated with increased rates of fatal and non-fatal cardiovascular disease (CVD) events in a cohort of older long-distance walkers, suggesting that exercise-induced increases in circulating troponins may not be a benign physiological response, but an early marker of CVD [6].

The American College of Sports Medicine (ACSM) and the European Society of Cardiology (ESC) provide pre-participation screening strategies to assist physicians in identifying individuals at high risk of exercise-related events [7, 8]. However, there is no consensus on optimal pre-participation screening content, taking efficacy, burden, and costs into account [9]. Comprehensive cardiovascular evaluations detect more cardiovascular risk factors and disease, but the incremental yield of individual investigations (e.g., physical examination, resting electrocardiography (ECG), exercise testing, echocardiography, and blood tests) remains unclear [9‒12].

We therefore pragmatically compared ACSM and ESC pre-participation screening outcomes against baseline findings from our 2021 Amsterdam Marathon study [13] comprising comprehensive cardiovascular evaluations and the consequent sports advice in a rigorously investigated cohort of middle-aged men participating in their first marathon. The current work reports findings from the baseline measurements of our study population and the clinical implications of our findings.

Our current analysis of pre-participation screening was conducted within the framework of a study that investigated the effects of first-time marathon running in men aged 35–50 years [13]. We recruited participants who responded to announcements made through the Amsterdam University Medical Centers’ newsletter, local newspapers, social media, and the Marathon organiser’s website. After confirming eligibility, an online screening subsequently took place wherein potential participants could reconfirm their interest, and were given general information about the study and inclusion and exclusion criteria [13] and what informed consent would entail. After giving informed consent, participants in the 2021 Amsterdam Marathon study underwent extensive testing at baseline, pre-marathon (after 4 months of training), directly post-marathon, and after 1 month of recovery. Testing comprised a comprehensive medical history, physical examination, ECG, blood tests, cardiopulmonary exercise testing (CPET), echocardiography, cardiac magnetic resonance imaging (MRI), and clinical follow-up if indicated.

We applied the ACSM and ESC pre-participation screenings to the participants’ baseline data. As outlined in the study design [13], the ACSM algorithm was applied before inclusion, while the ESC algorithm score was calculated post hoc. In short, the ACSM pre-participation screening for individuals aged 18–65 is based on (1) exercise participation 3 months prior and (2) cardiovascular, metabolic, or renal disease history/symptoms [8]. Participants are consequently classified as “no medical clearance necessary,” “medical clearance recommended for vigorous-intensity exercise,” or “discontinue exercise and seek medical clearance.” The ESC pre-participation screening for individuals aged ≥35 years is based on current physical activity levels and cardiovascular risk profile, assessed by symptoms, medical history, family history, and calculation of Systematic Coronary Risk Evaluation (SCORE). Individuals with SCORE-estimated 10-year cardiovascular mortality ≥5% or markedly elevated individual risk factor levels mandating further clinical analysis are considered “high-risk” [7].

We classified hypertension according to the 2020 ISH Global Hypertension Practice Guidelines [14]. Dyslipidaemia was diagnosed if one or more of the following was present: total cholesterol ≥5.0 mmol/L, LDL cholesterol ≥3.37 mmol/L, triglycerides >1.7 mmol/L, lipoprotein(a) ≥125.0 nmol/L, or HDL <1.0 mmol/L [15‒19]. The likelihood of familial hypercholesterolaemia was assessed using the Dutch Lipid Clinic Network score [20, 21]. All ECGs and exercise ECGs were interpreted according to the current international consensus [22]. Exercise tests were assessed according to the EACPR/AHA 2016 guideline [23], and echocardiography and MRI according to the most recent imaging recommendations [24]. We report final diagnoses in individuals where study findings prompted further clinical evaluation.

We included 25 men with a mean age of 42 ± 4.4 years and exercise levels of 28.8 ± 12.8 MET-hours per week for the past 3 months. The ACSM screening algorithm classified all participants as “medical clearance not necessary,” as all participants were physically active for the past 3 months and reported no signs or symptoms or known cardiovascular, metabolic, or renal disease. One participant with hypertension for the past 8 years stated to be compliant with medication and to have well-controlled blood pressure.

All participants had SCORE <5% when applying the ESC screening algorithm. Two participants were reclassified as “high-risk” due to total cholesterol ≥8.0 mmol/L. The first participant was cleared for high-intensity exercise after extensive cardiovascular evaluation. The second participant was given restrictive sports advice due to the finding of hypertrophic cardiomyopathy (HCM) rather than due to dyslipidaemia or dyslipidaemia-associated cardiovascular conditions. In this participant, CT angiography revealed a moderate stenosis (CAD-RADS 3) [25] of the left anterior descending coronary artery.

Our comprehensive study evaluation documented eight subjects without cardiovascular conditions and 17 with ≥1 abnormality and/or cardiovascular conditions. Four (16%) subjects had minor abnormalities (three with mitral regurgitation and one with a small atrial septal defect). Cardiovascular conditions were found in 16 (64%) participants: dyslipidaemia was found in 11 (44%) subjects, and hypertension was found in six (24%) participants. One participant with strongly elevated lipoprotein(a) levels underwent CT angiography, which revealed premature atherosclerosis with calcified coronary plaque (<25% stenosis of the left anterior descending coronary artery). Of the 17 participants with abnormalities and/or cardiovascular conditions, three (12%) were ultimately diagnosed with CVD. They were given restrictive sports advice due to a dilated aortic root (46 mm), the presence of anteroseptal myocardial fibrosis that was interpreted as recovered viral myocarditis, and a rare phenotypic presentation of HCM (interventricular septum 15 mm) with a pathogenic PKP2 (class 5) mutation (c.2146-1G>C) [26, 27]. The results are summarized in Figure 1 and detailed in Table 1.

Fig. 1.

Outcomes of extensive cardiovascular evaluations within the framework of a study on first-time marathon running, compared with the American College of Sports Medicine (ACSM) and European Society of Cardiology (ESC) pre-participation screening strategies. CPET, cardiopulmonary exercise test; CV, cardiovascular; CVD, cardiovascular disease; ECG, electrocardiogram; MRI, magnetic resonance imaging; TTE, transthoracic echocardiography.

Fig. 1.

Outcomes of extensive cardiovascular evaluations within the framework of a study on first-time marathon running, compared with the American College of Sports Medicine (ACSM) and European Society of Cardiology (ESC) pre-participation screening strategies. CPET, cardiopulmonary exercise test; CV, cardiovascular; CVD, cardiovascular disease; ECG, electrocardiogram; MRI, magnetic resonance imaging; TTE, transthoracic echocardiography.

Close modal
Table 1.

Outcomes of the ACSM and ESC screening algorithms and the sports advice of participants according to the clinical findings

Subject No.Age, yearsDiseases and signs or symptomsScreening algorithmClinically relevant findingsDiagnosisFinal sports advice
ACSMESC
risk categorySCORE (%)risk category
38 None NC 0.11 Low risk Echocardiography: mitral valve prolapse with minimal regurgitation Mitral valve prolapse No restrictions 
38 None NC 0.17 Low risk BP 130/90 mm Hg Hypertension grade 1 No restrictions 
Total cholesterol 5.42 mmol/L; triglycerides 2.32 mmol/L (DFH score: 0) Dyslipidaemia, FH unlikely 
Echocardiography: moderate mitral regurgitation Moderate mitral regurgitation 
44 None NC 0.38 Low risk BP 140/80 mm Hg Hypertension grade 1 No restrictions 
49 None NC 1.90 High risk* BP 150/90 mm Hg Hypertension grade 1 Discontinue exercise until further comprehensive evaluation 
ECG: inverted T-waves V4–V6 Dyslipidaemia, FH unlikely 
Total cholesterol 8.14 mmol/L, LDL cholesterol 4.97 mmol/L, triglycerides 4.34 mmol/L (DFH score: 1) Pathogenic PKP2 mutation, HCM 
Echocardiography: IVS 14 mm Premature atherosclerosis 
CT angiography: moderate stenosis (CAD-RADS 3) mid-LAD 
MRI: IVS 15 mm, subendocardial LGE inferoseptal 
Genetics: pathogenic (class 5) PKP2 mutation (c.2146-1G>C) 
46 None NC 0.75 High risk* Total cholesterol 8.03 mmol/L, LDL cholesterol 5.67 mmol/L, lipoprotein(a) 239 nmol/L (DFH score: 3) Dyslipidaemia, possible FH No restrictions 
40 None NC 0.12 Low risk  No restrictions 
43 None NC 0.20 Low risk Small atrial septal defect, jump-rope inter-atrial septum Small atrial septal defect No restrictions 
44 None NC 0.36 Low risk Total cholesterol 6.58 mmol/L, LDL cholesterol 4.52 mmol/L, lipoprotein(a) 82 nmol/L (DFH score: 1) Dyslipidaemia, FH unlikely No restrictions 
42 None NC 0.21 Low risk Lipoprotein(a) 134 nmol/L (DFH score: 0) Dyslipidaemia, FH unlikely No restrictions 
10 38 None NC 0.14 Low risk Total cholesterol 5.27 mmol/L, LDL cholesterol 3.48 mmol/L, lipoprotein(a) 161 nmol/L (DFH score: 0) Dyslipidaemia, FH unlikely No restrictions 
11 35 None NC 0.06 Low risk  No restrictions 
12 46 None NC 0.33 Low risk Echocardiography: aortic root diameter 47 mm Gene-elusive thoracic aortic aneurysm disease Low to moderate-intensity endurance exercise; no strength training, no extreme endurance sports 
MRI: aortic root diameter 46 mm 
13 46 None NC 0.42 Low risk No restrictions 
14 41 None NC 0.23 Low risk Total cholesterol 5.31 mmol/L, lipoprotein(a) 149 nmol/L (DFH score: 0) Dyslipidaemia, FH unlikely Discontinue exercise until further comprehensive evaluation 
MRI: myocardial fibrosis apical (infero)lateral and mid-septal Probably recovered viral myocarditis 
15 40 None NC 0.22 Low risk BP 130/90 mm Hg Hypertension grade 1 No restrictions 
ECG: pathological Q waves in inferolateral leads 
MRI and echocardiography normal 
16 48 None NC 0.58 Low risk BP 120/90 mm Hg Dyslipidaemia, FH unlikely No restrictions 
Total cholesterol 5.39 mmol/L, LDL cholesterol 3.46 mmol/L (DFH score: 0) Hypertension grade 1 
17 37 None NC 0.09 Low risk No restrictions 
18 38 None NC 0.12 Low risk No restrictions 
19 38 None NC 0.15 Low risk No restrictions 
20 47 None NC 0.69 Low risk Total cholesterol 5.97 mmol/L, LDL cholesterol 3.38 mmol/L (DFH score: 0) Dyslipidaemia, FH unlikely No restrictions 
21 35 None NC 0.07 Low risk Total cholesterol 5.17 mmol/L, LDL cholesterol 3.54 mmol/L, lipoprotein(a) 313 nmol/L (DFH score: 2) Dyslipidaemia, FH unlikely No restrictions 
CT angiography: calcified plaque (<25% stenosis) proximal LAD Premature atherosclerosis 
22 46 None NC 0.39 Low risk No restrictions 
23 42 Hypertension, stable and compliant with medication NC 0.35 Low risk BP: 140/70 mm Hg (with medication) Hypertension grade 1 No restrictions 
MRI: mild concentric LVH (septum 12 mm) 
24 39 None NC 0.24 Low risk Total cholesterol 7.09 mmol/L, LDL cholesterol 4.57 mmol/L, triglycerides 2.55 mmol/L (DFH score: 1) Dyslipidaemia, FH unlikely No restrictions 
Echocardiography: dilated left atrium (LAVI 55 mL/m2), GLS -16%, moderate mitral valve insufficiency Moderate mitral regurgitation 
MRI: septal wall thickness max. 12 mm Athlete’s heart 
25 50 None NC 0.68 Low risk No restrictions 
Subject No.Age, yearsDiseases and signs or symptomsScreening algorithmClinically relevant findingsDiagnosisFinal sports advice
ACSMESC
risk categorySCORE (%)risk category
38 None NC 0.11 Low risk Echocardiography: mitral valve prolapse with minimal regurgitation Mitral valve prolapse No restrictions 
38 None NC 0.17 Low risk BP 130/90 mm Hg Hypertension grade 1 No restrictions 
Total cholesterol 5.42 mmol/L; triglycerides 2.32 mmol/L (DFH score: 0) Dyslipidaemia, FH unlikely 
Echocardiography: moderate mitral regurgitation Moderate mitral regurgitation 
44 None NC 0.38 Low risk BP 140/80 mm Hg Hypertension grade 1 No restrictions 
49 None NC 1.90 High risk* BP 150/90 mm Hg Hypertension grade 1 Discontinue exercise until further comprehensive evaluation 
ECG: inverted T-waves V4–V6 Dyslipidaemia, FH unlikely 
Total cholesterol 8.14 mmol/L, LDL cholesterol 4.97 mmol/L, triglycerides 4.34 mmol/L (DFH score: 1) Pathogenic PKP2 mutation, HCM 
Echocardiography: IVS 14 mm Premature atherosclerosis 
CT angiography: moderate stenosis (CAD-RADS 3) mid-LAD 
MRI: IVS 15 mm, subendocardial LGE inferoseptal 
Genetics: pathogenic (class 5) PKP2 mutation (c.2146-1G>C) 
46 None NC 0.75 High risk* Total cholesterol 8.03 mmol/L, LDL cholesterol 5.67 mmol/L, lipoprotein(a) 239 nmol/L (DFH score: 3) Dyslipidaemia, possible FH No restrictions 
40 None NC 0.12 Low risk  No restrictions 
43 None NC 0.20 Low risk Small atrial septal defect, jump-rope inter-atrial septum Small atrial septal defect No restrictions 
44 None NC 0.36 Low risk Total cholesterol 6.58 mmol/L, LDL cholesterol 4.52 mmol/L, lipoprotein(a) 82 nmol/L (DFH score: 1) Dyslipidaemia, FH unlikely No restrictions 
42 None NC 0.21 Low risk Lipoprotein(a) 134 nmol/L (DFH score: 0) Dyslipidaemia, FH unlikely No restrictions 
10 38 None NC 0.14 Low risk Total cholesterol 5.27 mmol/L, LDL cholesterol 3.48 mmol/L, lipoprotein(a) 161 nmol/L (DFH score: 0) Dyslipidaemia, FH unlikely No restrictions 
11 35 None NC 0.06 Low risk  No restrictions 
12 46 None NC 0.33 Low risk Echocardiography: aortic root diameter 47 mm Gene-elusive thoracic aortic aneurysm disease Low to moderate-intensity endurance exercise; no strength training, no extreme endurance sports 
MRI: aortic root diameter 46 mm 
13 46 None NC 0.42 Low risk No restrictions 
14 41 None NC 0.23 Low risk Total cholesterol 5.31 mmol/L, lipoprotein(a) 149 nmol/L (DFH score: 0) Dyslipidaemia, FH unlikely Discontinue exercise until further comprehensive evaluation 
MRI: myocardial fibrosis apical (infero)lateral and mid-septal Probably recovered viral myocarditis 
15 40 None NC 0.22 Low risk BP 130/90 mm Hg Hypertension grade 1 No restrictions 
ECG: pathological Q waves in inferolateral leads 
MRI and echocardiography normal 
16 48 None NC 0.58 Low risk BP 120/90 mm Hg Dyslipidaemia, FH unlikely No restrictions 
Total cholesterol 5.39 mmol/L, LDL cholesterol 3.46 mmol/L (DFH score: 0) Hypertension grade 1 
17 37 None NC 0.09 Low risk No restrictions 
18 38 None NC 0.12 Low risk No restrictions 
19 38 None NC 0.15 Low risk No restrictions 
20 47 None NC 0.69 Low risk Total cholesterol 5.97 mmol/L, LDL cholesterol 3.38 mmol/L (DFH score: 0) Dyslipidaemia, FH unlikely No restrictions 
21 35 None NC 0.07 Low risk Total cholesterol 5.17 mmol/L, LDL cholesterol 3.54 mmol/L, lipoprotein(a) 313 nmol/L (DFH score: 2) Dyslipidaemia, FH unlikely No restrictions 
CT angiography: calcified plaque (<25% stenosis) proximal LAD Premature atherosclerosis 
22 46 None NC 0.39 Low risk No restrictions 
23 42 Hypertension, stable and compliant with medication NC 0.35 Low risk BP: 140/70 mm Hg (with medication) Hypertension grade 1 No restrictions 
MRI: mild concentric LVH (septum 12 mm) 
24 39 None NC 0.24 Low risk Total cholesterol 7.09 mmol/L, LDL cholesterol 4.57 mmol/L, triglycerides 2.55 mmol/L (DFH score: 1) Dyslipidaemia, FH unlikely No restrictions 
Echocardiography: dilated left atrium (LAVI 55 mL/m2), GLS -16%, moderate mitral valve insufficiency Moderate mitral regurgitation 
MRI: septal wall thickness max. 12 mm Athlete’s heart 
25 50 None NC 0.68 Low risk No restrictions 

*Classified as high risk because of total cholesterol ≥8.0 mmol/L.

NC, no medical clearance necessary; BP, blood pressure; ECG, electrocardiogram; DFH, Dutch criteria for familial hypercholesterolaemia; GLS, global longitudinal strain; IVS, interventricular septum; MRI, magnetic resonance imaging; LAD, left anterior descending; LAVI, left atrial volume index; LGE, late gadolinium enhancement.

Our extensive evaluation of male first-time marathon runners indicates that the sensitivity of internationally recommended pre-participation screenings has limitations in detecting subtle but serious CVD. In our study, the readiness and motivation to run a first marathon did not reflect optimal cardiovascular health. Indeed, in our small cohort of apparently healthy middle-aged men, we found a considerable number of serious CVDs, in addition to the majority demonstrating ≥1 CVD risk factor [28].

The number of studies comparing pre-participation algorithms with extensive cardiovascular examinations, including modalities such as MRI, is limited. New cardiovascular abnormalities have been reported to range from 2.8% [9] to 19% [10] of participants, which in some cases (0.4–7%) led to negative sports advice for (high-intensity) exercise [9‒11]. In line with our current findings, Ermolao et al. [10] found that in 525 middle-aged (≥35 years old) men wherein the ACSM and European Association of Cardiovascular Prevention and Rehabilitation (EACPR; the 2011 predecessor of the 2020 ESC guidelines for pre-participation screening) screening algorithms were applied and compared with comprehensive examinations including ECG and a maximal exercise test, new cardiovascular conditions were found in 19% of the participants, of which 49% went undetected when using the EACPR algorithm, and 50% with the ACSM algorithm.

In our study, the ESC pre-participation screening identified two participants at high risk (for atherosclerotic disease). The ACSM pre-participation screening did not identify any individuals at high risk. Yet, we identified three participants with serious CVDs constituting contra-indications to intensive sports. One of the participants with a serious CVD – an uncommon presentation of phenotypic HCM – was identified as high-risk by the ESC algorithm due to total cholesterol of 8.14 mmol/L, and not due to screening-detected structural heart disease. The screening algorithms did not identify the other two participants with serious CVD (aortic aneurysm and myocardial fibrosis post-myocarditis). Exercise tests are commonly added to screening strategies, and each of our high-risk CVD participants had undergone CPET with continuous ECG monitoring without any abnormalities. Consequently, exercise test findings would not have changed the sports advice based on the ACSM or ESC algorithms. Furthermore, data on exercise recommendations for HCM are scarce, and American Heart Association (AHA) and ESC recommendations differ. However, recent studies point towards the possibility of a more liberal approach [29]. Our sports advice for these individuals was based on the AHA [30] and ESC guidelines [7], but with the final advice formulated by our national multidisciplinary team [31]. The subject with an aortic aneurysm was advised to discontinue all intensive and explosive exercise. The other two participants, with HCM and recovered myocarditis, are still under medical follow-up and are currently advised to refrain from high-intensity exercise.

Our findings highlight that pre-participation screenings in middle-aged men aim to detect the most prevalent diseases in this group, i.e., acquired, risk-factor-driven CVD, and should not be interpreted as a comprehensive screening for less prevalent, structural or (uncommon) acquired CVDs. The major advantages of the ACSM pre-participation screening are that it is easy to implement, does not require physical examinations or additional testing, and can be performed in low-resource settings, markedly lowering implementation barriers. However, in our study sample, this advantage was offset by a lack of sensitivity to several subclinical conventional risk factors (e.g., hypertension, dyslipidaemia). All participants considered themselves active during the 3 months before screening. They had no cardiac (or other screened-for) complaints and were consequently all classified as “low risk” for cardiac events during exercise. While the ESC pre-participation screening also did not classify most individuals with risk factors as “high risk,” the SCORE calculation led to a higher detection rate of risk factors. These differences in screening content between the ESC and ACSM screening algorithms should be considered when implementing pre-participation screenings. Finally, the high-risk factor burden found in our study highlights the importance of not only focussing on sports eligibility but also on evaluating individual risk factors for atherosclerotic disease. This could be particularly relevant in endurance athletes because lifelong participation in endurance exercise has been shown to be associated with more coronary plaque relative to well-matched, healthy individuals with similar risk-factor profiles [32]. Additionally, an important limitation of both approaches is that it is unknown whether the individuals classified as “high risk” are indeed at high risk because unambiguous data on the interaction between intensive sports participation and cardiac pathology in rare CVDs are lacking.

Our cohort’s rates of serious CVD and risk factors are striking, considering that we aimed to include healthy first-time marathon runners. The inclusion criterion “intention to train and run for first-time marathon participation” could have influenced the composition of our study sample. Some of our participants may have been lifelong less active or inactive, only increasing their activity levels during the 3 months before study enrollment. Hence, they may have never provoked signs or symptoms that would have prompted cardiovascular evaluation. Joining a marathon study may also have been an incentive for individuals uncertain about their cardiovascular health and, as such, to run their first marathon in a highly monitored setting. Finally, despite implementing the recommended pre-participation screening, our rates of both structural and acquired cardiovascular condition findings are alarming and warrant replication in larger cohorts.

Commonly implemented pre-participation screening strategies fail to identify individuals with serious CVDs that would warrant highly restrictive sports advice. Numerous occult cardiovascular conditions are missed when applying current ACSM/ESC screening strategies to apparently healthy middle-aged men engaging in their first high-intensity endurance sports event. Our findings highlight the need for further study into the sensitivity of currently recommended screening strategies.

We thank Chantal Nieuwenhuizen, Ted Ronteltap, and the echocardiography and MRI technicians of the Amsterdam University Medical Centers for helping us with data collection.

The study protocol was approved by the Amsterdam University Medical Centers Medical Ethics Review Committee (NL70800.029.19). Written informed consent was obtained from all subjects prior to study participation.

The authors have no conflicts of interest to declare.

This work is supported by the Indonesia Endowment Fund for Education (LPDP – Grant No. 201803220412678). The funder had no role in the design, data collection, data analysis, and reporting of this study.

H.T.J. is responsible for the finished work and the conduct of the study. I.L. and T.G.H.W. contributed equally to this work and drafting of the article and literature research. Data collection: I.L., T.G.H.W., N.v.S., N.B., A.J.B., M.F., S.v.d.B.-F., F.H.d.H., R.H.A.C.M.B.-B., S.M.B., and R.N.P.; data analysis: I.L., T.G.H.W., and H.T.J.; checking of the content and proofreading of the text and supervision: E.V., A.J.B., and H.T.J.; writing original draft preparation: I.L. All authors have read and agreed to the published version of the manuscript.

Additional Information

Inarota Laily and Tom G.H. Wiggers contributed equally to this work.

Data are not publicly available due to ethical reasons. Further enquiries can be directed to the corresponding author (I.L.).

1.
Kyu
HH
,
Bachman
VF
,
Alexander
LT
,
Mumford
JE
,
Afshin
A
,
Estep
K
, et al
.
Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013
.
BMJ
.
2016
;
354
:
i3857
. .
2.
Merghani
A
,
Malhotra
A
,
Sharma
S
.
The U-shaped relationship between exercise and cardiac morbidity
.
Trends Cardiovasc Med
.
2016
;
26
(
3
):
232
40
. .
3.
Reusser
M
,
Sousa
CV
,
Villiger
E
,
Alvero Cruz
JR
,
Hill
L
,
Rosemann
T
, et al
.
Increased participation and decreased performance in recreational master athletes in “berlin marathon” 1974–2019
.
Front Physiol
.
2021
;
12
:
631237
. .
4.
Kleiven
Ø
,
Omland
T
,
Skadberg
Ø
,
Melberg
TH
,
Bjørkavoll-Bergseth
MF
,
Auestad
B
, et al
.
Occult obstructive coronary artery disease is associated with prolonged cardiac troponin elevation following strenuous exercise
.
Eur J Prev Cardiol
.
2020
;
27
(
11
):
1212
21
. .
5.
Mousavi
N
,
Czarnecki
A
,
Kumar
K
,
Fallah-Rad
N
,
Lytwyn
M
,
Han
SY
, et al
.
Relation of biomarkers and cardiac magnetic resonance imaging after marathon running
.
Am J Cardiol
.
2009
;
103
(
10
):
1467
72
. .
6.
Aengevaeren
VL
,
Hopman
MTE
,
Thompson
PD
,
Bakker
EA
,
George
KP
,
Thijssen
DHJ
, et al
.
Exercise-induced cardiac troponin I increase and incident mortality and cardiovascular events
.
Circulation
.
2019
;
140
(
10
):
804
14
. .
7.
Pelliccia
A
,
Sharma
S
,
Gati
S
,
Bäck
M
,
Börjesson
M
,
Caselli
S
, et al
.
2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease: the Task Force on sports cardiology and exercise in patients with cardiovascular disease of the European Society of Cardiology (ESC)
.
Eur Heart J
.
2021
;
42
(
1
):
17
96
. .
8.
American College of Sports Medicine
.
Guidelines for exercise testing and prescription
. 10 ed.
Philadelphia (PA)
:
Lippincott Williams & Wilkins
;
2018
; p.
22
43
.
9.
Menafoglio
A
,
Di Valentino
M
,
Porretta
AP
,
Foglia
P
,
Segatto
JM
,
Siragusa
P
, et al
.
Cardiovascular evaluation of middle-aged individuals engaged in high-intensity sport activities: implications for workload, yield and economic costs
.
Br J Sports Med
.
2015
;
49
(
11
):
757
61
. .
10.
Ermolao
A
,
Gasperetti
A
,
Rigon
A
,
Patti
A
,
Battista
F
,
Frigo
AC
, et al
.
Comparison of cardiovascular screening guidelines for middle-aged/older adults
.
Scand J Med Sci Sports
.
2019
;
29
(
9
):
1375
82
. .
11.
Aagaard
P
,
Sahlén
A
,
Bergfeldt
L
,
Braunschweig
F
.
Preparticipation evaluation of novice, middle-age, long-distance runners
.
Med Sci Sports Exerc
.
2013
;
45
(
1
):
130
7
. .
12.
Price
OJ
,
Tsakirides
C
,
Gray
M
,
Stavropoulos-Kalinoglou
A
.
ACSM preparticipation health screening guidelines: a UK university cohort perspective
.
Med Sci Sports Exerc
.
2019
;
51
(
5
):
1047
54
. .
13.
Laily
I
,
Wiggers
TGH
,
van Steijn
N
,
Verhagen
E
,
Bakermans
AJ
,
Jorstad
HT
.
Prospective evaluation of cardiac effects of first-time marathon training, running, and recovery in middle-aged men: cohort study rationale and design
.
Neth Heart J
.
2023
;
31
(
1
):
21
8
. .
14.
Unger
T
,
Borghi
C
,
Charchar
F
,
Khan
NA
,
Poulter
NR
,
Prabhakaran
D
, et al
.
2020 international society of hypertension global hypertension Practice guidelines
.
Hypertension
.
2020
;
75
(
6
):
1334
57
. .
15.
The Global Health Observatory
.
Mean total cholesterol
.
World Health Organization
;
2020
. [cited 1 September 2023]. Available from: https://www.who.int/data/gho/indicator-metadata-registry/imr-details/2384.
16.
Jacobson
TA
,
Ito
MK
,
Maki
KC
,
Orringer
CE
,
Bays
HE
,
Jones
PH
, et al
.
National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1 – executive summary
.
J Clin Lipidol
.
2014
;
8
(
5
):
473
88
. .
17.
Mach
F
,
Baigent
C
,
Catapano
AL
,
Koskinas
KC
,
Casula
M
,
Badimon
L
, et al
.
2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk
.
Eur Heart J
.
2020
;
41
(
1
):
111
88
. .
18.
Nissen
SE
,
Wolski
K
,
Cho
L
,
Nicholls
SJ
,
Kastelein
J
,
Leitersdorf
E
, et al
.
Lipoprotein(a) levels in a global population with established atherosclerotic cardiovascular disease
.
Open Heart
.
2022
;
9
(
2
):
e002060
. .
19.
Jellinger
PS
,
Handelsman
Y
,
Rosenblit
PD
,
Bloomgarden
ZT
,
Fonseca
VA
,
Garber
AJ
, et al
.
American association of clinical endocrinologists and American College of endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease
.
Endocr Pract
.
2017
;
23
(
Suppl 2
):
1
87
. .
20.
Nordestgaard
BG
,
Chapman
MJ
,
Humphries
SE
,
Ginsberg
HN
,
Masana
L
,
Descamps
OS
, et al
.
Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society
.
Eur Heart J
.
2013
;
34
(
45
):
3478
90a
. .
21.
Austin
M
.
Dutch criteria for familial hypercholesterolemia (FH)
.
MDCalc
.
2013
. Available from: https://www.mdcalc.com/calc/3818/dutch-criteria-familial-hypercholesterolemia-fh#next-steps.
22.
Drezner
JA
,
Sharma
S
,
Baggish
A
,
Papadakis
M
,
Wilson
MG
,
Prutkin
JM
, et al
.
International criteria for electrocardiographic interpretation in athletes: consensus statement
.
Br J Sports Med
.
2017
;
51
(
9
):
704
31
. .
23.
Guazzi
M
,
Arena
R
,
Halle
M
,
Piepoli
MF
,
Myers
J
,
Lavie
CJ
.
2016 focused update: clinical recommendations for cardiopulmonary exercise testing data assessment in specific patient populations
.
Eur Heart J
.
2018
;
39
(
14
):
1144
61
. .
24.
Pelliccia
A
,
Caselli
S
,
Sharma
S
,
Basso
C
,
Bax
JJ
,
Corrado
D
, et al
.
European Association of Preventive Cardiology (EAPC) and European Association of Cardiovascular Imaging (EACVI) joint position statement: recommendations for the indication and interpretation of cardiovascular imaging in the evaluation of the athlete’s heart
.
Eur Heart J
.
2018
;
39
(
21
):
1949
69
. .
25.
Cury
RC
,
Abbara
S
,
Achenbach
S
,
Agatston
A
,
Berman
DS
,
Budoff
MJ
, et al
.
CAD-RADSTM coronary artery disease: reporting and data system. An expert consensus document of the society of cardiovascular computed tomography (SCCT), the American College of radiology (ACR) and the north American society for cardiovascular imaging (NASCI). Endorsed by the American College of cardiology
.
J Am Coll Radiol
.
2016
;
10
(
4
):
269
81
. .
26.
van Tintelen
JP
,
Entius
MM
,
Bhuiyan
ZA
,
Jongbloed
R
,
Wiesfeld
ACP
,
Wilde
AAM
, et al
.
Plakophilin-2 mutations are the major determinant of familial arrhythmogenic right ventricular dysplasia/cardiomyopathy
.
Circulation
.
2006
;
113
(
13
):
1650
8
. .
27.
Thompson
BA
,
Spurdle
AB
,
Plazzer
JP
,
Greenblatt
MS
,
Akagi
K
,
Al-Mulla
F
, et al
.
Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
.
Nat Genet
.
2014
;
46
(
2
):
107
15
. .
28.
Sanchis-Gomar
F
,
Perez-Quilis
C
,
Leischik
R
,
Lucia
A
.
Epidemiology of coronary heart disease and acute coronary syndrome
.
Ann Transl Med
.
2016
;
4
(
13
):
256
. .
29.
Lampert
R
,
Ackerman
MJ
,
Marino
BS
,
Burg
M
,
Ainsworth
B
,
Salberg
L
, et al
.
Vigorous exercise in patients with hypertrophic cardiomyopathy
.
JAMA Cardiol
.
2023
;
8
(
6
):
595
605
. .
30.
Ommen
SR
,
Mital
S
,
Burke
MA
,
Day
SM
,
Deswal
A
,
Elliott
P
, et al
.
2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of cardiology/American heart association joint committee on clinical Practice guidelines
.
Circulation
.
2020
;
142
(
25
):
e558
631
. .
31.
van Hattum
JC
,
Verwijs
SM
,
Senden
PJ
,
Spies
JL
,
Boekholdt
SM
,
Groenink
M
, et al
.
The sports cardiology team: personalizing athlete care through a comprehensive, multidisciplinary approach
.
Mayo Clin Proc Innov Qual Outcomes
.
2022
;
6
(
6
):
525
35
. .
32.
De Bosscher
R
,
Dausin
C
,
Claus
P
,
Bogaert
J
,
Dymarkowski
S
,
Goetschalckx
K
, et al
.
Lifelong endurance exercise and its relation with coronary atherosclerosis
.
Eur Heart J
.
2023
;
44
(
26
):
2388
99
. .