Authors
- Zsolt Szelid — Department of Sports Medicine and Digital Health, Faculty of Health and Sport Sciences, Győr, Hungary — ORCID: 0009-0005-6391-9836
- Ágnes Sziva — Doctoral School of Health Sciences, Faculty of Health Sciences, Pécs, Hungary — ORCID: 0009-0007-7188-3620
Abstract
This summary article reviews the complex relationship between hypertension and sports, addressing key aspects of prevalence, risk factors, and management strategies. Hypertension is a leading cause of cardiovascular disease and mortality, and while regular exercise generally provides cardioprotective effects, certain sports disciplines and lifestyle choices may elevate blood pressure (BP) levels in athletes. The article highlights the role of isometric training, high body mass, and the use of performance-enhancing substances as contributors to increased risk. Additionally, it explores the implications of high BP on both athletic performance and long-term cardiovascular health in physically active patients. Diagnostic challenges are discussed, emphasizing the limitations of routine measurements and the need for advanced tools such as ambulatory BP monitoring. Updated European guidelines are presented as a framework for accurate hypertension diagnosis and risk assessment among athletes. Management approaches prioritize lifestyle interventions, including dietary changes, stress reduction, and tailored exercise programs. When necessary, pharmacological treatments are recommended with careful consideration of doping regulations and potential impacts on athletic performance. This article underscores the importance of individualized care in addressing hypertension in athletes, advocating for a multidisciplinary approach that integrates medical, nutritional, and training expertise. By consolidating current evidence, the article aims to provide practical guidance for clinicians, treating athletes and patients with regular physical activities, to better understand and manage hypertension in this population.
Keywords
hypertension in athletes, cardiovascular risk, lifestyle intervention, blood pressure screening, exercise-induced hypertension
DOI
https://doi.org/10.15836/ccar2026.93Full Text
## Introduction Arterial hypertension is unequivocally one of the primary causes of cardiovascular (CV) morbidity and mortality (1). However, establishing the diagnosis of hypertension in athletes poses a particular challenge, as otherwise healthy young individuals or adults rarely come into contact with healthcare professionals who would confront them with the potential disease and its associated risks. Nonetheless, hypertension does affect athletes as well, sometimes even at a young age (2). Elevated blood pressure (BP) is frequently detected during routine screening examinations in athletes (3). Long-standing hypertension leads to the development of subclinical pathological alterations, which substantially increase CV risk and thereby promote the development of overt CV disease later in life (4). In competitive athletes, the principal aim of the sports medicine examination is to detect subclinical abnormalities in asymptomatic individuals. In Hungary, compulsory medical screening is conducted once a year for competitive athletes between the ages of 16 and 65, while those under 16 or over 65 are examined every six months (5). However, brachial BP measured once during the examination is usually insufficient to establish the diagnosis of hypertension. It may raise clinical suspicion, which must be further investigated in additional steps. First and foremost, to determine resting BP, home or ambulatory 24-hour BP monitoring is required, as a single measurement during the sports medical examination may overestimate BP due to stress-induced elevation. ## Definition and interpretation of blood pressure Studies focusing on hypertension in athletes do not present a uniform picture, primarily due to the evolving definition of hypertension itself. Most investigations have been conducted in adults or adolescents, with elevated BP commonly defined as systolic >140 mmHg and diastolic >90 mmHg. In 2024, the European Society of Cardiology introduced a new guideline that, in addition to defining BP thresholds in adults, clearly outlines the correct procedure for BP measurement and the diagnostic steps for hypertension (6). According to the new European guideline, normal (non-elevated) BP in adults at rest is defined as systolic 35 years), supplementary laboratory tests indicating CV risk (e.g., lipid profile, blood glucose), all aimed at more accurate risk stratification (5). In hypertensive athletes, the most accessible imaging modality, transthoracic echocardiography, is also warranted (12). ## Prevalence of hypertension in athletes The prevalence of hypertension among athletes is primarily derived from the findings of screening examinations. Earlier studies have demonstrated that due to methodological differences across various investigations, the reported prevalence of hypertension in athletes varies widely—ranging from 0% to 83% (13). Nevertheless, it has generally been accepted that the prevalence of hypertension in athletes is lower than in the non-athlete population (3, 13), although this may change with advancing age and the appearance of comorbidities. However, an analysis of a large-scale athlete database conducted in 2019 (using a cutoff value of 140/90 mmHg) found that one-third of elite athletes were hypertensive (2), a rate clearly higher than that observed in the general population (14). This proportion would likely have been even greater if the study had also classified individuals within the newly defined European guideline range for high-normal BP (120–134/70–84 mmHg) as hypertensive (6). Interpreting BP readings obtained during athletic examinations in light of these new guidelines is of particular importance, as elevated BP at a young age significantly increases the risk of developing severe CV disease and elevates all-cause mortality in later life (15, 16). ## Substances contributing to elevated blood pressure in athletes In the development of hypertension in athletes, the risk factors well known in the general population also play a significant role. However, athletes often consume dietary supplements that are known to enhance performance. Occasionally, they use substances whose effects they have only heard about through advertising or informal sources. In such cases, primary considerations include avoiding preparations that may pose health risks and those that are potentially prohibited from an anti-doping perspective. Classical CV risk factors are particularly relevant among athletes engaged in high-intensity anaerobic training, especially those requiring greater body mass for optimal performance—typically in isometric disciplines. In these athletes, weight loss is often not a viable option for managing hypertension. On the contrary, to maintain their body mass and ideal body composition, they intentionally consume high-calorie, low-fiber diets (17). Among strength athletes—either competitive or recreational but highly committed—the use of performance-enhancing agents, including substances listed on anti-doping registers, must always be considered as a possible etiological factor in hypertension. Anabolic steroids increase BP and contribute to the development of atherosclerotic vascular disease and pathological left ventricular hypertrophy (18). While some may assume that the use of anabolic steroids is limited to a fringe group of “muscle enthusiasts,” studies indicate that their prevalence remains approximately 10–20% even among both recreational and elite athletes (19). In endurance sports, high sodium intake is often employed with the intent of enhancing performance and preventing exercise-associated muscle cramps. However, this practice increases the risk of hypertension and, furthermore, the ergogenic benefit of sodium loading remains highly questionable (20) (**Figure 1**). FIGURE 1. Specific considerations for hypertension in athletes. Stimulants, such as caffeine and energy drinks, are also frequently consumed, as they may transiently improve performance. However, regular and excessive use—particularly prior to training or competition—may contribute to the development of hypertension (21, 22). Due to frequent muscle and joint pain, athletes often use non-steroidal anti-inflammatory drugs (NSAIDs), most of which are available over-the-counter. Athletes, being highly aware of their pain thresholds during training and competition, often take NSAIDs prophylactically, which significantly increases overall consumption. Excessive NSAID use—especially in combat sports—is associated with an increased risk of hypertension (23). Lifestyle factors beyond nutrition also influence the development of hypertension. Chronic psychological stress and sustained high-intensity physical training—especially among elite athletes—likewise contribute to the elevated prevalence of hypertension in this population (13). ## Sport-specific considerations The type of sport is an important determinant in the development of hypertension among athletes. In assessing the risk of elevated BP, the classification of the given sport plays a critical role (24), as strength-based disciplines characterized by predominantly isometric training are associated with a higher prevalence of hypertension compared to purely endurance-based sports (13). Among endurance athletes, not only systolic but also diastolic BP tends to be lower than in strength athletes (13), which is partly attributable to a higher body mass index (BMI) observed in the latter group (25). Female athletes typically present with lower BP values compared to males; however, the differences observed between endurance and strength sports are also evident among women (26). It is also important to emphasize that the nature of training performed within a given sport—particularly under a specific coach or at a particular club—can significantly influence CV outcomes. For example, in youth football players, recent years have seen an increased emphasis on strength training aimed at improving postural stability, alongside traditional endurance and skill-based (ball) training (27). The higher BMI observed in strength athletes is associated not only with elevated BP, but also with a greater incidence of metabolic syndrome and dyslipidemia (25). ## Senior athletes Elite athletes over the age of 35 are typically referred to as senior athletes. The extent to which older athletes can remain competitive largely depends on the type of sport. In elite-level football, for example, older athletes usually transition to senior leagues and are no longer part of top-division teams. In contrast, in disciplines such as marathon running, it is common to find older age groups actively competing and achieving success. The prevalence of hypertension in senior athletes is lower than in non-athletic individuals of the same age group (28). This may be attributed to several factors, including lower BMI and a higher proportion of endurance training among older athletes. Former elite athletes who do not use antihypertensive medication tend to exhibit lower BP levels compared to individuals who did not engage in competitive sports, regardless of current physical activity levels (29). This difference was most pronounced in former endurance athletes, suggesting that intensive endurance training exerts long-term protective effects against the development of hypertension, even after cessation of regular training. However, senior endurance athletes are not healthier than non-athletes in every respect. Coronary computed tomography (CT) studies have shown that asymptomatic middle-aged athletes exhibit a higher degree of coronary artery calcification compared to age-matched non-athletic controls (30). The precise role of this finding in the long-term CV risk profile of athletes remains uncertain. One hypothesis suggests that the increased calcification may represent more stable, and thus less dangerous, plaques compared to those in non-athletes. This notion is partially contradicted by findings from a study that combined native cardiac CT and contrast-enhanced cardiac magnetic resonance imaging (MRI) in senior marathon runners and a non-athletic control group. In that study, the greater extent of coronary calcification observed in athletes was associated with increased late gadolinium enhancement, indicative of myocardial damage (31). ## Pharmacological Considerations in the Treatment of Hypertension in Athletes Because sport is generally regarded as a health-promoting activity—by both athletes and the public—it is often difficult to convey the reality of a disease diagnosis to the athlete. Moreover, since the majority of competitive athletes are young, initiating pharmacological treatment may require not only the athlete’s consent, but also the involvement and reassurance of parents, when applicable. In otherwise healthy young athletes, understanding the long-term risks and consequences of hypertension—and recognizing that elevated BP may impair current physical performance—can facilitate the acceptance of pharmacological therapy (32). The first step in managing hypertension in athletes involves lifestyle modification, including education and counseling aimed at addressing contributing behavioral factors. Only after this should pharmacologic treatment be considered (**Figure 1**). Aerobic exercise generally exerts a beneficial effect on BP and, in most cases, can be continued. This should be particularly emphasized in athletes whose primary training is strength-based (13). In this group, weight reduction is a critical recommendation; however, it should be acknowledged that discontinuing high-calorie diets may lead to a decline in performance. Regardless, all hypertensive athletes should be advised to reduce sodium intake and increase dietary potassium consumption (33). Although lifestyle changes are essential, they are often insufficient for achieving optimal BP control. In such cases, pharmacotherapy must be initiated. Two primary aspects should be taken into account: Rapid and aggressive BP lowering may lead to fatigue and diminished performance. Therefore, treatment should not begin with the maximum anticipated dose, as this may negatively impact treatment adherence. And in competitive athletes, anti-doping regulations must guide medication selection to avoid prohibited substances (34). First-line antihypertensive medications for athletes include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and dihydropyridine-type calcium channel blockers, either as monotherapy or in combination (35, 36). Among these, dihydropyridine calcium channel blockers are particularly preferred due to their efficacy and the lack of requirement for renal function monitoring. Beta-blockers, while not universally banned, fall under the category of sport-specific prohibited substances, meaning they are only restricted in certain sports such as golf and shooting (34). Nevertheless, beta-blockers are generally suboptimal for treating hypertension in athletes. They tend to further reduce resting heart rate in endurance athletes—who are often bradycardic at baseline—and they lower the attainable maximum heart rate during exertion. Moreover, non-selective beta-blockers inhibit β2-receptors in the airways, impairing respiratory efficiency and thus athletic performance (37). Diuretics are among the most widely prohibited classes of medications in competitive sport, including thiazides, loop diuretics, and mineralocorticoid receptor antagonists. This is primarily because they may be used to mask the presence of other performance-enhancing substances (34). In cases where diuretic use is medically justified, it may still be permitted—but only if a Therapeutic Use Exemption is formally requested and granted in advance (34). ## Return to sport in athletes with hypertension When hypertension is appropriately managed, participation in sports—including competitive sports—is generally permitted. However, during the initial phase of treatment or in cases where BP is not adequately controlled, particularly when systolic BP exceeds 160 mmHg, high-intensity training is not recommended until proper antihypertensive therapy has been established. If hypertension is well controlled but the athlete has a high CV risk (SCORE >5%) or documented target organ damage, then high-intensity resistance training is not advised. In contrast, athletes with well-managed hypertension and no evidence of organ damage may participate in any type of sport without restriction. For hypertensive adults engaging in preventive recreational sports, it is recommended to perform resistance training at least three times per week, in combination with moderate to high-intensity aerobic exercise (minimum 30 minutes per session, 5–7 days per week), as this helps reduce resting BP and overall CV risk (38). ## Conclusion Arterial hypertension is present not only among competitive athletes but also in individuals who engage in regular recreational physical activity. Sports medical screening examinations offer enhanced safety for competitive athletes by facilitating the early detection of hypertension and raising suspicion of subclinical CV abnormalities, thereby enabling timely diagnostic evaluation and, when necessary, the initiation of effective therapy. In the management of hypertension in athletes, lifestyle modifications—including adjustments to training regimens and the discontinuation of dietary supplements or prohibited substances that may contribute to elevated BP —can be effective on their own. Pharmacological treatment largely follows the same principles as in the general population; however, therapeutic strategies may require adjustment due to anti-doping regulations and the potential for performance impairment associated with certain medications.
Literature
- Nambiar L, LeWinter MM, VanBuren PC, Dauerman HL. Decade-Long Temporal Trends in U.S. Hypertension-Related Cardiovascular Mortality. J Am Coll Cardiol. 2020 May 26;75(20):2644–6. https://doi.org/10.1016/j.jacc.2020.03.009
- Hedman K, Moneghetti KJ, Christle JW, Bagherzadeh SP, Amsallem M, Ashley E, et al. Blood pressure in athletic preparticipation evaluation and the implication for cardiac remodelling. Heart. 2019 August;105(16):1223–30. https://doi.org/10.1136/heartjnl-2019-314815
- De Matos LD, Caldeira Nde A, Perlingeiro Pde S, dos Santos IL, Negrao CE, Azevedo LF. Cardiovascular risk and clinical factors in athletes: 10 years of evaluation. Med Sci Sports Exerc. 2011 June;43(6):943–50. https://doi.org/10.1249/MSS.0b013e318203d5cb
- Yano Y, Reis JP, Colangelo LA, Shimbo D, Viera AJ, Allen NB, et al. Association of Blood Pressure Classification in Young Adults Using the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline With Cardiovascular Events Later in Life. JAMA. 2018 November 6;320(17):1774–82. https://doi.org/10.1001/jama.2018.13551
- Laki J, Soós Á, Jákó P, Tállay A, Perjés Á, Szabó AM. Introducing the National Institute for Sports Medicine in Hungary: a complex sports medical healthcare and screening system. BMJ Open Sport Exerc Med. 2017 September 28;3(1):e000267. https://doi.org/10.1136/bmjsem-2017-000267
- McEvoy JW, McCarthy CP, Bruno RM, Brouwers S, Canavan MD, Ceconi C, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. Eur Heart J. 2024 October 7;45(38):3912–4018. https://doi.org/10.1093/eurheartj/ehae178
- SCORE2 working group and ESC Cardiovascular risk collaboration. SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe. Eur Heart J. 2021 July 1;42(25):2439–54. https://doi.org/10.1093/eurheartj/ehab309
- SCORE2-OP working group and ESC Cardiovascular risk collaboration. SCORE2-OP risk prediction algorithms: estimating incident cardiovascular event risk in older persons in four geographical risk regions. Eur Heart J. 2021 July 1;42(25):2455–67. https://doi.org/10.1093/eurheartj/ehab312
- de Simone G, Mancusi C, Hanssen H, Genovesi S, Lurbe E, Parati G, et al. Hypertension in children and adolescents. Eur Heart J. 2022 September 14;43(35):3290–301. https://doi.org/10.1093/eurheartj/ehac328
- Jones ESW, Esack I, Mangena P, Rayner BL. Hypertension in adolescents and young adults referred to a tertiary hypertension clinic in Cape Town, South Africa. Medicine (Baltimore). 2020;99(48):e23137. https://doi.org/10.1097/MD.0000000000023137
- Rimoldi SF, Scherrer U, Messerli FH. Secondary arterial hypertension: when, who, and how to screen? Eur Heart J. 2014 May 14;35(19):1245–54. https://doi.org/10.1093/eurheartj/eht534
- Tsioufis C. „Hearts that strain”: Distinguishing athlete’s heart from hypertensive disease in the echo lab and beyond. Hellenic J Cardiol. 2018 May-June;59(3):189–91. https://doi.org/10.1016/j.hjc.2018.06.006
- Berge HM, Isern CB, Berge E. Blood pressure and hypertension in athletes: a systematic review. Br J Sports Med. 2015 June;49(11):716–23. https://doi.org/10.1136/bjsports-2014-093976
- Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005 January 15-21;365(9455):217–23. https://doi.org/10.1016/S0140-6736(05)17741-1
- McCarron P, Smith GD, Okasha M, McEwen J. Blood pressure in young adulthood and mortality from cardiovascular disease. Lancet. 2000 April 22;355(9213):1430–1. https://doi.org/10.1016/S0140-6736(00)02146-2
- Whelton SP, McEvoy JW, Shaw L, Psaty BM, Lima JAC, Budoff M, et al. Association of Normal Systolic Blood Pressure Level With Cardiovascular Disease in the Absence of Risk Factors. JAMA Cardiol. 2020 September 1;5(9):1011–8. https://doi.org/10.1001/jamacardio.2020.1731
- Larson-Meyer DE, Krason RK, Meyer LM. Weight Gain Recommendations for Athletes and Military Personnel: a Critical Review of the Evidence. Curr Nutr Rep. 2022 June;11(2):225–39. https://doi.org/10.1007/s13668-022-00395-3
- Baggish AL, Weiner RB, Kanayama G, Hudson JI, Lu MT, Hoffmann U, et al. Cardiovascular Toxicity of Illicit Anabolic-Androgenic Steroid Use. Circulation. 2017 May 23;135(21):1991–2002. https://doi.org/10.1161/CIRCULATIONAHA.116.026945
- Sagoe D, Molde H, Andreassen CS, Torsheim T, Pallesen S. The global epidemiology of anabolic-androgenic steroid use: a meta-analysis and meta-regression analysis. Ann Epidemiol. 2014 May;24(5):383–98. https://doi.org/10.1016/j.annepidem.2014.01.009
- McCubbin A. Heterostyle Breeding Systems. In eLS, John Wiley & Sons, Ltd (Ed.). https://doi.org/10.1002/9780470015902.a0027953
- Pickering C, Grgic J. Caffeine and Exercise: What Next? Sports Med. 2019 July;49(7):1007–30. https://doi.org/10.1007/s40279-019-01101-0
- Seifert SM, Schaechter JL, Hershorin ER, Lipshultz SE. Health effects of energy drinks on children, adolescents, and young adults. Pediatrics. 2011 March;127(3):511–28. https://doi.org/10.1542/peds.2009-3592
- Tso J, Hollowed C, Liu C, Alkhoder A, Dommisse M, Gowani Z, et al. Nonsteroidal Anti-inflammatory Drugs and Cardiovascular Risk in American Football. Med Sci Sports Exerc. 2020 December;52(12):2522–8. https://doi.org/10.1249/MSS.0000000000002404
- Levine BD, Baggish AL, Kovacs RJ, Link MS, Maron MS, Mitchell JH. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 1: Classification of Sports: Dynamic, Static, and Impact: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol. 2015 December 1;66(21):2350–5. https://doi.org/10.1016/j.jacc.2015.09.033
- Guo J, Zhang X, Wang L, Guo Y, Xie M. Prevalence of metabolic syndrome and its components among Chinese professional athletes of strength sports with different body weight categories. PLoS One. 2013 November 8;8(11):e79758. https://doi.org/10.1371/journal.pone.0079758
- Taha YK, Rambarat CA, Reifsteck F, Hamburger R, Clugston JR, Handberg EM, et al. Blood pressure characteristics of collegiate female athletes: A call for more focused attention on young women’s health. Am Heart J Plus. 2022 January 17;13:100085. https://doi.org/10.1016/j.ahjo.2022.100085
- Ferley DD, Scholten S, Vukovich MD. Combined Sprint Interval, Plyometric, and Strength Training in Adolescent Soccer Players: Effects on Measures of Speed, Strength, Power, Change of Direction, and Anaerobic Capacity. J Strength Cond Res. 2020 April;34(4):957–68. https://doi.org/10.1519/JSC.0000000000003476
- Shapero K, Deluca J, Contursi M, Wasfy M, Weiner RB, Lewis GD, et al. Cardiovascular Risk and Disease Among Masters Endurance Athletes: Insights from the Boston MASTER (Masters Athletes Survey To Evaluate Risk) Initiative. Sports Med Open. 2016 August 9;2:29. https://doi.org/10.1186/s40798-016-0053-0
- Laine MK, Kujala UM, Eriksson JG, Wasenius NS, Kaprio J, Bäckmand HM, et al. Former male elite athletes and risk of hypertension in later life. J Hypertens. 2015 August;33(8):1549–54. https://doi.org/10.1097/HJH.0000000000000601
- Merghani A, Maestrini V, Rosmini S, Cox AT, Dhutia H, Bastiaenan R, et al. Prevalence of Subclinical Coronary Artery Disease in Masters Endurance Athletes With a Low Atherosclerotic Risk Profile. Circulation. 2017 July 11;136(2):126–37. https://doi.org/10.1161/CIRCULATIONAHA.116.026964
- Möhlenkamp S, Lehmann N, Breuckmann F, Bröcker-Preuss M, Nassenstein K, Halle M, et al. Heinz Nixdorf Recall Study Investigators. Running: the risk of coronary events: Prevalence and prognostic relevance of coronary atherosclerosis in marathon runners. Eur Heart J. 2008 August;29(15):1903–10. https://doi.org/10.1093/eurheartj/ehn163
- Mazic S, Suzic Lazic J, Dekleva M, Antic M, Soldatovic I, Djelic M, et al. The impact of elevated blood pressure on exercise capacity in elite athletes. Int J Cardiol. 2015 February 1;180:171–7. https://doi.org/10.1016/j.ijcard.2014.11.125
- Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018 June;71(6):1269–324. https://doi.org/10.1161/HYP.0000000000000066
- World Anti Doping Agency [Internet]. [cited 2025 Jan 26]. The Prohibited List. https://www.wada-ama.org/en/prohibited-list
- Tso JV, Kim JH. Hypertension in Athletes: Clinical Implications and Management Strategies. Card Electrophysiol Clin. 2024 March;16(1):15–24. https://doi.org/10.1016/j.ccep.2023.09.004
- Martinez MW, Kim JH, Shah AB, Phelan D, Emery MS, Wasfy MM, et al. Exercise-Induced Cardiovascular Adaptations and Approach to Exercise and Cardiovascular Disease: JACC State-of-the-Art Review. J Am Coll Cardiol. 2021 October 5;78(14):1453–70. https://doi.org/10.1016/j.jacc.2021.08.003
- Nielen JTH, de Vries F, van der Velde JHPM, Savelberg HHCM, Schaper NC, Dagnelie PC, et al. The Association Between β-Blocker Use and Cardiorespiratory Fitness: The Maastricht Study. J Cardiovasc Pharmacol Ther. 2019 January;24(1):37–45. https://doi.org/10.1177/1074248418778551
- Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, et al. ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021 September 7;42(34):3227–337. https://doi.org/10.1093/eurheartj/ehab484