MACE in running: a Canadian perspective on major adverse cardiac events (MACE) during running

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In July 2022, within a week, two fit Canadian doctors died suddenly after suffering a major adverse cardiac event (MACE) while running long distances (LDR) [1,2]. Paradoxically, the activity supposedly intended to prolong the life of an individual became the main factor responsible for his death. Such a paradox prompts further contemplation and investigation as to whether we have missed something in assessing the risk of MACE in fit individuals during LDR to prevent further loss of precious human life.

Historically, the origin of long distance or marathon races dates back to 490 BC. C., during the Persian invasion of Greece. [3]. Legend has it that Pheidippides, a 40-year-old Athenian, ran 26.2 miles from the city of Marathon to Athens to break the news of victory. However, once he arrived in Athens, he collapsed and died. Instead of declaring that long-distance running was the cause of Pheidippides’ death, the distance he ran was established as the official distance of the marathon race. [3]. Phidippides became the first recorded case of a fatal MACE during LDR.

In recent decades, LDR has become a mainstream sport, rather than being considered extreme and exclusive to the domain of a small group of ultra-athletes. This change was instigated in part by the work of Jim Fixx, a leading figure on the fitness scene in the 1970s. [3]. Fixx wrote the best selling book, The Complete Book of Running. Unfortunately, he suffered a fatal MACE, secondary to coronary atherosclerosis, during LDR at the age of 52. [3].

MACE are defined as myocardial infarction (MI), stroke, heart failure, and/or death from other cardiovascular diseases. [4]. The most common cause of exercise-induced MACE is myocardial infarction, with atherosclerosis being the most common etiopathogenesis of myocardial infarctions. [5]. Alarmingly, to date, the only credible and gold standard diagnostic modality of atherosclerosis is arterial catheterization, which is invasive and expensive and precludes its wide application among individuals and/or the health care system. [5]. In the absence of an objective method to diagnose atherosclerosis, autopsy studies have provided a more accurate view of the prevalence of this disease, particularly among the young. [6]. Atherosclerosis has been labeled as a disease of the old, inactive and obese. [5]. However, in a postmortem investigation of coronary blood vessels in the bodies of those killed in the Vietnam War, who were lean, physically active soldiers with an average age of 22, 50% showed evidence of atherosclerosis. [6].

One of the first autopsy studies investigating fatal MACE during LDR was conducted in California between 1973 and 1978 and identified 18 cases, the study was limited to deaths when autopsy was performed with the vast majority having MI as their recorded cause of death [7]. In a larger study of fatal MACE among athletes in the United States between 1980 and 2006, 1866 cases were identified and again MACE was the most common cause of death. [8].

Currently, it is unclear what the rates of LDR-induced MACE are in the general population, because research has focused on a small population of athletes who registered for and participated in official LDR events. But MACE in normal individuals who decide to adopt a “healthy” lifestyle by LDR are not included in the LDR MACE statistics.

Without a doubt, there is a large body of scientific evidence supporting the beneficial impact of physical exercise on longevity. [9]. Current physical activity guidelines for American adults recommend at least 150 to 300 minutes per week of moderate-intensity aerobic physical activity, 75 to 150 minutes per week of vigorous-intensity aerobic physical activity, or an equivalent combination of moderate and vigorous intensity aerobic physical activity. exercise [9]. Physicians are encouraged to prescribe exercise as primary prevention not only for fit people but also for cardiometabolic disorders. [10]. However, if clinicians are to prescribe exercise, like all other treatments, we must master not only the therapeutic dose of the proposed treatment, but also its margin of safety, including adverse effects and its toxic or fatal dose. Furthermore, the Supreme Court of Canada stated that even if a treatment risk is “a mere possibility” but carries serious consequences such as death or paralysis, it must be disclosed. [11]. Therefore, when prescribing exercise, we must disclose its rare but life-threatening and non-fatal MACE risk, precisely because there is no guarantee that physically fit and active individuals are protected against MACE during LDR.

To conclude, there is a considerable and growing body of evidence on the incidence of fatal and non-fatal MACE during LDR among professional athletes during official LDR. On the other hand, there is a paucity of research investigating the incidence of MACE during habitual vigorous exercise, such as LDR. Until the development of an objective test for atherosclerosis, clinicians should be cautious about prescribing exercise without disclosing that it carries an unlikely potential to induce fatal and non-fatal MACE. With the growing popularity of LDR, there is an urgent need to assess the safety of the sport and clearly define the population at risk. To increase vigilance for a life-threatening and disabling condition, physicians entering cause of death on death certificates must make a clear distinction between immediate, antecedent, and underlying cause of death. Finally, it is essential that clinicians educate their patients not only about the health benefits of physical exercise, but also about the life-threatening risk of that activity in certain populations. By doing so, we may be able to reduce the mortality and disability associated with MACE.


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