Exercise Health Benefits and Risks-In Search of the Perfect Balance

Nearly seven decades since the landmark study of Morris et al¹ the findings of many large and well-conducted epidemiologic studies consistently support an inverse and dose-response association between physical activity and health outcomes regardless of age, gender, ethnicity, socioeconomic status or disease burden.^2-10 In addition, biologic plausibility studies provide evidence of a cause-and-effect relationship between increased levels of physical activity (PA) and/or cardiorespiratory fitness (CRF) and reduced coronary heart disease events.^10,11 The AHA Scientific Statement on Related Acute Cardiovascular Events and Potential Deleterious Adaptations Following Long-Term Exercise Training¹² provides a much-needed and updated perspective on the balance between risks and benefits associated with exercise. The salient message from this statement is that the benefits of moderate exercise far outweigh the risks for the vast majority of individuals. However, despite the well-documented benefits of PA, current PA patterns are undeniably the lowest they have been in modern times.¹³

Thus, our task is no longer to further define the CRF-health outcomes association, but to refine it. Minimum CRF levels have been identified for different age groups beyond which health benefits are realized,¹⁴ but more work is needed. Some evidence suggests that current minimum PA levels recommended for health benefits may be too high and even too demanding for some populations and that benefits can be realized at lower exercise volume thresholds.^{11, 15} For example, a consistent finding from numerous epidemiologic studies that have examined associations between exercise, CRF, and risk of disease or mortality is a precipitous drop among individuals with relatively low CRF, low PA levels, or both.^{4,10, 11} Higher exercise volumes further reduce risk, but risk generally plateaus rapidly beyond the American College of Sports Medicine (ACSM) and American Heart Association criteria of ≥150 minutes of moderate exercise intensity or ≥75 minutes of vigorous exercise per week.16 Defining specific exercise thresholds for special populations (e.g. the elderly, those with limited function, etc.) will promote greater participation in PA by a large proportion of the population that may find current guidelines too demanding. Not surprisingly, there is also evidence to support the concept that PA that exceeds a certain volume or intensity can be deleterious for at least some individuals.¹¹

Is There a Pheidippides Syndrome?

In 490 BC the Persians were closing in on Athens. According to legend, Pheidippides, a messenger, was sent from Athens to Sparta before the battle in order to request assistance from the Spartans; he is said to have covered about 150 miles in about two days. He then turned around and returned to Athens (another 150 miles) to announce to the Athenians that the Spartans refused to assist them. A few days later, the Athenians faced the Persians alone in a place called Marathon, approximately 26 miles outside of Athens and after a fierce battle, they were victorious. Pheidippides was summoned to run to Athens and deliver the good news to the Athenians. He reached Athens in just under 3 hours, delivered his message “Nενικ?καμεν” (we were victorious), and then collapsed and died.

Although it remains unclear what killed Pheidippides, it is likely that it was an acute cardiac event triggered by extreme exercise, a reminder that extreme and vigorous exercise in rare instances can provoke acute cardiovascular events. Interestingly, it was not the 300 miles (Athens to Sparta and back) that killed Pheidippides, nor the march from Athens to the battlefield at Marathon a few days later or traversing the battlefield to relay important information to the Commanders the day of the battle (as he would undoubtedly do as he was a messenger). It was the 26 miles he ran at the end of the battle to deliver the victorious message to the Athenians. Could it be that the Pheidippides died from “a thousand papercuts?” That is, his death was the cumulative consequence of many small myocardial injuries sustained during the arduous run of 326 plus miles in just days without adequate time for the myocardium to recover and heal? Is there a “Pheidippides Syndrome?” an accretion of small, each alone relatively benign, myocardial injuries sustained during long, arduous and repeated exercise bouts, and without adequate time for recovery that ultimately lead to compromised myocardial function, arrhythmias and even death?

Reduced diastolic function, evidence of cardiac microdamage and elevated cardiac troponin concentrations have been widely reported after exercise of varying durations and intensities. Increased levels of cardiac biomarkers reflecting myocardial fibrosis and inflammation have been reported in marathon runners following competition and have been discussed extensively.^17-24 High concentrations of cardiac biomarkers observed after a half-marathon and full marathon races, but not after shorter runs, indicate that the strain imposed on the myocardium is related directly to the exercise volume.²⁴ Although exercise-associated cardiac troponin elevation has been considered a physiological and benign phenomenon representing reversible myocyte damage,¹⁸ recent findings suggest that high-volume and/or high-intensity exercise bouts could cause acute and irreversible myocardial injury in those with underlying subclinical cardiac pathology and even in apparently healthy individuals.^{25, 26} Elevated cardiac troponin concentrations were recently reported among 725 middle-aged participants after walking 30-55 km at 68±10% of their predicted maximum heart rate. In 63 of them (9%) troponin concentrations were above the 99th percentile (>0.040 µg/L). Of these, 27% died or had major adverse cardiac events during a mean of 43 months follow-up, compared to only 7% of the participants with troponin levels <0.040 µg/L. Interestingly, the mean exercise intensity was only moderate (approximately 11-12 minutes per km) suggesting that relatively high exercise volumes even at a moderate intensity can be injurious to the myocytes in some populations.²⁵ In another recent study, autopsies of sudden cardiac death victims revealed that about 50% of them had left ventricular scars, indicating previous silent myocardial infarctions (MI) that had healed. Previous silent myocardial ischemia was associated with myocardial hypertrophy and sudden cardiac death during physical activity. Of the 1,322 patients with silent myocardial ischemia, 241 (18.2%) died during physical activity, significantly higher than the 12.4% of the cohort without silent MI who also died during physical activity.²⁷

The findings of these studies are consistent with the concept that exercise-induced cardiac injury is physiological and transient, leading to compensatory and favorable cardiac adaptations. However, engaging in repetitive, excessively high-volume and or high-intensity exercise bouts could cause repetitive myocardial injury leading to deleterious cardiac adaptations in some individuals, especially when adequate recovery time to compensate for the cardiac injury is not allowed.^28-30 Available data suggest that this risk may be modulated by age, fitness status, genetic factors, disease burden, and perhaps other factors not yet determined. However, the precise exercise volume or intensity that can trigger cardiac injury in a given individual remains elusive and is likely to remain unresolved for some time.

This discussion requires a contextual perspective on the recently popular high-intensity-short duration interval training (HIIT). This method of training is promulgated as an alternative to moderate intensity continuous exercise even for cardiac rehabilitation, with at least similar if not superior gains in CRF.^{31, 32} Others dispute the superiority of HIIT,^{33, 34} but regardless, the safety of such training should be the foremost consideration and not the modest differences in aerobic capacity. Thus far, the risk of adverse cardiac events for patients with cardiovascular disease engaging in HIIT has been reported as very low and similar to moderate-intensity exercise.³⁵ However, when relating the number of adverse events to the number of patient-exercise hours, a recent review indicated that the event rate for HIIT was approximately 5.6 times higher than moderate intensity exercise (1 event per 129,456 hours of moderate-intensity exercise vs 1 per 23,182 hours of high-intensity exercise). ³⁶ The very small number of fatal and nonfatal complications (only 3) are a major limitation. Nevertheless, the findings merit further consideration as they suggest that the cardiac risk associated with HIIT for at least some populations may be unacceptably high. The emerging evidence of silent MI occurring with high-intensity and/or high-volume exercise suggest as much and should give us pause.²⁷ Since we lack the technology to define the level at which exercise becomes injurious for different populations, it seems reasonable that we err on the side of caution. At a minimum, it seems prudent to recommend that high-intensity and or high-volume exercise should not be recommended for elderly patients with known or suspected CAD, especially if they are training in non-medically supervised recreation facilities, and those with compromised cardiac function. For those who have been medically cleared and engage in such exercise, it is frequently recommended that an adequate recovery period is allowed before engaging in another long and/or intense exercise bout. The appropriate duration of recovery is difficult to define as it is likely to vary by age, fitness status, exercise intensity, duration of the event, and genetic factors.

The updated AHA Scientific Statement on Related Acute Cardiovascular Events and Potential Deleterious Adaptations Following Long-Term Exercise Training¹² provides practitioners and the public with valuable information on the ratio between risks and benefits of physical activity, including caveats associated with the recently-popular HIIT approaches to exercise. The important public health message remains the fact that exercise-related adverse events are extremely rare. Collectively, a plethora of evidence exists to support the fact that regular participation in physical activity or structured exercise that improves CRF is associated with significant health benefits. This association is inverse and independent. The health benefits are evident at relatively low exercise levels, follow a dose-response association and are optimized at relatively moderate intensities and exercise volumes with generally modest additional benefits at higher exercise volumes or intensities. Accordingly, regular and modest levels of physical activity have been emphasized by numerous public health organizations for several decades, including the ACSM and AHA.^{13, 37,38}

The risk for adverse cardiac events related to modest exercise levels, such as those consistent with international guidelines is exceedingly low;¹³ indeed, they are considerably lower than those associated with chronic physical inactivity.³⁹ This risk can potentially be minimized further as more precise exercise threshold levels are defined for special populations. Additionally, as was emphasized by the AHA Scientific Statement,¹² middle-aged and older individuals starting an exercise program should be advised to start with level walking (no graded walking or jogging) and to gradually increase the intensity over time, from moderate to vigorous, provided they remain asymptomatic. Finally, people who develop symptoms during exercise should be counseled to stop exercise and seek medical review/evaluation before resuming exercise again.

Excessive exercise characterized by high-intensity and or high-volume may be appropriate and even appealing for some individuals, especially the relatively young. However, the potential health risks of such activities, even if they are miniscule require consideration. It is prudent that we go forth guided by the age-old Hellenic concept of “Παν μ?τρον ?ριστον” roughly translated as “Everything in Moderation.”