A narrative review on exercise and cardiovascular disease: Physical activity thresholds for optimizing health outcomes

Barry A Franklin; Thijs M H  Eijsvogels

doi:10.4103/hm.hm_1_23

REVIEW ARTICLE

Year : 2023 | Volume : 7 | Issue : 1 | Page : 34-39

A narrative review on exercise and cardiovascular disease: Physical activity thresholds for optimizing health outcomes

Barry A Franklin¹, Thijs M H Eijsvogels²
¹ Division of Cardiovascular Diseases, Cardiac Rehabilitation/Preventive Cardiology, Beaumont Health, Royal Oak, Michigan, USA
² Department of Physiology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, Netherlands

Date of Submission	22-Dec-2022
Date of Acceptance	16-Jan-2023
Date of Web Publication	13-Mar-2023

Correspondence Address:
Prof. Barry A Franklin
Beaumont Health and Wellness Center, 4949 Coolidge Highway, Royal Oak 48073, Michigan
USA

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/hm.hm_1_23

Abstract

The favorable risk factor profiles and superb cardiac performance of elite long-distance runners, as well as the anti-aging effects of exercise, have likely contributed to the escalating number of adults worldwide who have embraced the notion that “more exercise is invariably better.≵ Nevertheless, vigorous-to-high-intensity physical activity (PA), particularly when unaccustomed, appears to be a trigger for acute cardiac events in individuals with known or occult atherosclerotic cardiovascular disease or structural cardiovascular abnormalities, most notably, hypertrophic cardiomyopathy. Although regular endurance exercise and moderate-to-vigorous PA provide established cardioprotective benefits, high-volume, high-intensity exercise training regimens appear to induce maladaptive cardiac remodeling in some individuals. These potential adverse cardiac adaptations include accelerated coronary artery calcification (CAC), elevated cardiac biomarker release, myocardial fibrosis, and atrial fibrillation (AF), which may be described by a reverse J-shaped curve. However, the risk for acute cardiovascular events is lower in fit/active persons compared to their unfit/inactive counterparts with the same CAC scores. Similarly, the risk of AF is the highest in habitually sedentary older adults, decreases with light-to-moderate intensity regular PA but increases with high-volume, high-intensity exercise regimens (i.e., reverse J-shaped curve). This review examines these relations and more, with specific reference to the World Health Organization exercise intensity and duration recommendations for optimal health, as well as the thresholds for other research-based exercise metrics, including steps/day and the concept of metabolic equivalents-minutes/week. The primary beneficiaries of exercise training programs and long-term goal training intensities, based on age, sex, and “good≵ fitness, are also discussed. In summary, the benefits of regular moderate-to-vigorous PA and the associated improvements in cardiorespiratory fitness far outweigh the risks for most individuals.

Keywords: Exercise and cardiovascular disease, extreme exercise regimens, high volume, high-intensity exercise, reverse J-shaped curve, training maladaptations

How to cite this article:
Franklin BA, H Eijsvogels TM. A narrative review on exercise and cardiovascular disease: Physical activity thresholds for optimizing health outcomes. Heart Mind 2023;7:34-9

How to cite this URL:
Franklin BA, H Eijsvogels TM. A narrative review on exercise and cardiovascular disease: Physical activity thresholds for optimizing health outcomes. Heart Mind [serial online] 2023 [cited 2023 May 29];7:34-9. Available from: http://www.heartmindjournal.org/text.asp?2023/7/1/34/371611

Introduction

Investigations documenting the physiologic profiles and extraordinary cardiorespiratory fitness (CRF) of distance runners, as well as the reported anti-senescent benefits of endurance exercise have contributed to the skyrocketing numbers of individuals who have embraced extreme exercise training regimens. Consequently, participation in distance running, competitive marathons and triathlons, and high-intensity interval training have increased exponentially in recent years. As people worldwide are investing more and more time in endurance training and competition, this review addresses common issues, questions, and misperceptions that often arise, with specific reference to evidence-based salutary exercise thresholds that the medical community can embrace and promote.

Are Endurance Athletes Protected from Atherosclerotic Cardiovascular Disease?

The widely-cited autopsy report on Clarence DeMar (“Mr. Marathon”), who had participated in >1,000 long-distance races and 100 marathons, revealed coronary arteries that were 2–3 times normal diameter.^[1] Only mild atherosclerotic coronary artery disease (CAD) was present, ~30% lumen reductions at selected sites. Subsequent studies of highly fit Masai warriors and Tarahumara Indians fueled speculation that these populations were, for the most part, free of CAD, largely due to their physically active lifestyles. Collectively, these data and other observational analyses suggested that active marathon runners may share this immunity. Nevertheless, subsequent case reports unequivocally refuted the “Bassler hypothesis,≵ that is, that marathon running confers immunity to CAD.^[2] In our experience, this was further substantiated when 3 men (aged 26, 36, and 65 years) experienced fatal cardiac events likely due to plaque rupture and/or ventricular arrhythmias while running in the 2009 Detroit Free Press Marathon.

Is It Possible to Overdose Exercise?

Although vigorous physical activity (PA) increases the likelihood of acute myocardial infarction and/or sudden cardiac death (SCD) in “at risk≵ individuals, the relative risk decreases with regular strenuous physical exertion. Atherosclerotic CAD is a common autopsy finding in individuals aged >40 years who suffer exertion-related cardiac arrest and SCD. In contrast, structural cardiovascular abnormalities, particularly hypertrophic cardiomyopathy, are a commonly cited cause of SCD during strenuous or competitive PA in younger persons. Other studies, however, have reported no identifiable cause at autopsy, classifying these as sudden arrhythmic death or SCD with a structurally normal heart.^[3]

Excessive endurance training (e.g., distance running) is also associated with adverse cardiac adaptations, including increased coronary artery calcium scores, elevated biomarkers, myocardial fibrosis, and incident atrial fibrillation (AF).^[4] Elevated coronary calcification has been reported among veteran endurance athletes as compared with their control counterparts. However, the significance of this finding remains unclear, since it does not appear to confer increased mortality or acute cardiac events. Countering cardioprotective training adaptations may include a lower prevalence of vulnerable mixed plaques, increased coronary size and dilating capacity, and higher levels of CRF, which may nullify the potentially deleterious impact of a heightened coronary artery calcium score. Extreme endurance training and competition have also been repeatedly linked to unhealthy coronary remodeling, including chronic AF.^[4] In addition, regular endurance exercise appears to accelerate the presentation and progression of arrhythmogenic right ventricular cardiomyopathy,^[4] and recent guidelines proscribe strenuous exercise in this patient subset. The relation between these maladaptive responses and the exercise training volume have been described by a reverse J-shaped or U-shaped dose-response curve [Figure 1].^[4]

Figure 1: Conceptual overview of the dose-response association between PA volume and cardiovascular health outcomes in line with Panel (a), the current dogma, and Panel (b), an alternative hypothesis. There is currently no compelling evidence to reject the curvilinear association [Figure a] between exercise volumes and cardiovascular health outcomes, with increasing coronary calcium, AF and arrhythmogenic right ventricular cardiomyopathy as possible exceptions. From reference #4, with permission. PA=Physical activity, AF=Atrial fibrillation

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Benefits versus Risks

Both endurance training and higher levels of CRF, expressed as metabolic equivalents (METs), are inversely associated with the risk of developing chronic diseases, including CAD. Although arterial dysfunction has been widely considered a marker of age-associated ischemic heart disease, endurance exercise training inhibits large artery stiffening and preserves endothelial function. Increased CRF is also associated with a 2.5–3.3 lower risk of incident heart failure, irrespective of the height-weight relation.^[5] Unfit individuals are up to three times more likely to die in follow-up studies as compared with their more fit counterparts, regardless of the risk factor profile^[6] or coronary artery calcium level.^[7] Regular PA before hospitalization for unstable angina pectoris and/or acute myocardial infarction appears to confer superior short-term outcomes, likely due at least in part to the cardioprotective effects of exercise preconditioning.^[8] Moreover, each 1-MET increase in CRF or aerobic capacity is associated with an ~15% decreased mortality risk in patients with and without CAD.^[9],[10]

Considering the cardiovascular benefits and risks of exercise, the former outweighs the latter for most adults, especially if a light-to-moderate-intensity exercise regimen is initially adopted. In fact, the overall risk of a cardiovascular event appears to be up to 50% lower in physically active adults. Health benefits are reported at moderate levels of PA and increase in a dose-response fashion. Accordingly, any PA is better than a sedentary lifestyle, moderate-intensity PA (40% to 59% functional capacity) and vigorous PA (≥60% functional capacity) appear to provide incremental benefits, respectively, in promoting favorable health outcomes. However, the mortality benefits of vigorous PA (e.g., running) appear to level-off beyond 35 min/day.^[11] Although high-intensity interval training may provide modestly greater increases (~0.5 MET) in CRF than moderate-intensity training, the associated increased risk of recurring near-maximum exercise bouts in individuals with documented or suspected CAD suggest that it should be cautiously prescribed or proscribed in unmonitored health-fitness facilities.^[12],[13]

Exercise Thresholds to Improve Health Outcomes

The 2020 World Health Organization (WHO) Guidelines provide research-based public health recommendations regarding the duration and intensity of PA that offers substantive health benefits and reduces the risk of chronic disease in adults 18–65⁺ years [Figure 2].^[14] These guidelines promote at least 150–300 min of moderate-intensity PA or 75–150 min of vigorous aerobic PA, or combinations throughout the week. This modification emphasizes that further increased PA volumes yield greater health benefits, rather than a minimum volume only for moderate (i.e., ≥150 min/week) and vigorous (i.e., ≥75 min/week) PA. Moreover, the aerobic component should be complemented by muscle strengthening activities ≥2 days/week and limiting sedentary behaviors (e.g., extended computer interactions and television watching) which have been linked to adverse health outcomes.^[15] In concert with these recommendations, the recent WHO guidelines deleted the previous suggestion that PA should be performed in ≥10-minute bouts. Accordingly, over the past decade, studies of activity trackers have revealed the beneficial adaptations resulting from repeated daily bouts of very short duration PA (i.e., 1–2 min).^[16],[17] Thus, regimented exercise and leisure-time PA bouts now comprise the total achieved exercise volume or amount. Finally, older adults (≥65 years) are also advised to perform multicomponent exercise and balance training, to increase the safety of PA and help reduce the likelihood of falls.

Figure 2: Contemporary PA recommendations for young, middle-aged and older adults, based on WHO Guidelines on PA and Sedentary Behaviour. PA=Physical activity, WHO=World Health Organization

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Comparing Varied Intensities of Physical Activity

Vigorous exercise appears to be more impactful than moderate-intensity training in facilitating cardiovascular risk reduction. Similarly, relative to the survival benefit conferred by regular exercise, lower-intensity PA requires a longer duration. Accordingly, the mortality reduction associated with walking appears to require 3–4 times the duration as running.^[11]

Several factors may explain why vigorous-intensity PA appears to provide greater cardiovascular benefits than moderate-intensity exercise, even at a comparable energy expenditure.^[18] Vigorous exercise intensities more effectively increase CRF,^[19] especially among individuals with higher baseline CRF.^[20] This finding has prognostic significance, since the level of CRF is inversely related to cardiovascular and all-cause mortality.^[21] Other potential autonomic, hemodynamic, and clinical adaptations associated with the added cardioprotective benefits of vigorous-intensity over moderate-intensity exercise, corresponding to ≥60% aerobic capacity or ≥6 METs versus 40%–59% aerobic capacity or 3.0–5.9 METs, respectively, are shown in [Table 1].^[22] Furthermore, greater reliance on carbohydrate utilization over fat metabolism evoked by increased sympathetic stimulation may be an important mechanism underlying enhanced glucose and insulin metabolism after vigorous-intensity training in obese individuals and obese noninsulin-dependent diabetes mellitus patients.^[23]

Table 1: Multiple physiologic, clinical, and hemodynamic mechanisms by which vigorous exercise may be more cardioprotective than moderate-intensity exercise training

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Research-Based Training Thresholds

The threshold intensity of physical conditioning to achieve a training effect can also be expressed as steps or MET-minutes/day. Each of these research-based thresholds is briefly described below.

Steps per day

Although covering 10,000 steps/day (~5 miles, with average stride length) has been the traditional exercise recommendation, fewer steps per day appear to confer significant survival benefits. In the Coronary Artery Risk Development in Young Adults (CARDIA) study of 2,110 African American and Caucasian middle-aged men and women (mean ± standard deviation age = 45.2 ± 3.6 years), researchers found that participants taking ≥7,000 steps/day, compared with <7,000 steps/day, had a 50%–70% lower risk of mortality over a 10.8-year follow-up.^[24] Interestingly, step intensity was unrelated to mortality. These findings suggest that step counts provide a viable alternative to novice and regular exercisers to track and quantitate the amount or volume of PA. Accordingly, physicians and allied health professionals should counsel patients to use pedometers or accelerometers to increase PA into their daily lives. In one widely-cited systematic review, pedometer users in selected exercise studies significantly increased their PA by an average of 2,491 steps/day more than those in comparative control groups.^[25]

The metabolic equivalents-minutes/week metric

This simple calculation enables one to translate guideline-driven moderate-to-vigorous PA doses (≥500–1,000 MET-min/week) into objective goals by quantifying accumulated exercise each week in a single formula: estimated METs per activity × number of minutes/session × days/week = MET-min/week.^[26] For example, 60 min of level walking at a 2.5 mph pace (~2.9 METs), 3 days/week = 522 MET-min/week. Alternatively, 45 min of singles tennis (~6.5 METs), 2 days/week = 585 MET-min/week. Or, for the recreational runner, 15 min of running at a 6-mph pace (~10 METs), 4 days/week = 600 MET-min/week. Accordingly, all 3 of these exercise regimens would meet the minimum dosage (≥500 MET-min/week) needed to yield significant health benefits.

Primary Beneficiaries? Climbing Out of the Least Fit, Least Active Subgroup

An initial training goal is to achieve an intensity of exercise that allows patients/clients to vacate the most unfit population cohort, or bottom 20%, which corresponds to the poorest prognosis. Although low fitness varies according to age and sex, this generally approximates an aerobic capacity or CRF ≤5 METs.^{[27],[28],[29]} Our experience suggests that an aerobic capacity >5 METs can generally be achieved by exercising above 3 METs, which corresponds to moderate-to-vigorous PA.^[30] This training intensity has been reported to reduce the health risks associated with chronic diseases and the likelihood of developing them.^[31] Moreover, progressing from a CRF level ≤5 METs to >5 METs appears to provide the greatest relative reduction in mortality with increasing levels of aerobic capacity.^[27] Once patients progress out of the “very low≵ fitness quintile (bottom 20%), with further improvements in fitness there are continued reductions in risk of CAD and cardiovascular disease but at a less dramatic rate.

Using the treadmill to achieve a training intensity ≥3 METs, without regard to age, sex, weight, or fitness, corresponds to walking at 2.0 mph, 3.5% grade, or on the level (0% grade) at 3.0 mph. Accordingly, both of these workloads ~3.3 METs. When employing the stationary cycle ergometer, work rates (kilogram meters per minute [kg∙m/min]), expressed as METs, are weight dependent. The minimum work rates based on increasing body weight to achieve an energy expenditure of ~3.4 METs are shown in [Table 2].^[30],[32] For outdoor bicycling, the speed corresponding to 3–4 METs is ~6 mph.

Table 2: Minimum work rates (kg·m/min) to achieve an energy expenditure of ~3.4 metabolic equivalents on the stationary cycle ergometer at progressive body weights*

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Long-Term Goal Training Intensities: Multivariate-Adjusted Targets

Because the added survival benefits when progressing from “good≵ to “excellent≵ levels of CRF are negligible, ultimately attaining an age/sex-adjusted “good≵ level of CRF should be a primary exercise training goal or objective.^[28],[29] Good fitness and recommended aerobic training requirements to achieve these for young, middle-aged and older men and women, corresponding to 60%–80% of oxygen uptake reserve (V̇O₂R), are shown in [Table 3].^[33] If individuals can progress to these training intensities over time without adverse signs/symptoms or excessive ratings of perceived exertion (i.e., ≥15 on the category scale or “hard work”), it is likely that they can attain CRF levels that confer a significant survival advantage. For example, “good≵ fitness for a 55-year-old man approximates ≥10.0 METs. A training intensity of 6.4–8.2 METs or 7.3 METs (70% V̇O₂R), achieved over time, should enable this individual to attain “good≵ fitness during peak or symptom-limited exercise testing. Although not all men and women will achieve “good≵ CRF levels for their age, most will be able to attain a training intensity ≥3 METs, suggesting an exercise capacity >5 METs, which provides the greatest relative reduction in mortality.

Table 3: “Good” fitness levels for men and women and the training metabolic equivalents likely to confer these cardiorespiratory fitness levels*

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Conclusions

If the “exercise is medicine≵ mantra is embraced, there are indications and contraindications, and under-dosing and overdosing are possible. Thus, exercise may have a typical curvilinear dose-response curve with a plateau in benefit or even adverse effects in selected individuals with CAD, structural cardiovascular disease, or genetic predispositions to cardiac electrical instability, manifested as threatening ventricular arrhythmias.^[34] Because prodromal or warning symptoms are harbingers of acute cardiovascular events, patients should be counseled that exertion-related symptomatology requires immediate cessation of endurance training/competition and medical review. Physical conditioning can be performed continuously or in shorter bouts that are repeated throughout the day, ideally complemented by adjunctive resistance training and activities that promote enhanced flexibility. Importantly, previously sedentary individuals should be counseled to start with light-to-moderate walking and gradually progress (~2–3 months) to vigorous exercise, provided they remain asymptomatic. The data presented herein provide evidence-based thresholds, including steps per day, MET-min/week, and minimum and optimum training intensities, expressed as METs, for beneficial treatment outcomes.

Ethical statement

The ethical statement is not applicable for this article.

Acknowledgment

The authors would like to thank Brenda White for her assistance with the preparation of this scientific review, diligently checking the placement and accuracy of our citations.

Financial support and sponsorship

Nil.

Conflicts of interest

Dr. Barry A. Franklin is an Editorial Board Member of Heart and Mind. The article was subject to the journal's standard procedures, with peer review handled independently of Dr. Barry A. Franklin and the research groups. There are no conflicts of interest.

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