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Quantitating the Dose of Physical Activity in Secondary Prevention: Relation of Exercise Intensity to Survival

  • Barry A. Franklin
    Correspondence
    Correspondence: Address to Barry A. Franklin, PhD, Preventive Cardiology and Cardiac Rehabilitation, Beaumont Health, Beaumont Health and Wellness Center, 4949 Coolidge Hwy, Royal Oak, MI 48073.
    Affiliations
    Preventive Cardiology and Cardiac Rehabilitation, Beaumont Health, Royal Oak, MI
    Oakland University William Beaumont School of Medicine, Rochester, MI
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  • Leonard A. Kaminsky
    Affiliations
    Clinical Exercise Physiology Laboratory, Fischer Institute of Health and Well-Being, Ball State University, Muncie, IN
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  • Peter Kokkinos
    Affiliations
    Veterans Affairs Medical Center, Georgetown University School of Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC
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      With the enormous current and projected economic burden of cardiovascular disease (CVD), which is expected to triple in the next 20 years,
      • Weintraub W.S.
      • Daniels S.R.
      • Burke L.E.
      • et al.
      American Heart Association Advocacy Coordinating CommitteeCouncil on Cardiovascular Disease in the YoungCouncil on the Kidney in Cardiovascular DiseaseCouncil on Epidemiology and PreventionCouncil on Cardiovascular NursingCouncil on ArteriosclerosisThrombosis and Vascular BiologyCouncil on Clinical Cardiology, and Stroke Council
      Value of primordial and primary prevention for cardiovascular disease: a policy statement from the American Heart Association.
      therapeutic strategies to improve cardiovascular outcomes and reduce cardiovascular mortality are urgently needed. Accordingly, interventions that may reduce the risk of recurrent cardiovascular events and/or the need for repeated coronary revascularization procedures, including aggressive lifestyle modification and complementary cardioprotective medications, collectively referred to as secondary prevention (Figure 1), are critically important.
      • Mozaffarian D.
      • Wilson P.W.
      • Kannel W.B.
      Beyond established and novel risk factors: lifestyle risk factors for cardiovascular disease.
      • Franklin B.A.
      • Cushman M.
      Recent advances in preventive cardiology and lifestyle medicine: a themed series.
      Structured exercise training, increased lifestyle physical activity (PA), or both have been reported in numerous randomized controlled trials and meta-analyses to reduce the overall mortality associated with atherosclerotic coronary artery disease (CAD). One systematic review and meta-analysis of 33 PA studies, including 883,372 participants, reported risk reductions of 30% to 50% for cardiovascular mortality and 20% to 50% for all-cause mortality, with pooled risk reductions of 35% and 33%, respectively.
      • Nocon M.
      • Hiemann T.
      • Müller-Riemenschneider F.
      • Thalau F.
      • Roll S.
      • Willich S.N.
      Association of physical activity with all-cause and cardiovascular mortality: a systematic review and meta-analysis.
      These epidemiologic analyses, when combined with adjunctive experimental and clinical investigations providing biologic plausibility,
      • Joyner M.J.
      • Green D.J.
      Exercise protects the cardiovascular system: effects beyond traditional risk factors.
      • Quindry J.C.
      • Franklin B.A.
      Cardioprotective exercise and pharmacologic interventions as complementary antidotes to cardiovascular disease.
      and other relevant reports,
      • Kokkinos P.
      • Myers J.
      Exercise and physical activity: clinical outcomes and applications.
      • Kaminsky L.A.
      • Arena R.
      • Beckie T.M.
      • et al.
      American Heart Association Advocacy Coordinating Committee, Council on Clinical Cardiology, and Council on Nutrition, Physical Activity and Metabolism
      The importance of cardiorespiratory fitness in the United States: the need for a national registry. A policy statement from the American Heart Association.
      • Ross R.
      • Blair S.N.
      • Arena R.
      • et al.
      American Heart Association Physical Activity Committee of the Council on Lifestyle and Cardiometabolic HealthCouncil on Clinical CardiologyCouncil on Epidemiology and PreventionCouncil on Cardiovascular and Stroke Nursing; Council on Functional Genomics and Translational BiologyStroke Council
      Importance of assessing cardiorespiratory fitness in clinical practice: a case for fitness as a clinical vital sign. A scientific statement from the American Heart Association.
      • Faselis C.
      • Kokkinos P.
      • Tsimploulis A.
      • et al.
      Exercise capacity and atrial fibrillation risk in veterans: a cohort study.
      • Harber M.P.
      • Kaminsky L.A.
      • Arena R.
      • et al.
      Impact of cardiorespiratory fitness on all-cause and disease-specific mortality: advances since 2009.
      support a cause-and-effect relation between increased levels of PA and cardiorespiratory fitness (CRF) and reduced cardiovascular mortality, rather than merely associations between these variables.
      • Blair S.N.
      • Kohl III, H.W.
      • Barlow C.E.
      • Paffenbarger Jr., R.S.
      • Gibbons L.W.
      • Macera C.A.
      Change in physical fitness and all-cause mortality: a prospective study of healthy and unhealthy men.
      • Kokkinos P.
      • Myers J.
      • Faselis C.
      • et al.
      Exercise capacity and mortality in older men: a 20-year follow-up study.
      Progressive exercise after an acute cardiovascular event and/or coronary revascularization procedure is often prescribed as an integral component of a secondary prevention program in outpatient cardiac rehabilitation. Nevertheless, delineating the optimal cardioprotective dosage, including the modulating impact of variations in the associated frequency, intensity, and duration on subsequent mortality in patients with known CAD, has remained controversial and elusive.
      Figure thumbnail gr1
      Figure 1Unhealthy lifestyle habits lead to traditional risk factors, the progression of cardiovascular disease, and ultimately, adverse outcomes or clinical end points, with specific reference to the types of prevention interventions: primordial (prevention of risk factors), primary (treatment of risk factors), and secondary (prevention of recurrent cardiovascular events). Bona fide interventions include lifestyle modification, pharmacotherapies (eg, aspirin, β-adrenergic blockers, statins, angiotensin-converting enzyme inhibitors), and emergent or elective coronary revascularization, when clinically indicated. CHF = congestive heart failure; MI = myocardial infarction; PAD = peripheral arterial disease.
      From Circulation, with permission.
      • Franklin B.A.
      Preventing exercise-related cardiovascular events: is a medical examination more urgent for physical activity?.
      Recently, researchers developed a new fitness metric, using the frequency, duration, and intensity of PA, the latter estimated from continuous heart rate (HR) monitoring in the Nord-Trøndelag Health Study (HUNT) Fitness Study cohort, to clarify the relation between exercise dose and health outcomes.
      • Nes B.M.
      • Gutvik C.R.
      • Lavie C.J.
      • Nauman J.
      • Wisløff U.
      Personalized activity intelligence (PAI) for prevention of cardiovascular disease and promotion of physical activity.
      Termed the personalized activity intelligence (PAI) score, it is derived from the cumulative 7-day modulations in activity HR over time, and gives more credit (ie, a higher PAI score) for vigorous exercise than for mild-to-moderate PA. For example, when compared with an hour-long 3-mile walk, a 30-minute strenuous bike ride earns 8 times the PAI score, 7 vs 56, respectively.
      • Fowler G.A.
      Stop counting 10,000 steps: check your personal activity intelligence.
      According to a recently published investigation regarding the prevention of CVD in the general population, using the HUNT study database over an average follow-up of 26.2 years, men and women achieving a weekly PAI score of greater than or equal to 100 had a 20% ± 3% reduced risk of CVD mortality, compared with an inactive control group.
      • Nes B.M.
      • Gutvik C.R.
      • Lavie C.J.
      • Nauman J.
      • Wisløff U.
      Personalized activity intelligence (PAI) for prevention of cardiovascular disease and promotion of physical activity.
      The findings indicated that this exercise dosage could potentially increase the lifespan by up to 10 years for persons younger than 50 years. In aggregate, these data, and other relevant investigations,
      • Lavie C.J.
      • Arena R.
      • Swift D.L.
      • et al.
      Exercise and the cardiovascular system: clinical science and cardiovascular outcomes.
      • George J.
      • Abdulla R.K.
      • Yeow R.
      • et al.
      Daily energy expenditure and its relation to health care costs in patients undergoing ambulatory electrocardiographic monitoring.
      suggest that large daily fluctuations in HR and associated energy expenditure, which can be assessed using the PAI score, appear to confer not only increased survival but decreased health care costs as well. The study by Kieffer et al
      • Kieffer S.K.
      • Zisko N.
      • Coombes J.S.
      • Nauman J.
      • Wisløff U.
      Personalized activity intelligence (PAI) and mortality in patients with cardiovascular disease, the HUNT study.
      published in the current issue of Mayo Clinic Proceedings extends these analyses to a large cohort of patients with self-reported CVD, defined as angina pectoris, previous myocardial infarction, stroke, or combinations thereof, in the HUNT database, with specific reference to selected subgroups of coronary patients, regardless of whether contemporary PA recommendations were simultaneously being met.
      Using a study population of 3133 patients with CVD (mean age, 67.6±10.3 years; 64% men) with complete baseline data on PAI, based on directly monitored HR fluctuations, habitual PA, and pertinent demographic and clinical characteristics, the investigators divided participants into 4 groups to further clarify the association between PAI and subsequent risk of mortality.
      • Kieffer S.K.
      • Zisko N.
      • Coombes J.S.
      • Nauman J.
      • Wisløff U.
      Personalized activity intelligence (PAI) and mortality in patients with cardiovascular disease, the HUNT study.
      These groups included the following: those with a PAI score of 0 (inactive, reference group); those with a PAI score of 50 or less; those with a PAI score of 51 to 99; and those with a PAI score of 100 or more. Over an average follow-up of 12.5 years, after adjusting for potential confounders in a multiadjusted model, participants attaining a weekly PAI score of 100 or more had a 36% and 24% lower risk of cardiovascular and all-cause mortality, respectively, as compared with the inactive group, irrespective of whether they were following contemporary PA guidelines.
      • Haskell W.L.
      • Lee I.M.
      • Pate R.R.
      • et al.
      Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association.
      After adjusting for sex, those attaining a PAI score of less than 100 demonstrated an average of 4.7 years of life lost as compared with their counterparts achieving a PAI score of 100 or more. Relative to younger (≤70 years) vs older (>70 years) participants, the corresponding years of life lost were 4.3 and 3.3, respectively. In contrast to the reverse J-shaped hypothesis regarding exercise,
      • O'Keefe J.H.
      • Franklin B.
      • Lavie C.J.
      Exercising for health and longevity vs peak performance: different regimens for different goals.
      there were no further reductions or loss of survival benefit beyond obtaining a weekly PAI score of 100 or more. Moreover, achieving a PAI score of 100 or more was associated with similar mortality risk reductions for both sexes and different age groups. Subgroup analyses were, for the most part, unremarkable.
      Despite several acknowledged observational study limitations (eg, cannot imply cause and effect, self-reported data, PA and PAI assessed at baseline only, no information on objectively measured CRF, left ventricular ejection fraction, or beta-blocker usage), and the fact that the study population was predominantly white, the present
      • Kieffer S.K.
      • Zisko N.
      • Coombes J.S.
      • Nauman J.
      • Wisløff U.
      Personalized activity intelligence (PAI) and mortality in patients with cardiovascular disease, the HUNT study.
      and previous findings
      • Nes B.M.
      • Gutvik C.R.
      • Lavie C.J.
      • Nauman J.
      • Wisløff U.
      Personalized activity intelligence (PAI) for prevention of cardiovascular disease and promotion of physical activity.
      suggest that the PAI metric applies to men and women with and without established CVD. The prognostic implications of higher PAI values (ie, ≥100) being associated with a reduced risk of mortality in patients with self-reported CVD are compatible with previous reports,
      • Swain D.P.
      • Franklin B.A.
      Comparison of cardioprotective benefits of vigorous versus moderate intensity aerobic exercise.
      • Wen C.P.
      • Wai J.P.
      • Tsai M.K.
      • et al.
      Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study.
      and may be explained, at least in part, by higher levels of CRF.
      • Kaminsky L.A.
      • Arena R.
      • Beckie T.M.
      • et al.
      American Heart Association Advocacy Coordinating Committee, Council on Clinical Cardiology, and Council on Nutrition, Physical Activity and Metabolism
      The importance of cardiorespiratory fitness in the United States: the need for a national registry. A policy statement from the American Heart Association.
      • Ross R.
      • Blair S.N.
      • Arena R.
      • et al.
      American Heart Association Physical Activity Committee of the Council on Lifestyle and Cardiometabolic HealthCouncil on Clinical CardiologyCouncil on Epidemiology and PreventionCouncil on Cardiovascular and Stroke Nursing; Council on Functional Genomics and Translational BiologyStroke Council
      Importance of assessing cardiorespiratory fitness in clinical practice: a case for fitness as a clinical vital sign. A scientific statement from the American Heart Association.
      • Harber M.P.
      • Kaminsky L.A.
      • Arena R.
      • et al.
      Impact of cardiorespiratory fitness on all-cause and disease-specific mortality: advances since 2009.
      • Blair S.N.
      • Kohl III, H.W.
      • Barlow C.E.
      • Paffenbarger Jr., R.S.
      • Gibbons L.W.
      • Macera C.A.
      Change in physical fitness and all-cause mortality: a prospective study of healthy and unhealthy men.
      • Kokkinos P.
      • Myers J.
      • Faselis C.
      • et al.
      Exercise capacity and mortality in older men: a 20-year follow-up study.

      Cardioprotective Benefits of Vigorous- vs Moderate-Intensity PA

      Although a key attribute of the PAI method is the classification of relative exercise intensity (ie, specific to the individual), in clinical practice it is more common to use absolute intensity where vigorous is considered as 6 or more metabolic equivalents (METs; 1 MET = 3.5 mL O2/kg/min) and moderate is 3.0 to 5.9 METs. To clarify whether vigorous- or moderate-intensity exercise has disparate effects on cardiovascular outcomes, specifically on the risk factors for and incidence of CAD, we previously reviewed relevant epidemiologic and clinical studies that evaluated the impact of varying intensity levels while controlling for total energy expenditure.
      • Swain D.P.
      • Franklin B.A.
      Comparison of cardioprotective benefits of vigorous versus moderate intensity aerobic exercise.
      Risk factors included resting blood pressure, blood lipids, glucose control, CRF, and body fatness. Relevant studies consistently found a greater reduction in the risk of atherosclerotic CVD and more cardioprotective risk factor profiles for individuals engaged in vigorous, as opposed to moderate-intensity PA, including more favorable changes in diastolic blood pressure, glucose control, and CRF, whereas improvements in systolic blood pressure, blood lipids, and body fatness were comparable. Collectively, our analysis suggested that if the total energy expenditure of exercise is held constant, regular vigorous-intensity exercise appears to be superior to moderate-intensity exercise in eliciting beneficial cardiovascular adaptations.
      Why vigorous-intensity exercise provides greater cardiovascular benefits than moderate-intensity PA,
      • Wisløff U.
      • Støylen A.
      • Loennechen J.P.
      • et al.
      Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study.
      even when the energy expenditure is equated,
      • Swain D.P.
      • Franklin B.A.
      Comparison of cardioprotective benefits of vigorous versus moderate intensity aerobic exercise.
      may be due to several mechanisms. Vigorous exercise intensities are more effective than moderate intensities at increasing CRF,
      • Swain D.P.
      • Franklin B.A.
      VO2 reserve and the minimal intensity for improving cardiorespiratory fitness.
      especially for individuals with higher baseline CRF.
      • Swain D.P.
      Moderate or vigorous intensity exercise: which is better for improving aerobic fitness?.
      Each 1-MET increase in CRF is associated with an average (median) reduction of 16% (range, 8%-35%) in mortality,
      • Myers J.
      • Herbert W.
      • Ribisl P.
      • Franklin B.
      Is new science driving practice improvements and better patient outcomes? Applications for cardiac rehabilitation.
      which compares favorably with the survival benefit conferred by low-dose aspirin, statins, β-blockers, and angiotensin-converting enzyme inhibitors after acute myocardial infarction.
      • Boden W.E.
      • Franklin B.A.
      • Wenger N.K.
      Physical activity and structured exercise for patients with stable ischemic heart disease.
      Other possible mechanisms associated with vigorous-intensity exercise training may include autonomic adaptations, specifically decreased sympathetic outflow and increased vagal tone, increased or maintained HR variability and endothelial function, decreased vascular stiffness, platelet adhesiveness, fibrinogen, and blood viscosity, increased diastolic filling time, augmenting coronary flow, and enhanced nitric oxide vasodilator function.
      • Joyner M.J.
      • Green D.J.
      Exercise protects the cardiovascular system: effects beyond traditional risk factors.
      • Quindry J.C.
      • Franklin B.A.
      Cardioprotective exercise and pharmacologic interventions as complementary antidotes to cardiovascular disease.
      In addition, escalating reliance on carbohydrate use over fat metabolism evoked by increased adrenergic stimulation at higher exercise intensities may be the mechanism underlying improvements in insulin sensitivity after vigorous-intensity training in obese individuals, with and without diabetes mellitus.
      • Kang J.
      • Robertson R.J.
      • Hagberg J.M.
      • et al.
      Effect of exercise intensity on glucose and insulin metabolism in obese individuals and obese NIDDM patients.
      A summary of these and other potential physiologic, antiischemic, and antiarrhythmic cardioprotective mechanisms associated with vigorous-intensity exercise is shown in Figure 2.
      Figure thumbnail gr2
      Figure 2Multiple mechanisms by which vigorous-intensity exercise training may be more effective than moderate-intensity exercise at reducing cardiovascular risk. AF = atrial fibrillation; HF = heart failure; NO = nitric oxide.

      Implications for Health Care Professionals

      “Wicks et al
      • Wicks J.R.
      • Oldridge N.B.
      • Nielsen L.K.
      • Vickers C.E.
      HR index−a simple method for the prediction of oxygen uptake.
      reported a simple method for the prediction of activity METs in patients with and without CAD, including those taking β-blockers, using the HR Index equation: METs = (6 × HR Index) − 5, where the HR Index equals the activity HR divided by the resting HR. For example, a tennis player's resting HR of 60 beats per minute (bpm) is increased to approximately 120 bpm during a match. His MET level is estimated as (6 × 120/60) − 5 = 7 METs.
      • Franklin B.A.
      • Brinks J.
      • Berra K.
      • Lavie C.J.
      • Gordon N.F.
      • Sperling L.S.
      Using metabolic equivalents in clinical practice.
      The larger the increase between the resting HR and the HR during PA, the greater the estimated MET level.
      Empiric experience has shown that although most cardiac patients initiate exercise-based rehabilitation programs at approximately 2 to 3 METs, uptitration of training intensities over time is often suboptimal, especially when direct early outpatient medical supervision and continuous electrocardiogram monitoring have ceased.
      • Squires R.W.
      • Kaminsky L.A.
      • Porcari J.P.
      • Ruff J.E.
      • Savage P.D.
      • Williams M.A.
      Progression of exercise training in early outpatient cardiac rehabilitation: an official statement from the American Association of Cardiovascular and Pulmonary Rehabilitation.
      Because fitness levels are influenced by age and sex, and little additional survival benefit occurs when moving from “good” to “excellent” fitness, suggesting a plateau in reduced relative risk, the Table provides “good” fitness levels and recommended aerobic training requirements (METs) for middle-aged and older men and women.
      • Kaminsky L.A.
      • Arena R.
      • Myers J.
      Reference standards for cardiorespiratory fitness measured with cardiopulmonary exercise testing: data from the Fitness Registry and the Importance of Exercise National Database.
      In our experience, if patients can progress to training levels that are 70% to 80% of VO2 reserve, without adverse signs/symptoms or excessive ratings of perceived exertion (ie, ≥15 [hard work] on the 6-20 scale), it is likely that they can attain these fitness levels that are compatible with increased longevity. For example, “good” CRF for a 55-year-old man would be 10.0 or more METs; accordingly, a training level of 7.3 to 8.2 METs would serve as a worthwhile goal. This approach is compatible with the PAI score, where more credit is given to larger fluctuations in HR and exercise intensity, which appear to confer greater survival benefits.
      • Nes B.M.
      • Gutvik C.R.
      • Lavie C.J.
      • Nauman J.
      • Wisløff U.
      Personalized activity intelligence (PAI) for prevention of cardiovascular disease and promotion of physical activity.
      Table“Good” Fitness Levels for Middle-Aged and Older Men and Women, and the Training Aerobic Requirements Associated With These Cardioprotective Fitness Levels
      MET = metabolic equivalent.
      ,
      Fitness levels are from the Fitness Registry and the Importance of Exercise National Database reference standards.33
      ,
      Table values represent “good” fitness levels, expressed as METs, for men and women, attained during peak or symptom-limited exercise testing, and the recommended aerobic training requirements (METs) to achieve these cardioprotective fitness levels. These training intensities are suggested as a goal, after 6 to 12 mo of slow progressive increases in exercise intensity, provided the patient remains asymptomatic, without adverse signs and/or symptoms, and perceived exertion (6-20 scale) remains below “15,” signifying “fairly light” to “somewhat hard” work.
      Age groups (y)
      30-3940-4950-5960-6970-79
      Men
       Good fitness≥12.9≥11.5≥10.0≥8.7≥7.7
       Training METs
      70%-80% VO2 reserve.
      9.3-10.58.4-9.47.3-8.26.4-7.25.7-6.4
      Women
       Good fitness≥9.2≥8.2≥7.2≥6.1≥5.5
       Training METs
      70%-80% VO2 reserve.
      6.7-7.66.0-6.85.3-6.04.6-5.14.2-4.6
      a MET = metabolic equivalent.
      b Fitness levels are from the Fitness Registry and the Importance of Exercise National Database reference standards.
      • Kaminsky L.A.
      • Arena R.
      • Myers J.
      Reference standards for cardiorespiratory fitness measured with cardiopulmonary exercise testing: data from the Fitness Registry and the Importance of Exercise National Database.
      c Table values represent “good” fitness levels, expressed as METs, for men and women, attained during peak or symptom-limited exercise testing, and the recommended aerobic training requirements (METs) to achieve these cardioprotective fitness levels. These training intensities are suggested as a goal, after 6 to 12 mo of slow progressive increases in exercise intensity, provided the patient remains asymptomatic, without adverse signs and/or symptoms, and perceived exertion (6-20 scale) remains below “15,” signifying “fairly light” to “somewhat hard” work.
      d 70%-80% VO2 reserve.
      In our current hypokinetic society, any PA is better than none, moderate intensity is better than low intensity, and vigorous-intensity exercise appears better yet.
      • Rankin A.J.
      • Rankin A.C.
      • MacIntyre P.
      • Hillis W.S.
      Walk or run? Is high-intensity exercise more effective than moderate-intensity exercise at reducing cardiovascular risk?.
      However, the risk of exertion-related acute cardiac events is highest among habitually sedentary individuals with known or occult CVD who perform unaccustomed vigorous- to high-intensity PA.
      • Mittleman M.A.
      • Maclure M.
      • Tofler G.H.
      • Sherwood J.B.
      • Goldberg R.J.
      • Muller J.E.
      Triggering of acute myocardial infarction by heavy physical exertion: protection against triggering by regular exertion. Determinants of Myocardial Infarction Onset Study Investigators.
      Accordingly, when previously sedentary patients with or without CAD initiate an exercise program, a “progressive transitional phase” should be prescribed to gradually allow improvement in their CRF, without being subjected to the large spikes in relative cardiac risk from vigorous-intensity bouts during this phase.
      • Riebe D.
      • Franklin B.A.
      • Thompson P.D.
      • et al.
      Updating ACSM’s recommendation for exercise preparticipation health screening.
      Once a vigorous exercise intensity is attained, the more frequently it is performed (ie, days/week), the lower the relative risk of each bout (Figure 3).
      • Franklin B.A.
      Preventing exercise-related cardiovascular events: is a medical examination more urgent for physical activity?.
      Nevertheless, because prodromal symptoms often precede exercise-related acute cardiac events,
      • Thompson P.D.
      • Stern M.P.
      • Williams P.
      • Duncan K.
      • Haskell W.L.
      • Wood P.D.
      Death during jogging or running: a study of 18 cases.
      patients should be strongly counseled to cease vigorous-intensity exercise at the initial onset of symptoms and seek medical evaluation before resuming training.
      Figure thumbnail gr3
      Figure 3Relative risk of acute myocardial infarction during vigorous physical exertion (≥6 METs) according to activity status and exercise frequency (days/week). Baseline or overall risk for the active subject is approximately half that of their sedentary counterpart, 0.5 and 1.0, respectively.
      From Circulation, with permission.
      • Franklin B.A.
      Preventing exercise-related cardiovascular events: is a medical examination more urgent for physical activity?.
      In summary, the study by Kieffer et al
      • Kieffer S.K.
      • Zisko N.
      • Coombes J.S.
      • Nauman J.
      • Wisløff U.
      Personalized activity intelligence (PAI) and mortality in patients with cardiovascular disease, the HUNT study.
      provides additional evidence of the importance of regular exercise training as a key cardioprotective intervention, with an emphasis on the time efficiency and effectiveness of using vigorous-intensity exercise, when appropriate.

      Acknowledgments

      Special thanks to Brenda White and Kim Sankey for their assistance with the preparation of and revisions for this manuscript, respectively.

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