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Cited by 237Cardiovascular and exercise physiologyPhysical Activity and HealthCardiovascular Effects of Exercise

Exercise benefits in cardiovascular diseases: From mechanisms to clinical implementation

Open access
Valenzuela, Pedro L, Ruilope, Luis M, Santos-Lozano, Alejandro, Wilhelm, Matthias, Kränkel, Nicolle, Fiuza-Luces, Carmen, Lucia, Alejandro·2023·European Heart Journal
DOI 10.1093/eurheartj/ehad170
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Abstract

There is a pandemic of physical inactivity that appears to parallel the widespread prevalence of cardiovascular disease (CVD). Yet, regular physical activity (PA) and exercise can play an important role not only in primary cardiovascular prevention but also in secondary prevention. This review discusses some of the main cardiovascular effects of PA/exercise and the mechanisms involved, including a healthier metabolic milieu with attenuation of systemic chronic inflammation, as well as adaptations at the vascular (antiatherogenic effects) and heart tissue (myocardial regeneration and cardioprotection) levels. The current evidence for safe implementation of PA and exercise in patients with CVD is also summarized.

AI snapshot

Written from the paper’s full text.

TL;DR

This review summarizes epidemiological and mechanistic evidence that regular physical activity/exercise reduces cardiovascular disease risk and mortality in primary and secondary prevention, with dose-dependent benefits and multiple biological mechanisms. It also discusses controversies around high-volume endurance exercise, atrial fibrillation, coronary calcification, and the occupational physical activity paradox.

Key findings

  • In primary prevention, meeting WHO recommendations for moderate or vigorous physical activity was associated with 19%–25% and 15%–31% lower CVD and all-cause mortality risk, respectively, in a 30-year follow-up of 116,221 adults; the highest quarter of total moderate-to-vigorous physical activity had 53% lower incident CVD risk, and each 2,000 daily steps was associated with 10% lower CVD incidence up to ∼10,000 steps/day.
  • In secondary prevention, a 6-year follow-up of 131,558 CVD patients found 14% mortality risk reduction per 500 MET-min/week versus 7% in CVD-free referents; cardiac rehabilitation participation was associated with 32% lower mortality, and a Cochrane review of 23,430 CHD patients found exercise-based rehabilitation reduced mortality and improved quality of life.
  • Regarding “too much” exercise, a meta-analysis of 35,920 athletes found 27% lower standardized mortality rate, and MVPA at 5,000 MET-min/week was associated with 27% lower CVD mortality than 750 MET-min/week; however, sports participation was associated with 64% higher atrial fibrillation risk, while no robust evidence was found for total or intense physical activity.
  • Mechanistic evidence includes exercise-induced exerkines, vascular and endothelial improvements, myocardial regeneration, antiarrhythmogenic autonomic effects, and cardiac preconditioning; in obese mice, exercise training reduced myocardial infarction lesions by 67%, and each 1-MET increase in cardiorespiratory fitness was associated with 13% lower CVD mortality risk, with 51% lower risk at highest versus lowest fitness.

Methods

  • Design: narrative review of epidemiological, clinical, and preclinical evidence on physical activity/exercise in cardiovascular disease prevention and mechanisms.
  • Data or sample: no primary data were generated or analysed; the paper synthesizes cited cohort studies, meta-analyses, randomized controlled trials, and preclinical studies.
  • Main analysis: narrative synthesis of dose-response associations, clinical outcomes, and proposed biological mechanisms, without a described systematic search or formal meta-analysis.

Limitations

  • Stated: the paper reports that no data were generated or analysed for the manuscript; it notes controversy about high-volume endurance exercise and potential methodological limitations in atrial fibrillation/physical activity studies, mainly non-objective determination of atrial fibrillation or physical activity.
  • Evident from the text: as a narrative review, it does not describe a systematic search strategy, formal risk-of-bias assessment, or quantitative pooling; conclusions rely heavily on observational and preclinical evidence, so causality is not established.

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Integrity signals

Registry

Crossref · 10.1093/eurheartj/ehad170

Cites

203 of 203 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 149 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    The combination of moderate-to-vigorous physical activity and strengthening activities provides the greatest improvements in cardiometabolic health and mortality risk.

    “although both MVPA and strengthening activities are associated with improvements in cardiometabolic health and mortality risk, it is the combination of the two that provides the greatest effects.[7][8][9]”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [7] Momma, 2022, Muscle-strengthening activities are associated with lower risk and mortality in major non-communicable diseases: a systematic review and meta-analysis of cohort studies, Br J Sports Med source

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    • cites [8] Coleman, 2022, Dose-response association of aerobic and muscle-strengthening physical activity with mortality: a national cohort study of 416 420 US adults, Br J Sports Med

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    • cites [9] Zhao, 2020, Recommended physical activity and all cause and cause specific mortality in US adults: prospective cohort study, BMJ

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  • Premisecitation

    A approximately 40% decrease in cardiovascular disease mortality risk is found at only 15-20 minutes per week of vigorous physical activity.

    “a ∼40% decrease in CVD mortality risk was nevertheless found at only 15-20 min/week. 6”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Ahmadi, 2022, Vigorous physical activity, incident heart disease, and cancer: how little is enough?, Eur Heart J source

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  • Premisecitation

    Higher daily step counts, particularly at high intensity, are associated with lower cardiovascular disease incidence, about 10% lower for each 2000 steps, at least up to approximately 10,000 steps per day.

    “a higher number of daily step counts, particularly if performed at high intensity (30/min) seems associated with a lower CVD incidence (-10% for each 2000 steps), at least up to ∼10 000 steps/day.5”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Del Pozo Cruz, 2022, Prospective associations of daily step counts and intensity with cancer and cardiovascular disease incidence and mortality and all-cause mortality, JAMA Intern Med source

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  • Premisecitation

    Forty to sixty minutes per week of strengthening activities is associated with 17% lower risk of cardiovascular disease mortality.

    “17% lower risk of CVD mortality with 40-60 min/ week of this type of activity).7”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [7] Momma, 2022, Muscle-strengthening activities are associated with lower risk and mortality in major non-communicable diseases: a systematic review and meta-analysis of cohort studies, Br J Sports Med source

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  • Premisecitation

    Meta-analytical evidence shows a positive association between excessive sedentary time greater than 10 hours per day and incident cardiovascular disease.

    “meta-analytical evidence showed a positive association between excessive sedentary time (>10 h/day) and incident CVD 12”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Pandey, 2016, Continuous dose-response association between sedentary time and risk for cardiovascular disease: a meta-analysis, JAMA Cardiol source

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  • The quote only partly states this claim. 1
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    Premisecitation

    Meeting WHO recommendations for moderate or vigorous physical activity was associated with 19%-25% and 15%-31% lower risk of cardiovascular disease and all-cause mortality, respectively.

    “(19%-25% and 15%-31% lower risk if meeting aforementioned WHO recommendations of MPA or VPA, respectively).3”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Lee, 2022, Long-Term leisure-time physical activity intensity and all-cause and cause-specific mortality: a prospective cohort of US adults, Circulation source

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    Premisecitation

    Regular moderate-to-vigorous physical activity has effects opposite to physical inactivity on incident cardiovascular disease and overall mortality, and these effects are largely dose-responsive.

    “whereas regular MVPA has the opposite (and largely dose-responsive) effects. 2”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] Visseren, 2021, 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice, Eur Heart J source

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    Premisecitation

    A meta-analysis of prospective studies with low risk of bias reported that sports participation was associated with a markedly 7-8-fold higher risk of atrial fibrillation, whereas self-reported moderate-to-vigorous physical activity was inversely associated with risk of medically ascertained atrial fibrillation.

    “a meta-analysis of prospective studies with low risk of bias reported that, as opposed to sports participation-which was associated with a markedly (7-8-fold) higher risk-self-reported (using validated questionnaires) MVPA was inversely associated with the risk of medically ascertained AF. 39”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [39] Valenzuela, 2022, What do we really know about the association between physical activity, sports, and atrial fibrillation? A systematic review and meta-analysis from unbiased studies, Eur J Prev Cardiol source

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    Premisecitation

    Recent evidence suggests no detrimental effects and an inverse association of objectively measured moderate-to-vigorous physical activity with atrial fibrillation, even at more than 395 minutes per week.

    “Recent evidence also suggests no detrimental effects (and actually an inverse association) of objectively measured MVPA, 40,41 even at >395 min/week.42”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [40] Khurshid, 2021, Accelerometer-derived physical activity and risk of atrial fibrillation, Eur Heart J source

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    • cites [41] Fletcher, 2022, Association of physical activity with the incidence of atrial fibrillation in persons > 65 years old: the Atherosclerosis Risk in Communities (ARIC) study, BMC Cardiovasc Disord source

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    • cites [42] O'Neal, 2020, Objectively measured physical activity and the risk of atrial fibrillation (from the REGARDS study), Am J Cardiol source

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    Premisecitation

    In patients with cardiovascular disease, an inverse dose-response association between physical activity and mortality persisted beyond 500 MET-minutes per week, and very high physical activity levels of at least 1000 MET-minutes per week resulted in mortality risk similar to nonpatients.

    “although the slope of the association tended to flatten in healthy individuals above 500 MET-min/week, an inverse dose-response association was still observed beyond this point in patients, and performing very high PA levels (≥1000 MET-min/week) resulted in a mortality risk similar to nonpatients.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [49] Jeong, 2019, Mortality reduction with physical activity in patients with and without cardiovascular disease, Eur Heart J source

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    Premisecitation

    Very high moderate-to-vigorous physical activity levels can be associated with higher coronary artery calcification scores in the general population, but these scores do not seem to be associated with increased incidence of cardiovascular disease events or mortality in exposed individuals.

    “although very high MVPA levels can be associated with higher CAC scores in the general population, the latter do not seem to be associated with an increased incidence of CVD events or mortality in 'exposed' individuals.32,33”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [32] Gao, 2022, Associations of long-term physical activity trajectories with coronary artery calcium progression and cardiovascular disease events: results from the CARDIA study, Br J Sports Med source

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    • cites [33] DeFina, 2019, Association of all-cause and cardiovascular mortality with high levels of physical activity and concurrent coronary artery calcification, JAMA Cardiol source

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    Premisecitation

    In a recent study, very high levels of self-reported leisure-time physical activity were associated with a reduced risk, about 15% lower, of major cardiovascular disease events during a 10-year follow-up, but high levels of occupational physical activity showed the opposite trend, about 35% higher.

    “very high levels of self-reported leisure-time PA were associated with a reduced risk (-15%) of major CVD events during a 10-year follow-up, but high levels of occupational PA showed the opposite trend (+35%).46”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [46] Holtermann, 2021, The physical activity paradox in cardiovascular disease and all-cause mortality: the contemporary Copenhagen General Population Study with 104 046 adults, Eur Heart J source

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    Premisecitation

    Meeting minimum WHO-recommended levels of moderate-to-vigorous physical activity, 150 minutes per week, does not seem enough to offset the association of prolonged sedentary time with higher all-cause mortality risk; higher levels of 30-40 minutes per day are needed.

    “meeting minimum WHO-recommended levels of MVPA (150 min/week, the equivalent of ∼20 min/day) does not seem enough to offset the association of prolonged sedentary time with higher all-cause mortality risk, with higher levels (30-40 min/day) needed.16”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] Ekelund, 2020, Joint associations of accelero-meter measured physical activity and sedentary time with all-cause mortality: a harmonised meta-analysis in more than 44 000 middle-aged and older individuals, Br J Sports Med source

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    Premisecitation

    Acute and unaccustomed heavy physical exertion can trigger acute cardiovascular disease events such as myocardial infarction and cardiac sudden death, particularly in habitually least active individuals, while higher habitual physical activity levels are associated with reduced risk.

    “although acute and unaccustomed heavy physical exertion can trigger the onset of acute CVD events such as myocardial infarction (MI) and cardiac sudden death, this is particularly true for the habitually least active individuals, with higher habitual PA levels associated with a reduced risk.27,28”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [27] Thompson, 2007, Exercise and acute cardiovascular events placing the risks into perspective: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism and the Council on Clinical Cardiology, Circulation source

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    • cites [28] Mittleman, 1993, Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. Determinants of Myocardial Infarction Onset Study Investigators, N Engl J Med source

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    Premisecitation

    In 15,486 patients with stable coronary heart disease, those in the highest physical activity tertile showed lower risk of a major cardiovascular disease event, about 19% lower, cardiovascular disease-specific mortality, about 29% lower, and all-cause mortality, about 30% lower, than those in the least active tertile.

    “In a cohort of 15 486 patients with stable coronary heart disease (CHD), those in the highest PA tertile showed a lower risk of a major CVD event (-19%), as well as of CVD-specific (-29%) and all-cause mortality (-30%), than those in the least active tertile.52”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [52] Stewart, 2017, Physical activity and mortality in patients with stable coronary heart disease, J Am Coll Cardiol source

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    Premisecitation

    In 122,007 participants, cardiorespiratory fitness was inversely associated with mortality risk during a median 8.4-year follow-up, with a magnitude similar to or greater than traditional cardiovascular disease risk factors and no apparent upper limit.

    “In a study with 122 007 participants, CRF was inversely associated with mortality risk during a median 8.4-year follow-up; the magnitude of this association was similar to-or even greater thanthe influence of traditional CVD risk factors and with no apparent upper limit for the observed benefits.19”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Mandsager, 2018, Association of cardiorespiratory fitness with long-term mortality among adults undergoing exercise treadmill testing, JAMA Netw Open source

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    Premisecitation

    There is no evidence for increased risk of cardiovascular disease mortality in former elite athletes, and consistent findings suggest the opposite trend, for example 27% lower standard mortality rate in a meta-analysis of 35,920 athletes.

    “There is, however, no evidence for an increased risk of CVD mortality in former elite athletes, and in fact, there are consistent findings for the opposite trend [23][24][25] (e.g.27% lower standard mortality rate in a meta-analysis including 35 920 athletes 23 ).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [23] Garatachea, 2014, Elite athletes live longer than the general population: a meta-analysis, Mayo Clin Proc source

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    • cites [24] Antero-Jacquemin, 2015, Mortality in female and male French Olympians: a 1948–2013 cohort study, Am J Sports Med source

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    • cites [25] Antero, 2021, Female and male US Olympic athletes live 5 years longer than their general population counterparts: a study of 8124 former US Olympians, Br J Sports Med source

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    Premisecitation

    An umbrella review of meta-analyses reported that sports participation was associated with a higher atrial fibrillation risk, about 64% higher, but no robust evidence was found for total or intense physical activity.

    “A recent umbrella review of meta-analyses reported that sports participation was indeed associated with a higher AF risk (+64%), but no robust evidence was found for total or intense PA. 38”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Valenzuela, 2021, Physical activity, sports and risk of atrial fibrillation: umbrella review of meta-analyses, Eur J Prev Cardiol source

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  • May combine two claims.

    Premisecitation

    In a 6-year follow-up of 131,558 patients with different types of cardiovascular disease, physical activity was inversely associated with mortality risk, and this association was stronger than in cardiovascular disease-free referents, with 14% versus 7% risk reduction per 500 MET-minutes per week.

    “A recent 6-year follow-up study in 131 558 patients with different types of CVD [e.g.stroke, ischaemic cardiomyopathy, heart failure (HF)] found an inverse association between PA and mortality risk that was actually stronger than in CVD-free referents (14% and 7% risk reduction in patients and nonpatients, respectively, with every 500 MET-min/week).49”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [49] Jeong, 2019, Mortality reduction with physical activity in patients with and without cardiovascular disease, Eur Heart J source

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  • May combine two claims.

    Premisecitation

    In 7,058 outpatients with cardiovascular disease, those with highest leisure-time but not occupational physical activity levels had lower risk of recurrent cardiovascular disease events and all-cause mortality, about 28% and 7% lower respectively, during a 9-year follow-up.

    “A study in 7058 outpatients with CVD also reported that those with highest leisure-time-but not occupational-PA levels had a lower risk of recurrent CVD events and all-cause mortality risk (-28% and -7%, respectively) during a 9-year follow-up than their less active peers.51”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [51] Bonekamp, 2022, Leisure-time and occupational physical activity and health outcomes in cardiovascular disease, Heart

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    Premisecitation

    In patients with atrial fibrillation, physical exercise improves physical capacity, symptoms' burden, and cardiac function.

    “In patients with AF, physical exercise does not only improve physical capacity but also symptoms' burden and cardiac function.63,64”
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    • cites [63] Malmo, 2016, Aerobic interval training reduces the burden of atrial fibrillation in the short term: a randomized trial, Circulation source

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    • cites [64] Smart, 2018, Exercise-based cardiac rehabilitation improves exercise capacity and health-related quality of life in people with atrial fibrillation: a systematic review and meta-analysis of randomised and non-randomised trials, Open Heart source

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    Premisecitation

    Meta-analytical evidence supports that exercise training improves exercise capacity and quality of life in patients with heart failure, as well as some cardiac function indicators such as left ventricular ejection fraction.

    “Meta-analytical evidence supports that exercise training improves exercise capacity and QoL in patients with HF, as well as some cardiac function indicators [e.g.left ventricular ejection fraction (LVEF)].62”
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    • cites [62] Edwards, 2022, Exercise training in heart failure with preserved and reduced ejection fraction: a systematic review and meta-analysis, Sports Med Open source

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    Premisecitation

    Lowering plasma low-density lipoprotein cholesterol has led to population-wide reductions in the prevalence of cardiovascular disease events and is associated with differences in atherosclerotic plaque morphology.

    “lowering plasma LDL-cholesterol-by reducing intestinal cholesterol resorption, hepatic cholesterol synthesis or, more recently, enhancing hepatic LDL-cholesterol uptake-has led to population-wide reductions in the prevalence of CVD events and is associated with differences in atherosclerotic plaque morphology.85”
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    • cites [85] Pasterkamp, 2017, Temporal shifts in clinical presentation and underlying mechanisms of atherosclerotic disease, Nat Rev Cardiol source

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    Premisecitation

    Self-reported physical activity levels are inversely associated with the risk of atrial fibrillation-related adverse events and cardiovascular disease-specific mortality in people with atrial fibrillation.

    “selfreported PA levels inversely associated with the risk of AF-related adverse events (e.g.thromboembolic event, bleeding) and CVD-specific mortality in affected people.55”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [55] Proietti, 2017, Self-reported physical activity and major adverse events in patients with atrial fibrillation: a report from the EURObservational Research Programme Pilot Survey on Atrial Fibrillation (EORP-AF) General Registry, Europace source

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    Premisecitation

    Resistance training has proven feasible and effective for most cardiovascular diseases.

    “The role of muscle strength or 'resistance' training (RT) should not be disregarded, as this modality has proven feasible and effective for most CVD 48 (e.g.recent MI, 73 end-stage HF, 74 chronic HF, 75 or CHD 76 ).”
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    • cites [48] Pelliccia, 2021, 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease, Eur Heart J source

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    • cites [73] Vona, 2009, Effects of different types of exercise training followed by detraining on endothelium-dependent dilation in patients with recent myocardial infarction, Circulation source

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    • cites [74] Dean, 2011, Resistance training improves vasoreactivity in end-stage heart failure patients on inotropic support, J Cardiovasc Nurs source

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    Meta-analytical evidence suggests that high-intensity interval training is more effective, or at least more time-efficient, than moderate-intensity continuous training to improve cardiorespiratory fitness and quality of life in patients with cardiovascular disease.

    “meta-analytical evidence suggests that this modality is more effective-or at least more time-efficient-than MICT to improve CRF and QoL in patients with CVD.[70][71][72]”
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    • cites [70] Gomes-Neto, 2017, High-intensity interval training versus moderate-intensity continuous training on exercise capacity and quality of life in patients with coronary artery disease: a systematic review and meta-analysis, Eur J Prev Cardiol source

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    • cites [71] Yue, 2022, Effects of high-intensity interval vs. moderate-intensity continuous training on cardiac rehabilitation in patients with cardiovascular disease: a systematic review and meta-analysis, Front Cardiovasc Med source

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    • cites [72] Hannan, 2018, High-intensity interval training versus moderate-intensity continuous training within cardiac rehabilitation: a systematic review and meta-analysis, Open Access J Sports Med source

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    Premisecitation

    Resistance training improves muscle strength, cardiorespiratory fitness, mobility, and body composition in patients with cardiovascular disease.

    “this modality has proven to improve not only muscle strength but also CRF, mobility, and body composition in patients with CVD, [77][78][79]”
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    • cites [77] Yamamoto, 2016, Effects of resistance training on muscle strength, exercise capacity, and mobility in middle-aged and elderly patients with coronary artery disease: a meta-analysis, J Cardiol source

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    • cites [78] Kirkman, 2022, Resistance exercise for cardiac rehabilitation, Prog Cardiovasc Dis source

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    • cites [79] Hwang, 2010, Resistance training increases 6-minute walk distance in people with chronic heart failure: a systematic review, J Physiother source

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    Premisecitation

    A Cochrane review of 23,430 patients with coronary heart disease concluded that exercise-based cardiac rehabilitation results in reduced mortality risk and improved quality of life.

    “A recent Cochrane review (n = 23 430 patients with CHD) concluded that exercise-based cardiac rehabilitation results in a reduced mortality risk and an improved quality of life (QoL).50”
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    • cites [50] Dibben, 2021, Exercise-based cardiac rehabilitation for coronary heart disease, Cochrane Database Syst Rev

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    Premisecitation

    A meta-epidemiological study including 16 meta-analyses and 305 randomized controlled trials found no consistent differences between drug and exercise intervention for secondary prevention of coronary heart disease or prediabetes, greater effects of exercise intervention in stroke, but greater mortality risk reduction by diuretics compared with exercise in heart failure.

    “A meta-epidemiological study including 16 meta-analyses and 305 randomized controlled trials found not only no consistent differences between drug and exercise intervention for secondary prevention of some conditions such as CHD or prediabetes, but also greater effects provided by exercise intervention in some conditions such as stroke-albeit with a greater mortality risk reduction induced by diu”
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    • cites [61] Naci, 2015, Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study, Br J Sports Med source

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    Premisecitation

    Chronically elevated plasma levels of low-density lipoprotein cholesterol and triglyceride-rich lipoproteins are both strongly associated with cardiovascular disease.

    “Chronically elevated plasma levels of low-density lipoprotein (LDL)-cholesterol and triglyceride-rich lipoproteins (e.g.very lowdensity lipoproteins) are both strongly associated with CVD.83,84”
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    • cites [83] Ginsberg, 2021, Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies-a consensus statement from the European Atherosclerosis Society, Eur Heart J source

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    • cites [84] Boren, 2020, Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel, Eur Heart J source

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    Premisecitation

    IL6 receptor signalling plays an important role in the reduction of cardiac-especially epicardial-fat depots and increases in LV mass with aerobic training.

    “In addition, there is evidence for an important role of IL6 receptor signalling on the reduction of cardiac-especially epicardial-fat depots and increases in LV mass with aerobic training.182”
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    • cites [182] Christensen, 2019, Aerobic exercise induces cardiac fat loss and alters cardiac muscle mass through an interleukin-6 receptor-dependent mechanism: cardiac analysis of a double-blind randomized controlled clinical trial in abdominally obese humans, Circulation source

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    Premisecitation

    Cardiac preconditioning reduces the size of the MI lesion and the risk of ventricular fibrillation.

    “which reduces the size of the MI lesion and the risk of ventricular fibrillation.193”
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    • cites [193] Thijssen, 2018, Association of exercise preconditioning with immediate cardioprotection: a review, JAMA Cardiol source

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    Premisecitation

    Exercise is cardioprotective against necrosis, an effect mediated-at least partly-by activation of δ-opioid receptors or other factors released in a dose-dependent manner with exertion such as adenosine and bradykinin.

    “Exercise is also cardioprotective against necrosis, an effect mediated-at least partly-by activation of δ-opioid receptors or other factors released in a dose-dependent manner with exertion such as adenosine and bradykinin.197”
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    • cites [197] Miller, 2015, Involvement of the delta-opioid receptor in exercise-induced cardioprotection, Exp Physiol source

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    Premisecitation

    With regular exercise training, blood vessels in barosensitive areas of the carotid arteries become more compliant and are thus able to distend better in response to a rise in BP, with this adaptation increasing afferent signalling to the brainstem and evoking reflex increases in PNS activity to the heart while at the same time decreasing SNS activity.

    “Additionally, with regular exercise training blood vessels in barosensitive areas of the carotid arteries become more compliant and are thus able to distend better in response to a rise in BP, with this adaptation increasing afferent signalling to the brainstem and evoking reflex increases in PNS activity to the heart while at the same time decreasing sympathetic nervous system (SNS) activity.[188”
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    • cites [188] Pearson, 2018, Exercise therapy and autonomic function in heart failure patients: a systematic review and meta-analysis, Heart Fail Rev source

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    • cites [189] Villafaina, 2017, Physical exercise improves heart rate variability in patients with type 2 diabetes: a systematic review, Curr Diab Rep source

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    • cites [190] Sandercock, 2005, Effects of exercise on heart rate variability: inferences from meta-analysis, Med Sci Sports Exerc source

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    The antiarrhythmogenic effect of exercise is mediated by the improvement in autonomic balance, specifically a higher PNS tone without changes in intrinsic sinoatrial node function together with a reduction of β2-adrenergic receptor sensitivity and expression.

    “The antiarrhythmogenic effect of exercise is mediated by the improvement in autonomic balance, specifically a higher PNS tone without changes in intrinsic sinoatrial node function together with a reduction of β 2 -adrenergic receptor sensitivity and expression 184,185”
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    • cites [184] Billman, 2015, Exercise training-induced bradycardia: evidence for enhanced parasympathetic regulation without changes in intrinsic sinoatrial node function, J Appl Physiol (1985) source

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    • cites [185] Billman, 2009, Cardiac autonomic neural remodeling and susceptibility to sudden cardiac death: effect of endurance exercise training, Am J Physiol Heart Circ Physiol source

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    Elevated IL6 levels are linked to an increased risk of death from CVD and all-cause death in the general elderly population.

    “and also linked to an increased risk of death from CVD and all-cause death in the general elderly population.179”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [179] Li, 2017, Circulating interleukin-6 levels and cardiovascular and all-cause mortality in the elderly population: a meta-analysis, Arch Gerontol Geriatr source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The mechanisms through which exercise induces cardiac preconditioning include heightened defence against oxidative stress, upregulated expression of sarcolemmal ATP-sensitive potassium channel subunits, mitochondrial adaptations, β3-adrenergic receptor stimulation, and increased cardiac storage of NO• metabolites.

    “The mechanisms through which exercise induces cardiac preconditioning include heightened defence against oxidative stress, upregulated expression of sarcolemmal ATP-sensitive potassium channel subunits, mitochondrial adaptations (i.e.improved capacity to withstand apoptotic stimuli or a higher capacity for scavenging endogenous ROS), 194 β 3 -adrenergic receptor stimulation, and increased cardiac”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [194] Frasier, 2011, Exercise-induced cardiac preconditioning: how exercise protects your achy-breaky heart, J Appl Physiol (1985) source

      Not checked in the free run.

    • cites [195] Calvert, 2011, Exercise protects against myocardial ischemia-reperfusion injury via stimulation of beta(3)-adrenergic receptors and increased nitric oxide signaling: role of nitrite and nitrosothiols, Circ Res source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    Exercise-mediated improvement in myocardial regenerative capacity after MI is mediated by VED.

    “VED 166 (see also previous section on 'endothelial function')”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [166] Vona, 2004, Impact of physical training and detraining on endothelium-dependent vasodilation in patients with recent acute myocardial infarction, Am Heart J source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In obese mice, exercise training reduced MI lesions (-67%), which was mediated by the activation of pro-survival kinases of the reperfusion injury salvage kinase pathway, a decrease in the levels of phosphatases, and an improved capacity of mitochondria to retain calcium.

    “In obese mice, exercise training reduced MI lesions (-67%), which was mediated by the activation of pro-survival kinases of the reperfusion injury salvage kinase pathway, a decrease in the levels of phosphatases, and an improved capacity of mitochondria to retain calcium.196”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [196] Pons, 2013, Regular treadmill exercise restores cardioprotective signaling pathways in obese mice independently from improvement in associated co-morbidities, J Mol Cell Cardiol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    IL6 release by contracting muscles leads to direct and indirect anti-inflammatory effects and improvement of skeletal muscle insulin resistance.

    “But, its release by contracting muscles leads to direct and indirect anti-inflammatory effects and improvement of skeletal muscle insulin resistance.180,181”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [180] Lambernd, 2012, Contractile activity of human skeletal muscle cells prevents insulin resistance by inhibiting pro-inflammatory signalling pathways, Diabetologia source

      Not checked in the free run.

    • cites [181] Pedersen, 2017, Anti-inflammatory effects of exercise: role in diabetes and cardiovascular disease, Eur J Clin Invest source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Other exerkine-induced effects include improved lipolysis, thermogenesis, and glucose metabolism.

    “Other exerkine-induced effects include improved lipolysis, thermogenesis, and glucose metabolism.169,172”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [169] Fiuza-Luces, 2013, Exercise is the real polypill, Physiology (Bethesda)

      Not checked in the free run.

    • cites [172] Chow, 2022, Exerkines in health, resilience and disease, Nat Rev Endocrinol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Physical exercise can upregulate myocardial telomere-regulating proteins, thereby decreasing the risk of HF, as suggested by research in aging mice.

    “Indeed, physical exercise can upregulate myocardial telomere-regulating proteins, thereby decreasing the risk of HF, as suggested by research in aging mice 122”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [122] Ludlow, 2017, Acute exercise activates p38 MAPK and increases the expression of telomere-protective genes in cardiac muscle, Exp Physiol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    There are numerous biological mechanisms supporting PA/exercise-induced cardiovascular benefits involving not only the heart tissue but also the metabolic and inflammatory milieu.

    “Notably, there are numerous biological mechanisms supporting PA/exercise-induced cardiovascular benefits involving not only the heart tissue but also the metabolic and inflammatory milieu.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    There is some evidence for PA benefits even above current WHO recommendations.

    “with some evidence for PA benefits even above current WHO recommendations”
    Quote in the paperNot a substantial claim
39 of 39

  • The paper relies on this without support.

    Maintenance of endothelial barrier function counteracts lipid accumulation in the subendothelial vascular wall, the initial step of atherosclerotic plaque formation.

    “Maintenance of endothelial barrier function counteracts lipid accumulation in the subendothelial vascular wall, the initial step of atherosclerotic plaque formation.”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Physical activity could alleviate risks of diabetic vascular events by improving obesity, hyperglycemia, and hyperlipidemia.

    “PA could alleviate the risks of developing vascular events associated with diabetes and prediabetes by improving the established vascular risk factors, including obesity, hyperglycemia, and hyperlipidemia.43,46”

    From Accelerometer-measured physical activity, sedentary behavior, and incidence of macrovascular and microvascular events in individuals with type 2 diabetes mellitus and prediabetes (2025) · cites this paper as [46]

    The ‘Mechanisms: Metabolism, inflammation, and cellular integrity’ section (page unavailable) reports that exercise improves blood lipids and reduces glycaemia, both relevant to cardiovascular risk. The ‘Primary prevention’ section also links regular physical activity to lower cardiovascular risk. However, the retrieved passages do not establish that physical activity improves obesity or specifically reduces vascular events associated with diabetes and prediabetes through all three listed factors. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

Cites

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2 of the 205 references couldn’t be matched to a known paper.

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Authors
Valenzuela, P. L., Ruilope, L. M., Santos-Lozano, A., Wilhelm, M., Kränkel, N., Fiuza-Luces, C., & Lucia, A.
Affiliations
  • Universidad de Alcalá (ES)
  • Research Institute Hospital 12 de Octubre (ES)
  • Physical Activity and Health Research Group (PaHerg), Research Institute of the Hospital 12 de Octubre (‘imas12’) , 7 Planta, Bloque D., Av. de Córdoba s/n, Madrid 28041 , Spain
  • University of Bern (CH)
  • Charité – Universitätsmedizin Berlin (DE)
  • CIBER of Frailty and Healthy Aging (CIBERFES) , Madrid 28007 , Spain
Corresponding author
Valenzuela, Pedro L
ORCID
Venue
European Heart Journal
Publisher
Oxford University Press (OUP)
Published
2023-04-03
Volume
44
Issue
21
Pages
1874-1889
ISSN
  • 0195-668X (ISSN-L)
  • 1522-9645
DOI
10.1093/eurheartj/ehad170
OpenAlex
W4362505991
Cited by
237
References
205
Citations by year
2026: 67 · 2025: 82 · 2024: 69 · 2023: 19
FWCI
13.88
Type
journal article
Language
en
Open access
Licence
Locations
  • European Heart Journal (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • BORIS (University Library Bern) (submittedVersion)
  • RUIdeRA - Institutional University Repository (University of Castilla-La Mancha) (submittedVersion)
Funders
  • postdoctoral
  • by Instituto de Salud Carlos III (CP18/00034, CD21/00138).)
  • Ministry of Economy and Competitiveness (PI18/00139, PI20/00605)
  • Wereld Kanker Onderzoek
  • World Cancer Research Fund International (IIG_FULL_2021_007)
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
  • Health Sciences › Medicine › Physiology › Physical Activity and Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
Keywords
physical activity, cardiovascular disease, primary prevention, secondary prevention, physical inactivity, chronic inflammation, antiatherogenic effects, vascular adaptation, cardiac regeneration, cardioprotection
MeSH terms
Cardiovascular Diseases, Cardiovascular System, Heart, Humans, Inflammation, Risk Factors, Exercise

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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