Review Article | Published:

Exercise benefits in cardiovascular disease: beyond attenuation of traditional risk factors

Nature Reviews Cardiology (2018) | Download Citation


Despite strong scientific evidence supporting the benefits of regular exercise for the prevention and management of cardiovascular disease (CVD), physical inactivity is highly prevalent worldwide. In addition to merely changing well-known risk factors for systemic CVD, regular exercise can also improve cardiovascular health through non-traditional mechanisms. Understanding the pathways through which exercise influences different physiological systems is important and might yield new therapeutic strategies to target pathophysiological mechanisms in CVD. This Review includes a critical discussion of how regular exercise can have antiatherogenic effects in the vasculature, improve autonomic balance (thereby reducing the risk of malignant arrhythmias), and induce cardioprotection against ischaemia–reperfusion injury, independent of effects on traditional CVD risk factors. This Review also describes how exercise promotes a healthy anti-inflammatory milieu (largely through the release of muscle-derived myokines), stimulates myocardial regeneration, and ameliorates age-related loss of muscle mass and strength, a frequently overlooked non-traditional CVD risk factor. Finally, we discuss how the benefits of exercise might also occur via promotion of a healthy gut microbiota. We argue, therefore, that a holistic view of all body systems is necessary and useful when analysing the role of exercise in cardiovascular health.

Key points

  • Regular exercise induces antiatherogenic adaptations in vascular function and structure, irrespective of traditional cardiovascular disease (CVD) risk factors.

  • Regular exercise training improves cardiac parasympathetic regulation, thereby conferring protection against malignant arrhythmias, and also provides cardioprotection against ischaemia–reperfusion injury.

  • Muscle-derived myokines are responsible for many of the beneficial effects of exercise, particularly by promoting a healthy anti-inflammatory milieu.

  • Exercise can improve myocardial regeneration capacity, in part through stimulation of circulating angiogenic cells.

  • Loss of muscle strength and mass is a forgotten hallmark of — and, in fact, a risk factor for — CVD that can be largely reversed with resistance (strength) training, including in elderly individuals.

  • Regular exercise can promote a healthy gut microbiota while protecting the permeability and function of the gut barrier.

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Research in the field of exercise and health by A.L. and M.I. is funded by Fondo de Investigaciones Sanitarias (Instituto de Salud Carlos III) and Fondos FEDER (grant #PI15/00558 and PI17/01814). C.F.-L. has a Juan de la Cierva postdoctoral fellowship from the Spanish Ministry of Economy, Industry, and Competitiveness (#JCI-2016-30253). The authors thank K. McCreath for editorial assistance.

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Author notes

  1. These authors contributed equally: Carmen Fiuza-Luces, Alejandro Santos-Lozano.


  1. Faculty of Sport Sciences, Universidad Europea de Madrid, Madrid, Spain

    • Carmen Fiuza-Luces
    • , Luis M. Ruilope
    •  & Alejandro Lucia
  2. CIBER de Enfermedades Raras (CIBERER), Madrid, Spain

    • Carmen Fiuza-Luces
  3. i+HeALTH Research Group, Department of Health Sciences, European University Miguel de Cervantes, Valladolid, Spain

    • Alejandro Santos-Lozano
  4. Research Institute of the Hospital 12 de Octubre (i+12), Madrid, Spain

    • Alejandro Santos-Lozano
    •  & Alejandro Lucia
  5. Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA

    • Michael Joyner
  6. Centre for Primary Health Care Research, Lund University/Region Skåne, Skåne University Hospital, Malmö, Sweden

    • Pedro Carrera-Bastos
  7. NutriScience — Education and Consulting, Lisbon, Portugal

    • Pedro Carrera-Bastos
    •  & Oscar Picazo
  8. Achucarro — Basque Center for Neuroscience, Bilbao, Spain

    • José L. Zugaza
  9. Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country, Leioa, Spain

    • José L. Zugaza
  10. IKERBASQUE, Basque Foundation for Science, Bilbao, Spain

    • José L. Zugaza
  11. Department of Health Sciences, Public University of Navarre, CIBER of Frailty and Healthy Aging (CIBERFES), Navarrabiomed, Pamplona, Spain

    • Mikel Izquierdo


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All authors contributed to researching data for this article, discussions of its content, writing the paper, and review and/or editing of the manuscript before submission.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Carmen Fiuza-Luces.


Physical activity

Any bodily movement produced by skeletal muscles that requires energy expenditure.

Moderate-to-vigorous physical activity

(MVPA). Any activity with an energy expenditure of ≥3 metabolic equivalents (for example, brisk walking); the WHO minimum recommendations are 150 min of MVPA each week (or 20 min or 10,000 steps on most days of the week) for adults and 60 min of active playing on most days of the week for children and adolescents.

Physical inactivity

Also termed ‘lack of physical activity’; defined as not meeting the WHO-recommended minimum levels of moderate-to-vigorous physical activity (note, physical inactivity is not a synonym for sedentary behaviour).


Also termed ‘exercise training’; a subset of physical activity that is planned, structured, and repetitive and has a final or an intermediate objective of improving or maintaining physical fitness. In this Review, the terms ‘exercise’ and ‘exercise training’ are used interchangeably to refer to the cardiovascular adaptations produced by this specific type of physical activity; a single bout of exercise is referred to as ‘acute exercise’.

Interval exercise

Exercise that typically involves short, repeated bouts of intense effort (for example, fast running or intensive bicycling) interspersed with short recovery periods (each lasting a few minutes or less); common variants are high-intensity interval training (HIIT), in which near maximal effort is expended in exercise bouts of 1 min, interspersed with 1-min recovery periods, and sprint interval training (SIT), in which supramaximal effort is expended in exercise bouts of ~30 min, interspersed with recovery periods lasting a few minutes.

Aerobic exercise

Exercise involving dynamic movements and large muscle groups that predominantly rely on aerobic metabolism for fuelling muscle contractions; examples include jogging, running, swimming, and rowing.


A cytokine or peptide produced by skeletal muscle cells and subsequently released into the circulation, where it exerts endocrine or paracrine effects in other cells, tissues, or organs.

Cardiorespiratory fitness

The capacity of the circulatory and respiratory systems to supply oxygen to skeletal muscles during sustained physical activity; the primary measure is maximal oxygen consumption (VO2 max) reached during graded exercise testing until exhaustion.

Metabolic equivalent

(MET). A unit for quantifying cardiorespiratory fitness: 1 MET is equivalent to the basal metabolic rate (consumption of 3.5 ml O2/kg/min, on average).

Sedentary behaviour

Any waking activities conducted in a sitting, reclining, or lying posture and characterized by an energy expenditure ≤1.5 metabolic equivalents.


Derived from the Greek ‘sarx’ (flesh) and ‘penia’ (loss); sarcopenia is the age-induced loss of muscle mass and function, which typically manifests as reduced gait speed.

Shear stress

The frictional force exerted by blood flow on the endothelium of vessel walls.

Resistance exercise

Movement performed against a specific external force that is regularly increased during training; examples include weightlifting and exercises using resistance machines.

Muscle strength

The ability of a muscle to exert force on physical objects; muscle strength is determined by the mass of the muscle and its ability to recruit motor units.

Gut microbiota

The collective microorganisms (bacteria, archaea, fungi, and viruses) that reside in the gastrointestinal tract.

Gut microbiome

The collective genomes of the gut microbiota.

Short-chain fatty acids

Fatty acids (such as butyrate) that are produced by the gut microbiota during the fermentation of partially digestible and indigestible carbohydrates; the highest levels of short-chain fatty acids are found in the proximal colon, where they are used locally by enterocytes or transported across the gut epithelium into the bloodstream.

Intestinal permeability

The capacity of material to pass from the lumen of the gastrointestinal tract through the cells lining the gut wall into the rest of the body.


Also known as endotoxin; an active component of the cell wall of Gram-negative bacteria originating from food intake and/or the microbiota of the oral cavity and gut.

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