Physicians' Academy for Cardiovascular Education

Exercise training is beneficial in many conditions but employed too little

Literature - Schuler G, Adams V, Goto Y. - Eur Heart J. 2013 Apr 7.

Role of exercise in the prevention of cardiovascular disease: results, mechanisms, and new perspectives.

Schuler G, Adams V, Goto Y.
Eur Heart J. 2013 Apr 7.


The first scientific evidence that exercise training (ET) might be good for one came in 1953 from a study that showed that the incidence of coronary artery disease (CAD) was less in bus conductors than in sedentary drivers of the same age. Subsequent larger studies have confirmed that the higher the level of physical fitness, the less likely an individual is to suffer from premature cardiovascular death. We here summarise the review article that discusses current knowledge on the effect of ET on cardiovascular disease (CVD), including the molecular mechanisms underlying these effects and strategies to improve compliance to guidelines that stimulate regular exercise.

Clinical studies proving the effectiveness of exercise training in cardiovascular disease prevention

Many studies have found an inverse relationship between physical activity and CVD mortality and all-cause mortality. Guidelines therefore recommend regular physical activity for primary CVD prevention. Studies that grouped participants in categories of different volumes of physical activity behaviour found inverse dose-response relations between degree of physical activity and all-cause mortality, CVD mortality and risk of CAD. 15 minutes of daily exercise is already associated with a reduction of all-cause mortality or CAD risk.
In diabetic individuals, the benefit of lifestyle intervention involving physical activity to improve glucose and insulin homeostasis and CVD risk factors has been established. In obese patients, high-calorie-expenditure exercise yielded more weight loss and favourable CVD risk profiles than did standard exercise as recommended in cardiac rehabilitation (CR) protocols.
Physical activity also appears worthwhile in secondary prevention, as inverse dose-response relations have been described between CR session attendance and mortality or myocardial infarction (MI) risk. The specific contribution of ET on the observed reduction of mortality was however not investigated in these studies. More recently, now that reperfusion therapy is widespread, the benefit of CR programs on all-cause mortality, MI and re-admission has not consistently been confirmed in randomized trials. Moreover, since modern CR programs also include patient education and counselling, which may result in reduction of major risk factors, it is less clear how much of the reduction in CVD/CAD risk is attributable to ET.

Molecular mechanisms

The underlying molecular mechanisms that explain the benefits of ET include alterations in the myocardium, skeletal muscle and the vascular system. The latter will be discussed in more detail.
Endothelial function and nitric oxide bioavailability
A key molecular consequence of regular exercise is the increase of vascular nitric oxide (NO) levels. NO causes vasodilatation, with lower peripheral resistance and higher perfusion as a result. Physical exercise upregulates endothelial NO synthase (eNOS) activity, which produces NO, through a complex signalling network on the luminal side of endothelial cells. HDL also activates eNOS, a reaction that seems impaired in CVD patients. ET furthermore impacts the generation and scavenging of reactive oxygen species.
Endothelial repair by stem cells
Endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) have the capacity for vascular regeneration and endothelial repair. ET appears to mobilise EPCs and MSCs from the bone marrow into the circulation, to a site of damaged endothelium. Activation of eNOS in the presence of multiple mobilising factors seems to be at the heart of this process.
Arterial stiffness
Systolic hypertension, left-ventricular hypertrophy and chronic heart failure are associated with increased arterial stiffness. Performing regular aerobic exercise decreases arterial stiffness. The underlying mechanisms are not clearly understood, but likely involve structural changes in collagen and elastin. Also advanced glycation end-products (AGEs) might be involved. AGEs normally accumulate with age, causing cross-linking of collagen and subsequently arterial stiffness. An inverse relation between AGE content in the skin and muscle strength has been described.
Impact of exercise training on microRNA
MicroRNAs (miRNAs) modulate the expression of multiple messenger RNA targets that often have related functions. Misregulation of certain miRNAs has been identified in CVDs. Recent studies reported the involvement of miRNAs in the cardiovascular adaptive response to ET in different model systems.  
Collateral growth
Animal studies have provided strong evidence that chronic intensive physical exercise yields an increased collateral growth (arteriogenesis) in the myocardium. Human studies have given conflicting results. Angiogenesis is thought to involve recruitment of progenitor cells and release of specific growth factors promoting collateral growth.

Limitations and new strategies to increase compliance

Although knowledge on exercise as a therapeutic intervention is far from complete, its benefit for a wide range of patients is convincing. It is unclear how this benefit can be extended to the general population, as compliance to guidelines is limited. Interventions have been recommended to improve physical activity on a large scale. It turns out there are many reasons not to exercise; thus, it is unwarranted to assume that any form of counselling will significantly and permanently change the lack of compliance to exercise guidelines.
It is suggested that an early adaptation to an active lifestyle may prevail throughout adulthood. However, evidence suggests that termination of school-based exercise under continuous supervision and encouragement causes the compliance to the active lifestyle to drop rapidly. It appears very difficult or impossible to change personal traits by prolonged training, even in young children. It might help to involve the child’s family, but logistic challenges should not be underestimated.  
It is interesting to draw a parallel to the reduction of tobacco consumption, which was successful due to a combination of interventions. While tobacco consumption is susceptible to negative incentives, efforts to stimulate physical activity should probably involve positive incentives. To a large extent these remain to be developed, or improved. When implementing rewards, e.g. by health insurance companies, it might be a challenge how ´adherence to an active lifestyle´ can be measured. After clearing some legal hurdles this might be done by assessment of physical fitness, which is standardised and of established predictive value.
In addition, recognising ´deconditioning´ as a syndrome or diagnosis would facilitate the education of the general population, as well as the medical community on the benefits of exercise training as a treatment option for multiple diseases.
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