Journal of Applied Physiology
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J Appl Physiol 105: 771, 2008; doi:10.1152/japplphysiol.90348.2008
8750-7587/08 $8.00
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LETTER TO THE EDITOR

Commentary on Viewpoint: Exercise and cardiovascular risk reduction: Time to update the rationale for exercise?

TO THE EDITOR: Since the 1990s, endothelial dysfunction has been increasingly recognized as a conditio sine qua non for atherogenesis (5a) and several studies documented its prognostic relevance for cardiovascular morbidity and mortality (6). Hence it is today regarded as an excellent surrogate endpoint in clinical studies.

The viewpoint article by Green et al. (3) in the Journal of Applied Physiology is a timely reminder that physical exercise has a direct beneficial effect on preservation of normal endothelial function independent from its effects on classical risk factors. This concept has evolved from a series of studies on the effects of exercise training in patients with coronary artery disease performed over the last decade. Among others, our Leipzig group was able to show that regular endurance exercise in patients with stable coronary artery disease without classical risk factors (i.e., diabetes, hyperlipidemia, smoking, hypertension) leads to improved endothelial function (5), higher expression and activity of the endothelial nitric oxide synthase (4), reduced ROS generation via vascular NADPH oxidases (1), and consequently an improved NO bioavailability.

The adequate stimulus by which exercise is able to mediate the endothelium-protective effects is most likely the intermittent increase in laminar shear stress associated with the increase in coronary and peripheral blood flow during endurance exercise—a pleiotropic mechanism that can not yet be activated pharmacologically. Although there certainly is a dose-response relationship between exercise time/day (2) and effects on endothelium-dependent vasodilation, it is the change from sedentary to active that has the greatest effect. It is now time to prescribe exercise to our patients as one of the most potent anti-atherogenic interventions.

FOOTNOTES


Address for reprint requests and other correspondence: S. Gielen, Univ. of Leipzig-Heart Center, Dept. of Internal Medicine/Cardiology, Strümpellstr. 39, 04289 Leipzig, Germany (e-mail: stephan.gielen{at}medizin.uni-leipzig.de)

REFERENCES

  1. Adams V, Linke A, Kränkel N, Erbs S, Gielen S, Möbius-Winkler S, Gummert JF, Mohr FW, Schuler G, Hambrecht R. Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease. Circulation 111: 555–562, 2005.[Abstract/Free Full Text]
  2. Gielen S, Erbs S, Linke A, Mobius-Winkler S, Schuler G, Hambrecht R. Home-based versus hospital-based exercise programs in patients with coronary artery disease: effects on coronary vasomotion. Am Heart J 145: E3, 2003.[CrossRef][Medline]
  3. Green DJ, O'Driscoll G, Joyner MJ, Cable NT. Viewpoint: Exercise and cardiovascular risk reduction: Time to update the rationale for exercise? J Appl Physiol; doi:10.1152/japplphysiol.01028.2007.[Free Full Text]
  4. Hambrecht R, Adams V, Erbs S, Linke A, Kränkel N, Shu Y, Baither Y, Gielen S, Thiele H, Gummert JF, Mohr FW, Schuler G. Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation 107: 3152–3158, 2003.[Abstract/Free Full Text]
  5. Hambrecht R, Wolff A, Gielen S, Linke A, Hofer J, Erbs S, Schoene N, Schuler G. Effect of exercise on coronary endothelial function in patients with coronary artery disease. N Engl J Med 342: 454–460, 2000.[Abstract/Free Full Text]
  6. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362: 801–809, 1993.[CrossRef][Web of Science][Medline]
  7. Schächinger V, Britten MB, Zeiher A. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 101: 1899–1906, 2000.[Abstract/Free Full Text]

Stephan Gielen1
Rainer Hambrecht2
Gerhard C. Schuler1
 1Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center, Leipzig; 2Department of Cardiology and Angiology, Klinikum Links der Weser, Bremen, Germany





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