Running to Keep Ahead of Coronary Artery Disease
By Michael H. Crawford, MD
Professor of Medicine, Lucy Stern Chair in Cardiology, University of California, San Francisco
- From 1,105 subjects meeting the study entry criteria, the authors enrolled a random sample of 558 (191 lifelong athletes, 191 late-onset athletes, and 176 non-athletic controls). The mean age of the entire population was 56 years and was similar in all three subgroups, as were blood pressure, cholesterol, hemoglobin A1c, and a family history of coronary atherosclerosis (CA).
- Peak oxygen uptake measurements were significantly higher in the athlete cohort when compared to the controls. An adjusted multivariate analysis showed life-long endurance training was associated with one or more coronary plaques, one or more proximal plaques, one or more calcified plaques, one or more calcified proximal plaques, one or more non-calcified plaques, one or more non-calcified proximal plaques, and one or more mixed plaques as compared to controls.
- The authors admitted there might be a J-shaped curve with exercise in relation to CA. Specifically, going from none to mild to moderate exercise training might progressively lower risk for CA, but prolonged extreme endurance exercise may be harmful and increase the risk of CA.
SYNOPSIS: In this cross-sectional review of the Master Athlete Heart study, the authors found lifelong endurance sport participation was not associated with a more favorable coronary plaque composition vs. a healthy lifestyle. Lifelong endurance athletes exhibited more coronary plaques.
SOURCE: De Bosscher R, Dausin C, Claus P, et al. Lifelong endurance exercise and its relation with coronary atherosclerosis. Eur Heart J 2023;44:2388-2399.
Is it possible that a highly trained endurance athlete could be living with more coronary atherosclerosis (CA), but still experience fewer cardiovascular events (CVEs)? Investigators from the Master Athlete Heart (MAH) study hypothesized lifelong endurance exercise would be associated with fewer non-calcified and mixed plaques compared to subjects with a healthy lifestyle, but who did not engage in regular endurance training.
MAH was a multicenter, prospective cohort study of men age 45-70 years who engaged in lifelong endurance exercise (i.e., started at younger than age 30 years) or late-onset regular endurance exercise (i.e., older than age 30 years), along with men who were physically active but not regularly engaging in endurance exercise. Exclusion criteria included a history of CV disease, risk factors for CA, current or past smoking, or a body mass index heavier than 27 kg/m2.
From 1,105 subjects meeting the study entry criteria, the authors enrolled a random sample of 558 (191 lifelong athletes, 191 late-onset athletes, and 176 non-athletic controls). Body fat percentage was measured by dual-energy X-ray absorptiometry, aerobic capacity, and peak oxygen uptake (VO2peak) was measured by a cardiopulmonary bicycle exercise test. Researchers used cardiac CT to measure coronary calcium Agatston scores, contrast coronary CT angiography (CTCA), and coronary plaque composition. The primary endpoint was the prevalence of coronary plaques and their composition.
The mean age of the entire population was 56 years and was similar in all three subgroups, as were blood pressure, cholesterol, hemoglobin A1c, and a family history of CA. The athletes mainly were cyclists. Seventy-seven percent of the controls performed three or fewer hours of exercise a week — mainly running. The rest did not exercise regularly.
VO2peak measurements were significantly higher in the athlete cohort when compared to the controls (48 mL/min/kg and 46 mL/min/kg when compared to a measurement of 37 mL/min/kg in the controls). An adjusted multivariate analysis showed lifelong endurance training was associated with one or more coronary plaques (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.17-2.94), one or more proximal plaques (OR, 1.96; 95% CI, 1.24-3.11), one or more calcified plaques (OR, 1.58; 95% CI, 1.01-2.49), one or more calcified proximal plaques (OR, 2.07; 95% CI, 1.28-3.35), one or more non-calcified plaques (OR, 1.95; 95% CI, 1.12-3.40), one or more non-calcified proximal plaques (OR, 2.8; 95% CI, 1.39-5.65), and one or more mixed plaques (OR, 1.78; 95% CI, 1.06-2.99) as compared to controls. Vulnerable plaques were uncommon in all three groups. However, in lifelong athletes, there was a lower prevalence (OR, 0.11; 95% CI, 0.01-0.98).
The authors concluded lifelong endurance athletes were living with more coronary plaques than non-athletes, and those plaques were more often non-calcified and in proximal locations.
In the 1980s, James Fixx, a running proponent and popular author, dropped dead while running at age 52. Tests revealed Fixx had been living with severe three-vessel disease. Fixx also was overweight and smoked cigarettes as a younger man.1 Nevertheless, the concept that serious endurance training would protect one from CA was shaken. CT studies of Egyptian mummies showed extensive arterial calcifications, suggesting atherosclerosis was inevitable.2 More recently, some researchers have found regular endurance exercise paradoxically increases the prevalence of CA compared to more sedentary controls.3
Contrast this to the data indicating regular exercise lowers blood pressure and cholesterol levels, prevents diabetes and myocardial infarction, and extends life expectancy.4 In addition, studies have shown engaging in more physical activity is associated with fewer CVEs.5 The hypothesis that would explain the paradox of more plaque, yet lower CVEs, was that plaque in physically fit subjects is more stable.
This report from the MAH study explores this hypothesis and finds the opposite is the case. The lifelong endurance athletes not only showed more plaque, but it was more likely to be non-calcified proximal plaque, which presumably is more likely to rupture. Thus, plaque composition does not seem to explain the reduction in CVEs in fit individuals shown in other studies.
For this topic, this was a relatively large study. Also, all three groups were fitter than the average individual, and subjects were excluded if they were living with classic risk factors for CA. Additionally, the overall plaque burden was low in all three groups. Still, a major limitation of this study was the lack of outcome data, which the MAH investigators plan on collecting. Other limitations were the fact all subjects were white men who denied using performance-enhancing drugs, but researchers did not perform drug tests. Although they used stringent inclusion criteria to eliminate those with CA risk factors, the authors did not monitor blood pressure or collect lipid panels. In addition, investigators did not ascertain training levels by questionnaires. Finally, the cross-sectional design of the study precludes concluding causation.
However, the authors admitted there might be a J-shaped curve with exercise in relation to CA. Specifically, going from none to mild to moderate exercise training might progressively lower risk for CA, but prolonged extreme endurance exercise may be harmful and increase the risk of CA. We await further data on this fascinating topic.
- Altman LK. The doctor’s world; James Fixx, the enigma of heart disease. The New York Times. July 24, 1984. https://www.nytimes.com/1984/07/24/science/the-doctor-s-world-james-fixx-the-enigma-of-heart-disease.html
- Thompson RC, Allam AH, Zink A, et al. Computed tomographic evidence of atherosclerosis in the mummified remains of humans from around the world. Glob Heart 2014;9:187-196.
- De Bosscher R, Dausin C, Claus P, et al. Endurance exercise and the risk of cardiovascular pathology in men: A comparison between lifelong and late-onset endurance training and a non-athletic lifestyle - rationale and design of the Master@Heart study, a prospective cohort trial. BMJ Open Sport Exerc Med 2021;7:e001048.
- Johns Hopkins Medicine. Exercise and the heart. https://www.hopkinsmedicine.org/health/wellness-and-prevention/exercise-and-the-heart
- Mora S, Cook N, Buring JE, et al. Physical activity and reduced risk of cardiovascular events: Potential mediating mechanisms. Circulation 2007;116:2110-2118.
In this cross-sectional review of the Master Athlete Heart study, the authors found lifelong endurance sport participation was not associated with a more favorable coronary plaque composition vs. a healthy lifestyle. Lifelong endurance athletes exhibited more coronary plaques.
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