First-time Marathon Training May Reverse Aortic Aging

Patrice Wendling

January 09, 2020

Training for and completing a marathon was associated with reductions in aortic stiffness and blood pressure that amounted to trimming about 4 years off the arterial age of novice runners, a new study shows.

"The take-home message is that it is possible to reverse age-related vascular stiffening through simple exercise intervention," senior author Charlotte Manisty, MD, University College London and Barts Heart Centre, London, told | Medscape Cardiology.

"What we don't know is how to sustain those effects or what the threshold of exercise needed is to deliver those benefits and those are the areas we need to explore further in the future."

The study was published January 7 in the Journal of the American College of Cardiology.

Aging is associated with progressive stiffening in larger arteries; however, previous work has shown that lifelong athletes have more distensible peripheral arteries and that even 3 months of supervised aerobic exercise benefits peripheral artery stiffness and brachial blood pressure.

The study sought to assess arterial stiffness in the aorta, rather than peripheral vessels, because it is a stronger prognostic marker and more closely associated with the natural aging process, the authors note.

Manisty and her colleagues studied 138 healthy, first-time marathon runners from the 2016 and 2017 London Marathon, who had no significant medical history and were running for not more than 2 hours a week at baseline. Their mean age was 37 years (range, 21 - 69 years) and 49% were men.

All participants were advised to follow the Beginner's Training Plan provided by the marathon, which consists of approximately 3 runs per week that increase in difficulty for a 17-week period leading up to the race. Participants could also follow alternative higher-intensity or longer training plans.

The average marathon running time was 5.4 hours for women and 4.5 hours for men, which is consistent with a training schedule of 6 to 13 miles per week.

Performance times were "suggestive of achievable exercise doses in real-world novice participants — approximately 30 min slower than the average completion time for the London Marathon," the authors note.

Participants were assessed 176 days before and 16 days after completing the race. Change in arterial stiffness was assessed at three levels of the thoracic aorta using cardiac MRI, with the operator blinded to the scan timing.

For the baseline ascending, proximal descending, and diaphragmatic descending aorta, a decade of aging resulted in a decrease in distensibility of 2.3, 1.9, and 3.1 × 10–3 mm Hg–1 and an increase in β-stiffness of 27%, 22%, and 16%, respectively.

After the marathon, both brachial and aortic systolic blood pressure were reduced by 4 mm Hg (P < .01 and P <.001, respectively), a magnitude comparable to first-line antihypertensive medications, Manisty observed.

Distensibility did not change in the ascending aorta (P = .14), but increased by 9% and 16% in the proximal descending and diaphragmatic descending aorta (P = .009 and P = .002, respectively).

The change in distensibility was independent of the change in mean arterial pressures. β-stiffness, a pressure-independent measure of arterial stiffness, showed less pronounced but similar regional trends.

The changes in distensibility translated to a reduction in biological aortic age of 1.5 years (95% CI, –0.9 to 5.4 years; P = .16), 3.9 years (95% CI, 1.1 to 7.6 years; P = .009), and 4.0 years (95% CI, 1.7 to 8.0 years; P = .002) in the ascending, proximal descending, and diaphragmatic descending aorta, respectively.

When estimated from β-stiffness, biological age was reduced by 0 years, 2.4 years, and 3.4 years, respectively, and achieved statistical significance only for the diaphragmatic descending aorta (95% CI, 0.1 - 6.2 years; P = .04).

The selective change in distensibility between aortic segments may be related to their composition, Manisty suggested. The proximal aorta media has a higher elastin/collagen ratio, whereas the distal aorta media contain a higher proportion of smooth muscle.

"It may be more easy to influence the distal aorta, whereas proximally, it's less modifiable; we think that's why it is but we're not certain," she said.

In contrast to previous studies showing less pronounced effects of exercise training in older adults and hypertensives, changes in aortic stiffness were greater in older, male runners with higher baseline blood pressure.

"We were slightly surprised by the finding, but it did seem to be a consistent message," Manisty observed. "It didn't matter how we corrected for age or baseline blood pressure; all these changes were significantly greater in those particular groups."

"In patients who have had hypertension for many years, possibly some of the changes in aortic stiffening become irreversible once you get significant fibrosis in your arteries," she said. "Therefore, in healthy volunteers who are older, it is possible that we were intervening before those changes became irreversible."

In an accompanying editorial, Julio Chirinos, MD, PhD, Hospital of the University of Pennsylvania, Philadelphia, applauded the investigators for executing a "detailed study of an important problem, using state-of-the-art methods in an innovative setting."

Marathons attract millions of people every year with low cardiac arrest rates of about one in 100,000 and support a multibillion-dollar industry, he observed.

The lack of a control group, however, limits the interpretation of some findings, in particular the more pronounced reduction in aortic stiffness among older participants with elevated blood pressure, which may have resulted from regression to the mean, Chirinos said.

"Moreover, successful marathon runners tend to be committed, health conscious, and adherent to training routines, which they must successfully endure without injuries, limiting the generalizability of these findings," he noted.

Despite these limitations, the findings "are important and add to the body of evidence supporting beneficial effects of exercise on multiple aging phenotypes," he said.

Exercise, however, remains underutilized and challenging to implement on a large scale, Chirinos added.

"Perhaps the contemporary marathon can teach us some lessons about exploiting the confluence of interests of the general public, media, industry, scientific community, and government to accomplish worthy goals at the individual and societal levels," he concluded.

The Marathon study was funded by the British Heart Foundation, Cardiac Risk in the Young, and the Barts Cardiovascular Biomedical Research Centre; and received cardiopulmonary exercise training equipment and technical support from COSMED. Manisty is supported by University College London Hospitals, NIHR Biomedical Research Centre, and the Biomedical Research Unit at Barts Hospital . Coauthor disclosures are listed in the paper.

Chirinos is supported by grants from the National Institutes of Health (NIH); has served as a consultant for Sanifit, Bayer, Bristol-Myers Squibb, OPKO Healthcare, Ironwood, Akros Pharma, Merck, Pfizer, Edwards Lifesciences, Microsoft, and Fukuda-Denshi; and has received research grants from the NlH, American College of Radiology Network, Fukuda Denshi, Bristol-Myers Squibb, and Microsoft. He is also an inventor listed in University of Pennsylvania patent applications for the use of inorganic nitrates/nitrites for the treatment of heart failure with preserved ejection fraction and neoepitope-based collagen biomarkers of tissue fibrosis in heart failure.

J Am Coll Cardiol. 2020;75:60-71 and 72-75. Abstract, Editorial

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