BRINGING SCIENCE TO TREATMENT

Pre-race aspirin: could it keep the grim reaper at bay?

Andrew Hamilton looks at the pros and cons of using pre-race aspirin in older marathon runners and other endurance athletes.

Peer-reviewed research supports, beyond doubt, the benefits of exercise in terms of health and longevity. However, sports clinicians seeking the best outcomes for clients should be cognizant that despite the health benefits, there are risks too – sports injury, of course, being one of these. But injury is not the only adverse health outcome that afflicts athletes. Although rare, vigorous exercise, particularly in middle-aged and older athletes, brings an associated risk of an adverse cardiac event.

The heart health conundrum

Regular, moderate-vigorous intensity exercise is known to confer a significant protective effect on cardiovascular health. A physically active lifestyle is pivotal in the prevention of cardiovascular disease (CVD) in both healthy adults and those with risk factors for CVD(1,2). Despite these benefits, however, something of a conundrum exists. While exercise confers very significant heart-health benefits, it also carries a short-term risk of an adverse cardiac event during the exercise itself.

The short-term risk during exercise is of more relevance for older athletes who take up sport later in life. The physiological loading on a previously sedentary body can bring to the fore a hitherto hidden problem relating to cardiovascular health. This explains why age is a significant factor in pre-exercise risk assessment screening (to reduce the risk of an adverse cardiovascular event) by bodies such as the American College of Sports Medicine(3).

Long-term and short-term health collision

Events such as cycling rallies, fun runs, and marathon/half-marathon races are where long-term health aspirations and short-term health risks often collide. Training for a target event tests the physiology of a previously sedentary person. These risks are likely to be higher during the actual race or event when the participant pushes himself further and harder than during training. Although very small in absolute terms, this increased risk is borne out by the data. While endurance exercise, such as marathon training, is cardioprotective, since the year 2000, there’s been a 2.3-fold increase in the frequency of race-related cardiac arrests and sudden deaths in middle-aged men (40 and over)(2).

Protective measures with aspirin?

The short-term risks of a life-threatening cardiac event during exercise, while low, cannot be ignored. The use of aspirin, taken before exercise, could mitigate these risks for older athletes participating in endurance events.

Researchers at Harvard University conducted a literature review of studies related to acute cardiac events, such as stroke and heart attack, during marathons and found that: (4)

  • Male runners were more susceptible to cardiac arrest than females.
  • Running a marathon was riskier than a half marathon.
  • There were 50 cardiac arrests in runners, 86% of whom were male with an average age of 42 years.
  • The leading cause of sudden death in at endurance events in those over the age of 40 was atherosclerotic heart disease.

Of note, elevated levels of inflammatory biomarkers and hypercoagulability were frequently observed in many male runners of the same average age without cardiac symptoms. Worryingly, these biomarkers are strongly predictive of a cardiac event, such as a heart attack.  This study suggests that older runners may unwittingly be at an increased risk of a cardiac event during a race.

Why do endurance events place older athletes at higher risk? Most likely, the additional physical stress combined with more turbulent blood flow leads a clot to rupture from the wall of a larger artery. The researchers concluded therefore that,

“The use of pre-race, low-dose aspirin is recommended in older male runners; the temporary reduction in blood stickiness provided by aspirin is an effective way of reducing the risk of a clot-induced heart attack during a running event such as a marathon” (see figure 1)

Figure 1: Mode of action of aspirin

Aspirin at low doses (75-150mgs) inhibits the action of COX-1 enzyme, slowing the conversion of arachidonic acid to thromboxane – a lipid that increases the tendency of blood platelets to stick together in the wall of the artery. The overall effect is to decrease blood ‘stickiness’. High-dose aspirin inhibits both COX-1 and COX-2 enzymes. The long-term use of COX-2-inhibiting medication is undesirable as it can decrease the production of prostacyclin in blood vessel walls, potentially leading to increased clot formation and higher blood pressure(5).

More support for aspirin use

Low-does daily aspirin use by otherwise healthy middle-aged males reduces the risk of an acute cardiac event by 44%(6). Thus, the International Marathon Medical Directors Association (IMMDA) recommends that males over 40-years-old consult with their physician about the use of pre-race aspirin(7). Running guru Professor Tim Noakes concurred with this recommendation in a 2017 paper on this topic(8). He further explained the benefit of aspirin use by older habitual marathoners with higher than desirable levels of atherosclerotic plaque. Running multiple races increases the overall risk of an acute cardiac event in this population, despite an active lifestyle.

Aspirin recommendations and cautions

While sports clinicians should be aware of the potential benefits of pre-race, low-dose (75-150mgs) aspirin for older clients, all athletes should consult their physician before its use. Health professionals caution against the long-term indiscriminate use of aspirin because of the risk of gastric and other bleeds. Whereas the benefits of long-term, daily aspirin use in patients with an existing cardiovascular condition are well documented, the evidence for benefits in otherwise healthy middle-aged individuals is far less convincing(9). A joint position statement by the American Heart Association and the American College of Cardiology recommended the long-term use of aspirin only in those whose 10-year risk of a cardiovascular event was greater than 10%. Physicians should evaluate those with a 10-year risk between 5% and 10% on a case-by-case basis(10). Aspirin use is also NOT advised in the following individuals(11):

  • Those with clotting or bleeding disorders.
  • Those taking another anti-inflammatory medication (eg, Ibuprofen).
  • Those with a known allergy to aspirin.
  • Those taking angiotensin converting enzyme (ACE) inhibitors.
  • Those taking diuretics or with renal insufficiency.

That said, there is no evidence in the literature that the single use of pre-race, low-dose of aspirin poses any risk or drawback to the older athlete, which is why the International Marathon Medical Directors Association has recommended its use. As Amby Burfoot, the 1968 Boston Marathon champion, veteran runner, and champion of aspirin put it, “Just because the cardiac risk of marathon running is low, it doesn’t mean it can’t be lower!”

References

  1. Prog Cardiovasc Dis. 2018 Nov – Dec;61(5-6):484-490
  2. Circ Res. 2019 Mar;124(5):799-815
  3. J Neurosci. 2019 Jan 9; 39(2): 197–198
  4. Open Heart. 2015 Jul 2;2(1):e000102
  5. Science 2102. (336)6087 1386-1387
  6. Engl J Med. 1989 Jul 20; 321(3):129-35
  7. Siegel AJ. IMMDA Advisory, 2015: pre-race aspirin to prevent heart attack and/or cardiac arrest during long distance running
  8. J Sports Med. 2017 Nov; 51(22): 1579–1581
  9. Circulation. 2016;134:1579–1594
  10. Circulation. 2015;132:691–718
  11. J Am Coll Cardio 2005. (46)6, 963-966
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