Mohlenkamp 28/7/08 11:54 am Page 25
Risk Stratification for Coronary Artery Disease in Marathon Runners
Coronary Artery Calcium
Figure 2: Prevalence of Coronary Artery Calcium in
CAC is a measure of the extent of total coronary atherosclerosis as it closely
Marathon Runners
correlates with total coronary plaque burden.
31
It is not an index for stenosis
50
severity at the site of CAC, but an increasing CAC burden increases the
likelihood of a significant and potentially vulnerable lesion somewhere else
in the coronary tree. This concept seems to hold in marathon runners.
33
The
40
CAC score has been suggested to have value for improved risk stratification
in intermediate-risk subjects
31
and to add prognostic information beyond 30
established CV risk factors in the general population.
40
Historically, the CAC
alence (%) *
score is classified into groups of 0–10 (none to minimal), 10–100 (mild),
*
Prev
20
100–400 (moderate), 400–1,000 (severe) and >1,000 (extensive).
41
As age *
and gender are the main determinants of CAC burden, a CAC value >75th
10
age- and sex-specific percentile is also advocated for clinical use in addition
to absolute score values.
5
0
Zero CAC CAC >100 CAC >75th percentile
Coronary Atherosclerosis in Marathon Runners
Marathon runners Controls matched by age Controls matched by age + RF
In the 1970s, marathon running was still believed to induce ‘immunity
* p<0.03 versus marathon runners
against coronary atherosclerosis’, a theory referred to as the ‘Bassler
Hypothesis’. This hypothesis was invalidated in the late 1970s and early
Marathon runners have a higher rate of no CAC compared with age-matched controls, indicating that regular
marathon running may delay or even prevent atherosclerosis onset in runners free from atherosclerosis.
1980s, initially by Noakes et al.,
42
then by others.
35,43
It is now established
However, runners have a very similar prevalence of CAC >100 and CAC >75th percentile, which is even higher
that coronary atherosclerosis accounts for the majority of CV events in
compared with controls matched by age and risk factors. These controls may have had lifelong protection from
the atherosclerotic effect of risk factor exposure, while marathon runners may have had a more unfavourable
older athletes.
13,15
Interestingly, studies of exercise-related acute risk factor profile earlier in life. CAC = coronary artery calcium; RF = risk factors.
myocardial infarction demonstrate less extensive CAD in sport participants
than in controls,
44,45
which may reflect either selection bias for less severe CV risk in marathon runners may be underestimated if it is assessed
atherosclerosis in those capable of exercising at high intensity or the ability based on established risk factors alone.
of exercise to provoke events in individuals with less severe disease.
6
Myocardial Late Gadolinium Enhancement
In the Marathon Study, we have measured the prevalence and extent of Using cardiac magnetic resonance imaging (cMRI), the prevalence of
calcified coronary atherosclerosis and found an unexpectedly high CAC myocardial damage can be directly visualised by late myocardial
burden that did not differ from that in age-matched controls from an enhancement after infusion of gadolinium. ‘Myocardial damage’ is a term
unselected general population (see Figure 2) even though the that we use here to summarise a variety of causes that can contribute to
Framingham risk score was only half of that in age-matched controls this imaging phenomenon, such as myocardial infarction, myocarditis,
(7.0±3.6 versus 14.3±8.2% in 10 years; p<0.0001; see Figure 1). When cardiomyopathy and vasculitis.
46
Myocardial late gadolinium enhancement
the CAC score in marathon runners was compared with that in males (LGE) has been shown to be associated with an impaired prognosis in a
from the general population with a similar risk factor profile, marathon population-based cohort including many subjects with known CAD.
47
runners had an even higher CAC score. A CAC score >100 was present
in 36% of runners. A CAC score below 15, which has been suggested as Out of 102 runners who were studied with cMRI, 12 (12%) had
a threshold below which high-intensity sports such as marathon running evidence of LGE.
22
This is a three-fold higher prevalence compared with
are safely recommendable,
32
was found in only 43% of runners. an age-matched control group derived from a CV screening
programme (4%).
48
The extent of CAC burden and the number of
We found no association of CAC burden with any of the exercise-related marathons completed were independent predictors of LGE. The
variables such as numbers of marathon completed, training mileage and mechanisms underlying this observation are as yet unclear. Coronary
frequency or years of regular marathon running. Hence, currently it is microembolisation from epicardial plaque material after superficial
unclear whether frequent exhaustive exercise such as marathon running plaque fissuring or erosion due to epicardial shear stress and mechanical
has direct pro-atherosclerotic effects. This is unlikely given the forces may play a role.
49
Furthermore, microthrombi from the surface of
substantial evidence on the benefits of regular physical activity on epicardial plaque or due to an increased systemic thrombogenicity, in
coronary atherosclerosis, but no epidemiological studies have so far part triggered by catecholamine-induced platelet aggregation or an
examined individuals engaged in such prodigious amounts of exercise. It imbalance in fibrinolytic/prothrombotic factors,
5,51
may obstruct
is possible that the observed mismatch between a low risk factor burden intra-myocardial microvessels. Repeat inflammation during exhaustive
and a high CAC score may be explained by a higher risk factor exposure marathon running and its required training may challenge endothelial
earlier in life in marathon runners, and supports the limitations of antioxidative capacity, impair intramyocardial microvascular integrity and
conventional risk-stratification algorithms in master athletes. accelerate the atherosclerotic disease process.
Alternatively, repetitive bouts of exhaustive exercise with the associated
oxidant and inflammatory cytokine bursts may have contributed to the Therefore, we cannot exclude the possibility that frequent marathon
development of coronary atherosclerosis. The CAC burden is an running itself has contributed to myocardial damage in our runners via
independent predictor for myocardial damage and seems to contain mechanisms that still need to be determined. Irrespective of their
prognostic information in marathon runners like in other asymptomatic aetiology, such areas of damaged myocardium could be the substrate for
cohorts (see below).
39,31
The implication of our findings is that the true catecholamine-triggered arrhythmic activity during exercise.
EUROPEAN CARDIOLOGY 25
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116