JCM 200048

Does sports activity enhance the risk of sudden

cardiac death?
Domenico Corrado, Cristina Basso, Maurizio Schiavon and
Gaetano Thiene
Vigorous physical exercise may precipitate acute fatalities
in both adults and young competitive athletes with
concealed heart diseases. However, the riskbenefit ratio
of physical exercise differs among these two age groups. In
adults, physical activity can be regarded as a double-edged
sword: vigorous exertion increases the incidence of acute
coronary events in individuals who did not exercise
regularly, whereas habitual physical activity reduces the
overall risk of myocardial infarction and sudden coronary
death by preventing development and progression of
atherosclerotic coronary artery disease. On the other hand,
in adolescents and young adults sports activity is
associated with a significant increase of the risk of sudden
death. Sport is not per se the cause of the enhanced
mortality in this age group; rather, it acts as a trigger of
cardiac arrest in those athletes who are affected by silent
cardiovascular conditions, mainly cardiomyopathy,

Introduction
Physical inactivity is a leading health risk factor, having
strong association with morbidity and mortality from
cardiovascular causes. Regular physical exercise is recommended by the medical community because it offers the
potential to prevent the development of atherosclerotic
coronary artery disease and to decrease the incidence of
coronary artery disease events [1,2]. On the other hand,
vigorous exertion may act as a trigger of acute myocardial
infarction and sudden cardiac death in susceptible individuals [3,4].
The riskbenefit ratio of physical exercise differs
between adults and young competitive athletes [5]. This
may be explained by the different nature of cardiovascular substrates underlying sport-related sudden death in
the two populations. As reported in Table 1, the causes of
sudden death reflect the age of participants. Although
atherosclerotic coronary artery disease accounts for the
vast majority of fatalities in adults (age > 35 years), in
younger athletes a broad spectrum of cardiovascular
substrates (including congenital and inherited heart disorders) has been reported.
This review article will address whether sport activity
enhance the risk of cardiovascular events, with particular
reference to sudden death in young competitive athletes.
1558-2027 ! 2006 Italian Federation of Cardiology

premature coronary artery disease and congenital coronary

anomalies, which predispose to life-threatening ventricular
arrhythmias during physical exercise. J Cardiovasc Med
7:000000 Q 2006 Italian Federation of Cardiology.

Journal of Cardiovascular Medicine 2006, 7:000000

Keywords: athletes, cardiomyopathy, coronary artery disease, sudden death,
ventricular fibrillation
Department of Cardiology and Institute of Pathological Anatomy, University of
Padova; Center for Sports Medicine, Padova, Italy
Correspondence and requests for reprints to Domenico Corrado, MD, PhD,
Department of Cardiology, Via Giustiniani, 2 35121 Padova, Italy
Tel: +39 49 8212322; fax: +39 49 8212309; e-mail: domenica.corrado@unipd.it
Sponsorship: supported in part by the Ministry of Health, Rome, Italy.
Received ??? 2005 Revised ???
Accepted ??? 2005

2005

Cardiovascular risk associated with physical

activity in adults
Several epidemiologic studies have assessed the relationship between physical exercise and the risk of sudden
coronary death in the middle-aged and older population
in which physical activity can be regarded as a doubleedged sword [37]. The available evidence indicates
that there is an increased risk of acute coronary events,
mainly in persons who did not exercise regularly. Cardiac
arrest has been reported to occur significantly more often
during exertion than during more leisurely activity. In the
Rhode Island study the exercise-related sudden death
rate was 7.6 times higher than the hourly death rate
during sedentary activity [6].
In the Seattle study, among previously asymptomatic
individuals the incidence of cardiac arrest during exercise
was 25-fold higher than the incidence at rest or lighter
activity [7]. A similar pattern of increased risk of exerciserelated acute myocardial infarction has been observed.
Vigorous physical exertion has been reported within 1 h
of myocardial infarction in 4 to 10% of cases [8,9]. This
rate is two to 10 times higher than that during sedentary
activity. Although these data suggest that vigorous exertion transiently increases the incidence rate of both
cardiac arrest and myocardial infarction, there is compelling evidence that the benefit of physical activity

AQ1

2 Journal of Cardiovascular Medicine 2006, Vol 7 No 00

Table 1

Cardiovascular causes of sudden death associated with

sports
Adults (age > 35 years):
Atherosclerotic coronary artery disease
Young competitive athletes (age " 35 years):
Hypertrophic cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy
Congenital anomalies of coronary arteries
Myocarditis
Aortic rupture
Valvular disease
Pre-excitation syndromes and conduction diseases
Ion channel disease
Congenital heart disease, operated or unoperated

outweighs the cardiovascular risk. Considerable epidemiologic evidence supports the concept that habitual
sport activity may offer protection over the long term
against cardiovascular events. In the Seattle study, the
relative risk of cardiac arrest was greater during exercise
than at rest for all levels of habitual physical activity, but
the total incidence of cardiac arrest, both at rest and
during exercise, decreased with increasing exercise levels
[7]. Specifically, the overall incidence decreased from 18
events per million person-hours in the least active to only
five in the most active subjects. The risk of an exerciserelated acute myocardial infarction also decreases with
increasing amounts of physical activity [9]. Regular exercise is deemed to prevent development and progression
of atherosclerotic coronary artery disease by favorable
effects on lipid metabolism and weight reduction and to
enhance both coronary artery plaque and myocardial
electrical stability [1012].

Cardiovascular risk in young

competitive athletes
Little is known about the risk of sudden death in young
people engaged in competitive sports [1317]. We
recently tested whether sport activity in adolescents

and young adults provides health benefits as in older

subjects or, instead, enhances the risk of sudden death.
To establish the impact of sport activity on the risk of
sudden death, we examined the incidence and causes of
sudden death in the athletic and non-athletic young
population (12 to 35 years old) of the Veneto Region
of Italy. From 1979 to 1999, there were 300 cases of
sudden death in adolescents and young adults, producing
an overall cohort incidence rate of one per 100 000
persons per year. Fifty-five sudden deaths occurred
among athletes (2.3 per 100 000 per year) and 245 among
non-athletes (0.9 per 100 000 per year), with an estimated
relative risk (RR) of sudden death from all causes of 2.5
[95% confidence interval (CI), 1.83.4; P < 0.0001] AQ2
(Fig. 1). The relative risk of sudden death among athletes
versus non-athletes was 1.95 (95% CI, 1.32.6;
P 0.0001) for men and 2.02 (95% CI, 0.64.9;
P 0.15) for women.
The rates of sudden death by cardiovascular diseases
were 2.1 in 100 000 athletes per year, compared with 0.7
in 100 000 non-athletes per year (RR, 2.8; 95% CI, 1.9
3.7; P < 0.001) (Fig. 1). The estimated RR of cardiovascular sudden death was 2.0 for male athletes (95% CI,
1.42.8; P 0.0001) and 2.6 for female athletes (95% CI,
0.86.4; P 0.06). The cardiovascular causes at highest
risk of sport-related sudden death were anomalous origin
of coronary artery from the wrong coronary sinus
(RR 79), arrhythmogenic right ventricular cardiomyopathy (ARVC) (RR 5.4) and premature coronary artery
disease (RR 2.6) (Fig. 2).
By Poisson multivariate regression analysis, the estimated RRs of sports activity for total sudden death
and cardiovascular sudden death were 1.95 and 2.1,
respectively, whereas the estimated RR of male gender
was 2.5 and 2.8, respectively. The interaction between

Fig. 1

SD per 100 000 person-years

(a) 4.0
3.5
3.0

(b) 4.0
RR = 2.5
CI = 1.83.4
P < 0.001

3.5
3.0

(c) 4.0
RR = 2.8
CI = 1.93.7
P < 0.001

3.5
3.0

2.5

2.5

2.5

2.0

2.0

2.0

1.5

1.5

1.5

1.0

1.0

1.0

0.5

0.5

0.5

RR = 1.7
CI = 0.325.7
P = 0.39 (NS)

0
total

Athletes
Non-Athletes

cardiovascular

non-cardiovascular

Incidence and relative risk (RR) of sudden death (SD) among young athletes and non-athletes from total (a), cardiovascular (b) and noncardiovascular (c) causes. CI, 95% confidence interval.

Risk of sudden death during sport Corrado et al. 3

Fig. 2

SD per 100 000 person-years

(a) 2.0

(c) 2.0

(b) 2.0

Athletes
Non-Athletes
1.5

1.0

1.5

RR = 5.4
CI = 2.511.2
P < 0.001

0.5

1.0

1.5

RR = 2.6
CI = 1.25.1
P < 0.008

0.5

ARVC/D

1.0

RR = 79.0
CI = 103564
P < 0.001

0.5

CAD

CCA

Incidence and relative risk (RR) of sudden death (SD) among young athletes and non-athletes from specific cardiovascular causes. ARVC/D,
arrhythmogenic right ventricular cardiomyopathy/dysplasia; CAD, coronary artery disease; CCA, congenital coronary artery anomalies; CI, 95%
confidence interval.

sports involvement and gender, for both total and cardiovascular sudden death, was not significant.
The Veneto Region study was the first to quantify the
hazard of physical exercise in adolescents and young
adults. The major finding was that competitive sport
activity enhances by 2.5 times the risk of total sudden
death and by 2.8 the risk of cardiovascular sudden death
in young individuals. Sports is not itself the cause of the
enhanced mortality, but it triggers sudden death in those
athletes who are affected by cardiovascular conditions,
such as ARVC, premature coronary artery disease and
anomalous coronary artery origin, which predispose to
life-threatening ventricular arrhythmias during physical
exercise.

Epidemiology of sudden death in young

competitive athletes
The assessment of the precise frequency with which
sudden death occurs in young athletes during organized
competitive sports encounters a number of practical
obstacles and encounters limitations mostly related to
retrospective analysis. Studies in the United States probably led to an underestimation of the true prevalence
of sports-related sudden death because they relied on
reporting from individual schools and institutions, or on
media accounts. In a nationally based survey Van Camp
et al. [18] estimated the prevalence of sudden death in
high-school and college athletes from United States to
be 0.4 per 100 000 athlete-years; estimated rates in male
athletes (aged 13 to 24 years, mean 16.9 # 2.0) were
0.66 per 100 000 high-school athlete-years and 1.45 per
100 000 college athlete-years, and estimated rates in
female athletes (aged 14 to 22 years, mean 16.2 # 2.4)
were 0.12 per 100 000 high-school athlete-years
and 0.28/100 000 college-athlete-years. However, the

methodology employed in that study was largely dependent on news media accounts with the inherent limitations. Maron et al. [19] estimated the prevalence of
cardiovascular sudden death in competitive high school
athletes (age range, 13 to 19 years; mean 16 years) from
Minnesota to be 0.35/100 000 sports participations and
0.46/100 000 individual participants annually (0.77/
100 000 male athletes).
In the Veneto Region study, the incidence of sudden
death by all causes was 2.3 per 100 000 athlete-years and
that of sudden death from cardiovascular diseases was 2.1
per 100 000 athlete-years. The reasons for the higher
mortality rates found in the present study in comparison
with those reported by Maron et al. may include: (1) our
prospective versus their retrospective analysis; (2) different underlying pathologic substrates which, in part,
reflect differences in ethnic and genetic factors; (3)
participation at a higher level of intensity among Italian
competitive athletes; and (4) the higher mean value of the
age in our athlete series (mean age, 23 years) in comparison with US high school and college participants
(mean age 16 years). Ino this regard, it is noteworthy
that the development of phenotypic manifestation and
arrhythmic substrates of most heart diseases at risk of
sudden death during sports, including cardiomyopathies,
premature coronary artery disease, ion channel diseases
(such as Brugada syndrome) and progressive cardiac
conduction disease (such as Lene`gre disease) is agedependent and occurs during young adulthood [20
24]. Therefore, the risk of fatal events in US high-school
and college participants is expected to be lower and may
explain differences with Italian estimates.
Moreover, in the Veneto region study the athletic field
sudden deaths showed a clear gender predilection with

4 Journal of Cardiovascular Medicine 2006, Vol 7 No 00

striking male predominance (male : female ratio, 10 : 1).

This predominance of fatal events in male athletes is
consistent with the findings of previous surveys of
athletic field deaths and has been explained by the fact
that women participate less commonly in competitive
sports programs than men. Accordingly, the prevalence of
sports participation in the young female population in
the Veneto region study was only 25% of that of the male
individuals. However, male gender was itself an independent risk for sudden death in athletes. Men are
usually exposed to generally more intensive training
and greater levels of intensity during athletic competition
than women. Moreover, in the age range of competitive
sports, men have a higher prevalence and/or phenotypic
expression of lethal cardiac diseases, such as hypertrophic cardiomyopathy, ARVC, and premature coronary
artery disease [2123].

Cardiovascular causes of sudden death in

young competitive athletes
ARVC and premature coronary artery disease are the
most common pathologic substrates underlying sudden
death in young athletes in the Veneto region of Italy
[1517]. Other studies in the United States have shown
a higher prevalence of other pathologic substrates such
as hypertrophic cardiomyopathy, anomalous coronary
arteries and myocarditis [14,18]. This discrepancy may
be explained by several factors. There have been no
previous studies like the Veneto region study that have
prospectively investigated a consecutive series of sudden
deaths in young people occurring in a well-defined geographic area with a homogeneous ethnic group. Therefore, the previously reported causes may have been
influenced by the unavoidable limitations in patient
selection because of retrospective analysis. Moreover,
with studies of large series, autopsy investigation is
usually performed by multiple examiners, including local
pathologists and medical examiners. In the present study,
to obtain a higher level of confidence in the results,
morphological examination of all hearts was performed
by the same team of experienced cardiovascular pathologists according to a standard protocol. Comparison
between the previous and the present study with regard
to the prevalence of ARVC among the causes of sudden
death in young people and athletes is limited by the fact
that ARVC is a clinico-pathologic condition that has been
discovered only recently [20]. ARVC is rarely associated
with cardiomegaly and usually spares the left ventricle, so
that affected hearts may be erroneously diagnosed as
normal hearts. In the past, therefore, a number of sudden
deaths in young people and athletes, in which the routine
pathologic examination disclosed a normal heart, may, in
fact, have been due to an unrecognized ARVC. The high
incidence of ARVC in our series may be due to a genetic
factor in the population of the Veneto region of Italy
[25,26], although ARVC cannot be longer considered as
a peculiar Venetian disease since there is growing

evidence that it is ubiquitary, still largely underdiagnosed both at clinical and post-mortem investigation,
and accounts for significant arrhythmic morbidity and
mortality worldwide [27]. Finally, pre-participation
screening of young people embarking in competitive
athletic activity, which has been in practice in Italy for
more than 20 years, has changed the natural prevalence of
pathologic substrates of sports-related sudden death. We
recently demonstrated that sudden death from hypertrophic cardiomyopathy in the athletic fields was successfully prevented by identification and disqualification of
the affected athletes at pre-participation screening [16].
As a consequence of this process, other cardiovascular
conditions such as ARVC and premature coronary artery
disease have thereby come to account for a greater
proportion of all sudden deaths in Italian athletes.

Mechanisms of sudden death in young

competitive athletes
Sudden cardiac death is usually the result of an interaction between structural lesions of the heart (substrate)
and transient acute abnormalities (trigger). In contrast to
adults where physical activity appears to reduce the
overall risk of sudden death by preventing or delaying
the progression of atherosclerotic coronary artery disease,
physical exercise in young competitors with occult cardiovascular disease may increase both exercise and nonexercise-related sudden death.
The mechanisms of exercise-related sudden death in
young competitive athletes include a number of triggers
such as acute myocardial ischemia, sympathetic stimulation and abrupt hemodynamic changes leading to
life-threatening ventricular arrhythmias. In the Veneto
region study, cardiovascular causes at highest risk of
sport-related sudden death were anomalous origin of
coronary artery from the wrong coronary sinus
(RR 79) and arrhythmogenic right ventricular cardiomyopathy (RR 5.4). The pathophysiology of cardiac
arrest in athletes with anomalous coronary arteries has
been related to abrupt ventricular fibrillation precipitated
by exercise-related myocardial ischemia which, in turn, is
the result of the aortic expansion which compresses the
anomalous vessel against the pulmonary trunk, increases
the acute angulation of the coronary take-off and aggravates the slit-like shape of the lumen [28,29]. The
propensity for ARVC to precipitate effort-dependent
sudden cardiac arrest is still unclear. Physical exercise
may acutely increase the RV afterload and cavity enlargement, which in turn, may elicit ventricular arrhythmias
by stretching the diseased RV myocardium [30]. Alternatively, a denervation supersensitivity of the RV to
catecholamines has been advanced [31]. Sympathetic
nerve trunks may be damaged and/or interrupted by
the RV fibrofatty replacement, which distinctively progresses from the epicardium to the endocardium, resulting in a denervation supersensitivity to cathecholamines.

Risk of sudden death during sport Corrado et al. 5

Arrhythmogenic mechanisms in the denervated, supersensitive myofibers include dispersion of refractoriness

and re-entry, triggered activity, or both. Recently, in a
subgroup of patients with familial ARVC a cardiac
ryanodine receptor (RYR2) missense mutation leading
to abnormal calcium release from the sarcoplasmic reticulum has been identified [32]. It is noteworthy that wall
mechanical stress, such as that induced by RV volume
overload during exercise, is expected to exacerbate the
cardiac ryanodine channel dysfunction. Therefore, a
potential arrhythmogenic mechanism of sport-related
cardiac arrest in patients with ARVC is triggered activity
due to late afterdepolarizations, which are provoked by
intracellular calcium overload and enhanced by adrenergic stimulation [33].

AQ3

Intensive athletic training itself may increase the risk of

sudden death in the young athlete with heart disease by
altering the substrate. This occurs by promoting disease
progression or worsening the arrhythmogenic substrate
(either structurally or electrically) over a period of time.
For example, in patients with hypertrophic cardiomyopathy, recurrent episodes of exercise-induced myocardial
ischemia during intensive training could produce cell
death and myocardial replacement fibrosis, which in turn
enhances ventricular electrical instability [34]. In patients
with ARVC, regular and intense physical activity could
provoke right ventricular volume overload and cavity
enlargement, which in turn may accelerate fibrofatty
atrophy [15]. In Marfan syndrome, the hemodynamic
stress placed on the aorta by increased blood pressure
and stroke volume during intense activity could increase
the rate of aortic enlargement thereby increasing the risk
of aortic rupture.

early identification and disqualification of those subjects

affected by cardiovascular diseases and at risk of sudden
death [35].

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1

3
4
5
6

10

11
12

Conclusions
The riskbenefit ratio of physical exercise differs
between young competitive athletes and older subjects
with occult cardiovascular disease.

13
14
15

Although vigorous exertion may trigger acute coronary

events in habitually sedentary adults (age > 35 years)
with occult or diagnosed atherosclerotic artery disease,
regular physical activity reduces the overall risk of myocardial infarction and sudden death. On the other hand,
sport activity is associated with a significantly increased
risk of sudden death in young competitive athletes
(age " years). In this age group, sports is not per se the
cause of the enhanced mortality; rather, it acts as a trigger
of cardiac arrest in those athletes who are affected by
silent cardiovascular conditions, mostly cardiomyopathy,
premature coronary artery disease and congenital coronary anomalies, which predispose to life-threatening
ventricular arrhythmias during physical exercise. These
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