Exercise and Acute Cardiovascular Events: Placing the Risks into Perspective

Paul D. Thompson, MD, FAHA; Barry A. Franklin, PhD, FAHA; Gary J. Balady, MD, FAHA; Steven N. Blair, PED, FAHA; Domenico Corrado, MD, PhD; N.A. Mark Estes III, MD, FAHA; Janet E. Fulton, PhD; Neil F. Gordon, MD, PhD, MPH; William L. Haskell, PhD, FAHA; Mark S. Link, MD; Barry J. Maron, MD; Murray A. Mittleman, MD, FAHA; Antonio Pelliccia, MD; Nanette K. Wenger, MD, FAHA; Stefan N. Willich, MD, FAHA; Fernando Costa, MD, FAHA.

Disclosures

March 02, 2010

Relative Risk of Cardiovascular Events during Exercise versus Total Risk

Vigorous exercise increases the risk of a cardiovascular event during or soon after exertion in both young subjects with inherited cardiovascular disease and adults with occult or diagnosed CHD. Nevertheless, no evidence suggests that the risks of physical activity outweigh the benefits for healthy subjects. Indeed, the converse appears to be true. 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.^[5] Specifically, the overall incidence decreased from 18 events per 1 million person-hours in the least active to only 5 in the most active subjects. The risk of an exercise-related AMI also decreases with increasing amounts of physical activity.^[6,31,32] Considerable other epidemiological evidence, albeit no random-assignment, controlled study, supports the concept that regular physical activity, including vigorous activity, reduces CHD events over time.^[3]

In contrast to adults in whom vigorous exercise appears to reduce the overall risk of CHD, exercise in young subjects with occult cardiovascular disease may increase both exercise- and non-exercise-related sudden death. SCD during exertion in a young athlete results from the interaction between the underlying heart disease or substrate and the acute trigger of exertion plus other possible triggers associated with exercise, including emotional stress, hemodynamic changes, altered parasympathetic tone, and myocardial ischemia. Athletic training itself may increase the risk of sudden death in the young athlete with heart disease by altering the substrate. This alteration could occur by promoting disease progression or by increasing the risk of cardiac arrhythmia by structural or electrical changes. 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 enhance ventricular electrical instability. In patients with arrhythmogenic right ventricular cardiomyopathy, regular and intense physical activity could provoke right ventricular volume overload and cavity enlargement, which in turn may accelerate fibrofatty atrophy. 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. Consequently, the risk-to-benefit ratio of exercise differs between young and older subjects with occult cardiovascular disease.

The Risk of Special Situations and Activities

The rarity of exercise-related events makes the examination of special situations and activities difficult because of small sample sizes.

Morning versus Afternoon Exercise

AMI and SCD in adults are more frequent in the early morning hours. This has prompted speculation as to whether vigorous exercise should be best restricted to afternoon hours in individuals at increased risk.

Young Athletes. In contrast to adults, sudden death and cardiac arrest among young athletes occur primarily in the afternoon and early evening and are associated with training and competition.^[9] However, sudden death among nonathlete patients with hypertrophic cardiomyopathy is more frequent in the early waking hours, much like CHD.^[42] The explanation for this observation is not clear, and the timing of cardiac events in other young subjects with inherited cardiac disease is not known.

Adults. Murray and colleagues^[43] found 5 cardiovascular events in 168,111 patient-hours of supervised cardiac rehabilitation exercise in the morning (3.0 events per 100,000 patient-hours) and 2 events during the 84,491 patient-hours of afternoon exercise (2.4 events per 100,000 patient-hours). This difference was not significant, but conclusions are limited by the number of subjects and available events. Similarly, Franklin and collaborators^[37] reported that time of day had little or no influence on the rate of cardiovascular complications during exercise-based cardiac rehabilitation. Given the likely benefits of exercise in reducing cardiovascular events and the low overall rate of exercise-related events, it is probably more important that individuals exercise regularly at a convenient time of day than at a specific time of day.

High-risk Activities

Few systematic studies have identified high-risk activities, again because of the rarity of exercise-related cardiovascular events. In general, the risk of any vigorous physical activity is an interaction of the exercise per se and the individual's physical fitness because identical physical tasks evoke lower cardiac demands in physically fit subjects than in unfit persons. Snow shoveling has repeatedly been associated with increased cardiovascular events,^[44,45] probably because it can elicit higher rate-pressure products than does treadmill exercise testing,^[46] because it is often performed out of necessity by unfit individuals, and because some cardiac patients develop angina at lower rate-pressure products, suggesting a coronary vasoconstrictor response, during exercise in cold temperatures.^[47]

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Cite this: Exercise and Acute Cardiovascular Events: Placing the Risks into Perspective - Medscape - May 01, 2007.

Abstract and Introduction
Pathophysiological Basis for Exertion-related Cardiovascular Events
The Importance of Age and Pathological Substrate
Incidence of Exercise-related Acute Cardiovascular Events
Does Exercise Increase the Risk of Acute Cardiovascular Events?
Relative Risk of Cardiovascular Events during Exercise versus Total Risk
Strategies to Reduce Exercise-related Cardiovascular Events
Summary
References
Sidebar

Table 1. Cardiovascular causes of exercise-related SCD in young athletes.*
	Van Camp et al.^[8] (n = 100),^† %	Maron et al.^[9] (n = 134), %	Corrado et al. (25) (n = 55),^‡ %
Hypertrophic cardiomyopathy	51	36	1
Probable hypertrophic cardiomyopathy	5	10
Coronary anomalies^§	18	23	9
Valvular and subvalvular aortic stenosis	8	4
Possible myocarditis	7	3	5
Dilated and nonspecific cardiomyopathy	7	3	1
Atherosclerotic CAD	3	2	10
Aortic dissection/rupture	2	5	1
Arrhythmogenic right ventricular cardiomyopathy	1	3	11
Myocardial scarring		3
Mitral valve prolapse	1	2	6
Other congenital abnormalities		1.5
Long-QT syndrome		0.5	1
Wolff-Parkinson-White syndrome	1		1
Cardiac conduction disease			3
Cardiac sarcoidosis		0.5
Coronary artery aneurysm	1
Normal heart at necropsy	7	2	1
Pulmonary thromboembolism			1

* Ages ranged from 13 to 24 (8), 12 to 40 (9), and 12 to 35 years (25) for the 3 studies, respectively. Van Kamp et al.^[8] and Maron et al.^[9] used the same database and include many of the same athletes. All (8), 90% (9), and 89% (25) had symptom onset during or within 1 hour of training or competition.
^† Total exceeds 100% because several athletes had multiple abnormalities.
^‡ Includes some athletes whose deaths were not associated with recent exertion.
^§ Includes aberrant artery origin and course, tunneled arteries, and other abnormalities.

Table 2. Summary of contemporary exercise-based cardiac rehabilitation program complication rates.
Investigator	Year	Patient-Exercise Hours	Cardiac Arrest	MI	Fatal Events	Major Complications*
Van Camp and Peterson^[35]	1980–1984	2,351,916	1/111,996^†	1/293,990	1/783,972	1/81,101
Digenio et al.^[36]	1982–1988	480,000	1/120,000^‡	1/160,000	1/120,000
Vongvanich et al.^[38]	1986–1995	268,503	1/89,501^§	1/268,503^§	0/268,503	1/67,126
Franklin et al.^[37]	1982–1998	292,254	1/146,127^§	1/97,418^§	0/292,254	1/58,451
Average		1/116,906	1/219,970	1/752,365	1/81,670

* MI and cardiac arrest.
^† Fatal, 14%.
^‡ Fatal, 75%.
^§ Fatal, 0%.

Table 3. Physical stress as a trigger of acute cardiovascular events during vigorous exertion.*
Study	Effect Period	End Point	RR (95% CI)
Seattle study (5) (1984)	< 1 h	Primary cardiac arrest	56 (23–131)^†
Onset study (32) (1993)	1 h	Nonfatal MI	5.9 (4.6–7.7)
TRIMM study (31) (1993)	1 h	Nonfatal MI	2.1 (1.1–3.6)
Hartford Hospital AMI study (6) (1999)	1 h	Nonfatal MI	10.1 (1.6–55.6)
SHEEP study (40) (2000)	< 15 min	Nonfatal MI	6.1 (4.2–9.0)
Physician's Health Study (7) (2000)	30 min	SCD	16.9 (10.5–27)

RR indicates relative risk and compares the risk of the cardiac event during exertion with that during sedentary activities; TRIMM, Triggers and Mechanisms of Myocardial Infarction Study; and SHEEP, Stockholm Heart Epidemiology Programme.
* Vigorous exertion is exercise intensity ≥6 METs (1 MET = 3.5 mL·kg⁻¹·min⁻¹).
^† This RR (56) is the exertion RR for habitually sedentary men. The RR (vs no prior vigorous exercise) for the most active men (Q 140 min/wk vigorous exertion) was 5 (95% CI, 2 to 14).
Adapted from Mittleman,^[41] with permission from Blackwell Publishing.

Table 4. ACC/AHA, ACSM, and USPSTF recommendations for exercise testing before exercise training.
ACC/AHA	ACSM	USPSTF
Asymptomatic persons with diabetes mellitus who plan to start vigorous exercise (Class IIa)	Asymptomatic persons with diabetes mellitus (or other metabolic disease) who plan to start moderate (40% to 59% o2 reserve) to vigorous (≥ 60% o2 reserve) exercise	Recommends against routine exercise testing of low-risk adults in general and finds insufficient evidence for exercise testing before exercise training
Asymptomatic men > 45 y of age and women > 55 y of age who plan to start vigorous exercise (Class IIb)	Asymptomatic men > 45 y of age and women > 55 y of age or those who meet the threshold for > 2 risk factors who plan to start vigorous exercise

ACC/AHA Class IIa indicates that the weight of evidence/opinion is in favor of usefulness/efficacy; Class IIb indicates that the usefulness/efficacy is less well established by evidence/opinion. Reproduced from Northcote et al.,^[57] with permission from the BMJ Publishing Group.

Table 5. Prodromal symptoms reported by 45 subjects within 1 week of their SCD.
Symptom	Reports, n
Chest pain/angina	15
Increasing fatigue	12
Indigestion/heartburn/gastrointestinal symptoms	10
Excessive breathlessness	6
Ear or neck pain	5
Vague malaise	5
Upper respiratory tract infection	4
Dizziness/palpitations	3
Severe headache	2

Adapted from Northcote et al.^[57]

Sidebar

Writing Group Disclosures
Writing Group Member	Employment	Research Grant	Other Research Support	Speakers' Bureau/Honoraria	Ownership Interest	Consultant/Advisory Board	Other
Paul D. Thompson	Hartford Hospital	Merck; Pfizer; AstraZeneca; Kos Pharma	NIH Donaghue Foundation	Merck; Pfizer; AstraZeneca; Kos; Abbott; Reliant	AstraZeneca	AstraZeneca	None
Barry A. Franklin	William Beaumont Hospital	None	None	None	None	None	None
Gary J. Balady	Boston Medical Center	None	None	None	None	None	None
Steven N. Blair	Cooper Institute	None	None	None	None	None	None
Domenico Corrado	University of Padova	None	None	None	None	None	None
N.A. Mark Estes III	Tufts-New England Medical Center	None	None	Guidant; Medtronic; St Jude Medical*	None	Guidant*	None
Janet E. Fulton	Centers for Disease Control and Prevention	None	None	None	None	None	None
Neil F. Gordon	St Joseph's/Candler Health System	None	None	None	INTERVENT USA, Inc^†	None	None
William L. Haskell	Stanford Medical School	None	None	None	None	None	None
Mark S. Link	New England Medical Center	None	None	None	None	None	None
Barry J. Maron	Minneapolis Heart Institute Foundation	Medtronic	None	None	None	None	Minneapolis Heart Institute Foundation
Murray A. Mittleman	Beth Israel Deaconess Medical Center	None	None	None	None	None	None
Antonio Pelliccia	Institute of Sports Science	None	None	None	None	None	None
Nanette K. Wenger	Emory University	Eli Lilly^†; AstraZeneca*	Pfizer Steering Committee^†	Pfizer; Novartis; Merck; Bristol-Myers Squibb; Eli Lilly*	None	None	None
Stefan N. Willich	Humboldt University, Berlin	None	None	None	None	None	None
Fernando Costa^‡	Reliant Pharmaceuticals	None	None	None	None		None
This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all members of the writing group are required to complete and submit. A relationship is considered to be 'significant' if (1) the person receives $10,000 or more during any 12-month period or 5% or more of the person's gross income or (2) the person owns 5% or more of the voting stock or share of the entity or owns $10,000 ormore of the fair market value of the entity. A relationship is considered to be 'modest' if it is less than 'significant' under the preceding definition. * Modest. ^† Significant. ^‡ Dr Costa was affiliated with the American Heart Association at the time this statement was written.

Reviewer Disclosures
Reviewer	Employment	Research Grant	Other Research Support	Speakers' Bureau/Honoraria	Ownership Interest	Consultant/Advisory Board	Other
Elliott M. Antman	Brigham and Women's Hospital	None	None	None	None	None	None
Gerald Fletcher	Mayo Clinic Jacksonville	None	None	None	None	None	None
Carl Foster	University of Wisconsin-La Crosse	None	None	None	None	None	None
Benjamin D. Levine	University of Texas Southwestern Medical Center at Dallas	None	None	None	None	None	None
This table represents the relationships of reviewers that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire, which all reviewers are required to complete and submit.

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