“Exercise Safely: How Big Is The Risk
James W. Ziccardi DO, FACC
Pheidippides delivers the news of the victory of the Athenians over
the Persians
“The condition of the athlete is not natural.”
--Hippocrates
Over the last several decades there has been a dramatic
change in activity levels of the population in their 50’s and
older participating in moderate and sometimes high levels
of exercise, including marathons. Since cardiac disease risk
increases with age, many of these participants will have
underlying cardiovascular disease and be at risk for an
acute event during or after performing exercise. Patients
with known cardiac disease may also be on several
medications, the side effects of which may be potentiated
by exercise or inhibit obtaining reasonable levels of
performance. The potential cardiovascular risk of exercise,
especially in reference to endurance events, actions to
reduce risk, the potential side effects of cardiac
medications and choosing drug regimens hemodynamically
favorable to exercise will be reviewed.
Cardiac Complications of Endurance
Running
1.
2.
3.
4.
Acute Mydocardial Infarction
Arrhthmia: SVT, AFIB, PVC
Sudden Death: VT, V-FIB
Hypotension
Non-Cardiac Problems
Complicating Cardiac Disease
1. Dehydration
2. Hyponatremia
3. Hyperthermia
4. Hypothermia
Risk of Death – Distance Running
1. 10K to ½ Marathon


Men 38 to 84 Y.O.A.
Incidence: 1/327,344
(Frere J. 2004)
2. Marathon



1/50,000
Marine Corp, Twin Cities Marathon 1982 – 1994
4 deaths (3 during race, 15-24 mi.)
(Maron B. 1996)
3. Joggers


Rhode Island, 1975-1980. 1 Death/Yr./7,620 Joggers
Without known cad. 1/15,240
(Thompson P. 1982)
4. Marathon – Post Infarction - Safety


8 Pt. Boston Marathon – No CV Events (4/73)
Age 36 to 57
(Kavanagh T. 1974)
Cardiac Arrests in Long Distance
Running Races

10.9 Million Runners, 59 arrests (51 men)
– Ages 43 +/- 13 yrs
– Incidence rate = .54/100k
 Majority Due to CAD
 1.01 per 100k in the marathon

Best Prognosis
– Bystander cardiopulmonary resuscitation
– Dx other than HCM
 NEJM: Jan 12, 2012
CV Risks in Cardiac Rehabilitation

30 programs: 1960-1977
– 1 Non-Fatal MI in 346,733 Pt. Hrs
– 1 Fatal MI in 116,402 Pt. Hrs

142 Programs: 1980-1984
– 1 Non-Fatal MI in 294k Pt. Hrs
– 1 Cardiac Death in 780k in Pt. Hrs
– 21 Cardiac Sudden Death (17 resuscitated) Chest: 1998

167 Programs: 105 Centers, 51k Patients, 2,361,967 Hrs
– 1 Cardiac Death in 60k Pt. Hrs (Medicine and Science in
Sports and Exercise July 1994)
Acute Coronary Thrombosis in
Boston Marathon Runners (2011)
3 Myocardial infractions (Men) Post
Completion
 All:

– Had coronary thrombosis
– Traveled more than 4 Hrs. by Plane Prior
– Elevated Thrombin, Anti-Thrombin Complex
– None on cardiac medications
 NEJM: Jan 12, 2012
Sudden Cardiac Death
Detrimental Effects of Prolonged
Endurance Exercise
Increased: Heart Rate, BP and prolonged
periods of Anaerobic Exercise.
 Increased: Aortic Stiffness, documented
by increased Pulse Wave Velocity.
 Greater: Coronary Calcium and increased
Calcified Plaque Volume- 274mm cubed in
prolonged endurance exercise group vs
169mm cubed in the control group.
Scwartz, Am. Coll. Card. Sc. Sess., 3/16/10

Timing of Infarction/Exercise

(A) Increased: In First Hour Post Exercise
1. 218 Pts.: 4.4% Reported Heavy Exertion 1 Hr. Prior to MI
2. Fitness Level: Sedentary – 107 X Risk
– Exercise: 1 – 2 X Week – 19.4 X Risk
3 – 4 X Week – 8.6 X Risk
4 – 5 X Week – 2.4 X Risk
*Heavy physical exertion is much more likely to trigger
infarction in the least fit.
(Mittleman M. 1993)
Mechanisms of MI/Exercise

1. Increased Inflammatory/Hemostatic Markers
 Increased: VWF
: D-Dimer
: WBC
: Platelet Aggregation
: CRP (Siegel A. 2001)

2. Changes in Cardiac Markers
 Increased: Troponin I, Elevated 4 Hr. – 72 Hr.
: CPK – MB – Peak 24 Hr.
: Myoglobin – Peak 4 Hr.
: BNP Peak 24 Hr. (Siegel A. 2001)

3. Plaque Rupture
Coagulation-Thrombolysis is in
equilibrium during exercise
Post-Exercise: A Hypercoagulable
State is Present
Plaque Rupture/Thrombosis

Atherosclerotic Heart Disease
- Primary Cause of Death in Exercise Related Disease
 81 Died suddenly, 75 Deaths – 2nd to CAD
(Ragosta M. 1984)

Plaque Rupture/Intra-Coronary Clots
- 640 Pts: (64) – Exercise VS. (576) – Rest
- Clots 2MM Present in: 64% of Exercising Patients
: 35% at Rest
(Giri S. 1999)
Prodromal Symptoms
(A). Chest Pain, Unexpected Dyspnea, Palpitations
 (B). Seek Attention Immediately
 (C). Denial (IE) Jim Fixx (Tragedy)


1. (6/13) Deaths during or immediately after exercise had prodromal
symptoms before the event.
(Thompson P. 1979)

2. (36) Marathoners/Sudden Death: 71% had prodromal symptoms.
(Noakes T. 1987)

3. (47%) prodromal symptoms at rest with ACS/Sedentary Men, 8% of
athletes exercising.
(Ciampricotti R. 1994
CV Meds – No Significant Effect
on Exercise Capacity
1. Alpha-blockers – prazosin, terazosin and doxazosin.
 2. ACE Inhibitors/ARBS – captopril, lisinopril, quinapril, ramipril/losartan,
valsartan
 3. Venodilators – nitrates.
 Calcium Channel Blockers – the dihydropyridines, diltiazem and verapamil.

Cardiovascular Meds
Having the Potential to Effect Exercise







1.
2.
3.
4.
5.
6.
7.
Beta-blockers: inderal, metoprolol, atenolol and bisoprolol
Alpha beta-blockers: labetalol, carvedilol
Calcium channel blockers: verapamil
Amiodarone – alpha beta-blocker
Central alpha-blockers – clonidine
Diuretics – thiazides, loop diuretics, potassium sparing
Pure Vasodilators – hydralazine
– (*1-5 have potential to limit heart rate response to exercise)
Beta - Blockers





1.
2.
3.
4.
5.
Decrease heart rate and cardiac output
Decrease myocardial contractility
Decrease coronary blood flow
Decrease muscle blood flow
Cause premature fatigue during exercise
 A. Especially in non-selective beta-blockers
 B. Increased rating of perceived exertion (local)
– a. Alters glycolytic metabolism
– b. Decreased muscle blood flow
Beta – Blockers, Continued




6. Decrease in VO2 max
7. Decreased heart dissipation during exercise in hot weather.
8. May cause hyperkalemia
9. Beta-blockers are certainly necessary in many patients who have
coronary artery disease, however, an attempt should be made to
adjust the dosage of beta-blockers to attain at least 70% of
predicted maximal heart rate or keep heart rate at levels below that
causing ST depression, angina, adequate controlled ventricular
response of atrial fibrillation or acceptable suppression of exercise
induced arrhythmia.
(Gullested L. 1996)
Diuretics





1. Will decrease plasma volume, which is the opposite effect of endurance
training, which increases plasma volume, however cardiac output may not
be appreciably affected.
2. Hypokalemia may occur. Potassium regulates the maintenance of muscle
blood flow. During exercise, marked hypokalemia may cause
rhabdomyolysis and acute renal failure.
3. Diuretics may also cause low magnesium, which can precipitate tetani
and may cause hypocalcemia and further aggravate hypokalemia.
4. Potassium sparing diuretics may obviously spare potassium and
magnesium, however, frequent monitoring of serum potassium should be
performed to exclude hyperkalemia.
5. Hyponatremia, dehydration and hypovolemia. Certainly hyponatremia
would also be more easily precipitated in excessive water drinkers who are
“tanking up” for a long run.
Vasodilators and Central Alpha Blockers

1. Vasodilators
– Hydralazine – may cause edema and reflex tachycardia. It is
usually never used alone but in combination with a diuretic
and/or beta-blocker and would be a poor choice for someone
exercising.

2. Central Alpha Blockers
– Clonidine – may cause fatigue, bradycardia and/or heart block.
Miscellaneous

1. Amiodarone – will decrease heart rate and long term, may cause
pulmonary complications leading to severe pulmonary insufficiency.

2. Pacemaker – should be activity modulated and programmed to
react to appropriate levels of exercise to avoid pacer syndrome,
allow an adequate heart rate to be attained at peak exercise.

3. Post exercise hypotension – all anti hypertensive exaggerate the
post exercise hypotensive response seen in normal subjects.

4. HMG – CoA reductase – inhibitors (statins) can cause muscle
soreness. Rhabdomyolosis, increased skeletal muscle injury.
(Thompson P. 1997)
Cardiovascular Drugs
The cardiovascular drugs that have the most
favorable profile would be the class of alpha
blockers, ACE inhibitors and ARB’s –
venodilators, nitrates and slow calcium channel
blockers with the exception of verapamil, which
may cause a significant decrease in heart rate
response at peak exercise. Also, of all the
calcium channel blockers, it is more likely to
cause muscle spasm or muscle fatigue.
Medications That May Prohibit
Hyper-Coagulable State PostExercise
ASA
Beta
Blockers
Statins
ACE Inhibitors
ASA
Decreased platelet aggregation
 Inhibit Cox-1 which produces
Thromboxane A-2

– Necessary for platelet aggregation
Decreased Tissue Factor in atherosclerotic
plaques
 Lowers CRP

Beta Blockers
Blocks adrenaline increase in Factor VIII
 Reduces sympathetic response to
exercise/arrhythmias
 Reduces oxidative stress
 Reduces CRP

Statins
Down regulation of coagulation cascade
 Beneficial effect on endothelial dependent
vasodilation
 Reduced Thrombin production
 Anti-inflammatory properties
 May stabilize plaques
 Lowers CRP

Ace Inhibitors
Anti-inflammatory and anti-fibrotic
properties
 Reduces Tissue Factor in atherosclerotic
plaques
 Reduces CRP

Principles to Guide CV Therapy in Patients
Who are Moderate to Competitive in their Levels of
Exercise

1.
Risk profile for all patients prior to starting exercise program.

2. Stress testing in patients who have multiple risk factors.

3. Aggressively treat diabetes, hypertension, hyperlipidemia.

4. Instruct patients not to ignore prodromal symptoms.

5. Choose medications that are appropriate both for the patient’s
diagnosis yet are least likely to limit their activity.

6. Patient’s need to understand that they may need to readjust their
exercise levels that are safe for them, i.e., keep heart rate response
below angina or production of ST depression. Many times this is the
difficult part of the equation (tell a runner that he or she needs to
slow down.)

7.Recommended heart rate monitors to all CV patients who exercise
so that they can stay within their acceptable heart rate zone.
Principles to Guide CV Therapy in Patients
Who are Moderate to Competitive in their Levels of Exercise

8. Recommend that each patient carry an ID card with as much
medical
information as possible. This may include lists of drugs,
miniaturized copy of EKG, etc.

9. Stress the importance of warm up and cool down to avoid
precipitation of angina and/or arrhythmia in the early stages of
exercise and post exercise postural hypotension.

10. It may be wise for the patient to have their own blood
pressure cuff and frequently check their blood pressure and
weight prior to and after exercise as during long endurance runs,
especially the morning of. It might also be wise to reduce the
dosage of medications that are administered on a daily basis.

11. Balancing exercise levels and CV meds is at least time
consuming and may require frequent visits for serial exercise
testing to determine the dosage or choice of these medications.
Summary
Individuals participating in long distance running have
a minimal risk for precipitation of acute cardiac events. This
risk can probably be lowered by taking proper precautions
and following prudent recommendations. Addressing
treatable risk factors and risk profiling patients prior to
participation is paramount. Patients on cardiac medications
need to be made aware of potential side effects, which may
be precipitated by exercise and the ability of these
medications to limit performance. Following these principles,
those with risk factors or known coronary artery disease, can
reduce their risk for cardiac events during exercise and
participate at levels of exercise promoting fitness and
endurance.
Summary
Physicians treating this group of patients should be able to
recommend activity levels with hemodynamic
parameters and prescribe cardiovascular medications
both appropriate for the patient’s disease, yet preserving
adequate hemodynamic response. Albeit a small cardiac
risk will persist, especially in longer endurance events,
which each participant needs to understand. Further
data needs to be collected to increase understanding of
these risks. Hopefully, future findings will assist in the
reduction of acute cardiac events related to exercise.
Hypothesis
Patients with known stable CAD
who are receiving optimal medical
treatment may be a lower risk for
cardiovascular events than a
similar age/gender groups during
and in the one hour post-exercise
period
Bibliography

1. Frere J, et al: The risk of death in running road races. The Physician and Sports
Medicine 2004;32 (4): 33-40.

2. Maron B, et al: Risk for sudden cardiac death associated with marathon running.
AM J Cardiology 1996;28 (2): 428-431.

3. Thompson P, et al: Incidence of death during jogging in Rhode Island from 1975
through 1980. JAMA 1982;247 (18): 2535-2538.

4. Kavanagh T, et al: Marathon running after myocardial infarction. JAMA 1974;229
(12): 1602-1606.

5. Mittleman M, et al: Triggering of acute myocardial infarction by heavy exertion:
protection against triggering by regular exercise. N Eng J Med 1993;329 (23):
1677-1683.

6. Siegel A, et al: Effect of marathon running on inflammatory and hemostatic
markers. AM J Cardiol 2001;88: 918-920.
Bibliography

7. Siegel A, et al: Changes in cardiac markers including B-Natriuretic Peptide in
runners after the Boston Marathon. AM J of Cardiol 2001;88: 920-923.

8. Rogosta M, et al: Death during recreational exercise in the state of Rhode Island.
Med Sci Sports Exer 1984;16 (4): 339-342.

9. Giri S, et al: Clinical and angiographic characteristics of exertion related acute
myocardial infarction. JAMA 1999;228 (18): 1731-1736.

10. Thompson PD, et al: Death during jogging or running: a study of 18 cases. JAMA
1979;242 (12): 1265-1267.

11. Noakes TD: Heart disease in marathon runners: a review. Med Sci Sports Exer
1987;19 (3): 187-194.

12. Ciampricotti R, et al: Characteristics of conditioned and sedentiary men with
acute coronary syndromes. Am J Cardiol 1994;74 (4): 219-222.
Bibliography

13. Gullested L, et al: The effect of acute vs. chronic treatment with B-adrenoceptor
blockade on exercise performance, haemodynamics and metabolic parameters
in healthy men and women. Br J Clin Pharmacal 1996;41: 57-67.

14. Thompson P, et al: Lovastatin increased exercise induced skeletal muscle injury.
Metabolism 1997;46 (10): 1206-1210.
Suggested Reading

1. ACSM’s Guide for Exercise Testing and Prescription—
Eighth Edition. 2010. Lippincott Williams and Wilkins.

2. Thompson PD: Exercise and Sports Cardiology. 2001.
McGraw Hill.