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Supplemental digital content is available in the text., Purpose Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate left ventricular (LV) wall thickness. Adaptations to exercise can occasionally mimic certain HCM characteristics. However, it is unclear whether physical activity affects HCM genotype expression and disease characteristics. Consequently, we compared lifelong physical activity volumes between HCM gene carriers with and without HCM phenotype, and compared disease characteristics among tertiles of physical activity in phenotypic HCM patients. Methods We enrolled n = 22 genotype positive/phenotype negative (G+/P−) HCM gene carriers, n = 44 genotype positive/phenotype positive (G+/P+) HCM patients, and n = 36 genotype negative/phenotype positive (G−/P+) HCM patients. Lifelong physical activity was recorded using a questionnaire and quantified as metabolic equivalent of task hours per week. Results We included 102 participants (51 ± 16 yr, 49% male). Lifelong physical activity volumes were not different between G+/P+ and G+/P− subjects (16 [10–29] vs 14 [6–26] metabolic equivalent of task‐hours per week, P = 0.33). Among phenotypic HCM patients, there was no difference in LV wall thickness, mass, and late gadolinium enhancement across physical activity tertiles. Patients with the highest reported physical activity volumes were younger at the time of diagnosis (tertile 1: 52 ± 14 yr, tertile 2: 49 ± 15 yr, tertile 3: 41 ± 18 yr; P = 0.03), and more often had a history of nonsustained ventricular tachycardia (4% vs 30% vs 30%, P = 0.03). Conclusions Lifelong physical activity volumes are not associated with genotype-to-phenotype transition in HCM gene carriers. We also found no difference in LV wall thickness across physical activity tertiles. However, the most active HCM patients were younger at the time of diagnosis and had a higher arrhythmic burden. These observations warrant further exploration of the role of exercise in HCM disease development.

AB Purpose: The purpose of the study was to examine the relation between serum 25-hydroxy vitamin D (25(OH)D) levels and muscle strength in 419 healthy men and women over a broad age range (20-76 yr). Methods: Isometric and isokinetic strength of the arms and legs was measured using computerized dynamometry, and its relation to vitamin D was tested in multivariate models controlling for age, gender, resting HR, systolic blood pressure, diastolic blood pressure, body mass index, maximal oxygen uptake (V[spacing dot above]O2max,), physical activity counts, and season of vitamin D measurement. Results: Vitamin D was significantly associated with arm and leg muscle strength when controlling for age and gender. When controlling for other covariates listed previously, vitamin D remained directly related to both isometric and isokinetic arm strength but only to isometric leg strength. Conclusion: These data suggest that there may be a differential effect of vitamin D on upper and lower body strength. The mechanism for this difference remains unclear but could be related to differences in androgenic effects or to differences in vitamin D receptor expression. Our study supports a direct relation between vitamin D and muscle strength and suggests that vitamin D supplementation be evaluated to determine whether it is an effective therapy to preserve muscle strength in adults.

KOSTEK, M. A., T. J. ANGELOPOULOS, P. M. CLARKSON, P. M. GORDON, N. M. MOYNA, P. S. VISICH, R. F. ZOELLER, T. B. PRICE, R. L. SEIP, P. D. THOMPSON, J. M. DEVANEY, H. GORDISH-DRESSMAN, E. P. HOFFMAN, and L. S. PESCATELLO. Myostatin and Follistatin Polymorphisms Interact with Muscle Phenotypes and Ethnicity. Med. Sci. Sports Exerc., Vol. 41, No. 5, pp. 1063–1071, 2009. Purpose: We examined associations among myostatin (MSTN) 2379 A 9 G and 163 G 9 A and follistatin (FST) j5003 A 9 T and j833 G 9 T single nucleotide polymorphisms (SNP) on the muscle size and the strength response to resistance training (RT). Methods: Subjects (n = 645, age = 24.1 T 0.2 yr, body mass index [BMI] = 24.2 T 0.2 kgIm j2 ) self-disclosed themselves as Caucasian (78.9%), African American (3.6%), Asian (8.4%), Hispanic (5.0%), or Other (4.2%). They were genotyped for MSTN 2379 A 9 G( n = 645), MSTN 163 G 9 A( n = 639), FST j5003 A 9 T( n = 580), and FST j833 G 9 T( n = 603). We assessed dynamic (one repetition maximum [1RM]) and isometric (maximum voluntary contraction [MVC]) muscle strength and size (crosssectional area [CSA]) of the elbow flexors before and after 12 wk of unilateral upper-arm RT. Repeated-measures ANCOVA tested associations among genetic variants and muscle phenotypes with age and BMI as covariates. Results: Baseline MVC was greater among African Americans who were carriers of the MSTN G 2379 allele (AG/GG, n = 15) than the A2379A homozygotes (n = 8; 64.2 T 6.8 vs 49.8 T 8.7 kg). African Americans who were carriers of the FST T j5003 allele (n = 12) had greater baseline 1RM (11.9 T 0.7 vs 8.8 T 0.5 kg) and CSA (24.4 T 1.3 vs 19.1 T 1.2 cm 2 ) than African Americans with the A-5003A genotype (n = 14; P G 0.05). No MSTN or FST genotype and muscle phenotype associations were found among the other ethnic groups (P Q 0.05). Conclusion: MSTN 2379 A 9 G and FST j5003 A 9 T were associated with baseline muscle strength and size among African Americans only. These ethnic-specific associations are hypothesis generating and should be confirmed in a larger sample of African Americans.

Introduction/Methods: We performed a systematic search for medical reports on the Boston Marathon, run annually since April 19, 1897 and studied medically since 1899. Results: We identified 66 articles: 25 were related to cardiology; 10, exercise physiology; 8, metabolism; 5, neurology; 4, gastroenterology; 3, hematology; 3, several disciplines; and 8, nephrology, orthopedics, and general topics. The predominance of cardiology articles reflects concerns about the cardiac risks of exercise present in the early 20th century and persistent to this day. The authors and contributors included luminaries from the medical and exercise community including Drs. Paul Dudley White, Samuel Levine, Kenneth Cooper, Paul Zoll, Ellsworth Buskirk, and David Costill. The articles identified or confirmed many of the presently accepted principles of marathon medicine. Conclusions: Medical studies on the Boston Marathon not only provide lessons applicable to managing modern athletes but also demonstrate the interests and concerns of researchers who have used the event to study the physiology of prolonged exercise for more than a century

Habitual physical activity reduces coronary heart disease events, but vigorous activity can also acutely and transiently increase the risk of sudden cardiac death and acute myocardial infarction in susceptible persons. This scientific statement discusses the potential cardiovascular complications of exercise, their pathological substrate, and their incidence and suggests strategies to reduce these complications. Exercise-associated acute cardiac events generally occur in individuals with structural cardiac disease. Hereditary or congenital cardiovascular abnormalities are predominantly responsible for cardiac events among young individuals, whereas atherosclerotic disease is primarily responsible for these events in adults. The absolute rate of exercise-related sudden cardiac death varies with the prevalence of disease in the study population. The incidence of both acute myocardial infarction and sudden death is greatest in the habitually least physically active individuals. No strategies have been adequately studied to evaluate their ability to reduce exercise-related acute cardiovascular events. Maintaining physical fitness through regular physical activity may help to reduce events because a disproportionate number of events occur in least physically active subjects performing unaccustomed physical activity. Other strategies, such as screening patients before participation in exercise, excluding high-risk patients from certain activities, promptly evaluating possible prodromal symptoms, training fitness personnel for emergencies, and encouraging patients to avoid high-risk activities, appear prudent but have not been systematically evaluated.

Purpose: To examine associations among the angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and the response to a 12-wk (2 d·wk-1) unilateral, upper-arm resistance training (RT) program in the trained (T, nondominant) and untrained (UT, dominant) arms. Methods: Subjects were 631 (mean ± SEM, 24.2 ± 0.2 yr) white (80%) men (42%) and women (58%). The ACE ID genotype was in Hardy-Weinberg equilibrium with frequencies of 23.1, 46.1, and 30.8% for ACE II, ID, and DD, respectively (?2 = 1.688, P = 0.430). Maximum voluntary contraction (MVC) and one-repetition maximum (1RM) assessed peak elbow flexor muscle strength. Magnetic resonance imaging measured biceps muscle cross-sectional area (CSA). Multiple variable and repeated-measures ANCOVA tested whether muscle strength and size differed at baseline and pre- to post-RT among T and UT and ACE ID genotype. Results: Baseline muscle strength and size were greater in UT than T (P < 0.001) and did not differ among ACE ID genotype in either arm (P = 0.05). In T, MVC increases were greater for ACE II/ID (22%) than DD (17%) (P < 0.05), whereas 1RM (51%) and CSA (19%) gains were not different among ACE ID genotype pre- to post-RT (P = 0.05). In UT, MVC increased among ACE II/ID (7%) (P < 0.001) but was similar among ACE DD (2%) pre- to post-RT (P = 0.05). In UT, 1RM (11%) and CSA (2%) increases were greater for ACE DD/ID than ACE II (1RM, 7%; CSA, -0.1%) (P < 0.05). ACE ID genotype explained approximately 1% of the MVC response to RT in T and approximately 2% of MVC, 2% of 1RM, and 4% of CSA response in UT (P < 0.05). Conclusion: ACE ID genotype is associated with the contralateral effects of unilateral RT, perhaps more so than with the muscle strength and size adaptations that result from RT.

Serum creatine kinase (CK) levels are commonly used to judge the severity of muscle damage and to determine when to hospitalize patients who present with symptoms of exertional rhabdomyolysis in order to prevent renal failure. However, no CK standard exists because of the limited information available regarding exercise-induced CK elevation and renal function. This study determined the magnitude of CK elevation and the effect on renal function produced by exercise in a large subject group.Blood samples were obtained from 203 volunteers who performed 50 maximal eccentric contractions of the elbow flexor muscles. The samples, taken before and 4, 7, and 10 d after exercise, were analyzed for markers of muscle damage (CK, myoglobin (Mb), lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase and for measures of renal function (creatinine, blood urea nitrogen, phosphorus, potassium, osmolality, and uric acid).All indicators of muscle damage increased significantly after exercise (P0.01). CK levels were 6420, 2100, and 311% above baseline on days 4, 7, and 10 after the exercise, respectively (P0.01), and Mb was 1137, 170, and 28% above baseline on days 4, 7, and 10 after exercise, respectively (P0.01). Of the 203 participants, 111 had CK values at 4 d postexercise2,000 U x L(-1) and 51 had values10,000 U x L(-1), levels used to diagnose myopathy (e.g., statin myositis) and rhabdomyolysis, respectively. There were no significant increases in any measure of renal function. Despite marked CK and Mb elevations in some subjects, none experienced visible myoglobinuria or required treatment for impaired renal function.Exertional muscle damage produced by eccentric exercise in healthy individuals can cause profound CK and Mb elevations without renal impairment.

THOMPSON, P. D., N. MOYNA, R. SEIP, T. PRICE, P. CLARKSON, T. ANGELOPOULOS, P. GORDON, L. PESCATELLO, P. VISICH, R. ZOELLER, J. M. DEVANEY, H. GORDISH, S. BILBIE, and E. P. HOFFMAN. Functional Polymorphisms Associated with Human Muscle Size and Strength. Med. Sci. Sports Exerc., Vol. 36, No. 7, pp. 1132–1139, 2004. Introduction: Skeletal muscle is critically important to human performance and health, but little is known of the genetic factors influencing muscle size, strength, and its response to exercise training. The Functional single nucleotide polymorphisms (SNP) Associated with Muscle Size and Strength, or FAMuSS, Study is a multicenter, NIH-funded program to examine the influence of gene polymorphisms on skeletal muscle size and strength before and after resistance exercise training. Methods: One thousand men and women, age 18 – 40 yr, will train their nondominant arm for 12 wk. Skeletal muscle size (magnetic resonance imaging) and isometric and dynamic strength will be measured before and after training. Individuals whose baseline values or response to training deviate 1.5 SD will be defined as outliers and examined for genetic variants. Initially candidate genes previously associated with muscle performance will be examined, but the study will ultimately attempt to identify genes associated with muscle performance. Conclusion: FAMuSS should help identify genetic factors associated with muscle performance and the response to exercise training. Such insight should contribute to our ability to predict the individual response to exercise training but may also contribute to understanding better muscle physiology, to identifying individuals who are susceptible to muscle loss with environmental challenge, and to developing pharmacologic agents capable of preserving muscle size and function. Key Words: SKELETAL MUSCLE, GENETICS, QUANTITATIVE TRAIT LOCI (QTL), HYPERTROPHY, GENOMICS

Background: Spontaneous coronary artery dissection is a rare cause of acute cardiac events and occurs most frequently in the peripartum period. Coronary artery dissection related to exercise is even more unusual, with only a few cases reported in the literature. We report a case of acute coronary artery dissection related to exercise in a 17-yr-old high school athlete, and we review the available literature on exercise-related coronary dissection. Methods: We performed a PubMed literature search using the search terms exercise, sports, spontaneous coronary dissection, and athletics. We found seven cases of spontaneous coronary artery dissection that had occurred during intense physical exercise. Vigorous exercise can provoke acute ischemic events, but such events occur primarily in adults with atherosclerotic disease. Many of the cases reported as spontaneous coronary artery dissection are more likely atherosclerotic plaque rupture, in which cases they are not truly spontaneous. Because spontaneous coronary dissection is so rare, there are no available recommendations on how to manage young athletes with this condition. We permitted this athlete to return to limited competition, without data to support either a total restriction or even a limited restriction, with the written understanding that a recurrent event is possible but probably unlikely. In summary, spontaneous coronary artery dissection should be considered in young individuals presenting with exercise-related acute ischemic cardiac events.

ISKANDAR, E. G., and P. D. THOMPSON. Exercise-Related Sudden Death due to an Unusual Coronary Artery Anomaly. Med. Sci. Sports Exerc., Vol. 36, No. 2, pp. 180–182, 2004. Coronary artery anomalies are, after hypertrophic cardiomyopathy, the second most common cause of exercise-related sudden cardiac death in young American athletes. These anomalies have been associated with myocardial ischemia, arrhythmia, and sudden death during exercise. A 14-yr-old male with no previous abnormal medical history collapsed during soccer practice and was successfully resuscitated without defibrillation. An extensive cardiac workup did not reveal any abnormalities. Two weeks later, he experienced a cardiac arrest while running and could not be resuscitated. Autopsy demonstrated an acute angle take-off of the left main coronary artery and a transverse slit-like opening with a fibrous cushion, which created a kink near its origin. This case report illustrates the difficulty in diagnosing coronary artery anomalies in general, and acute angle take-off and ostial ridges in particular.

PURPOSE: Endurance exercise can elevate cardiac troponin (cTn) concentrations in healthy subjects. cTn is preferred biomarker for diagnosing myocardial infarction and indicates cardiac injury. Subjects with cardiovascular disease demonstrate elevated cTn-concentrations at baseline, but it is unknown how cTn concentrations change following endurance exercise. We investigated the impact of cardiovascular (CV) risk and disease (CVD) on exercise-induced cTn elevations. METHODS: We measured baseline and immediate post-exercise cTn-concentrations in 356 subjects who performed 30-50 km of walking. Subjects were classified as healthy (i.e. controls, n=133), having increased CV risk (hypertension, hypercholesterolemia, type 2 diabetes or BMI ≥30 kg/m2, n=131) or having diagnosed CVD (heart failure, myocardial infarction, stroke, n=92). cTn-subunit I (cTnI) was determined using a high-sensitive assay (ADVIA Centaur TnI-Ultra, Siemens) with a detection limit of 6 ng/L and upper reference limit of 40 ng/L. RESULTS: Subjects walked 8.0±1.4 hours at 68±10% of their maximum predicted heart rate. Baseline and post-exercise cTnI concentrations were significantly higher in CVD patients compared to controls (p CONCLUSIONS: Exercise-induced cardiac troponin elevations are significantly larger in subjects with cardiovascular disease, but this difference is small and does not result in a higher incidence of cases exceeding the clinical cut-off value.