Although American-style football (ASF) remains the most popular team sport among American youths, research has demonstrated a high prevalence of hypertension and evidence of sub-clinical arterial stiffening in collegiate ASF participants. Of concern to public health is the recent finding of increased cardiovascular mortality in retired professional ASF linemen compared to the general population. For ultra-endurance athletes, recent data suggest the possibility that long-term and excessive endurance exercise may lead to the development of an exercise-induced right ventricular cardiomyopathy. However, more definitive insights to these observations, including detailing the mechanisms underlying ASF-induced vascular dysfunction, are lacking. This research will use a comprehensive array of cardiac imaging, vascular function testing, and high- resolution, liquid chromatography-mass spectrometry metabolomics to fully characterize the impact of ASF participation versus endurance exercise on cardiovascular structure and function and metabolism in a large cohort of high school and collegiate ASF athletes. The scientific goals of this research are to: 1) provide insight into the mechanisms and pathophysiology of ASF-induced vascular dysfunction; and 2) generate novel characterization of metabolic phenotypic adaptations present in sport-specific athletic training regimens. The working hypotheses of this project are: 1) ASF-induced arterial stiffness begins during high school ASF participation and predicts increased left ventricular hypertrophy (LVH) and reduced tissue-Doppler derived diastolic parameters in ASF participants, 2) ASF participants and endurance athletes will demonstrate distinct metabolic profiles that will be associated with specific clinical characteristics and cardiovascular phenotypic patterns, and 3) mechanisms underlying ASF-induced vascular dysfunction are multi-factorial and include oxidative stress, undiagnosed and untreated obstructive sleep apnea, and over-used non-steroidal anti- inflammatory medications.
Aim 1 will address the temporal change in metrics of arterial stiffness associated with ASF participation and the relationships of changes in vascular function with cardiac structural and functional adaptations in post-season ASF participants.
Aim 2 will investigate changes in the metabolic profile of ASF participants and endurance athletes and the relationships of changes in the metabolic phenotype of these athletes with changes in cardiac structure and function, clinical characteristics, and vascular function.
Aim 3 is an exploratory aim that will investigate possible mechanisms responsible for the development of ASF- induced hypertension and vascular dysfunction including weight gain, oxidative stress, obstructive sleep apnea, and overused non-steroidal anti-inflammatory medications. For this K23 Mentored Career Development Award, I will gain new mentored research and training from a multidisciplinary team of expert mentors (Drs. Arshed A. Quyyumi, Aaron L. Baggish, Dean P. Jones, and Laurence S. Sperling). The primary goal of the career development plan is to develop expertise in clinical research (Master of Science), advanced imaging techniques, vascular function testing, and high-resolution metabolomics for use in future clinically oriented sports cardiology research. This will complement my sports cardiology training to-date and distinguish my career moving forward. The proposed research, in combination with the structured mentoring and training plan will facilitate my long-term goal of developing an independently funded clinical and translational sports cardiology research program consistent with the mission of the NHLBI.

Public Health Relevance

Recent studies have shown that even the 'healthiest' of athletes, particularly American-style football players and ultra-endurance athletes, may be at risk for certain cardiovascular diseases such as hypertension, congestive heart failure, and atrial fibrillation. Understanding who is at risk for developing these conditions and why these conditions develop is paramount to guiding the appropriate medical treatments and preventive care options for these athletes. This study of high school and collegiate football players and endurance athletes includes a comprehensive and detailed analysis of cardiac structure and function, vascular function, and metabolism and will help answer these questions as well as provide the framework for future research that will implement treatment options for high-risk athletes who develop cardiovascular disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23HL128795-01A1
Application #
9107678
Study Section
NHLBI Mentored Patient-Oriented Research Review Committee (MPOR)
Program Officer
Scott, Jane
Project Start
2016-04-01
Project End
2021-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Emory University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Kim, Jonathan H; Zafonte, Ross; Pascuale-Leon, Alvaro et al. (2018) American-Style Football and Cardiovascular Health. J Am Heart Assoc 7:
Churchill, Timothy W; Krishnan, Supriya; Weisskopf, Marc et al. (2018) Weight Gain and Health Affliction Among Former National Football League Players. Am J Med 131:1491-1498
Kim, Jonathan H; Hollowed, Casey; Patel, Keyur et al. (2018) Temporal Changes in Cardiovascular Remodeling Associated with Football Participation. Med Sci Sports Exerc 50:1892-1898
Hedley, Jeffrey S; Al Mheid, Ibhar; Alikhani, Zoubin et al. (2017) Arrhythmogenic Right Ventricular Cardiomyopathy in an Endurance Athlete Presenting with Ventricular Tachycardia and Normal Right Ventricular Function. Tex Heart Inst J 44:290-293
Gleason, Patrick T; Kim, Jonathan H (2017) Exercise and Competitive Sport: Physiology, Adaptations, and Uncertain Long-Term Risks. Curr Treat Options Cardiovasc Med 19:79
Kim, Jonathan H; Hollowed, Casey; Irwin-Weyant, Morgan et al. (2017) Sleep-Disordered Breathing and Cardiovascular Correlates in College Football Players. Am J Cardiol 120:1410-1415
Kim, Jonathan H; Ko, Yi-An; Hedley, Jeff et al. (2017) The impact of moderate distance recreational running and ageing on cardiac physiology. Heart 103:219-226
Sperling, Laurence S; Sandesara, Pratik B; Kim, Jonathan H (2017) Exercise Is Medicine: Proof . . . and Possibilities? JACC Cardiovasc Imaging 10:1469-1471