Longitudinal Aortic Root Dilatation in Collegiate American-Style Football Athletes.

Background Clinically relevant aortic dilatation (>40 mm) and increased cardiovascular risk are common among retired professional American-style football athletes. Among younger athletes, the effect of American-style football participation on aortic size is incompletely understood. We sought to determine changes in aortic root (AR) size and associated cardiovascular phenotypes across the collegiate career. Methods and Results This was a multicenter, longitudinal repeated-measures observational cohort study of athletes across 3 years of elite collegiate American-style football participation. A total of 247 athletes (119 [48%] Black, 126 [51%] White, 2 [1%] Latino; 91 [37%] linemen, 156 [63%] non-linemen) were enrolled as freshmen and studied at pre- and postseason year 1, postseason year 2 (N=140 athletes), and postseason year 3 (N=82 athletes). AR size was measured with transthoracic echocardiography. AR diameter increased over the study period from 31.7 (95% CI, 31.4-32.0) to 33.5 mm (95% CI, 33.1-33.8; P<0.001). No athlete developed an AR ≥40 mm. Athletes also demonstrated increased weight (cumulative mean Δ, 5.0 [95% CI, 4.1-6.0] kg, P<0.001), systolic blood pressure (cumulative mean Δ, 10.6 [95% CI, 8.0-13.2] mm Hg, P<0.001), pulse wave velocity (cumulative mean Δ, 0.43 [95% CI, 0.31-0.56] m/s, P<0.001), and left ventricular mass index (cumulative mean Δ, 21.2 [95% CI, 19.2-23.3] g/m2, P<0.001), and decreased E' velocity (cumulative mean Δ, -2.4 [95%CI, -2.9 to -1.9] cm/s, P<0.001). Adjusting for height, player position, systolic blood pressure, and diastolic blood pressure, higher weight (ß=0.030, P=0.003), pulse wave velocity (ß=0.215, P=0.02), and left ventricular mass index (ß=0.032, P<0.001) and lower E' (ß=-0.082, P=0.001) were associated with increased AR diameter. Conclusions Over the collegiate American-style football career, athletes demonstrate progressive AR dilatation associated with cardiac and vascular functional impairment. Future studies delineating aortic outcomes are necessary to determine whether AR dilation is indicative of maladaptive vascular remodeling in this population.

Metabolic Alterations Differentiating Cardiovascular Maladaptation from Athletic Training in American-Style Football Athletes.

PURPOSE: Metabolomics identifies molecular products produced in response to numerous stimuli, including both adaptive (includes exercise training) and disease processes. We analyzed a longitudinal cohort of American-style football (ASF) athletes, who reliably acquire maladaptive cardiovascular (CV) phenotypes during competitive training, with high-resolution metabolomics to determine whether metabolomics can discriminate exercise-induced CV adaptations from early CV pathology. METHODS: Matched discovery ( n = 42) and validation ( n = 40) multicenter cohorts of collegiate freshman ASF athletes were studied with longitudinal echocardiography, applanation tonometry, and high-resolution metabolomics. Liquid chromatography-mass spectrometry identified metabolites that changed ( P < 0.05, false discovery rate <0.2) over the season. Metabolites demonstrating similar changes in both cohorts were further analyzed in linear and mixed-effects models to identify those associated with left ventricular mass, tissue-Doppler myocardial E ' velocity (diastolic function), and arterial function (pulse wave velocity). RESULTS: In both cohorts, 20 common metabolites changed similarly across the season. Metabolites reflective of favorable CV health included an increase in arginine and decreases in hypoxanthine and saturated fatty acids (heptadecanoate, arachidic acid, stearate, and hydroxydecanoate). In contrast, metabolic perturbations of increased lysine and pipecolate, reflective of adverse CV health, were also observed. Adjusting for player position, race, height, and changes in systolic blood pressure, weight, and pulse wave velocity, increased lysine ( ß = 0.018, P = 0.02) and pipecolate ( ß = 0.018, P = 0.02) were associated with increased left ventricular mass index. In addition, increased lysine ( ß = -0.049, P = 0.01) and pipecolate ( ß = -0.052, P = 0.008) were also associated with lower E ' (reduced diastolic function). CONCLUSIONS: ASF athletes seem to develop metabolomic changes reflective of both favorable CV health and early CV maladaptive phenotypes. Whether metabolomics can discriminate early pathologic CV transformations among athletes is a warranted future research direction.

Nonsteroidal Anti-inflammatory Drugs and Cardiovascular Risk in American Football.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with adverse cardiovascular outcomes and reportedly overused in American-style football (ASF). However, assessment of ASF NSAID use in the context of cardiovascular risk has not been performed. We sought to characterize NSAID use patterns and the association with cardiovascular risk in a diverse cohort of high school and collegiate ASF athletes. METHODS: A total of 226 ASF athletes, 60 endurance athletes, and 63 nonathletic controls were studied pre- and postseason with echocardiography, vascular applanation tonometry, and clinical data assessment. Qualitative NSAID use throughout the season was recorded at postseason. RESULTS: ASF athletes gained weight (Δ0.86 ± 3.9 kg, P < 0.001), increased systolic blood pressure (SBP, Δ3.1 ± 12 mm Hg, P < 0.001) and pulse wave velocity (Δ0.2 ± 0.6 m·s, P < 0.001), and decreased E' (Δ-1.4 ± 2.8 cm·s, P < 0.001) across one athletic season. Seventy-seven percent (n = 173) of ASF athletes reported that sport-specific NSAID use began in middle school. ASF NSAID use was more frequent with "weekly" (n = 42.19%) and "daily" (n = 32.14%) use compared with endurance athletes (P < 0.001) and controls (P = 0.02). ASF NSAID use increased in parallel with postseason SBP and weights. "Daily" ASF NSAID users demonstrated the highest postseason SBP (137 ± 13 vs 128 ± 13 mm Hg, P = 0.002) and weight (109.0 ± 18.6 vs 95.8 ± 20.5 kg, P = 0.002) compared with "never/rare" users. Adjusting for player position, SBP, pulse wave velocity, and E', increased weight (odds ratio = 1.04, 95% confidence interval = 1.0-1.08, P = 0.037) was associated with more frequent NSAID use. CONCLUSIONS: Habitual NSAID use commonly begins during adolescence, before full physical maturation, and is associated with cardiovascular risk, particularly increased weight, in ASF athletes. NSAID use frequency should be considered when risk stratifying high-risk ASF athletes.

Weight Gain, Hypertension, and the Emergence of a Maladaptive Cardiovascular Phenotype Among US Football Players.

Importance: Former US football athletes are at increased risk of cardiovascular (CV) morbidity and mortality compared with the general population and other professional athletes. However, responsible maladaptive CV phenotypes have not been fully characterized. Objective: To address the emergence and progression of multiple independent factors associated with CV risk across serial years of collegiate US football participation. Design, Setting, and Participants: Collegiate US football athletes from 2 National Collegiate Athletic Association Division I programs were recruited as freshmen between June 2014 and June 2017 and analyzed at multiple points throughout 3 complete years of collegiate US football participation (until January 2019). Excluded athletes were those who did not complete any season of US football training because of injury, illness, or leaving the team. Factors associated with CV risk assessed clinically, by transthoracic echocardiography, and by vascular applanation tonometry were recorded. Exposures: The exposure of interest was seasonal US football exposure, including training, competition, and the training environment. Main Outcomes and Measures: Primary outcome measures were left ventricular mass index and geometry (cardiac structure), early diastolic myocardial relaxation velocity (E'; diastolic function), and pulse-wave velocity (arterial stiffness). Results: Of 186 individuals recruited as freshmen, 126 athletes were included in analyzed data. Collegiate US football athletes (62 white individuals [49%]; 63 black individuals [50%]; 77 nonlinemen [61%]; 49 linemen [39%]; 126 male individuals [100%]) weighed a mean (SD) of 101.1 (21.0) kg, with a mean systolic blood pressure of 129.1 (11.6) mm Hg at baseline of the freshman season. Adjusting for race, height, and player position, there were significant increases in weight (mean [SE] Δ, 4.74 [0.6] kg; P < .001), systolic blood pressure (mean [SE] Δ, 11.6 [1.6] mm Hg; P < .001), and pulse-wave velocity (mean [SE] Δ, 0.24 [0.09] m/s; P = .007), and significant declines in E' (mean [SE] Δ, -1.7 [0.3] cm/s; P < .001) across 3 years of US football participation. Weight gain was associated with both arterial stiffening (increased pulse-wave velocity, ß = 0.01 [SE, 0.004]; P = .003) and the development of concentric left ventricular hypertrophy (odds ratio, 1.09 [95% CI, 1.05-1.14]; P < .001); increased systolic blood pressure was also associated with arterial stiffening (ß = 0.01 [SE, 0.003]; P = .007) and the development of concentric left ventricular hypertrophy (odds ratio, 1.04 [95% CI, 1.01-1.07]; P = .02). Conclusions and Relevance: Collegiate US football athletes who gain weight and develop increased systolic blood pressure levels are at risk for the development of a pathologic CV phenotype characterized by concentric left ventricular hypertrophy, arterial stiffening, and reduced left ventricular diastolic function. Future work aimed at optimizing CV health in this population, who are young but uniquely at risk, is warranted.