David S. Owens

BACKGROUND: Limited information is available regarding genetic contributions to valvular calcification, which is an important precursor of clinical valve disease. METHODS: We determined genomewide associations with the presence of aortic-valve calcification (among 6942 participants) and mitral annular calcification (among 3795 participants), as detected by computed tomographic (CT) scanning; the study population for this analysis included persons of white European ancestry from three cohorts participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (discovery population). Findings were replicated in independent cohorts of persons with either CT-detected valvular calcification or clinical aortic stenosis. RESULTS: One SNP in the lipoprotein(a) (LPA) locus (rs10455872) reached genomewide significance for the presence of aortic-valve calcification (odds ratio per allele, 2.05; P=9.0×10(-10)), a finding that was replicated in additional white European, African-American, and Hispanic-American cohorts (P<0.05 for all comparisons). Genetically determined Lp(a) levels, as predicted by LPA genotype, were also associated with aortic-valve calcification, supporting a causal role for Lp(a). In prospective analyses, LPA genotype was associated with incident aortic stenosis (hazard ratio per allele, 1.68; 95% confidence interval [CI], 1.32 to 2.15) and aortic-valve replacement (hazard ratio, 1.54; 95% CI, 1.05 to 2.27) in a large Swedish cohort; the association with incident aortic stenosis was also replicated in an independent Danish cohort. Two SNPs (rs17659543 and rs13415097) near the proinflammatory gene IL1F9 achieved genomewide significance for mitral annular calcification (P=1.5×10(-8) and P=1.8×10(-8), respectively), but the findings were not replicated consistently. CONCLUSIONS: Genetic variation in the LPA locus, mediated by Lp(a) levels, is associated with aortic-valve calcification across multiple ethnic groups and with incident clinical aortic stenosis. (Funded by the National Heart, Lung, and Blood Institute and others.).

BACKGROUND: The incidence and cause of sudden cardiac death (SCD) in athletes is debated with hypertrophic cardiomyopathy often reported as the most common cause. METHODS AND RESULTS: A database of all National Collegiate Athletic Association deaths (2003-2013) was developed. Additional information and autopsy reports were obtained when possible. Cause of death was adjudicated by an expert panel. There were 4 242 519 athlete-years (AY) and 514 total student athlete deaths. Accidents were the most common cause of death (257, 50%, 1:16 508 AY) followed by medical causes (147, 29%, 1:28 861 AY). The most common medical cause of death was SCD (79, 15%, 1:53 703 AY). Males were at higher risk than females 1:37 790 AY versus 1:121 593 AY (incidence rate ratio, 3.2; 95% confidence interval, 1.9-5.5; P<0.00001), and black athletes were at higher risk than white athletes 1:21491 AY versus 1:68 354 AY (incidence rate ratio, 3.2; 95% confidence interval, 1.9-5.2; P<0.00001). The incidence of SCD in Division 1 male basketball athletes was 1:5200 AY. The most common findings at autopsy were autopsy-negative sudden unexplained death in 16 (25%), and definitive evidence for hypertrophic cardiomyopathy was seen in 5 (8%). Media reports identified more deaths in higher divisions (87%, 61%, and 44%), whereas the percentages from the internal database did not vary (87%, 83%, and 89%). Insurance claims identified only 11% of SCDs. CONCLUSIONS: The rate of SCD in National Collegiate Athletic Association athletes is high, with males, black athletes, and basketball players at substantially higher risk. The most common finding at autopsy is autopsy-negative sudden unexplained death. Media reports are more likely to capture high-profile deaths, and insurance claims are not a reliable method for case identification.

Sudden cardiac death (SCD) is the leading cause of death in athletes during sport. Whether obtained for screening or diagnostic purposes, an ECG increases the ability to detect underlying cardiovascular conditions that may increase the risk for SCD. In most countries, there is a shortage of physician expertise in the interpretation of an athlete's ECG. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from abnormal findings suggestive of pathology. On 13-14 February 2012, an international group of experts in sports cardiology and sports medicine convened in Seattle, Washington, to define contemporary standards for ECG interpretation in athletes. The objective of the meeting was to develop a comprehensive training resource to help physicians distinguish normal ECG alterations in athletes from abnormal ECG findings that require additional evaluation for conditions associated with SCD.