Results:

Since the CARDIA study published the prevalence of HCM in 1995, more than 11 genes have been identified, which primarily encode over 1,500 cardiac sarcomere and sarcomere-related single nucleotide mutations. The CARDIA cohort study was a biracial cohort of 4,111 unrelated people ages 23-35 years, randomly selected from the general population in community-based urban centers and census tracts. In 2012, Seidman and colleagues described the frequency of pathogenic mutations in a community-based cohort that included 3,600 participants ages 30-84, 1,637 unrelated individuals in the offspring cohort of the Framingham Heart Study, and 1,963 unrelated individuals from the Jackson Heart Study cohort. The CARDIA study phenotyped patients using an echocardiogram, while the Seidman study performed genotyping. By screening for the eight main HCM-causing sarcomere protein genes, Seidman and colleagues were able to identify at least one rare nonsynonymous sarcomere variant in 11.2% of the general population, of which 0.6% were considered pathogenic. Based on this, the minimum prevalence of HCM gene carriers could be estimated as high as 1 in 200. Genetic testing has allowed for the identification of patients who are at risk, but who are not yet clinically affected (genotype +/phenotype-); therefore, earlier studies were not able to identify this subgroup. Other sources of underestimation of HCM prevalence stem from exclusion of certain age groups and family members. In addition, newer imaging modalities, such as cardiac magnetic resonance imaging, may enhance the identification of HCM.