Genotype-negative hypertrophic cardiomyopathy: Exploring the role of cardiovascular risk factors in disease expression

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited myocardial disease. An inheritable cause is identified in approximately half of patients. Earlier research has identified clinical differences between genotype-positive (G+) and genotype-negative (G-) HCM patients, which this study aimed to further explore. Methods and results: Differences in baseline characteristics, including cardiovascular risk factors (CVRF), and phenotypical factors between G+ and G- patients were explored. Subanalyses among distinct age groups and sexes were performed. A total of 422 HCM (46 % G-, 54 % G+) patients were included. G- patients were older (62 vs 54 years, p < 0.001), experienced more limiting cardiac symptoms (47 % vs 28 %, p = 0.008), and more frequent left ventricular outflow tract obstruction (57 % vs 38 %, p < 0.001). CVRF were more prevalent in G- than in G+ HCM patients (70 % vs 41 %, p < 0.001), with hypertension being the most prevalent factor (51 % vs 22 %, p < 0.001). Despite adjusting for patient age, CVRF presence significantly predicted G- classification (OR 2.3, 95 %CI 1.5–3.6, p < 0.001). Female G- patients were less prevalent in younger age groups, and only in the older age group (>60 years) were female G- patients diagnosed later than their G+ counterparts. Conclusion: CVRF, particularly hypertension, are more prevalent in G- patients independent of age, suggesting that cardiovascular health may contribute to HCM disease development. Male-female differences suggest female-specific factors affecting the development of HCM in women. Recognizing G- HCM as a distinct clinical entity may have important implications for patient management, and a more comprehensive understanding of its aetiology may aid in tailoring future therapies.