TY - JOUR
T1 - Sex-Specific Clinical and Genetic Factors Associated With Adverse Outcomes in Hypertrophic Cardiomyopathy
AU - Butters, Alexandra
AU - Arnott, Clare
AU - Sweeting, Joanna
AU - Claggett, Brian
AU - Cuomo, Anna
AU - Abrams, Dominic
AU - Ashley, Euan A.
AU - Day, Sharlene M.
AU - Helms, Adam S.
AU - Lampert, Rachel
AU - Lin, Kim
AU - Michels, Michelle
AU - Miller, Erin M.
AU - Olivotto, Iacopo
AU - Owens, Anjali
AU - Parikh, Victoria N.
AU - Pereira, Alexandre C.
AU - Rossano, Joseph W.
AU - Ryan, Thomas D.
AU - Saberi, Sara
AU - Stendahl, John C.
AU - Ware, James S.
AU - Atherton, John
AU - Semsarian, Christopher
AU - Lakdawala, Neal K.
AU - Ho, Carolyn Y.
AU - Ingles, Jodie
N1 - Publisher Copyright:
© 2025 American Heart Association, Inc.
PY - 2025/1/24
Y1 - 2025/1/24
N2 - BACKGROUND:Females with hypertrophic cardiomyopathy present at a more advanced stage of the disease and have a higher risk of heart failure and death. The factors behind these differences are unclear. We aimed to investigate sex-related differences in clinical and genetic factors affecting adverse outcomes in the Sarcomeric Human Cardiomyopathy Registry. METHODS: Cox proportional hazard models were fit with a sex interaction term to determine if significant sex differences existed in the association between risk factors and outcomes. Models were fit separately for females and males to find the sex-specific hazard ratio (HR). RESULTS: After a mean follow-up of 6.4 years, females had a higher risk of heart failure (HR, 1.51 [95% CI, 1.21-1.88]; P=0.0003) but a lower risk of atrial fibrillation (HR, 0.74 [95% CI, 0.59-0.93]; P<0.0001) and ventricular arrhythmia (HR, 0.60 [95% CI, 0.38-0.94]; P=0.027) than males. No sex difference was observed for death (P=0.84). Sarcomere-positive males had higher heart failure (HR, 1.34 [95% CI, 1.06-1.69]) and death risks (HR, 1.48 [95% CI, 1.08-2.04]) not seen in females (HR, 0.85 [95% CI, 0.66-1.08] versus HR, 0.86 [95% CI, 0.71-1.21]). MYBPC3 variants lowered heart failure risk in females (HR, 0.56 [95% CI, 0.41-0.77]) but not in males (HR, 1.29 [95% CI, 0.99-1.67]). A sex difference appeared in moderate (4% to <6%) versus low risk (<4%) European Society of Cardiology hypertrophic cardiomyopathy risk score, with females at moderate risk more prone to ventricular arrhythmia (HR, 3.57 [95% CI, 1.70-7.49]), unobserved in males (HR, 1.13 [95% CI, 0.63-2.03]). CONCLUSIONS: We found that clinical and genetic factors contributing to adverse outcomes in hypertrophic cardiomyopathy affect females and males differently. Thus, research to inform sex-specific management of hypertrophic cardiomyopathy could improve outcomes for both sexes.
AB - BACKGROUND:Females with hypertrophic cardiomyopathy present at a more advanced stage of the disease and have a higher risk of heart failure and death. The factors behind these differences are unclear. We aimed to investigate sex-related differences in clinical and genetic factors affecting adverse outcomes in the Sarcomeric Human Cardiomyopathy Registry. METHODS: Cox proportional hazard models were fit with a sex interaction term to determine if significant sex differences existed in the association between risk factors and outcomes. Models were fit separately for females and males to find the sex-specific hazard ratio (HR). RESULTS: After a mean follow-up of 6.4 years, females had a higher risk of heart failure (HR, 1.51 [95% CI, 1.21-1.88]; P=0.0003) but a lower risk of atrial fibrillation (HR, 0.74 [95% CI, 0.59-0.93]; P<0.0001) and ventricular arrhythmia (HR, 0.60 [95% CI, 0.38-0.94]; P=0.027) than males. No sex difference was observed for death (P=0.84). Sarcomere-positive males had higher heart failure (HR, 1.34 [95% CI, 1.06-1.69]) and death risks (HR, 1.48 [95% CI, 1.08-2.04]) not seen in females (HR, 0.85 [95% CI, 0.66-1.08] versus HR, 0.86 [95% CI, 0.71-1.21]). MYBPC3 variants lowered heart failure risk in females (HR, 0.56 [95% CI, 0.41-0.77]) but not in males (HR, 1.29 [95% CI, 0.99-1.67]). A sex difference appeared in moderate (4% to <6%) versus low risk (<4%) European Society of Cardiology hypertrophic cardiomyopathy risk score, with females at moderate risk more prone to ventricular arrhythmia (HR, 3.57 [95% CI, 1.70-7.49]), unobserved in males (HR, 1.13 [95% CI, 0.63-2.03]). CONCLUSIONS: We found that clinical and genetic factors contributing to adverse outcomes in hypertrophic cardiomyopathy affect females and males differently. Thus, research to inform sex-specific management of hypertrophic cardiomyopathy could improve outcomes for both sexes.
UR - https://www.scopus.com/pages/publications/85217139694
U2 - 10.1161/CIRCGEN.124.004641
DO - 10.1161/CIRCGEN.124.004641
M3 - Article
C2 - 39851041
AN - SCOPUS:85217139694
SN - 1942-325X
VL - 18
SP - e004641
JO - Circulation: Genomic and Precision Medicine
JF - Circulation: Genomic and Precision Medicine
IS - 1
M1 - e004641
ER -
