Inmaculada Pérez-Sánchez1, Antonio José Romero-Puche2, Esperanza García-Molina Sáez3, María Sabater-Molina4, José María López-Ayala5, Carmen Muñoz-Esparza5, David López-Cuenca5, Gonzalo de la Morena5, Francisco José Castro-García6, Juan Ramón Gimeno-Blanes7. 1. Unidad de Cardiopatías Hereditarias, Instituto Médico de Investigación Biosanitaria (IMIB-Arrixaca), Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain. 2. Servicio de Cardiología, Hospital Universitario Morales Meseguer, Murcia, Spain. 3. Biobanco, Instituto Médico de Investigación Biosanitaria (IMIB-Arrixaca), Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain; Departamento de Medicina Interna, Universidad de Murcia, Murcia, Spain. 4. Unidad de Cardiopatías Hereditarias, Instituto Médico de Investigación Biosanitaria (IMIB-Arrixaca), Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain; Departamento de Medicina Interna, Universidad de Murcia, Murcia, Spain. Electronic address: mariasm79es@hotmail.com. 5. Servicio de Cardiología, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain. 6. Servicio de Pediatría, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain. 7. Unidad de Cardiopatías Hereditarias, Instituto Médico de Investigación Biosanitaria (IMIB-Arrixaca), Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain; Departamento de Medicina Interna, Universidad de Murcia, Murcia, Spain; Servicio de Cardiología, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
Abstract
INTRODUCTION AND OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is a disorder with variable expression. It is mainly caused by mutations in sarcomeric genes but the phenotype could be modulated by other factors. The aim of this study was to determine whether factors such as sex, systemic hypertension, or physical activity are modifiers of disease severity and to establish their role in age-related penetrance of HCM. METHODS: We evaluated 272 individuals (mean age 49 ± 17 years, 57% males) from 72 families with causative mutations. The relationship between sex, hypertension, physical activity, and left ventricular hypertrophy was studied. RESULTS: The proportion of affected individuals increased with age. Men developed the disease 12.5 years earlier than women (adjusted median, 95%CI, -17.52 to -6.48; P < .001). Hypertensive patients were diagnosed with HCM later (10.8 years of delay) than normotensive patients (adjusted median, 95%CI, 6.28-17.09; P < .001). Individuals who performed physical activity were diagnosed with HCM significantly earlier (7.3 years, adjusted median, 95%CI, -14.49 to -1.51; P = .016). Sex, hypertension, and the degree of physical activity were not significantly associated with the severity of left ventricular hypertrophy. Adjusted survival both free from sudden death and from the combined event were not influenced by any of the exploratory variables. CONCLUSIONS: Men and athletes who are carriers of sarcomeric mutations are diagnosed earlier than women and sedentary individuals. Hypertensive carriers of sarcomeric mutations have a delayed diagnosis. Sex, hypertension, and physical activity are not associated with disease severity in carriers of HCM causative mutations.
INTRODUCTION AND OBJECTIVES:Hypertrophic cardiomyopathy (HCM) is a disorder with variable expression. It is mainly caused by mutations in sarcomeric genes but the phenotype could be modulated by other factors. The aim of this study was to determine whether factors such as sex, systemic hypertension, or physical activity are modifiers of disease severity and to establish their role in age-related penetrance of HCM. METHODS: We evaluated 272 individuals (mean age 49 ± 17 years, 57% males) from 72 families with causative mutations. The relationship between sex, hypertension, physical activity, and left ventricular hypertrophy was studied. RESULTS: The proportion of affected individuals increased with age. Men developed the disease 12.5 years earlier than women (adjusted median, 95%CI, -17.52 to -6.48; P < .001). Hypertensivepatients were diagnosed with HCM later (10.8 years of delay) than normotensive patients (adjusted median, 95%CI, 6.28-17.09; P < .001). Individuals who performed physical activity were diagnosed with HCM significantly earlier (7.3 years, adjusted median, 95%CI, -14.49 to -1.51; P = .016). Sex, hypertension, and the degree of physical activity were not significantly associated with the severity of left ventricular hypertrophy. Adjusted survival both free from sudden death and from the combined event were not influenced by any of the exploratory variables. CONCLUSIONS:Men and athletes who are carriers of sarcomeric mutations are diagnosed earlier than women and sedentary individuals. Hypertensive carriers of sarcomeric mutations have a delayed diagnosis. Sex, hypertension, and physical activity are not associated with disease severity in carriers of HCM causative mutations.