Long-term sex differences in atherosclerotic cardiovascular disease in individuals with heterozygous familial hypercholesterolaemia in Spain: a study using data from SAFEHEART, a nationwide, multicentre, prospective cohort study
Por:
de Isla, LP, Vallejo-Vaz, AJ, Watts, GF, Muñiz-Grijalvo, O, Alonso, R, Diaz-Diaz, JL, Arroyo-Olivares, R, Aguado, R, Argueso, R, Mauri, M, Romero, MJ, Alvarez-Baños, P, Mañas, D, Cepeda, JM, Gonzalez-Bustos, P, Casañas, M, Michan, A, Muñoz-Torrero, JFS, Faedo, C, Barba, MA, Dieguez, M, de Andrés, R, Hernandez, AM, Gonzalez-Estrada, A, Padró, T, Fuentes, F, Badimon, L, Mata, P
Publicada:
1 sep 2024
Ahead of Print:
1 ago 2024
Resumen:
Background Sex differences in atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolaemia have been reported but are not fully established. We aimed to assess sex differences in the risk of ASCVD and life-time burden of ASCVD in patients with heterozygous familial hypercholesterolaemia. Methods SAFEHEART is a nationwide, multicentre, long-term prospective cohort study conducted in 25 tertiary care hospitals and one regional hospital in Spain. Participants in the SAFEHEART study aged 18 years or older with genetically confirmed familial hypercholesterolaemia were included in our analysis. Data were obtained between Jan 26, 2004, and Nov 30, 2022. ASCVD and age at onset were documented at enrolment and at follow-up. Our aim was to investigate the differences by sex in the risk and burden of ASCVD in patients with heterozygous familial hypercholesterolaemia, over the study follow-up and over the life course. The SAFEHEART study is registered with ClinicalTrials.gov, NCT02693548. Findings Of the 5262 participants in SAFEHEART at the time of analysis, 3506 (1898 [541%] female and 1608 [459%] male participants) met the inclusion criteria and were included in the current study. Mean age was 461 years (SD 155) and median follow-up was 103 years (IQR 64-130). Mean on-treatment LDL-cholesterol at follow-up was 31 mmol/L (SD 14) in females and 30 mmol/L (15) in males. LDL-cholesterol reductions over time were similar in both sexes (139 mmol/L [95% CI 130-147] absolute reduction in females vs 139 mmol/L [129-148] in males; p=098). At enrolment, 130 (68%) females and 304 (189%) males (p<00001) had cardiovascular disease. During follow-up, 134 (71%) females and 222 (138%) males (p<00001) had incident cardiovascular events. Median age at first ASCVD event (mostly due to coronary artery disease) was 616 years (IQR 500-714) in females and 506 years (420-586) in males (p<00001). The adjusted hazard ratio for ASCVD in males compared with females during follow-up was 190 (95% CI 149-242) and for cardiovascular death was 174 (111-273). Major adverse cardiovascular disease event (MACE)-free survival from birth was lower in males than females (hazard ratio 352 [95% CI 298-416]; p<00001). Median MACE-free survival time was 901 years (95% CI 865-not estimable) in females and 710 years (692-746) in males. The age at which 25% of female participants have had a MACE event was 749 years, this figure was 555 years in male participants. Interpretation Our findings suggest that the burden and risk of ASCVD are markedly lower in females than males with familial hypercholesterolaemia. The impact of sex needs to be considered to improve risk stratification and personalised management in patients with heterozygous familial hypercholesterolaemia. Funding Fundaci & oacute;n Hipercolesterolemia Familiar, the Instituto de Salud Carlos III, and Next Generation EU funds from the Recovery and Resilience Mechanism Program. Copyright (c) 2024 Published by Elsevier Ltd.
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Filiaciones:
de Isla, LP:
Univ Complutense, Hosp Clin San Carlos, Fac Med, Cardiol Dept, Madrid 28040, Spain
Fdn Hipercolesterolemia Familiar, Madrid 28010, Spain
Vallejo-Vaz, AJ:
Univ Seville, Fac Med, Dept Med, Seville, Spain
Univ Seville, Clin Epidemiol & Vasc Risk, Inst Biomed Sevilla IBiS, IBiS,Hosp Univ Virgen del Rocio,CSIC, Seville, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Epidemiol & Salud Publ, Madrid, Spain
Watts, GF:
Univ Western Australia, Sch Med, Perth, WA, Australia
Royal Perth Hosp, Dept Cardiol, Cardiometab Serv, Perth, WA, Australia
Royal Perth Hosp, Dept Internal Med, Cardiometab Serv, Perth, WA, Australia
Muñiz-Grijalvo, O:
Univ Seville, Clin Epidemiol & Vasc Risk, Inst Biomed Sevilla IBiS, IBiS,Hosp Univ Virgen del Rocio,CSIC, Seville, Spain
Hosp Virgen del Rocio, Dept Internal Med, Seville, Spain
Alonso, R:
Fdn Hipercolesterolemia Familiar, Madrid 28010, Spain
Ctr Adv Metab Med & Nutr, Santiago, Chile
Diaz-Diaz, JL:
Hosp Abente & Lago, Dept Internal Med, La Coruna, Spain
Arroyo-Olivares, R:
Fdn Hipercolesterolemia Familiar, Madrid 28010, Spain
Aguado, R:
Hosp Gen Leon, Dept Endocrinol, Leon, Spain
Argueso, R:
Hosp Univ Lucus Augusti, Dept Endocrinol, Lugo, Spain
Mauri, M:
Hosp Terrassa, Dept Internal Med, Terrassa, Spain
Romero, MJ:
Hosp Infanta Elena, Dept Internal Med, Huelva, Spain
Alvarez-Baños, P:
Hosp Univ Burgos, Dept Endocrinol, Burgos, Spain
Mañas, D:
Hosp Univ Ciudad Real, Dept Internal Med, Ciudad Real, Spain
Cepeda, JM:
Hosp Comarcal Vega Baja, Dept Internal Med, Orihuela, Spain
Gonzalez-Bustos, P:
Hosp Univ Virgen de las Nieves, Dept Internal Med, Granada, Spain
Casañas, M:
Hosp San Pedro, Dept Internal Med, Logrono, Spain
Michan, A:
Hosp Jerez de la Frontera, Dept Internal Med, Jerez de la Frontera, Spain
Muñoz-Torrero, JFS:
Hosp San Pedro de Alcantara, Dept Internal Med, Caceres, Spain
Faedo, C:
Hosp Cent Asturias, Dept Endocrinol, Oviedo, Spain
Barba, MA:
Complejo Hosp Univ Albacete, Dept Internal Med, Albacete, Spain
Dieguez, M:
Hosp Cabuenes, Dept Endocrinol, Gijon, Spain
de Andrés, R:
Fdn Jimenez Diaz, Dept Internal Med, Madrid, Spain
Hernandez, AM:
Hosp Clin Univ Virgen de la Arrixaca, Dept Endocrinol, Murcia, Spain
Gonzalez-Estrada, A:
Univ Seville, Clin Epidemiol & Vasc Risk, Inst Biomed Sevilla IBiS, IBiS,Hosp Univ Virgen del Rocio,CSIC, Seville, Spain
Hosp Virgen del Rocio, Dept Internal Med, Seville, Spain
Padró, T:
Hosp Santa Creu & Sant Pau, Res Inst, IIBSt Pau, CiberCV, Barcelona, Spain
Fuentes, F:
Univ Cordoba, Lipids & Atherosclerosis Unit, CIBERObn, IMIBIC,Reina Sofia Univ Hosp, Cordoba, Spain
Badimon, L:
Hosp Santa Creu & Sant Pau, Res Inst, IIBSt Pau, CiberCV, Barcelona, Spain
Mata, P:
Fdn Hipercolesterolemia Familiar, Madrid 28010, Spain
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