Leopoldo Pérez de Isla1,2, Gerald F Watts3,4, Rodrigo Alonso2,5, José Luis Díaz-Díaz6, Ovidio Muñiz-Grijalvo7, Daniel Zambón8, Francisco Fuentes9, Raimundo de Andrés10, Teresa Padró11, José López-Miranda9, Pedro Mata2. 1. Cardiology Department, Hospital Clínico San Carlos, IDISSC, Facultad de Medicina, Universidad Complutense, C/Profesor Martín Lagos s/n, 28040 Madrid, Spain. 2. Fundación Hipercolesterolemia Familiar, Madrid, Spain. 3. School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia. 4. Lipid Disorders Clinic, Cardiometabolic Services, Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia. 5. Center for Advanced Metabolic Medicine and Nutrition, Santiago de Chile, Chile. 6. Department of Internal Medicine, Hospital Abente y Lago, A Coruña, Spain. 7. Department of Internal Medicine, Hospital Virgen del Rocío, Sevilla, Spain. 8. Department of Endocrinology, Hospital Clinic, Barcelona, Spain. 9. Lipids and Atherosclerosis Unit, CIBERObn, IMIBIC/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain. 10. Department of Internal Medicine, Fundación Jiménez Díaz, Madrid, Spain. 11. Programa-ICCC Cardiovascular, Institut de Recerca del Hospital Santa Creu i Sant Pau, IIB Santa Pau, Barcelona, Spain.
Abstract
AIMS: Familial hypercholesterolaemia (FH) and elevated lipoprotein(a) [Lp(a)] are inherited disorders associated with premature atherosclerotic cardiovascular disease (ASCVD). Aortic valve stenosis (AVS) is the most prevalent valvular heart disease and low-density lipoprotein cholesterol (LDL-C) and Lp(a) may be involved in its pathobiology. We investigated the frequency and predictors of severe AVS requiring aortic valve replacement (AVR) in molecularly defined patients with FH. METHODS AND RESULTS: SAFEHEART is a long-term prospective cohort study of a population with FH and non-affected relatives (NAR). We analysed the frequency and predictors of the need for AVR due to AVS in this cohort. Five thousand and twenty-two subjects were enrolled (3712 with FH; 1310 NAR). Fifty patients with FH (1.48%) and 3 NAR (0.27%) required AVR [odds ratio 5.71; 95% confidence interval (CI): 1.78-18.4; P = 0.003] after a mean follow-up of 7.48 (3.75) years. The incidence of AVR was significantly higher in patients with FH (log-rank 5.93; P = 0.015). Cox regression analysis demonstrated an association between FH and AVR (hazard ratio: 3.89; 95% CI: 1.20-12.63; P = 0.024), with older age, previous ASCVD, hypertension, increased LDL-CLp(a)-years, and elevated Lp(a) being independently predictive of an event. CONCLUSION: The need for AVR due to AVS is significantly increased in FH patients, particularly in those who are older and have previous ASCVD, hypertension, increased LDL-CLp(a)-years and elevated Lp(a). Reduction in LDL-C and Lp(a) together with control of hypertension could retard the progression of AVS in FH, but this needs testing in clinical trials.ClinicalTrials.gov number NCT02693548. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Familial hypercholesterolaemia (FH) and elevated lipoprotein(a) [Lp(a)] are inherited disorders associated with premature atherosclerotic cardiovascular disease (ASCVD). Aortic valve stenosis (AVS) is the most prevalent valvular heart disease and low-density lipoprotein cholesterol (LDL-C) and Lp(a) may be involved in its pathobiology. We investigated the frequency and predictors of severe AVS requiring aortic valve replacement (AVR) in molecularly defined patients with FH. METHODS AND RESULTS: SAFEHEART is a long-term prospective cohort study of a population with FH and non-affected relatives (NAR). We analysed the frequency and predictors of the need for AVR due to AVS in this cohort. Five thousand and twenty-two subjects were enrolled (3712 with FH; 1310 NAR). Fifty patients with FH (1.48%) and 3 NAR (0.27%) required AVR [odds ratio 5.71; 95% confidence interval (CI): 1.78-18.4; P = 0.003] after a mean follow-up of 7.48 (3.75) years. The incidence of AVR was significantly higher in patients with FH (log-rank 5.93; P = 0.015). Cox regression analysis demonstrated an association between FH and AVR (hazard ratio: 3.89; 95% CI: 1.20-12.63; P = 0.024), with older age, previous ASCVD, hypertension, increased LDL-CLp(a)-years, and elevated Lp(a) being independently predictive of an event. CONCLUSION: The need for AVR due to AVS is significantly increased in FH patients, particularly in those who are older and have previous ASCVD, hypertension, increased LDL-CLp(a)-years and elevated Lp(a). Reduction in LDL-C and Lp(a) together with control of hypertension could retard the progression of AVS in FH, but this needs testing in clinical trials.ClinicalTrials.gov number NCT02693548. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Rodrigo Alonso; Rosa Argüeso; Pilar Álvarez-Baños; Ovidio Muñiz-Grijalvo; Jose Luis Diaz-Diaz; Pedro Mata Journal: Curr Atheroscler Rep Date: 2022-04-07 Impact factor: 5.113