The Added Value of Coronary Calcium Score in Predicting Cardiovascular Events in Familial Hypercholesterolemia

Antonio Gallo (1, 2, 3) , Leopoldo Pérez de Isla (4, 5) , Sybil Charrière (6) , Alexandre Vimont (7) , Rodrigo Alonso (5) , Ovidio Muñiz-Grijalvo (8) , José Díaz-Díaz (9) , Daniel Zambón (10) , Philippe Moulin (6) , Eric Bruckert (1, 3) , Pedro Mata (5) , Sophie Béliard (11, 12) , Denis Angoulvant , Franck Boccara , Bertrand Cariou , Valérie Carreau , Alain Carrie (3) , Sybil Charrieres , Yves Cottin , Mathilde Di Filippo , Pierre-Henri Ducluzeau , Sonia Dulong , Vincent Durlach , Michel Farnier , Emile Ferrari , Dorota Ferrieres (13) , Jean Ferrieres , Philippe Giral (3) , Sophie Gonbert , Regis Hankard , Jocelyn Inamo , Olga Kalmykova , Michel Krempf , Julie Lemale , François Paillard , Noel Peretti , Agnes Perrin , Alain Pradignac , Jean Pierre Rabes , Vincent Rigalleau , François Schiele , Patrick Tounian , René Valero , Bruno Verges , Cecile Yelnik , Olivier Ziegler , Rocío Aguado , Ma Pilar Álvarez-Baños , Rosa Argüeso , Francisco Arrieta , Miguel Ángel Barba , Marta Casañas , José María Cepeda , Raimundo de Andrés , Gonzalo Díaz-Soto , Jose Luis Díaz-Diaz , Marta Dieguez , Ceferino Faedo , Francisco Fuentes , Juan Garrido , Aurora González , Pablo González-Bustos , Ma Dolores Mañas , Marta Mauri , Juan Diego Mediavilla , Alfredo Michán , Pablo Miramontes , Ovidio Muñiz , Leire Pérez , Leopoldo Perez de Isla , Xavier Pintó , Manuel Romero , Patricia Rubio , Juan Sánchez Muñoz-Torrero , Jose Vidal-Pardo , Ariane Sultan (14, 15)

1 CHU Pitié-Salpêtrière [AP-HP]
2 LIB - Laboratoire d'Imagerie Biomédicale [Paris]
3 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
4 IdISSC - Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain]
5 FHF - Fundación Hipercolesterolemia Familiar
6 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
7 Public Health Expertise [Paris, France]
8 Hospital Universitario Virgen del Rocío [Sevilla]
9 Hospital Abente y Lago [A Coruña]
10 IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer
11 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
12 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
13 Equipe Vieillissement (CERPOP)
14 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
15 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]

Objectives: This study aimed at investigating the additional contribution of coronary artery calcium (CAC) score to SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) risk equation (SAFEHEART-RE) for cardiovascular risk prediction in heterozygous familial hypercholesterolemia (HeFH). Background: Common cardiovascular risk equations are imprecise for HeFH. Because of the high phenotype variability of HeFH, CAC score could help to better stratify the risk of atherosclerotic cardiovascular disease (ASCVD). Methods: REFERCHOL (French Registry of Familial Hypercholesterolemia) and SAFEHEART are 2 ongoing national registries on HeFH. We analyzed data from primary prevention HeFH patients undergoing CAC quantification. We used probability-weighted Cox proportional hazards models to estimate HRs. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of CAC score when added to the SAFEHEART-RE for ASCVD prediction. ASCVD was defined as coronary heart disease, stroke or transient ischemic attack, peripheral artery disease, resuscitated sudden death, and cardiovascular death. Results: We included 1,624 patients (mean age: 48.5 ± 12.8 years; men: 45.7%) from both registries. After a median follow-up of 2.7 years (interquartile range: 0.4-5.0 years), ASCVD occurred in 81 subjects. The presence of a CAC score of >100 was associated with an HR of 32.05 (95% CI: 10.08-101.94) of developing ASCVD as compared to a CAC score of 0. Receiving-operating curve analysis showed a good performance of CAC score alone in ASCVD prediction (AUC: 0.860 [95% CI: 0.853-0.869]). The addition of log(CAC + 1) to SAFEHEART-RE resulted in a significantly improved prediction of ASCVD (AUC: 0.884 [95% CI: 0.871-0.894] for SAFEHEART-RE + log(CAC + 1) vs AUC: 0.793 [95% CI: 0.779-0.818] for SAFEHEART-RE; P < 0.001). These results were confirmed also when considering only hard cardiovascular endpoints. The addition of CAC score was associated with an estimated overall net reclassification improvement of 45.4%. Conclusions: CAC score proved its use in improving cardiovascular risk stratification and ASCVD prediction in statin-treated HeFH.

Mots clés: cardiovascular disease; coronary artery calcium; coronary imaging; familial hypercholesterolemia; genetic disease; risk prediction

Domaines: Sciences du Vivant [q-bio]

Antonio Gallo, Leopoldo Pérez de Isla, Sybil Charrière, Alexandre Vimont, Rodrigo Alonso, et al.. The Added Value of Coronary Calcium Score in Predicting Cardiovascular Events in Familial Hypercholesterolemia. JACC: Cardiovascular Imaging, 2021, 14 (12), pp.2414-2424. ⟨10.1016/j.jcmg.2021.06.011⟩. ⟨hal-03328261⟩