Predicting resilience in heterozygous familial hypercholesterolaemia: A cohort study of octogenarian patients


      • Defining FH patients destined not to develop disease has significant implications.
      • This study shows that a low SAFEHEART-Risk Equation score was predictor of OR-FH.
      • This risk equation may be useful to detect who may require less intensive treatment.


      Defining patients with familial hypercholesterolemia (FH) destined not to develop clinical atherosclerotic cardiovascular disease (ASCVD) has significant implications for precision and discovery medicine. We investigated the predictors of resilience to ASCVD in a cohort of 248 octogenarian patients with FH enrolled in the SAFEHEART study. Median age at the time of analysis was 84.7 years (82.3–88.1) and 83.6 years (81.9–86.4) in the octogenarian resilient FH (OR-FH) and octogenarian controls non-resilient FH (OCNoR-FH) groups, respectively (p=0.073); 92 (80.0%) and 68 (51.1%) patients were female in the first compared with the second group (p<0.001). Multivariate logistic regression showed that a low 10-year score in SAFEHEART-Risk Equation was the only independent predictor of OR-FH. Application of this simple and validated risk equation may potentially be useful for predicting patients ultra-resilient to the ASCVD sequelae of FH who may require less intensive use of healthcare resources.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Clinical Lipidology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Watts GF
        • Gidding SS
        • Mata P
        • et al.
        Familial hypercholesterolaemia: evolving knowledge for designing adaptive models of care.
        Nat Rev Cardiol. 2020; 17: 360-377
        • Pérez de Isla L
        • Watts G
        • Muñiz-Grijalvo O
        • et al.
        A resilient type of familial hypercholesterolaemia: case-control follow-up of genetically characterized older patients in the SAFEHEART cohort.
        Eur J Prev Cardiol. 2021; Dec 2 (zwab(Epub ahead of print))
        • Pérez De Isla L
        • Alonso R
        • Mata N
        • et al.
        Predicting cardiovascular events in familial hypercholesterolemia: the SAFEHEART registry (Spanish Familial hypercholesterolemia cohort study).
        Circulation. 2017; 135: 2133-2144
        • Coutinho ER
        • Miname MH
        • Rocha VZ
        • et al.
        Familial hypercholesterolemia and cardiovascular disease in older individuals.
        Atherosclerosis. 2021; 318: 32-37
        • Khoury E
        • Brisson D
        • Roy N
        • Tremblay G
        • Gaudet D.
        Identifying markers of cardiovascular event-free survival in familial hypercholesterolemia.
        J Clin Med. 2020; 10: 64
        • Lacaze P
        • Sebra R
        • Riaz M
        • et al.
        Familial hypercholesterolemia in a healthy elderly population.
        Circ Genom Precis Med. 2020; 13: 337-339
        • Pérez de Isla L
        • Alonso R
        • Muñiz-Grijalvo O
        • et al.
        Coronary computed tomographic angiography findings and their therapeutic implications in asymptomatic patients with familial hypercholesterolemia. Lessons from the SAFEHEART study.
        J Clin Lipidol. 2018; 12: 948-957
        • Cooney MT
        • Dudina A
        • D'Agostino R
        • Graham IM
        Cardiovascular risk-estimation systems in primary prevention: do they differ? do they make a difference? can we see the future?.
        Circulation. 2010; 122: 300-310
        • Fahed AC
        • Wang M
        • Homburger JR
        • et al.
        Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions.
        Nat Commun. 2020; 11: 3635