Predicting Cardiovascular Events in Familial Hypercholesterolemia: The SAFEHEART Registry (Spanish Familial Hypercholesterolemia Cohort Study)
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Leopoldo Pérez de Isla1, Rodrigo Alonso1, Nelva Mata1
1From Cardiology Department, Hospital Clínico San Carlos, IDISSC, Universidad Complutense, Madrid, Spain (L.P.d.I.); Fundación Hipercolesterolemia Familiar, Madrid, Spain (L.P.d.I., R. Alonso, N.M., A.S., P.M.); Clínica las Condes, Santiago, Chile (R. Alonso); Department of Epidemiology, Madrid Health Authority, Madrid, Spain (N.M.); Clinical Epidemiology Unit, Servicio de Medicina Preventiva, Instituto de Investigación Sanitaria San Carlos, Universidad Complutense, Madrid, Spain (C.F.-P.); Department of Internal Medicine, Hospital Virgen del Rocío, Sevilla, Spain (O.M.); Department of Internal Medicine, Hospital Abente y Lago, A Coruña, Spain (J.L.D.-D.); Cardiology Department, Hospital del Tajo, Universidad Alfonso X el Sabio, Madrid, Spain (A.S.); Lipids and Atherosclerosis Unit, Instituto Maimónides de Investigación Biomédica de Córdoba/Reina Sofia University Hospital/University of Cordoba, Cordoba, Spain (F.F.-J.); Department of Internal Medicine, Fundación Jiménez Díaz, IIS, Madrid, Spain (R.d.A.); Department of Endocrinology, Hospital Clinic, Barcelona, Spain (D.Z.); Department of Internal Medicine, Hospital Universitario de Elche, Alicante, Spain (M.P.); Department of Internal Medicine, Hospital de Vega Baja, Orihuela, Alicante, Spain (J.M.C.); Department of Internal Medicine, Hospital de Terrassa, Barcelona, Spain (M.M.); Department of Internal Medicine, Hospital de Ciudad Real, Spain (J.G.); Department of Internal Medicine, Hospital de San Pedro, Logroño, Spain (A.B.); Department of Internal Medicine, Hospital San Pedro de Alcántara, Cáceres, Spain (J.F.S.M.-T.); Instituto Catalán Ciencias Cardiovasculares, Instituto de Investigación Biomédica-Sant Pau, Barcelona, Spain (T.P., L.B.); Department of Endocrinology, Hospital Universitario de Lugo, Spain (R. Argueso); Department of Internal Medicine, Hospital Universitariode Salamanca, Spain (J.P.M.-G.); Lipid Clinic Heart Institute (InCor), University of São Paulo Medical School Hospital and Preventive Centre and Cardiology Program, Hospital Israelita Albert Einstein, Brazil (R.D.S.); and Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia (G.F.W.).
Insights
This study developed a new risk equation to predict atherosclerotic cardiovascular disease (ASCVD) in patients with familial hypercholesterolemia (FH). The SAFEHEART equation improves risk stratification for better ASCVD management in FH patients.
Area of Science:
- Cardiology
- Genetics
- Public Health
Background:
- Familial hypercholesterolemia (FH) is a genetic condition leading to high LDL cholesterol and increased risk of atherosclerotic cardiovascular disease (ASCVD).
- Existing models for ASCVD risk prediction have not been specifically validated or developed for the unique population with FH.
Purpose of the Study:
- To define key risk factors for incident ASCVD in patients with FH.
- To develop and validate a novel risk prediction equation for ASCVD in FH patients using data from the SAFEHEART registry.
Main Methods:
- A multicenter, nationwide, long-term prospective cohort study (SAFEHEART) followed 2404 adult patients with FH.
- Risk factors were analyzed to build a prediction equation, which was then tested for its ability to discriminate incident ASCVD events.
Main Results:
- Over a mean follow-up of 5.5 years, 134 patients experienced incident ASCVD (fatal or nonfatal).
- Independent predictors of ASCVD included age, male sex, prior ASCVD, hypertension, obesity, smoking, LDL cholesterol, and lipoprotein(a).
- The derived SAFEHEART risk equation demonstrated strong predictive performance (Harrell C index = 0.85), outperforming modified Framingham and ACC/AHA equations.
Conclusions:
- Simple clinical predictors can effectively estimate ASCVD risk in individuals with FH.
- The SAFEHEART risk equation offers improved risk stratification for FH patients.
- This tool can guide more precise therapeutic interventions for managing ASCVD risk in FH.
Background:
Although risk factors for atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolemia (FH) have been described, models for predicting incident ASCVD have not been reported. Our aim was to use the SAFEHEART registry (Spanish Familial Hypercholesterolemia Cohort Study) to define key risk factors for predicting incident ASCVD in patients with FH.
Methods:
SAFEHEART is a multicenter, nationwide, long-term prospective cohort study of a molecularly defined population with FH with or without previous ASCVD. Analyses to define risk factors and to build a risk prediction equation were developed, and the risk prediction equation was tested for its ability to discriminate patients who experience incident ASCVD from those who did not over time.
Results:
We recruited 2404 adult patients with FH who were followed up for a mean of 5.5 years (SD, 3.2 years), during which 12 (0.5%) and 122 (5.1%) suffered fatal and nonfatal incident ASCVD, respectively. Age, male sex, history of previous ASCVD, high blood pressure, increased body mass index, active smoking, and low-density lipoprotein cholesterol and lipoprotein(a) levels were independent predictors of incident ASCVD from which a risk equation with a Harrell C index of 0.85 was derived. The bootstrap resampling (100 randomized samples) of the original set for internal validation showed a degree of overoptimism of 0.003. Individual risk was estimated for each person without an established diagnosis of ASCVD before enrollment in the registry by use of the SAFEHEART risk equation, the modified Framingham risk equation, and the American College of Cardiology/American Heart Association ASCVD Pooled Cohort Risk Equations. The Harrell C index for these models was 0.81, 0.78, and 0.8, respectively, and differences between the SAFEHEART risk equation and the other 2 were significant (P=0.023 and P=0.045).
Conclusions:
The risk of incident ASCVD may be estimated in patients with FH with simple clinical predictors. This finding may improve risk stratification and could be used to guide therapy in patients with FH.
Clinical Trial Registration:
URL: http://clinicaltrials.gov. Unique identifier: NCT02693548.
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