Author + information
- Received May 14, 2017
- Revision received August 1, 2017
- Accepted August 8, 2017
- Published online September 25, 2017.
- Almudena Amor-Salamanca, MDa,
- Sergio Castillo, PhDb,
- Emiliano Gonzalez-Vioque, PhDc,
- Fernando Dominguez, MDa,d,
- Lucía Quintana, PhDb,
- Carla Lluís-Ganella, PhDb,
- Juan Manuel Escudier, MDa,
- Javier Ortega, MDa,
- Enrique Lara-Pezzi, PhDd,e,
- Luis Alonso-Pulpon, MD, PhDa,d and
- Pablo Garcia-Pavia, MD, PhDa,d,f,∗ ()
- aInherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain
- bGendiag.exe, Inc/Ferrer inCode, Inc., Barcelona, Spain
- cDepartment of Biochemistry, Hospital Universitario Puerta de Hierro, Madrid, Spain
- dCIBER in Cardiovascular Diseases (CIBERCV), Madrid, Spain
- eMyocardial Biology Program, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
- fFaculty of Health Sciences, University Francisco de Vitoria (UFV), Pozuelo de Alarcon, Madrid, Spain
- ↵∗Address for correspondence:
Dr. Pablo Garcia-Pavia, Department of Cardiology, Hospital Universitario Puerta de Hierro, Manuel de Falla, 2. Majadahonda, Madrid, 28222, Spain, Facultad de Ciencias de la Salud, Universidad Francisco de Vitoria (UFV), Ctra. M-515 Pozuelo-Majadahonda Km 1,800, 28223, Pozuelo de Alarcón, Madrid, Spain.
Background Genetic screening programs in unselected individuals with increased levels of low-density lipoprotein cholesterol (LDL-C) have shown modest results in identifying individuals with familial hypercholesterolemia (FH).
Objectives This study assessed the prevalence of genetically confirmed FH in patients with acute coronary syndrome (ACS) and compared the diagnostic performance of FH clinical criteria versus FH genetic testing.
Methods Genetic study of 7 genes (LDLR, APOB, PCSK9, APOE, STAP1, LDLRAP1, and LIPA) associated with FH and 12 common alleles associated with polygenic hypercholesterolemia was performed in 103 patients with ACS, age ≤65 years, and LDL-C levels ≥160 mg/dl. Dutch Lipid Clinic (DLC) and Simon Broome (SB) FH clinical criteria were also applied.
Results The prevalence of genetically confirmed FH was 8.7% (95% confidence interval [CI]: 4.3% to 16.4%; n = 9); 29% (95% CI: 18.5% to 42.1%; n = 18) of patients without FH variants had a score highly suggestive of polygenic hypercholesterolemia. The prevalence of probable to definite FH according to DLC criteria was 27.2% (95% CI: 19.1% to 37.0%; n = 28), whereas SB criteria identified 27.2% of patients (95% CI: 19.1% to 37.0%; n = 28) with possible to definite FH. DLC and SB algorithms failed to diagnose 4 (44%) and 3 (33%) patients with genetically confirmed FH, respectively. Cascade genetic testing in first-degree relatives identified 6 additional individuals with FH.
Conclusions The prevalence of genetically confirmed FH in patients with ACS age ≤65 years and with LDL-C levels ≥160 mg/dl is high (approximately 9%). FH clinical algorithms do not accurately classify patients with FH. Genetic testing should be advocated in young patients with ACS and high LDL-C levels to allow prompt identification of patients with FH and relatives at risk.
This research was supported in part by the Instituto de Salud Carlos III (grants RD012/0042/0066 and CB16/11/00432), Spanish Ministry of Economy and Competitiveness (grant SAF2015-71863-REDT), and Alexion through an Investigator Initiated Research Grant. Grants from the Instituto de Salud Carlos III and the Spanish Ministry of Economy and Competitiveness are supported by the Plan Estatal de I+D+I 2013–2016 European Regional Development Fund (FEDER), “A way of making Europe.” The sponsors played no role in the design, collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication. Drs. Castillo, Lluís-Ganella, and Quintana are employees of Gendiag.exe/Ferrer inCode. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Karol Watson, MD, served as Guest Editor for this paper.
- Received May 14, 2017.
- Revision received August 1, 2017.
- Accepted August 8, 2017.
- 2017 American College of Cardiology Foundation