2024-03-28T10:09:36Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/79832022-11-08T09:39:57Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
00925njm 22002777a 4500
dc
Amor-Salamanca, Almudena
author
Castillo, Sergio
author
Gonzalez-Vioque, Emiliano
author
Dominguez, Fernando
author
Quintana, Lucía
author
Lluís-Ganella, Carla
author
Escudier, Juan Manuel
author
Virues-Ortega, Javier
author
Lara-Pezzi, Enrique
author
Alonso-Pulpon, Luis
author
Garcia-Pavia, Pablo
author
2017-10-03
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.
J Am Coll Cardiol. 2017; 70(14):1732-1740
0735-1097
http://hdl.handle.net/20.500.12105/7983
28958330
10.1016/j.jacc.2017.08.009
1558-3597
Journal of the American College of Cardiology
Dutch Lipid Clinic
Simon Broome criteria
Cholesterol
Genetics
Low-density lipoprotein cholesterol
Genetically Confirmed Familial Hypercholesterolemia in Patients With Acute Coronary Syndrome