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Genetically Confirmed Familial Hypercholesterolemia in Patients With Acute Coronary Syndrome
Almudena Amor-Salamanca1, Sergio Castillo2, Emiliano Gonzalez-Vioque3
1Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
Insights
Genetic testing confirms familial hypercholesterolemia (FH) in approximately 9% of acute coronary syndrome (ACS) patients with high LDL-C. Clinical criteria miss many FH cases, highlighting the need for genetic testing in this population.
Area of Science:
- Cardiovascular Genetics
- Lipidology
- Genetic Diagnostics
Background:
- Genetic screening for familial hypercholesterolemia (FH) in general populations yields limited success.
- Identifying FH is crucial for preventing premature cardiovascular events.
Purpose of the Study:
- To determine the prevalence of genetically confirmed FH in patients experiencing acute coronary syndrome (ACS).
- To compare the diagnostic accuracy of established FH clinical criteria against genetic testing in ACS patients.
Main Methods:
- Genetic analysis of 7 FH-associated genes and 12 polygenic hypercholesterolemia alleles in 103 ACS patients (age ≤65, LDL-C ≥160 mg/dl).
- Application of Dutch Lipid Clinic (DLC) and Simon Broome (SB) clinical criteria for FH diagnosis.
- Cascade genetic testing in first-degree relatives of identified FH patients.
Main Results:
- Genetically confirmed FH was present in 8.7% of ACS patients.
- DLC and SB criteria failed to diagnose 44% and 33% of genetically confirmed FH cases, respectively.
- Cascade testing identified 6 additional relatives with FH.
Conclusions:
- Approximately 9% of ACS patients under 65 with elevated LDL-C have genetically confirmed FH.
- Current clinical criteria for FH diagnosis are insufficient in ACS patients.
- Genetic testing is recommended for early identification of FH in young ACS patients and their at-risk relatives.
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.
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