Genetic testing for familial hypercholesterolemia among survivors of acute coronary syndrome
P Benedek1,2, M Eriksson1,2, K Duvefelt3
1Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden.
Insights
Familial hypercholesterolemia (FH) affects 6.9% of acute coronary syndrome (ACS) patients. Genetic testing for FH is recommended for ACS patients with a high Dutch Lipid Clinical Network (DLCN) score.
Area of Science:
- Cardiology
- Genetics
- Lipidology
Background:
- Familial hypercholesterolemia (FH) is a genetic disorder that can increase the risk of acute coronary syndrome (ACS).
- Identifying FH in ACS patients is crucial for timely intervention and secondary prevention.
Purpose of the Study:
- To determine the frequency of FH-causing mutations in ACS patients.
- To identify optimal criteria for selecting ACS patients for genetic testing for FH.
Main Methods:
- 116 ACS patients were analyzed using registry data (2009-2015).
- Patients met specific criteria for high cholesterol and triglyceride levels or lipid-lowering medication use.
- Genetic testing was performed using an FH mutation panel and commercial analysis.
Main Results:
- 6.9% of ACS patients carried FH-causative mutations, primarily in the LDL-receptor gene.
- FH-positive patients had significantly higher Dutch Lipid Clinical Network (DLCN) scores and LDL levels.
- The DLCN score demonstrated good discrimination for identifying FH.
Conclusions:
- Genetic testing for FH should be considered in patients presenting with ACS.
- A high DLCN score is a key indicator for FH genetic testing in ACS patients.
Background:
Familial hypercholesterolemia could be prevalent among patients with acute coronary syndrome.
Objective:
To investigate both the frequency of causative mutations for familial hypercholesterolemia (FH) and the optimal selection of patients for genetic testing among patients with an acute coronary syndrome (ACS).
Methods:
One hundred and sixteen patients with an ACS during 2009-2015 were identified through the SWEDEHEART registry. Patients who had either a high total cholesterol level ≥7 mmol L-1 combined with a triglyceride level ≤2.6 mmol L-1 , or were treated with lipid-lowering medication and had a total cholesterol level >4.9 mmol L-1 and a triglyceride level ≤2.6 mmol L-1 were included. Genetic testing was performed first with a regionally designed FH mutation panel (118 mutations), followed by testing with a commercially available FH genetic analysis (Progenika Biopharma).
Results:
A total of 6.9% (8/116) patients had a FH-causative mutation, all in the LDL-receptor. Five patients were detected on the panel, and further testing of the remaining 111 patients detected an additional 3 FH-causative mutations. Baseline characteristics were similar in FH-positive and FH-negative patients with respect to age, gender, prior ACS and diabetes. Patients with a FH-causative mutation had higher Dutch Lipid Clinical Network (DLCN) score (5.5 (5.0-6.5) vs 3.0 (2.0-5.0), P < 0.001) and a higher low-density lipoprotein level (5.7 (4.7-6.5) vs 4.9 (3.5-5.4), P = 0.030). The Dutch Lipid Clinical Network (DLCN) score had a good discrimination with an area under the curve of 0.856 (95% CI 0.763-0.949).
Conclusion:
Genetic testing for FH should be considered in patients with ACS and high DLCN score.
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