Significance of Clinical and Genetic Signatures of Familial Hypercholesterolemia Among Patients With Severe Hypercholesterolemia
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Published on: September 15, 2018
Hayato Tada1, Atsushi Nohara2, Soichiro Usui1
1Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
Insights
Familial hypercholesterolemia (FH) clinical and genetic signs predict coronary artery disease (CAD) events in severe hypercholesterolemia patients. These indicators offer valuable risk assessment beyond LDL cholesterol levels.
Area of Science:
- Cardiology
- Genetics
- Metabolic Disorders
Background:
- Familial hypercholesterolemia (FH) diagnosis relies on clinical indicators like family history, xanthomas, or pathogenic FH-variants.
- Severe hypercholesterolemia is defined as LDL cholesterol ≥180 mg/dL.
Purpose of the Study:
- To determine if clinical and genetic markers of FH predict coronary artery disease (CAD) events independently of LDL cholesterol levels in patients with severe hypercholesterolemia.
- To assess the added value of FH signatures in cardiovascular risk stratification.
Main Methods:
- Retrospective analysis of 1,273 patients (≥15 years) with severe hypercholesterolemia (LDL-C ≥180 mg/dL) from 2000-2022.
- Patients categorized into four groups based on clinical FH signs and/or FH-variant presence.
- Cox proportional hazard models used to analyze factors associated with CAD events, adjusting for risk factors including LDL cholesterol scores.
Main Results:
- 144 CAD events occurred during a median 12.4-year follow-up.
- Patients with FH signs had higher baseline LDL cholesterol.
- FH-variant (HR: 1.44) and clinical FH signs (HR: 2.27) significantly increased CAD event risk.
- Combined FH-variant and clinical signs showed a >5-fold increased HR for CAD (HR: 5.02) after adjustment.
Conclusions:
- Clinical and genetic indicators of FH are valuable for discriminating CAD risk in patients with severe hypercholesterolemia.
- These FH signatures provide risk stratification beyond elevated LDL cholesterol levels alone.
- The findings support incorporating FH assessment for improved cardiovascular event prediction.
Background:
Familial hypercholesterolemia (FH) is diagnosed based on clinical signs of FH, including family history and/or xanthomas, or pathogenic FH-variant.
Objectives:
The authors aimed to clarify whether these signatures are associated with coronary artery disease (CAD) events beyond low density lipoprotein (LDL) cholesterol level among patients with severe hypercholesterolemia.
Methods:
We retrospectively reviewed the data of patients with severe hypercholesterolemia (LDL cholesterol ≥180 mg/dL) aged ≥15 years (N = 1,273; male, n = 631) admitted to Kanazawa University Hospital between 2000 and 2022. We divided the patients into 4 groups based on clinical signs of FH and/or presence of FH-variant and assessed the factors associated with CAD events using the Cox proportional hazard model.
Results:
We identified 144 CAD events during the 12.4-year median follow-up. Baseline LDL cholesterol level in patients with any signs of FH tended to be significantly higher than non-FH patients. Compared with the reference group of patients without any signs of FH, patients with FH-variant or clinical signs of FH had significantly higher HRs of developing CAD events (HR: 1.44; 95% CI: 1.02-1.86; P = 0.007 and HR: 2.27; 95% CI: 1.41-3.13; P < 0.001, respectively), whereas those with clinical signs of FH and FH-variant had more than 5-fold higher HR for CAD (HR: 5.02; 95% CI: 2.60-7.44; P < 0.001) after adjusting for known risk factors, including LDL cholesterol year score.
Conclusions:
Among patients with severe hypercholesterolemia, clinical and genetic signatures of FH are useful for risk discrimination for CAD beyond their hypercholesterolemia.
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