Related Experiment Video
Updated: Jun 8, 2025
Network Pharmacology Prediction and Metabolomics Validation of the Mechanism of Fructus Phyllanthi against Hyperlipidemia
Published on: April 7, 2023
Cardiovascular disease risk in patients with elevated LDL-C levels: FH vs. non-FH
Haomin Huang1, Lamei Li2, Anni Yang2
1Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Insights
Familial hypercholesterolemia (FH) mutations did not increase coronary artery disease (CAD) risk in patients with high LDL-C. However, FH mutations significantly increased the risk of severe CAD (triple vessel disease) in patients with normal kidney function.
Area of Science:
- Cardiology
- Genetics
- Nephrology
Background:
- Coronary artery disease (CAD) is a leading global cause of death.
- Familial hypercholesterolemia (FH) is a common genetic disorder that significantly increases CAD risk.
- High low-density lipoprotein cholesterol (LDL-C) levels are a major risk factor for CAD.
Purpose of the Study:
- To investigate the differential CAD risk between FH and non-FH patients with elevated LDL-C.
- To identify genetic risk factors for CAD severity in patients with hypercholesterolemia.
Main Methods:
- Enrolled 223 individuals (≥18 years) who underwent coronary angiography (CAG) and had LDL-C levels ≥4.0 mmol/L.
- Performed next-generation sequencing on 11 genes associated with FH.
- Analyzed CAD presence and severity (triple vessel disease - TVD) in relation to FH mutations and estimated glomerular filtration rate (eGFR).
Main Results:
- No significant difference in FH gene proportions was observed between CAD and non-CAD groups.
- The TVD group showed a higher proportion of FH gene mutations (P<0.05) and lower eGFR.
- Multivariate analysis identified eGFR as an independent risk factor for TVD; however, in patients with high eGFR, FH mutations in 3 major genes independently predicted TVD (OR 3.00).
Conclusions:
- FH mutations did not elevate CAD rates in individuals with LDL-C ≥4.0 mmol/L.
- Among CAD patients with normal renal function, FH mutations in 3 major genes were associated with a 3-fold increased risk of TVD.
Introduction:
Coronary artery disease (CAD) remains the primary cause of death worldwide, and familial hypercholesterolemia (FH) is a common disease that leads to CAD. This study aimed to explore the difference in CAD risk between FH and non-FH patients with high low-density lipoprotein cholesterol (LDL-C) levels.
Methods:
Individuals (≥18 years) who underwent coronary angiography (CAG) from June 2016 to September 2020 were consecutively enrolled. Participants with LDL-C levels ≥4.0 mmol/L were ultimately included in this study. For all participants, next-generation sequencing was performed with expanded gene panels including 11 genes (LDLR, APOB, PCSK9, LDLRAP1, ABCG5, ABCG8, LIPA, LPA, APOBR, LRPAP1, and STAP1).
Results:
A total of 223 individuals were included in this study. According to the CAG findings, 199 CAD patients and 24 non-CAD patients were included. The proportions of FH genes, regardless of whether 3 major genes or all 11 genes were sequenced, were not significantly different between the CAD and non-CAD groups (P > 0.05). In addition, all CAD patients were divided into a triple vessel disease (TVD) group and a non-TVD group. The TVD group had a greater proportion of patients with mutations in 3 FH major genes (P < 0.05). In addition, TC, LDL-C and modified LDL-C (MLDL-C) levels were higher and the estimated glomerular filtration rate (eGFR) was lower in the TVD group than in the non-TVD group (all P < 0.05). However, multivariate logistic regression analyses revealed that only the eGFR was an independent risk factor for TVD (OR 0.99; 95% CI: 0.98-1.00, P < 0.05). To eliminate the impact of the eGFR, subgroup analysis was conducted, and the results indicated that among CAD patients in the high-eGFR group, having FH mutations in 3 major genes was an independent risk factor for TVD (OR 3.00; 95% CI: 1.16-7.79, P < 0.05). In total, 104 FH-related mutations were detected in this study.
Conclusions:
FH mutation did not increase the rate of CAD in individuals with an MLDL-C level ≥4.0 mmol/L. However, among CAD patients (MLDL-C level ≥4.0 mmol/L) with almost normal renal function (≥87.4 ml/min/1.73 m2), the probability of enduring TVD in those with FH mutations in 3 major genes was 3.00 times greater than that in those without FH mutations.
More Related Videos
10:56A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes
Published on: September 15, 2018
07:29Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein
Published on: October 12, 2017
Related Concept Videos
01:25Blood Studies for Cardiovascular System III: Serum Lipid Profile
Serum lipids are fats and fatty substances in the blood and are crucial for various bodily functions, including energy storage, cellular structure, and hormone production. Serum lipids consist of cholesterol, triglycerides, and phospholipids.
Cholesterol is a soft, fat-like substance found in all body cells. It is crucial for producing hormones, vitamin D, and substances that aid...
01:29Cholesterol: Significance and Regulation
Considering cholesterol and...
01:18Lipids: Dietary Sources and Requirements
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
01:24Overview of Lipid Metabolism
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...
01:38Inflammation