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Early Changes in the Plasma Lipidome of People at Very High Cardiovascular Risk: A New Approach to Assessing the Risk
Joanna Waś1, Piotr Dobrowolski2, Aleksander Prejbisz2
1Department of Medical Biology, National Institute of Cardiology, State Research Institute, 42 Alpejska Str., 04-628 Warsaw, Poland.
Insights
Early plasma lipidome changes in high cardiovascular risk individuals may serve as biomarkers for atherosclerotic cardiovascular disease (ASCVD). This study identified specific glycerophospholipid alterations linked to ASCVD comorbidities, offering new diagnostic and therapeutic avenues.
Area of Science:
- Biochemistry
- Cardiovascular Medicine
- Metabolomics
Background:
- Cardiovascular disease (CVD) is a leading global cause of mortality.
- Familial hypercholesterolemia (FH) significantly elevates CVD risk, yet its pathogenesis requires further elucidation.
- Genetic testing for FH has advanced, but unexplained cases persist.
Purpose of the Study:
- To identify early alterations in the plasma lipidome of individuals at high cardiovascular risk (HCVR).
- To explore potential lipid biomarkers for early assessment of cardiovascular risk.
- To investigate the association of lipid changes with comorbidities of atherosclerotic cardiovascular disease (ASCVD).
Main Methods:
- Lipidomic analysis of over 400 compounds using liquid chromatography-mass spectrometry.
- Comparison of 20 individuals with suspected FH/very high cardiovascular risk (VHCVR) and no identified mutations to a control group.
- Qualitative-quantitative analysis of plasma lipid profiles.
Main Results:
- Statistically significant alterations in glycerophospholipids (GC) were observed in HCVR patients.
- Increased phosphatidylcholines, phosphatidylethanolamines, and phosphatidylglycerol were noted in HCVR individuals.
- Specific lipid species correlated with arterial hypertension, atherosclerosis, and insulin resistance, implicating them in ASCVD pathogenesis.
Conclusions:
- Early changes in the plasma lipidome are evident in individuals at HCVR.
- Identified lipid alterations, particularly in GC, show potential as early biomarkers for ASCVD.
- These findings suggest novel therapeutic targets and personalized approaches for ASCVD diagnosis and management.
Abstract:
Background/Objectives: Cardiovascular disease (CVD) remains the leading cause of death worldwide and requires a deeper understanding of its pathogenesis for effective prevention and treatment. Familial hypercholesterolemia (FH), characterized by high levels of LDL cholesterol, is a significant risk factor for CVD. FH background remains unexplained despite advances in genetic testing. The aim was identification early changes in the plasma lipidome of individuals at high cardiovascular risk (HCVR) using liquid chromatography coupled with mass spectrometry. Methods: The lipidomic analysis examined over 400 compounds. Twenty individuals with suspected FH, very high cardiovascular risk (VHCVR), and undetectable mutations in the LDLR, APOB, or PCSK9 genes were compared to control group in a qualitative-quantitative analysis. Results: Multivariate analyses revealed statistically significant alterations in glycerophospholipids (GC), with a notable increase in phosphatidylcholines ((O-36:0/16:0), OR (95% CI): 1.246 (1.042-1.490), p = 0.0157), phosphatidylethanolamines ((O-40:7/22:6), OR (95% CI): 1.119 (1.039-1.205), p = 0.0028), and phosphatidylglycerol ((40:8/20:4), OR (95% CI): 1.053 (1.008-1.101), p = 0.0219) only in patients with HCVR. These changes, particularly in major classes of GC, underscored their potential as biomarkers for early assessment of cardiovascular risk. Lipidomic profiling revealed associations between specific lipid species and the comorbidities of arterial hypertension, atherosclerosis, and insulin resistance, implicating their role in atherosclerotic cardiovascular disease (ASCVD). Conclusions: This study points early changes in the plasma lipidome in individuals at HCVR, underline potential biomarkers, therapeutic targets for ASCVD, and offer opportunities to improve ASCVD diagnosis, therapy, and risk management strategies through detailed personalized medical approach.
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