A Clinical Lipidomics Platform: Development and Validation of a High-Throughput LC-MS Assay for Cardiovascular...

Area of Science:

• Clinical Chemistry
• Biomarker Discovery
• Cardiovascular Disease Research

Background:

• Traditional lipid biomarkers (cholesterol, HDL, LDL, triglycerides) offer limited insight into cardiometabolic health.
• Lipidomic profiling via LC-MS/MS measures hundreds of lipids but faces challenges in throughput and data processing for clinical use.

Purpose of the Study:

• To develop and validate a high-throughput Clinical Lipidomics Platform (CLP) for comprehensive lipidomic profiling.
• To assess the clinical utility of the CLP for cardiovascular risk prediction.

Main Methods:

• Developed a rapid (6 min runtime) LC-MS/MS assay measuring 270 lipid species across 37 subclasses in human plasma.
• Implemented automated data processing and normalization using NIST SRM 1950 for accuracy and reproducibility.
• Validated the CLP against a research platform (RLP) in a large cohort (n=994) and calculated a previously established Lipidomic Risk Score (LRS).

Main Results:

• CLP lipid measurements strongly correlated with RLP measurements (high correlation).
• CLP-derived LRS showed excellent correlation with RLP-derived LRS (R² = 0.97).
• The LRS derived from CLP outperformed traditional scores like the Framingham Risk Score (FRS) in predicting coronary artery calcium score (CACS), especially in intermediate-risk individuals.

Conclusions:

• The Clinical Lipidomics Platform (CLP) provides a high-throughput, accurate, and reproducible method for comprehensive lipidomic profiling.
• The CLP enables the calculation of a Lipidomic Risk Score (LRS) that enhances cardiovascular risk prediction beyond traditional methods.
• The CLP demonstrates significant clinical utility for cardiovascular risk assessment and holds potential for broader clinical applications.