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Update on the laboratory investigation of dyslipidemias
1Worcester Royal Hospital, UK.
Insights
Current lab tests for cardiovascular disease (CVD) risk have limitations. Emerging methods like lipoprotein particle concentration and HDL function assays show promise for better risk assessment and targeted therapy.
Area of Science:
- Clinical Chemistry
- Cardiovascular Medicine
- Biomarker Discovery
Background:
- Traditional LDL-cholesterol (LDL-C) measurements have limitations in accurately assessing cardiovascular disease (CVD) risk.
- Emerging evidence suggests lipoprotein particle size and concentration, as well as HDL function, may offer superior CVD risk prediction.
- Current laboratory methods for these novel markers lack standardization and validation for widespread clinical use.
Purpose of the Study:
- To review the limitations of current laboratory technologies for CVD risk assessment.
- To explore the evidence supporting emergent biomarkers, including lipoprotein subclasses and HDL function, for improved CVD risk prediction.
- To highlight the need for robust analytical methods for novel CVD risk markers.
Main Methods:
- Review of existing literature on laboratory methods for CVD risk assessment.
- Analysis of studies investigating lipoprotein particle concentration (e.g., NMR, ion mobility) and HDL function assays.
- Discussion of alternative lipid measurements like non-HDL-C and apolipoprotein B.
Main Results:
- Established methods like Friedewald calculation for LDL-C have significant limitations.
- Lipoprotein particle concentration and HDL function assays show potential as alternative CVD risk predictors.
- Apolipoprotein B may offer a more accurate reflection of LDL particle numbers than LDL-C.
- Non-fasting lipid measurements and early diagnosis of genetic dyslipidemias present practical advantages.
Conclusions:
- There is a need for validated, robust analytical methods for lipoprotein subclasses and HDL function assays.
- Novel biomarkers and genetic factors (ApoCIII, lipoprotein (a)) may enhance CVD risk assessment, especially in familial dyslipidemias.
- Clinical laboratories must evolve to incorporate advanced diagnostics for more effective CVD risk stratification and personalized therapy.
Abstract:
The role of the clinical laboratory is evolving to provide more information to clinicians to assess cardiovascular disease (CVD) risk and target therapy more effectively. Current routine methods to measure LDL-cholesterol (LDL-C), the Friedewald calculation, ultracentrifugation, electrophoresis and homogeneous direct methods have established limitations. Studies suggest that LDL and HDL size or particle concentration are alternative methods to predict future CVD risk. At this time there is no consensus role for lipoprotein particle or subclasses in CVD risk assessment. LDL and HDL particle concentration are measured by several methods, namely gradient gel electrophoresis, ultracentrifugation-vertical auto profile, nuclear magnetic resonance and ion mobility. It has been suggested that HDL functional assays may be better predictors of CVD risk. To assess the issue of lipoprotein subclasses/particles and HDL function as potential CVD risk markers robust, simple, validated analytical methods are required. In patients with small dense LDL particles, even a perfect measure of LDL-C will not reflect LDL particle concentration. Non-HDL-C is an alternative measurement and includes VLDL and CM remnant cholesterol and LDL-C. However, apolipoprotein B measurement may more accurately reflect LDL particle numbers. Non-fasting lipid measurements have many practical advantages. Defining thresholds for treatment with new measurements of CVD risk remain a challenge. In families with genetic variants, ApoCIII and lipoprotein (a) may be additional risk factors. Recognition of familial causes of dyslipidemias and diagnosis in childhood will result in early treatment. This review discusses the limitations in current laboratory technologies to predict CVD risk and reviews the evidence for emergent approaches using newer biomarkers in clinical practice.
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