Inter-Individual Variability in Lipid Response: A Narrative Review.

Area of Science:

• Cardiology
• Pharmacology
• Genetics

Background:

• Lipid-lowering guidelines promote shared decision-making, requiring patients to predict therapy response.
• Physicians face challenges in managing lipid levels due to response variability from factors like adherence, genetics, and lipoprotein (a).

Purpose of the Study:

• To review the variability in low-density lipoprotein cholesterol (LDL-C) response to various guideline-directed lipid-lowering interventions.
• To propose a multifactorial hypothesis for observed individual differences in lipid response.
• To provide a practical tool for identifying factors influencing patient response.

Main Methods:

• Narrative review of lipid-lowering therapies including statins, ezetimibe, bile acid sequestrants, fibrates, PCSK9 inhibitors, and diets.
• Analysis of factors contributing to variability in LDL-C response.
• Development of an illustrative model and checklist for clinical use.

Main Results:

• Individual responses to LDL-C lowering interventions are highly variable.
• Non-adherence, genetic factors, lipoprotein (a) levels, and rare systemic responses contribute to this variability.
• A multifactorial approach is necessary to understand and manage lipid response.

Conclusions:

• Variability in LDL-C response to lipid-lowering therapies is a significant clinical challenge.
• Identifying patient-specific factors is crucial for optimizing lipid management.
• The proposed model and checklist can aid clinicians in assessing and addressing response variability.