Case-Based Review Advocates Phenotype-Driven Dyslipidemia Assessment Beyond LDL-C Alone

Traditional dyslipidemia management often relies heavily on LDL-C levels, yet this single biomarker may not fully capture the complex atherogenic particle burden, metabolic risk, or individual treatment response. Many patients present with complex lipid profiles or genetic predispositions that are missed by conventional targets, leading to suboptimal risk stratification and management. This review addresses the critical gap in current practice by illustrating scenarios where a more comprehensive, phenotype-driven approach is essential for accurate diagnosis and effective intervention in diverse dyslipidemia presentations.

This study is a case-based review presenting three distinct dyslipidemia phenotypes to illustrate common diagnostic and management challenges. The authors selected cases that highlight the limitations of relying solely on LDL-C. Each case was analyzed for its unique lipid profile, metabolic context, treatment response, and genetic factors. The review integrates various diagnostic tools, including advanced lipid panels (e.g., LDL particle number, ApoB), imaging for subclinical atherosclerosis, and selective genetic testing, to demonstrate a more comprehensive assessment strategy.

The review identified three distinct dyslipidemia phenotypes challenging conventional LDL-C-centric management. The first case demonstrated significant diet-sensitive LDL particle and lipoprotein insulin resistance changes, even with LDL-C near conventional targets, in a patient with subclinical coronary atherosclerosis. The second case highlighted persistently low HDL-C and HDL particle number despite substantial LDL-C reduction with non-statin and incretin-era therapies in an obese patient with a strong family history. The third case revealed genetically confirmed familial hypercholesterolemia due to a pathogenic LDLR variant, despite the absence of classic physical stigmata. These cases collectively underscore the need for a broader diagnostic perspective.

The review concludes that an integrated, phenotype-driven approach incorporating LDL-C, ApoB or LDL particle number, diet response, metabolic context, imaging, medication tolerance, and selective genetic testing is crucial for individualized dyslipidemia risk assessment and treatment.