The American Journal of the Medical Sciences · Oct 22, 2026

Beyond LDL-C: A Case-Based Review of Complex Dyslipidemia

By Fanaropoulou NM, Varghese RT

Dyslipidemia is clinically heterogeneous, and LDL-C alone may not fully capture atherogenic particle burden, metabolic risk, treatment response, or inherited disease. This case-based review presents three dyslipidemia phenotypes that illustrate common diagnostic and management challenges. The first case describes diet-sensitive LDL particle and lipoprotein insulin resistance changes despite LDL-C values near conventional targets in a patient with subclinical coronary atherosclerosis. The second highlights persistent low HDL-C and HDL particle number despite substantial LDL-C reduction with non-statin and incretin-era therapies in the setting of obesity and strong family history. The third demonstrates genetically confirmed familial hypercholesterolemia due to a pathogenic LDLR variant despite absent classic physical stigmata. Together, these cases support a phenotype-driven approach that integrates LDL-C, ApoB or LDL particle number, diet response, metabolic context, imaging, medication tolerance, and selective genetic testing to individualize dyslipidemia risk assessment and treatment.

doi.org/10.1016/j.amjms.2026.10.008PubMed 42914050Biomarkers