AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
When the LDL Doesn’t Add Up: A Case-Based Exploration
By Iftikhar M, Ibrahim S, Noureldine H et al.
Introduction: Low-density lipoprotein cholesterol (LDL-C) on standard lipid panels is calculated and may not reflect true LDL levels. In cholestatic liver disease, lipoprotein X (LpX) can artifactually elevate LDL-C, causing pseudo hypercholesterolemia. Case: A 58-year-old woman with insulin-dependent diabetes, coronary artery disease status post coronary artery bypass grafting, and hyperlipidemia developed progressive jaundice and markedly abnormal liver enzymes in the setting of chronic biliary obstruction. She underwent multiple endoscopic retrograde cholangiopancreatography procedures with stenting, followed by bile duct resection; pathology demonstrated inflammation without malignancy. Her lipid profile had previously been well controlled on statin therapy (LDL 65-86 mg/dL) but began to rise progressively. However, statin therapy was discontinued due to worsening liver function tests. LDL-C subsequently increased to 255 mg/dL, prompting reinitiation of statin given intolerance to alternative agents. This was complicated by suspected statin-induced liver injury, rhabdomyolysis, and acute kidney injury requiring hospital admission. She remained persistently cholestatic with a markedly elevated LDL-C of 1009 mg/dL. There was no personal or family history suggestive of familial hypercholesterolemia, and physical examination revealed no xanthomas or other lipid stigmata. Given the severe LDL-C elevation, she was started on plasma exchange, and lipid-lowering therapies were discontinued, resulting in progressive improvement in LDL levels. A linear relationship between worsening liver function and rising LDL-C was observed over several months, prompting further evaluation. Notably, apolipoprotein B (apo B) was 128 mg/dL despite an LDL-C of 450 mg/dL, indicating significant discordance. Subsequent lipoprotein metabolism profiling confirmed lipoprotein X (LpX), establishing pseudohypercholesterolemia in the setting of secondary sclerosing cholangitis. Discussion: LpX forms in cholestasis due to impaired bile acid synthesis, leading to accumulation of free cholesterol and phospholipids. It lacks apo B, making it non-atherogenic but indistinguishable from LDL on routine assays, resulting in falsely elevated LDL-C. This can lead to inappropriate use of lipid-lowering therapies, which are often ineffective and potentially harmful, as statins are biliary-eliminated and may accumulate in cholestasis. In this case, statins likely contributed to rhabdomyolysis without lipid benefit. Diagnosis relies on specialized testing and recognition of cholestasis with elevated cholesterol and discordantly low apo B. Conclusion: LpX should be suspected in patients with cholestatic liver disease and disproportionate LDL-C elevation. Management focuses on treating the underlying cholestatic process, as lipid-lowering agents have a limited role. .