Little Evidence of Atherosclerosis in a Middle-aged Japanese Woman with Familial Hypercholesterolemia Carrying PCSK9 (p.Glu32Lys) and ABCG8 (p.Ile419Asn) Variants despite Elevated Lipoprotein (a) Levels.

A 44-year-old Japanese woman presented with low-density lipoprotein cholesterol (LDL-C) 214 mg/dL and lipoprotein (a) 65 mg/dL. Targeted next-generation sequencing identified heterozygous proprotein convertase subtilisin/kexin type 9 (PCSK9) (p.Glu32Lys) and ATP-binding cassette subfamily G member 8 (ABCG8) (p.Ile419Asn) variants. Despite lifelong untreated hypercholesterolemia, she only exhibited Achilles tendon thickening, without any other atherosclerotic signs. Combination therapy with rosuvastatin (5 mg) and ezetimibe (10 mg) lowered her LDL-C levels to approximately 70 mg/dL. This paradoxical mild atherosclerosis, despite multiple genetic and lipoprotein risks, highlights the heterogeneity of familial hypercholesterolemia and the utility of genotype-guided risk stratification.