Cholesterol Synthesis and Regulation

A 48-year-old woman on atorvastatin 40 mg daily for hypercholesterolaemia reports muscle pain and weakness. Her serum creatine kinase (CK) is 2200 U/L (normal <200 U/L). Which investigation is most appropriate to determine whether statin-induced muscle toxicity is due to myopathy versus rhabdomyolysis?

Which regulatory mechanism is responsible for the decrease in HMG-CoA reductase expression when intracellular cholesterol levels are elevated?

A 52-year-old man with a family history of premature coronary artery disease presents with xanthomas on his Achilles tendons and eyelids. Serum total cholesterol is 580 mg/dL and LDL cholesterol is 420 mg/dL despite dietary modification. Which investigation is most appropriate to confirm the suspected diagnosis of familial hypercholesterolaemia?

A 58-year-old Indian male with hypertension and dyslipidemia presents with LDL cholesterol of 180 mg/dL despite dietary modification. The structure marked **B** in the cholesterol synthesis pathway diagram is the rate-limiting enzyme. Which of the following drugs acts on this enzyme to reduce LDL cholesterol and is most effective for cardiovascular mortality reduction in this patient?

A 42-year-old Indian man presents with severe hypercholesterolaemia (LDL 520 mg/dL), premature coronary artery disease at age 38, and Achilles tendon xanthomas. Genetic testing reveals a heterozygous PCSK9 gain-of-function mutation. Which feature best distinguishes this PCSK9-FH phenotype from LDLR-FH?