What is the principal mechanism by which statins reduce cardiovascular risk?

• A. Inhibit PCSK9 enzyme.
• B. Increase triglyceride synthesis.
• C. Inhibit HMG-CoA reductase, lowering hepatic cholesterol synthesis and LDL.
• D. Stimulate LDL receptor degradation.

Answer: (C)

Statins work mainly by blocking HMG-CoA reductase, the enzyme that drives the rate-limiting step of cholesterol production in the liver. When this enzyme is inhibited, the liver makes less cholesterol, so it upregulates LDL receptors to take in more LDL cholesterol from the blood. That increased clearance lowers plasma LDL levels, which slows the development of atherosclerosis and reduces cardiovascular events.

The other options describe mechanisms that either aren’t how statins work or would worsen LDL levels. Inhibiting PCSK9 lowers LDL via a different pathway, increasing LDL receptor availability but not via HMG-CoA reductase. Increasing triglyceride synthesis would not reduce cardiovascular risk and is not a effect of statins. Stimulating LDL receptor degradation would raise LDL cholesterol, opposite of the statin effect.