Statin drugs are helping many people lower their cholesterol, but a new study in the February Journal of Lipid Research reveals that statins actually increase the production of another protein that limits their benefit.
Proprotein convertase type 9 (PCSK9) has recently gained attention as a key regulator of LDL cholesterol (the “bad” cholesterol). PCSK9 degrades LDL receptors that remove LDL cholesterol (LDL-C) from the blood; mutations that result in extra PCSK9 activity produce familial hypercholesterolemia, while mutations causing less PCSK9 activity lower LDL-C and cardiovascular risk.
Studies in mice have indicated that statins may increase PCSK9 expression, so Robert Konrad and colleagues studied the effect of atorvastatin (Lipitor) or placebo on PCSK9 levels in humans. After 16 weeks of treatment, 40 mg/day atorvastatin increased circulating PCSK9 levels by 34% over placebo, while decreasing LDL-C levels by 42%. In comparison, a 10 mg/day dosage did not increase PCSK9 levels at all, yet still reduced LDL-C by 30%.
The researchers note these results, although preliminary, suggest that adding a PCSK9 inhibitor to statin therapy could be an approach to further decrease LDL-C levels in patients unable to reach desired results on statin therapy alone, or to effectively lower the dosage in patients who experience unwanted statin side effects.