This does seem to answer a question....

If cholesterol lowering itself isn’t a panacea, why is it that statins do work for people with existing heart disease? 


In his laboratory at the Vascular Medicine unit of Brigham & Women’s Hospital in Cambridge, Mass., Dr. James K. Liao began pondering this question more than a decade ago. 

The answer, he suspected, was that statins have other biological effects. 

Since then, Liao and his team have proved this theory. 

First, a bit of biochemistry. Statin drugs work by bollixing up the production of a substance that gets turned into cholesterol in the liver, thus reducing levels in the blood. But the same substance turns out to be a building block for other key chemicals as well. 

Think of a toy factory in which the same plastic is fashioned into toy cars, trucks, and trains. Reducing production of the plastic cuts not only the output of toy cars (cholesterol) but also trucks and trains.

In the body, these additional products are signaling molecules that tell genes to turn on or off, causing both side effects and benefits.

Liao has charted some of these biochemical pathways. 

His recent work shows that one of the trucks, as it were—a molecule called Rho-kinase—is key. By reducing the amount of this enzyme, statins dial back damaging inflammation in arteries. When Liao knocks down the level of Rho-kinase in rats, they don’t get heart disease. 

“Cholesterol lowering is not the reason for the benefit of statins,” he concludes. 

The work also offers a possible explanation of why that benefit is mainly seen in people with existing heart disease and not in those who only have elevated cholesterol. Being relatively healthy, their Rho-kinase levels are normal, so there is little inflammation. But when people smoke or get high blood pressure, their Rho-kinase levels rise. 

Statins would return those levels closer to normal, counteracting the bad stuff. Add it all together, and “current evidence supports ignoring LDL cholesterol altogether,” says the University of Michigan’s Hayward. In a country where cholesterol lowering is usually seen as a matter of life and death, these are fighting words

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