Study after study has shown the benefit of statin drugs in reducing the risk of heart attack and stroke. Almost buried in this barrage of positive results, however, is the growing research evidence that this reduction of cardiovascular disease morbidity and mortality from statin use has occurred independently of cholesterol effect.
Statins, originally felt to work solely as an inhibitor of cholesterol biosynthesis, now appear to work independently of cholesterol. Adding to cholesterol's innocence is its vital role in our body - mediator of synaptic transmissions, precursor of vital hormones and the most abundant biochemical in our brains.
Despite this evidence of a new non-cholesterol factor in cardiovascular disease risk, our nutritional and pharmaceutical world remains steadfastly focused on cholesterol as the villain.
Statins appear to work by another mechanism, some researchers now say. They relieve inflammation in the endothelial lining of blood vessels - this reduces sclerotic change. The good I see from the large numbers of excellent studies having to do with this new anti-inflammatory role of statin drugs is that the attention of clinicians is now beginning to be focused on the true cause of arteriosclerosis and atherosclerosis and the realization will soon dawn that cholesterol is conspicuously absent in the "usual suspects" line-up.
Since the development of statin drugs, the end-point for judging effectiveness has been the cholesterol response. If cholesterol seemed reluctant to be lowered, a higher dosage of statin was the almost automatic response.
Our focus on cholesterol as the culprit has led to higher and higher statin dosages over the years as target levels for serum cholesterol have been progressively lowered. Today it is almost standard that the starting dose be at least 20 to 40 mg, of Lipitor or Zocor, (or its equivalent in the other statins) and 80mg doses have become increasingly common.
Since cholesterol response no longer seems to be a valid end-point in determining statin dose, the entire strategy for dosing these drugs must be reviewed. The effectiveness of statins on cardiovascular disease risk at radically lower dosages must be defined.
The obvious problem with this philosophy is the apparent lack of a meaningful end-point that defines anti-inflammatory success. C-reactive protein is an inflammatory marker that has shown considerable usefulness in defining high risk for cardiovascular disease but, unfortunately, it is non-specific and more specific inflammatory markers must be found.
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor
