The JUPITER Study: Should everybody take Crestor?
The JUPITER study has been the subject of countless headlines reporting the unprecedented reduction in heart attacks with the cholesterol drug, Crestor
®. The study has received gushing pronouncements of the inestimable value of statins by my cardiology colleagues.
Pharmaceutical giant, AstraZeneca, sponsored this study of nearly 18,000 people (men 50 years and over, women 60 years and over). Participants took 20 mg per day Crestor or placebo for two years.
The premise being explored was whether a cholesterol drug like Crestor
® yields any benefit in people without high cholesterol but with a high measure of the body's inflammatory state, c-reactive protein, or CRP. Participants therefore were selected to have starting LDL cholesterols in the "normal" range of no higher than 130 mg/dl and elevated CRP of 2 mg/dl or greater.
® treatment resulted in 44% reduction in nonfatal heart attack, nonfatal stroke, hospitalization for unstable angina, revascularization (bypass surgery, stents) and death from cardiovascular causes. The reduction in nonfatal heart attack was most marked at 55%.
Before we consider what this study means to those of us interested in prevention of heart disease, let's discuss: What is C-reactive protein (CRP)?
What is C-reactive protein (CRP)?
CRP is a blood-borne protein that originates in the liver and serves as an index of the body's inflammatory state. It is triggered by yet another inflammatory signal molecule, interleukin-6.
What triggers this cascade of inflammatory markers? Any inflammatory stimulus will trigger an increase in CRP, such as being overweight, lack of exercise, vitamin D deficiency, viral illness no matter how trivial, any inflammatory disease like arthritis, small LDL, high triglycerides, poor diet rich in processed foods, resistance to insulin, any injury, incipient diabetes, hidden cancer, lack of education (no kidding), etc.
In other words, many, many conditions, from trivial to serious, trigger increased inflammatory markers like CRP.
A recent analysis (Genetically elevated C-reactive protein and ischemic vascular disease of persons with genetically elevated levels of CRP here) suggests that CRP does not, by itself, cause atherosclerotic disease. CRP is therefore simply a marker for conditions that heighten inflammatory responses.
It has already been confidently demonstrated that, the higher the CRP, the greater the future risk of heart attack, cancer, and diabetes. That is no longer in dispute. What is not entirely clear is whether reduction of CRP is beneficial to health.
Back to JUPITER.
First of all, let me make clear that I am not a fan of prescription drugs. I view drugs as a necessary evil necessary in selected situations, e.g., antibiotics for pneumonia or wound infection, clot-busting drugs when blood clots are present, and acute or catastrophic situations. I am definitely not a fan of drugs in chronic conditions whenever they can also be addressed with simple, more natural means.
Nonetheless, the JUPITER trial results are, admittedly, impressive. Benefits held true for both males and females. At the very least, JUPITER should put to rest some of the fringe arguments that statins do not reduce cardiovascular events. They do. There is no sense in arguing against that. While we might argue about the value of statins in various subsets of people, there is no doubt that they do indeed exert a significant effect.
However, here is my problem with the basic concept: CRP is elevated in numerous conditions (above), from simple causes like excess junk foods, to complex causes like cancer. It is especially increased when excess weight is present (and, indeed, the mean BMI in the JUPITER trial was 28â”€substantially overweight).
Rather than shotgun the inflammatory response with a statin drug regardless of cause, doesn't it make more sense to ask why a specific individual has an increased CRP in the first place? For instance, if the answer is vitamin D deficiency, doesn't correction of the deficiency make more sense? (Vitamin D by itself reduces CRP around 60%--more than statin drugs.) Not to mention you obtain all the extraordinary benefits of vitamin D restoration, such as reduced cancer risk, increased bone density, relief from winter "blues," rise in HDL, etc. How about junk foods, obesity, and unrelated inflammatory conditions? (Would we therefore indirectly be treating obesity with Crestor?) Surely addressing these factors are preferable to a lifelong commitment to an expensive drug with clear-cut side-effects.
In addition, Crestor 20 mg per day, in my experience and contrary to the study and to many other statin studies, will not be tolerated for long by the majority. Muscles aches are not common--they are inevitable, sometimes incapacitating. While JUPITER showed 15% of both treatment and placebo groups experienced side-effects--no different--this is wildly contrary to my experience. (And I am a consultant for complex hyperlipidemia, i.e., complex cholesterol patterns.)
So I view the JUPITER experience as yet another interesting observation made in a drug manufacturer-sponsored study, conducted by a principal investigator (Dr. Paul Ridker) who holds the patents on CRP technology. Interesting, yes. Perhaps something to bear in mind in an overall program of heart disease prevention.
But a mandate for all of us to add Crestor
®? Absolutely not.