Much ballyhoo has accompanied the premature termination of AstraZeneca’s JUPITER trial (Justification for the Use of statins in primary Prevention: an Intervention Trial Evaluating Rosuvastatin). On the face of it, the study provides remarkable insight into the cause and prevention of cardiovascular events (i.e., heart attacks and strokes).
The central character in the trial, arterial inflammation (as measured by high-sensitivity C-reactive protein, or hs-CRP) was apparently ameliorated by the administration of rosuvastatin (Crestor). The drug reportedly effected a near-50% reduction in the incidence of heart attacks in the study group. (Ridker PM, Danielson E, Fonseca FAH, et al.; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. NEJM 2008;359:2195-2207)
Causes for Elevated CRP
As it turns out, there are many causes for an elevated CRP (which is less specific than the hs-CRP used in the JUPITER trial). Any inflammatory process will lead to an abnormally high CRP; it is merely a nonspecific marker for inflammation. CRPs can vary from day to day, and increase with:
- Hypertension
- Alcohol use
- High protein diet
- Smoking
- Aging
- Sedentary lifestyle
- Pregnancy or contraceptive use
- Coffee consumption
- Metabolic syndrome (insulin resistance)
- Diabetes
- Sleep deprivation
- Obesity, especially abdominal adiposity
- Elevated triglycerides
- Infection
- Burns
- Autoimmune disease (lupus, Crohn’s, ulcerative colitis, rheumatoid arthritis, etc.)
- Gout
- Cancer
- Pancreatitis
- Others…
Obviously, CRP is affected by a multitude of conditions; some of them—like pregnancy or aging—are normal processes.
When is a CRP Useful in Predicting Heart Disease?
Risk factors for coronary artery disease and arterial inflammation should be addressed prior to prescribing expensive drugs, but those who should consider hs-CRP screening include:
- Those with a family history of early (prior to age 50) heart disease
- Those with a family history of heart attack in individuals with normal cholesterol levels
- Those with other risk factors for heart disease (smoking, hypertension, diabetes, high cholesterol, sedentary lifestyles)
- Those with central obesity (increased waist size)
- Men over 45; women over 55
Since JUPITER showed statistically significant reductions in cardiac events when rosuvastatin was administered to people with normal cholesterol levels and high hs-CRPs, there is clearly a population that might benefit from such treatment. But it’s doubtful that a responsible physician would prescribe a statin on the basis of a single measurement.
How Should I Interpret My Results?
A hs-CRP above 3 indicates the possibility of arterial inflammation. Measures to address any potential underlying problems should be strongly considered:
- Low-fat diet
- Exercise
- Weight loss
- Smoking cessation
- Reduction in alcohol consumption
- Controlling treatable conditions (e.g., hypertension, diabetes)
Why Not Just Start Rosuvastatin if My hs-CRP is High?
Rosuvastatin is probably not the only statin that will effect a reduction in arterial inflammation, but most of the other statin drugs on the market have not been similarly tested.
The long-term effects of further lowering cholesterol levels in people whose levels are already normal are unknown. JUPITER trial subjects who took rosuvastatin had a slightly higher incidence of diabetes.
Rosuvastatin costs approximately $1200 per year, and it isn’t clear yet if insurance companies will pay for the medication when the patient has not been diagnosed with hypercholesterolemia.
Before taking statins, individuals should remember that these drugs, as a class, have side effects:
- Depletion of CoQ-10 (needed for cellular energy production)
- Rhabdomyolysis (muscle damage and kidney failure), potentially fatal
- Memory loss
- Nerve damage
- Liver damage (usually transient)
While high-sensitivity CRPs may soon be a part of routine medical examinations, we still have many things to learn before rosuvastatin is universally recommended as first-line therapy. Hopefully, we won’t have statins in our drinking water any time soon.
