Today’s NEJM has two articles on statin therapy and achieved LDL and CRP levels in relation to coronary disease.
The first article, from Harvard, is a substudy of the Pravastatin or Atorvastatin Evaluation and Infection Therapy – Thrombolysis in Myocardial Infarction 22 study (I challenge you to reread the name of this study once and then repeat it from memory). This trial was a 2×2 study of 80 mg vs. 40 mg of atorvastatin and of the antibiotic gatifloxacin vs. placebo, looking at event rates in 3745 patients who had had acute coronary syndromes. In this substudy, LDL levels and CRP levels were evaluated at 30 days after randomization.
Statin therapy reduced LDL levels significantly; CRP levels were also reduced. There was very little correlation between LDL levels achieved and CRP levels achieved. Cardiac event rates correlated independently with both LDL and CRP. In other words, lower CRP levels correlated with lower event rates, independently of achieved cholesterol reduction.
The second study, from the Cleveland Clinic, was also a substudy of another trial, Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL), which examined atherosclerosis progression using intracoronary ultrasound in patients randomized to 80 mg of atorvastatin vs. 40 mg of pravastatin. Ultrasound was performed and lipids and CRP were obtained at baseline and after 18 months.
The results of this trial were similar to the first: there was little correlation between CRP and lipid levels. Atherosclerosis progression was independently correlated with both LDL and CRP changes between baseline and follow-up.
Now that the homocysteine fad has waned a bit, commercial laboratories are aggressively promoting profitable high sensitivity CRP measurement. It certainly is an interesting concept, since atherosclerosis is not the gradual, pipe-clogging process that it used to be viewed as, but rather a much more dynamic and inflammatory one. Inflammation and CRP are related, and CRP has prognostic value in vascular disease. It may well turn out that targetting CRP levels when deciding on and dosing statin therapy will be just as important as following LDL levels. Perhaps CRP will allow us to forgo statin therapy in some patients and force us to be more aggressive in others.
However, just because statin-treated patients with lower CRP reductions do better than those with lesser reductions does not automatically prove that targetting statin doses to CRP levels will guarantee the same results. What is needed is a clinical trial that demonstrates that patients whose therapy is guided by CRP do as well as patients whose therapy is fixed and high-dose, for example.
Having said that, the increasingly convincing inflammatory theory of atherosclerosis does make measurement and use of the CRP attractive. One more piece of the puzzle.