Evolution of C-Reactive Protein as a Cardiac Risk Factor

Paula J. D'Amore, PhD, D(ABMLI)


Lab Med. 2005;36(4):234-238. 

In This Article

Treatment for CVD

Because of the high numbers of mortalities due to cardiovascular diseases, primary prevention is of the utmost importance. It has been firmly established that the control of lipid levels is beneficial to reducing CVD. Numerous clinical trials of 3-hydroxyl, 3-methyl glutamyl coenzyme A inhibitors (statins) have demonstrated the ability of these drugs to lower LDL-C, triglycerides, and total cholesterol, and increase the level of HDL.

A goal of the National Cholesterol Educational Program (NCEP) for primary prevention in 2001 was to assess new individual risk markers of CVD.[5] We now know that chronic, low-grade inflammation plays a large role in atherosclerosis and that hsCRP is an excellent marker for risk assessment of cardiovascular diseases. Consequently, therapeutic measures for lowering hsCRP levels should be part of a treatment strategy. Several studies indicate that statins exhibit anti-inflammatory effects thereby lowering hsCRP levels.[20,21,22] In the CARE study,[20] patients who had a previous myocardial infarction, treatment with the statin, pravastatin, over a period of 5 years significantly reduced hsCRP levels independent of the LDL-C levels. Similar results were evident in the Pravastatin Inflammation/CRP Evaluation (PRINCE).[21] Men and women with no history of CVD were treated with pravastain or a placebo. Again, the statin treatment lowered hsCRP levels regardless of the LDL-C. In the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS-TexCAPS), lovastatin effectively reduced the risk of coronary events by lowering hsCRP levels in subjects with or without high levels of LDL-C.[22] This study demonstrated that now statins could be used in the primary prevention of CVD by targeting patients with high hsCRP levels even with normal or low lipid levels. Patients with high hsCRP/low LDL-C levels were found to be at extremely high risk for CVD; higher than those with low hsCRP/high LDL-C levels. Additionally, patients with high hsCRP/low LDL-C levels had the same CVD risk as those with high LDL-C levels.

In a recent report on the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study, intensive treatment with 80 mg of atorvastatin as compared to 40 mg of pravastatin reduced LDL-C levels below the current guidelines of less than 100 mg and hsCRP levels by 36.4%.[23] Interestingly, the investigators examined the effect of the treatment on the actual size of the atheroma within the coronary artery and the rate of progression by measuring the volume of the atheroma burden by intravascular ultrasound. Intensive treatment with atorovastin halted progression of atherosclerosis whereas progression was apparent in those treated with pravastatin. It would be interesting to reanalyze this data using stratified groups according to hsCRP levels with low or high LDL-C. This may provide evidence as to whether the decrease in LDL-C or hsCRP made the difference in the atheroma volume. The REVERSAL study was composed of only 502 patients followed for 18 months. As the authors stated, much larger trials will need to be conducted.

Larger clinical trials are also needed to determine whether patients without CVD who have increased levels of hsCRP without high levels of plasma lipids should be placed on a therapeutic treatment of statins. A large study of 15,000 patients across the United States and Canada is underway (Justification for the Use of Statins in Primary Prevention-JUPITER).[24] Healthy middle-age men (greater than 55 years old) and women (greater than 65 years old) with no history of CVD, LDL-C of less than 130 mg/dL and hsCRP levels of greater than 2 mg/L will be divided into 2 groups. One group will receive a high dose of rosuvastatin and the control group will be given a placebo. Patients will be followed for a period of 3 and a half years in order to determine whether statin treatment in patients with high hsCRP/low LDL-C levels will prevent future CVD events.


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