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What is C-Reactive Protein?

By: Hratch L Karamanoukian, MD

December 10, 2008

C-reactive protein (CRP) is a molecule that is primarily produced in the liver. CRP is known to be involved in the body’s immediate response to inflammation. For example, damage to the lining of the arterial tree leads to the expression of signaling molecules which results in the expression of CRP in the liver. Since inflammation plays a significant role in the initiation and progression of atherosclerosis, eventually this leads to rupture of an atherosclerotic plaque which leads to obstruction of coronary arteries. This can result in a heart attack.

C-reactive protein has been the target of investigation regarding its role as a predictor of future cardiovascular events. This is done using a simple blood test which measures CRP in a high-sensitivity assay (hs-CRP). This compound is rather stable and has little day-to-day variation in a stable patient and can be monitored over years to determine the potential risk of "first" and subsequent cardiovascular events.

Investigations in the early 1990’s first showed that elevated CRP levels lead to increased risk of recurrent angina, heart attacks and death. Subsequent studies have supported the hypothesis that CRP is an independent predictor of future cardiovascular events in men and women, both middle-aged and elderly. Other studies have also shown that high levels of CRP are associated with future cardiovascular events in patients with premature coronary artery disease.

Interestingly, CRP levels are weakly associated with the size of the atherosclerotic plaque and may actually increase the risk of adverse events by making the plaque unstable. The active inflammatory process denoted by the elevated CRP levels, in conjunction with cells of inflammation (like macrophages)and other cell-cell signal molecules (cytokines) may lead to a thinning of the fibrous cap covering the atherosclerotic plaque. This makes the plaque more susceptible to rupture with resultant obstruction of the coronary artery, leading to a heart attack.

In patients with heart attacks, peak hs-CRP levels have correlated with cardiac failure, cardiac rupture, ventricular aneurysm formation and cardiac death. Furthermore within 6 months of coronary artery bypass grafting, high levels of hs-CRP also predict the recurrence of ischemic events. As well, elevated levels of hs-CRP following angioplasty and stenting of coronary arteries is associated with a significantly higher 30-day mortality.

Elevated levels of CRP is also associated with obesity. Thus, a healthy diet, weight loss, exercise, and smoking cessation are all encouraged in patients with elevated levels of CRP. Pharmacological therapy includes aspirin, which has been shown to have the greatest effect in reducing future episodes of heart attack in those who have the highest levels of CRP. Additionally, statin therapy has been shown to lower CRP levels independent of their LDL (the "bad cholesterol") lowering effects. Thus, the benefits of statin therapy may be greatest in those patients with elevated CRP.

In Summary, elevated levels of hs-CRP has been shown to correlate with increased risk of future cardiovascular events. Furthermore, high levels are also associated with increased complications following intervention such as angioplasty/stenting or coronary artery bypass grfting.

Highly reproducible levels of baseline CRP over time and the easy and reliable assay combined with available pharmacological therapy to treat the abnormality leaves hs-CRP assays a viable method of monitoring and guiding therapy for patients with increased risk of developing future cardiovascular events.

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For more information about varicose veins, spider veins, venous reflux and treatment options such as the closure procedure or guided sclero, contact Dr. Karamanoukian at the Vein Treatment Center, a National Center of Excellence for Vein Disorders by email or by phone at (716) 839-3638.



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