Inflammation, C- Reactive Protein and Heart Disease Risk (Published August 12, 2002)

Recent reports have headlined that inflammation may be an important contributor to atherosclerosis and that doctors should be screening their patients for C-reactive protein. It has been asserted that this test may be more important than cholesterol levels. Is this true? What is behind this?

First, let's start with what inflammation is. When there is injury or damage to tissues, the body generates a cellular and chemical response to help contain the problem and facilitate its healing. This injury can be traumatic, infectious or even immunologic if the body gets confused about friend or foe signals. This coordinated defensive response to damage is what produces an inflammatory response.

As I have reported in prior columns, atherosclerosis is a complex process that involves, among other things, chemical modification of bad cholesterol, i.e., LDL-cholesterol, and products of fat metabolism, so called remnant particles. It turns out that these modified fats trigger cellular and chemical responses in the lining of blood vessels as the body reacts to these moieties. That is, an inflammatory response is initiated.

When tissues in the body are injured, chemical signals are sent out to other organs to get help. These messenger chemicals can cause the liver to make proteins called acute phase reactants. Amongst these is the protein that has been making headlines, C-reactive protein, which I will now call CRP.

CRP is indeed a marker for inflammatory events in the body. Researchers have linked elevated levels of CRP to heart attacks, strokes and peripheral arterial disease. It does seem to have independent predictive value as do classical cardiovascular risk factors. However, when you add CRP to the other risk factors, its impact is synergistically increased.

However, the difference is that these other risk factors are causally related to atherosclerosis and CRP is statistically related. This translates into the fact that treatments that affect the other risk factors have been shown consistently to modify subsequent risk of developing disease. Only one study has suggested that lowering CRP seems to have a positive impact, and that study looked at CRP only as a side issue. CRP has been found in the plaques and in the cells that are part of the inflammatory response. But this does not mean that it is the cause of the problem. As corroborating studies become available, we may indeed find that CRP is an important contributor to the cause of atherosclerosis, and not just a marker.

CRP may play its most valuable role as a marker of inflammation. Elevated levels may signal your doctor that you may be at risk for rupturing a high-risk plaque that could cause a sudden heart attack. But the treatments available to lower CRP are limited. At this point, the best interventions for modifying CRP are statin drugs and medications like aspirin. We will have to wait for the corroborating clinical trials to show that lowering CRP as an independent risk factor benefits patients. Doctors have to make sure that the test was not done in the shadow of a recent infection that could cause the CRP level to be falsely elevated, as well as to ensure that the correct, highly-sensitive CRP test for heart disease risk is the one ordered.

There will be guidelines later this year that may put C-reactive protein in perspective for both the healthcare profession and the public. At this time, it is too soon to run to your doctors asking for this CRP test to be done routinely. And as far as the assertion that CRP supplants cholesterol testing. It doesn't. But it may add information to estimating your cardiovascular risk when added to the cholesterol levels and other risk factors.



2003 Ventura Heart Institure.  All rights reserved.  Minimum requirements:  Microsoft Internet Explorer 5.5 or Netscape Communicator 4.7.  For optimal use of the site, download Adobe Acrobat Reader and either Windows Media Player or RealPlayer G2.  AOL users should use AOL 5.0 and AOL Plus for optimal usage.  Technical questions about our Web site?  Please send e-mail to