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By DrRich

Recently, two new blood tests have been promoted as predictors of heart disease.  Both of these blood tests – C-reactive protein (CRP) and fibrinogen – have now been correlated with a significantly increased risk of future heart attacks.  The problem is, unlike other risk factors (such as obesity, smoking and cholesterol) it is not at all clear what should be done about high CRP and fibrinogen levels.

What are CRP and fibrinogen?

CRP is a protein released into the bloodstream any time there is active inflammation in the body. (Inflammation occurs in response to infection, injury, or various conditions such as arthritis.)  Evidence is accumulating that atherosclerosis (coronary artery disease) is an inflammatory process.  Some even think that coronary artery disease may be promoted by infection.  The fact that elevated CRP levels are associated with an increased risk of heart attack tends to support the proposed relationship between inflammation and atherosclerosis.

Fibrinogen is a blood-clotting factor.  Most acute myocardial infarctions (heart attacks) are now known to be due to acute thrombosis, or the sudden formation of a blood clot at the site of an atherosclerotic plaque.  It makes sense, therefore, that elevated fibrinogen levels (that is, a protein that promotes blood clotting) would be associated with an increased risk of heart attack.

Why all the interest in CRP and fibrinogen now?

Two reasons.  First, large studies were published this year that, essentially, “clinched” the relationship between these two blood proteins and the risk of heart attack.  And second, new commercial tests for measuring these proteins were developed.  (Aside to conspiracy theorists: this means there is money to be made by measuring them.) Thus, physicians now have a clinically relevant reason to do the tests, and a means for doing so.

Can high CRP and fibrinogen levels be treated?

The short answer is, no.

Regarding CRP levels, it is not the CRP level itself that is thought to be the problem, but the presumed inflammation in the coronary arteries that is reflected by the high CRP level.  So the real question is whether the inflammation (and not the CRP) can be treated.

There is some evidence that infection with an organism called Chlamydia pneumoniae may be a factor in the development of coronary artery disease.  If so, then antibiotics might be effective in eliminating the infection and reducing the risk of heart attacks (and, incidentally, in reducing CRP levels).  But the only published trial testing whether antibiotics help to prevent heart attacks (in patients with serum markers for Chlamydia) showed no benefit. Two larger trials are underway, however.  If antibiotics should prove effective in the future, measuring CRP levels may turn out to be a useful screening tool to select patients who might benefit from antibiotic therapy.

Further, there is accumulating evidence that the statin drugs – drugs used to treat high cholesterol – may also have the effect of reducing inflammation in the coronary arteries.  Trials are underway to assess this possible beneficial effect of the statin drugs.  CRP levels may turn out to be a useful screening tool here, also.

Fibrinogen, unlike CRP (which is thought to be merely a marker for inflammation,) is thought to play a direct role in coronary artery thrombosis.  Ideally, therefore, when fibrinogen levels are high, reducing those levels should be the goal of therapy. Unfortunately, there are no known therapies that reduce fibrinogen levels.

So what good are they?

What should doctors and patients do when CRP or fibrinogen levels are elevated?

Asked in another way, if there aren’t any specific treatments that can be used in response to elevated CRP or fibrinogen levels, why should they ever be measured?  (As DrRich always tells his medical students: Never order a test when you know ahead of time you’re not going to know what to do with the results.)

At the moment, the only good answer to this question is: knowing the CRP and/or fibrinogen levels may help to more accurately characterize the risk of coronary artery disease, so the doctor and patient can decide how aggressive to be in attacking risk factors that can be changed.

For instance, both the patient and the doctor may be reluctant to begin statin drugs when cholesterol levels are only borderline elevated.  In this case, elevated CRP or fibrinogen levels may tip the scales in favor of beginning therapy, whereas normal CRP or fibrinogen levels may be tip the scales in favor of withholding therapy.  Measuring one or both of these new risk factors may therefore play directly into therapeutic decisions.

Conceivably, knowing that the CRP or fibrinogen level is elevated might be the straw that finally breaks the camel’s back – the factor that finally compels the smoker to quit, the sedentary to exercise, or the obese to radically alter their lifestyles. 

But it is also possible that measuring risk factors that cannot themselves be changed might merely provoke unrequited anxiety.  In a nonsmoker with normal weight, normal cholesterol, and an active lifestyle, for instance, it is hard to see what benefit might be gained by knowing the CRP is elevated.  Indeed, it might cause anxiety that could not be easily allayed.  It would not be wrong to make the measurements, but (analogous to measuring genetic markers) the patient should be made aware before doing the test that there is no specific treatment available.  And (like genetic markers) having such a risk factor on the medical record might conceivably affect insurability in the future.

A lot of research is being done to find ways of treating inflammation affecting the coronary arteries. If antibiotics, statins, or some other therapy eventually were shown to be of benefit, it would make a lot of sense to measure CRP and/or fibrinogen levels, even in patients with no other risk factors.

Measuring CRP and fibrinogen levels can be useful in many circumstances, and is likely to be far more useful in the future.  But before ordering these tests, the doctor and the patient ought to be able to say ahead of time how the results might be useful. Especially  in patients with no other risk factors, doing these tests may cause more harm than good, and patients need to understand that before the measurements are made.

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