Yesterday (seems weeks ago) morning I commented at length on the duodenal ulcer story over the past 25 years. The acute coronary syndrome story also should intrigue us. Over the past several years, much literature has focused on inflammation as a precursor to acute coronary events. A variety of inflammation markers show up in these studies, but the most ubiquitous is CRP (C-reactive protein). Now the American Heart Association is preparing a guideline relative to screening for inflammation - Surprising discovery: Inflammation May Be Worse For the Heart Than Cholesterol. While the data do not yet reach the level to entirely convince me, I am impressed by the ongoing accumulation of evidence.

In the past year or two, experts say, the evidence has become overwhelming that inflammation hidden deep in the body is a common trigger of heart attacks, even when clogging in the arteries is minimal. Now the main question is: How aggressively should otherwise healthy people be tested to find and treat it?

The new recommendations are still being drawn up, but they will offer the first formal blueprint to answer this, probably sometime in the fall. Doctors writing them say they will almost certainly recommend broad testing.

Inflammation can be measured with a generic $10 test that looks for high levels of a chemical called C-reactive protein, one of many that increase during inflammation. Experts expect it to quickly become a standard part of physical exams. As a result, many people ordinarily considered at low risk will probably be put on statin drugs, which lower inflammation as well as cholesterol.

No one disputes the importance of cholesterol. Yet half of all heart attack victims have levels that are normal or even low. Clearly, something big was missing from the equation, and that appears to be inflammation.

As time passes, I become more cautious about new ideas in medicine. All physicians see ideas come and go. This idea seems to "have legs".

CRP probably will not matter much for heart attack survivors and others who already know they have heart disease, since presumably doctors are already doing everything they can to keep their condition from getting worse.

"We believe the niche for C-reactive protein - and it is a large niche - is the healthy population who want to do what they can to lower their risk of cardiovascular disease," says Dr. Richard Cannon of the National Heart, Lung and Blood Institute.

Screening is important because inflammation can be readily lowered in several ways. One of the most powerful is losing weight. Exercise also helps, as does moderate alcohol intake, giving up smoking and lowering blood pressure.

Of course, this amounts to the same healthy living advice that doctors have long dispensed. But now they have a much better understanding of why it works so well. Furthermore, they are likely to urge these habits on people with bad CRP readings who until now would have seemed to be at no special risk of heart problems.

Medpundit urges caution about this story today -

Why not wait until the studies are finished before putting out guidelines? I don’t have access to all of the journals that come up in a PubMed search of C-reactive protein and coronary artery disease, but I do have access to the New England Journal of Medicine article that started it all. The results in the abstract state that treating someone with normal cholesterol but a high C-reactive protein with a cholesterol lowering drug, specifically a statin, prevented heart disease. In truth, the people with high C-reactive protein values and normal cholesterol who took a statin had a 3% incidence of heart attacks compared to a 5% incidence in people who took placebo. That’s not much of a difference. Especially when you’re recommending that someone take a drug for the rest of their lives to achieve it. Furthermore, an aspirin a day could prove just as effective, or more so, in preventing heart disease in people with elevated inflammation markers alone. We don't know. No studies have been done to compare the two.

While I am not as skeptical as she is, her points do provide some balance. I am giving a talk on acute coronary syndromes later this year, and had already planned to include a section on the inflammation hypothesis. If you want to read more about the inflammation hypothesis I recommend an article in the July 2, 2002 issue of Circulation - 'Need to Test the Arterial Inflammation Hypothesis', Deepak L. Bhatt and Eric J. Topol; Circulation 2002 106: 136 - 140. This article develops the question very nicely, and proposes

It is vital that the "inflammation hypothesis" be tested in a large-scale clinical trial, which has the potential to change radically the approach used with patients with cardiovascular disease. Patients with a history of cardiovascular events and an elevated baseline CRP could be randomized to either usual-care or a CRP-guided strategy. All patients would be treated with aspirin at a moderate dose of 81 to 162 mg.41 Patients with an LDL cholesterol level greater than 100 mg/dL would be treated with a statin. ACE-Is would be prescribed to patients with left ventricular dysfunction. Further therapy in the group randomized to the CRP-guided strategy would be based on a prespecified algorithm of tiered therapy and response of CRP levels to initiation of a particular medication ...

The inflammation story is fascinating and makes much sense. I am not against the enthusiasm for using the available data, however, we should always strive to refine our knowledge and continue our quest for understanding.