HealthLINK: Cardiac: CRP may displace LDL as risk factor for heart attack

Heart disease risk and C-reactive protein

The evidence linking inflammation to heart disease risk has been building over the last few years, and this latest study adds some solid data to support the thesis.

What is inflammation?
Inflammation is one of the ways the body heals itself. It is an integral part of the body's basic emergency response system. When anything threatens our health—from disease-causing germs to the buildup of fatty plaque in the walls of a heart vessel—the immune system sends in waves of cells to swarm and destroy the invader. This is usually beneficial. It helps us prevent infection and helps stop bleeding; but when it occurs in the blood vessels, layers of these immune cells may pile up, creating lesions that become unstable and may eventually rupture, triggering a heart attack.

“The presence of C-reactive protein is a signal that inflammation is present,…”

The presence of C-reactive protein is a signal that inflammation is present, and, as this study shows, its presence is correlated with an elevated risk of heart attack and stroke. How does it compare with LDL cholesterol as a risk factor?

We've known for decades that high levels of LDL increase an individual's risk of heart disease, but only about half of those who have a heart attack are found to have high LDL. We know there are other factors—smoking, high blood pressure, family history and others—but sometimes there is no apparent risk factor present. We suspect that CRP and other yet-unidentified factors may be the culprits.

As one of the compounds in the body's inflammatory response, C-reactive protein has been shown to be a suspect in several small studies, but Dr. Ridker's work provides us with a very large, very well-designed study that adds fuel to the building body of evidence against CRP.

After eight years of following thousands of women, Dr. Ridker tallied up heart attacks and strokes among the women. Adjusting for risk factors like smoking and diabetes, he found that high cholesterol increased the women's heart attack risk up to 1.5 times—but high CRP (more than 3 milligrams per liter of blood) increased it as much as 2.3 times. He calls it the "strongest and most significant" predictor of heart disease, heart attack and stroke.

Testing for CRP
The test for CRP is a simple, relatively inexpensive, blood test, and some researchers are advocating that people be screened routinely for high levels of CRP as we currently check for cholesterol. There is evidence that statin and beta blocker drugs are also effective in lowering CRP. What we lack is a large, randomized trial to show us whether lowering CRP reduces an individual's risk of a heart attack or other heart-disease related event.

Lowering CRP
Statins and beta blockers have side effects as do many other drugs, so if we treat the millions of people we suspect have elevated levels of CRP, we are going to be treating a large number of people who may experience these side effects without knowing whether we're helping them or not.

When my patients ask me about having a CRP test, I tell them my dilemma. If their CRP is found to be high, I don't have any convincing data on how best to treat them. I am uncomfortable presenting patients with information that may only serve to frustrate them. What is usually the case, however, is that my patients already have some heart disease and they are already on medication.

“Some advocate that people be screened routinely for high levels of CRP—others urge caution.”

A high CRP reading would be most helpful and important for primary prevention in an individual who is not currently being treated for heart disease. We need to know whether treating CRP will benefit these patients and we need a better understanding of what levels of CRP are healthy and what levels place someone at risk. At this point, we don't have good answers to those questions.

What's important about this information?

We know LDL is not the whole answer to heart attack risk. Seventy-seven percent of all the women in the study who had a cardiac event had LDL readings below 160, which is pretty low.
And we know that CRP was found to be a better predictor of subsequent heart disease than LDL cholesterol.
We also know there is little correlation between LDL and CRP. They are clearly signals of different risk factors.

The screening question
In 1968, physicians developed criteria for new screening programs that suggested if there is no generally accepted treatment, it is premature to embark on routine screening. In an editorial that accompanied the NEJM research, Dr. Lori Mosca states we have many clinical examples of treatments that initially appeared to be beneficial, but which rigorous research later proved to be not beneficial and actually harmful.

“Whether the value of CRP testing will be confirmed in randomized trials is unknown,” Dr. Mosca states. “Such research will provide vital information to confirm or refute the inflammatory hypothesis, but before these data become available, it may be premature to adopt widespread assessment of C-reactive protein. A major criterion in the process of developing evidence-based screening guidelines should be that routine assessment of a new biologic marker has been demonstrated to enhance patient care and reduce the burden of cardiovascular disease.”

In other words, the jury is still out. We need more information.

Dr. Freed is a cardiologist and an associate with The Cardiology Group with offices in New Haven and Branford. She is an attending physician at Yale-New Haven Hospital and Yale-New Haven Heart Center.

Can we help?