If you have been watching TV, listening to the radio, or riding the T lately, you’re likely to have seen or heard a lot of public service announcements raising awareness of heart disease, particularly in women. Heart disease is one of the leading causes of death for both men and women in the United States, even though heart disease is often thought of something that affects men more often. Most people are aware that high cholesterol is a risk factor for heart attack and stroke and have heard the advice to stop smoking, exercise regularly, and control their weight to reduce their risk of heart disease. More recently, a marker of inflammation that can be detected in the blood called C-reactive protein, or CRP, has emerged as an important potential signal of the risk of heart disease. Inflammation in the arteries has long been recognized as a contributor to heart disease and being able to test individuals for inflammation may help identify those at high risk for disease so they can reduce their risk and receive appropriate treatment.

Inflammation and Heart Disease

So how does inflammation contribute to heart disease? Inflammation is your body’s response to injury. In the case of heart disease, that injury often begins with LDL (bad) cholesterol burrowing into the wall of your arteries. This damages the lining of the blood vessels, and your body sends immune system cells to the site of the injury. These special immune system cells eat up the LDL cholesterol that’s causing the damage. The problem is that these cells don’t go away once their job is done: they remain in the arterial wall, causing what’s called a fatty streak. Over time, more cholesterol and cellular debris accumulate at the fatty streak, turning it into a plaque, or a hardened area in the wall of the artery. The artery attempts to heal itself and get rid of the plaque by creating a fibrous cap around it. However, some of the immune system cells in the plaque kill the cells in the cap and break down the material forming the cap, causing the cap to rupture. If a blood clot then forms around the ruptured cap, blood flow through the artery is blocked, triggering a heart attack. If this happens inside an artery that provides blood to the brain, a clot in the artery will cause a stroke instead.

A New Test for Risk of Heart Disease?

One common treatment for people at high risk of heart disease is to prescribe them drugs that lower LDL (bad) cholesterol. These types of drugs are called statins and can reduce the risk of heart disease because lower LDL levels lead to lower rates of injury to the arterial walls. Statins are typically only prescribed as a preventative to people with high levels of LDL cholesterol.

However, a recent large clinical trial (the Jupiter trial) tested whether statin treatment as a preventative might be useful for individuals with more moderate levels of LDL cholesterol, but with elevated levels of a marker of inflammation called C-reactive protein, or CRP. Because they did not have very high levels of LDL cholesterol, the individuals in this trial would not have normally been prescribed a statin as a preventative measure. The authors of this study reasoned that since statins lower both CRP levels and cholesterol, treating individuals with low LDL but high CRP with a statin might decrease their risk of heart disease. This trial looked at one particular statin called rosuvastatin (brand name: Crestor) and the results were published last November. The trial was so successful that it was actually halted early, after an average of 1.9 years of follow-up rather than the planned 4 years. Because the rosuvastatin treatment group had a 20% decreased risk of death when compared to the placebo group, it would not have been ethical to continue the trial when the benefits of treatment with the drug were so clear. Preventative statin treatment in these individuals clearly reduced the incidence of major cardiovascular events.

CRP, or Just Inflammation?

So what do the findings from the Jupiter trial indicate? Should everyone get a test for CRP and in cases of high CRP, start taking a statin? Not necessarily. Although CRP is a marker of inflammation, it’s a relatively non-specific one: CRP levels can also rise to high levels when you have a cold, a sprained ankle, or another non-heart-related problem. So having high levels of CRP alone doesn’t necessarily indicate an increased risk of heart disease. In fact, a recent study in the New England Journal of Medicine found that individuals with chronically elevated CRP levels due to a genetic mutation did not have an increased risk of heart disease when compared to individuals with normal CRP levels.

Implications for Treatment

The treatment implications of the findings of the Jupiter trial are currently being debated. About half of clinicians now believe that individuals should be routinely tested for CRP when they have their cholesterol checked, while the other half feel such additional tests are not yet indicated based on the data. Additional testing can often cause worry and stress for the patient, as well as increasing cost. Further studies are necessary to explore the relationship of markers of inflammation to the risk of heart disease. Many scientists would like to see further trials that look specifically at the relationship of CRP to heart disease rather than the effect of a particular drug on risk of heart disease. Although the individuals in the Jupiter trial had elevated levels of CRP, the trial was more focused on the possible benefits of the drug rosuvastatin than on exploring the relationship between CRP and heart disease directly. Developing tests that can look directly at inflammation of the arterial wall (which would be much more specific to heart disease) may also prove helpful.

Caring for Your Heart

While it’s unclear at this point whether measuring CRP levels is helpful in all individuals, reducing inflammation can be helpful in protecting against heart disease. Losing excess weight and stopping smoking are two methods that have been clearly shown to reduce signs of inflammation. The data on whether exercise, fish oil, and soy foods reduce inflammation directly are less clear-although all of those are good ways to help lose weight, which in turn reduces inflammation. Taking care of your teeth may also help protect your heart, perhaps because gum disease tends to lead to chronic inflammation. The mechanism through which gum disease affects heart disease isn’t yet fully understood, but the evidence supporting a link between the two is accumulating. Soon there may be new tests for inflammatory markers that indicate your heart disease risk, but at this point, further study appears necessary before everyone should go running out to have their CRP tested along with their cholesterol.

–Zofia Gajdos, Harvard Medical School

For More Information:

Slow Burn: How Inflammation Can Trigger a Heart Attack, from Nutrition Action Health Letter, January-February 2009:
< http://www.thefreelibrary.com/Slow+burn:+how+inflammation+can+trigger+a+heart+attack.-a0192898839 >

New Thinking on How to Protect the Heart, From the New York Times, January 13, 2009:
< http://www.nytimes.com/2009/01/13/health/13brod.html >

Primary Literature:

Ridker, P.M., E. Danielson, F.A.H. Fonseca, et al., Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. New England Journal of Medicine 359(21):2195-2207 (2008)

Hlatky, M.A., Expanding the Orbit of Primary Prevention-Moving Beyond JUPITER. New England Journal of Medicine 359(21):2280-2282 (2008)

Zacho, J., A. Tybjaerg-Hansen, J.S. Jensen, P. Grande, H. Sillesen, and B.G. Nordestgaard, Genetically Elevated C-Reactive Protein and Ischemic Vascular Disease. New England Journal of Medicine 359(18):1897-1908 (2008)