The first heart disease indicator to be recommended by the American Heart Association in twenty years entails only a surprisingly simple, inexpensive blood test. This high sensitivity C-reactive protein (hs-CRP) test takes the traditional cardiac check-up a step further, pinpointing those people who are at a much higher risk than others for heart disease, America’s leading cause of death. From hs-CRP results, doctors gain crucial insight into inflammation of the blood vessels around the heart, a factor not considered until now for patients at risk.
Q: What is C-reactive protein? How does it relate to heart disease?
A: The body produces C-reactive protein (CRP) during the general process of inflammation. When a disease called atherosclerosis damages arteries around the heart, they become inflamed, which triggers CRP production. For years we thought that diseased arteries around the heart slowly narrow, then clog or collapse and cause a heart attack. While this does occur, it is much more rare than had been anticipated. And that theory didn’t explain the patients who were fine one day, but had a heart attack the next week. We have since found that in some people inflamed, softened artery walls develop weak areas that can rupture suddenly, causing a heart attack. Also, plaque can build up quickly in inflamed arteries, increasing the risk of blood clots.
THE INFLAMED VESSEL In the blood vessel above, cholesterol buildup is present (yellow); but that’s not the only heart disease risk factor pictured. Doctors are also turning their attention to the diseased area of the vessel marked by inflammation (dark red and white).
Q: How do doctors test for CRP?
A: Physicians measure CRP with a simple, convenient blood test that does not require fasting. General CRP blood testing has been around for years, but only one kind, the high-sensitivity C-reactive protein (hs-CRP) test, helps determine heart disease risk. Patients should ask their doctors about hs-CRP specifically. With hs-CRP test results, a level above three raises major concern because it means a person’s risk for heart attack is at least doubled. One to three merits some concern, but is not serious. Below two is where we want all patients. Readings of 50 and above are possible, but we generally attribute a level higher than 10 to an infection or other source of inflammation somewhere in the body, not arterial inflammation.
Q: How does the hs-CRP test compare to other indicators, such as cholesterol and stress tests?
A: The exercise stress test tells us when narrowed arteries cause a shortage of blood going to the heart. It is still a vital risk indicator. LDL cholesterol is important to watch because it can narrow and clog arteries. There are two types of cholesterol, the bad kind (LDL) and the good kind (HDL). A total cholesterol test does not differentiate between these two types; It is therefore recommended that cholesterol screening be done with what is called a "fasting lipid profile", which includes determination of the total cholesterol, the HDL cholesterol, anther lipid risk factor called triglycerides, and calculation of LDL cholesterol level. Elevated LDL, and triglycerides, and low HDL, are all independent risk factors for heart disease, and provide independent and additive risk information to CRP. Arteries can produce CRP directly at sites where there is cholesterol buildup , and the liver makes most CRP and LDL . hs-CRP testing offers a window into one's overall inflammation, something not captured by LDL and other lipid related risk factors.
Q: How do people know if they need an hs-CRP test?
A: People who have suffered a heart attack or stroke and those with at least one risk factor, such as family history, high blood pressure, high cholesterol, smoking or diabetes, should be tested. While the American Heart Association and Centers for Disease Control just recently recommended hs-CRP testing as an option for those already at risk, The Cleveland Clinic has used the hs-CRP test routinely for at-risk patients for several years. Hs-CRP is a useful test for people with one or two risk factors who wonder if they are really in jeopardy of a heart attack or a stroke.
A recent large clinical trial called JUPITER was just reported showing the benefits of hsCRP testing. In JUPITOR, subjects with elevated hs-CRP but who otherwise had normal cholesterol levels were randomized against sugar pill to see if taking a high potency statin (a LDL cholesterol, and hsCRP lowering drug) reduced cardiac risks. The study was so successful, that it was stopped prematurely, because individuals taking the statin had 30-50% reduction in risk for heart attack, stroke and death compared to those not taking the medication - even though at the start none of the subjects had elevated LDL cholesterol levels (only elevated hs-CRP).
Q: How often should CRP levels be tested?
A: There’s no cookbook solution. In general, if we see an elevated hs-CRP on more than one occasion, we simply recommend more globally aggressive preventive cardiovascular medicine risk reducing measures. We do not the keep monitoring serial levels, but rather, focus on lowering known risks such as borderline blood pressure elevations, more aggressive (lower) nutritional and diet/exercise programs, and more aggressive LDL cholesterol goals. If someone comes in high and then works on lowering their CRP levels and global cardiac risks , we might re-check it in 2-3 month s. But, if the initial level is low, we may not check it again for two-to-five years. It really depends on the patient and adoption of lifestyle changes or other treatments.
Q: Is arterial inflammation the only cause of high CRP?
A: Inflammation in the body due, for instance, to infection or a serious arthritic flare, can raise CRP. Even periodontal disease can cause elevated CRP (and is associated with increased cardiac risks). Before getting an hs- CRP test, patients should tell their doctors if they are experiencing health problems that can cause general inflammation, for example, joint problems or a respiratory infection. If tested while ill (e.g. cold or flue) or injured, and hs-CRP comes back elevated, it’s important to get re-tested once healthy. But, pinpointing an alternative reason for a high hs-CRP reading doesn’t eliminate the increased risk for heart disease or the value of the hs-CRP test. For example, individuals with rheumatoid arthritis often have elevated CRP due to the joint and other problems related to the rheumatoid arthritis. Yet these patients also have increased cardiac risks - so we are very aggressive with global preventive risk reducing efforts in these patients. Chronic inflammation anywhere in the body can make the arteries more vulnerable because the cells and substances in the body that drive inflammation are thrown into high gear. Inflammation itself fuels further inflammation.
Q: What can I do if my hs-CRP level is high?
A: More aggressive preventive cardiovascular medicine risk reduction efforts are warranted. If the hs-CRP is very high (e.g. > 10) a search for a root cause may be in order, such as looking for periodontal disease, or an occult infection (e.g. in a person with diabetes). Inflammation should be treated by lifestyle changes , such as losing weight, exercising, controlling diabetes, stopping smoking and reducing alcohol intake. Closer attention to controlling high blood pressure, lower LDL (bad) cholesterol goals are also something to discuss with your physician. Low dose aspirin may also be recommended (provided there are no contraindications - so discuss this with your doctor). Cholesterol-lowering statin drugs both reduce CRP and LDL, and lower cardiac risks . Your doctor will prescribe the correct medications and dosage to treat your condition.
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Reviewed by Dr. Stanley Hazen M.D., Ph.D., Section Head of Preventive Cardiology at the Miller Family Heart & Vascular Institute at Cleveland Clinic.
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