C-Reactive Protein (CRP)

What is CRP and how is it tied to heart disease?

C-reactive protein (CRP) is a substance that is released into the blood in response to inflammation, the process by which the body responds to injury. Elevated levels of CRP in the blood mean that there is inflammation somewhere in the body, but other tests are needed to determine the cause and location of the inflammation.

Physicians now believe that atherosclerosis, or hardening of the arteries, is an inflammatory process. Atherosclerosis causes only a small amount of CRP to be released into the blood. Therefore, a very sensitive test called a high-sensitivity CRP test (hs-CRP) is used to measure CRP levels.

CRP Levels

CRP Risk Levels
Risk Category CRP (mg/L)
Low Less than 1.0
Average 1.0 to 3.0
High Above 3.0

CRP is measured in milligrams per liter of blood (mg/L). The risk categories above were established by the American Heart Association (AHA) and the Centers for Disease Control and Prevention (CDC) in 2003 using information drawn from largely white populations. Since then, studies have shown that CRP levels vary by race/ethnicity and are higher in women than in men. CRP may be tested in people hospitalized for heart attack or unstable chest pain. In these cases a level above10 mg/L is considered high. CRP is affected by some medications—hormone therapy increases CRP levels.

Are CRP levels higher in women?

When the AHA and CDC set cutoffs for high and low CRP, it was assumed that levels were similar in men and women. Research now shows that women have higher levels of CRP than men. A Dallas study of nearly 2,750 people aged 30 to 65 years (more than half were women) found that CRP levels were almost twice as high in women than in men (3.3 vs. 1.8 mg/L). Even after accounting for traditional heart disease risk factors and the use of hormone therapy or the cholesterol lowering statin drugs (both closely tied to CRP levels), white women were 60% more likely, and black women were 70% more likely to have high CRP than white men. Being overweight or obese was very strongly associated with high CRP. Excess weight appears to raise women’s CRP levels more so than men’s.

Do CRP levels vary by race/ethnicity?

An analysis of the Women’s Health Study that included more than 25,500 female health professionals older than 45 years showed that CRP levels vary by race. Black women had higher CRP levels (2.96 mg/L) than white (2.02 mg/L), Hispanic (2.06 mg/L), or Asian (1.12 mg/L) women. Asian women had lower, and Hispanic women had similar, CRP levels when compared with white women. A Canadian study of more than 1200 people found that CRP levels are higher in South Asians (2.59 mg/L) than in Chinese men and women (1.18 mg/L).

CRP testing of more than 3,200 American Indians aged 45 to 74 years (64% were women) found that levels were much higher than those reported for other populations. The AHA and CDC cutoffs were not useful for predicting the risk of heart attack or dying from heart disease in this population. The authors suggested an alternative upper cutoff (above 4.0 mg/L) for Native Americans.

CRP & Heart Risk

Does high CRP increase the risk of heart disease in healthy women?

Most of the information on CRP in healthy women has come from the ongoing Women’s Health Study of almost 28,000 female health professionals 45 years and older. Women with high CRP and low LDL (bad) cholesterol had a higher risk [of having a heart attack or dying from heart disease than women with low CRP and high LDL cholesterol. Another analysis of more than 15,000 women found that both CRP and blood pressure independently predicted risk of cardiovascular problems including heart attack or stroke. Women with high CRP and high blood pressure were 3 times more likely to suffer cardiovascular problems than women with low levels of both. It was also shown that CRP helps predict cardiovascular problems in women with the metabolic syndrome. The metabolic syndrome is a clustering of risk factors including higher than normal blood pressure and blood sugar levels and a large waistline (more than 35 inches).

Does high CRP increase the risk of heart problems in people with heart disease?

High CRP is associated with a higher risk of dying early in men and women with stable angina. This may be because fatty plaque buildup appears to progress more rapidly in angina patients with high CRP. High CRP is also associated with a higher risk of heart problems in patients hospitalized for unstable angina/mild heart attack. A CRP test may be particularly helpful when the usual blood tests are negative (e.g., troponins).

During a typical heart attack, CRP levels rise dramatically, peaking at days 2 to 4, and returning to baseline within 4 weeks. Testing for CRP early on does not help predict who is at risk for dying or suffering a repeat attack. There is some evidence that a CRP reading taken when levels have stabilized may identify patients at a higher risk of dying early.

Is high CRP a stronger risk factor for men than women?

There is evidence that high CRP may be more of a risk for men than women. CRP levels are higher in women than in men, yet men develop heart disease more often and at an earlier age than women.

An analysis from the Nurses’ Health Study and the Health Professionals Follow-up study compared 265 men and 239 women who had a heart attack or died from heart disease with similar men and women who did not. While high CRP was associated with an 80% increase in the risk of these heart problems in men, there was no association seen in women. A study of nearly 4,000 men and women 65 years of age or older found that 33% of the men with high CRP developed heart disease within 10 years compared with only 17% of women with high CRP.

Does lowering CRP help the heart?

It is not clear if lowering CRP itself can reduce your heart risk. However, cholesterol – lowering statin medications (which also lower CRP levels) can cut heart risk in women with high CRP. In 2009, the JUPITER study found that among 6,801 otherwise healthy women with elevated CRP, those taking statin drugs had a 46% lower chance of developing heart problems, even if they did not have high cholesterol. However, it is not clear if these benefits were caused by lowering CRP, lowering cholesterol, or by some other mechanism. If you are concerned about the effect CRP is having on your heart risk, discuss with your doctor whether treatment with statin drugs may be right for you.

Aspirin, exercise, weight loss, moderate alcohol consumption, and following the Mediterranean diet (a diet high in fruits, vegetables, bread, and other cereals, beans, nuts, olive oil, and fish) can also lower CRP levels, and have other beneficial effects on your heart health as well.

Should I have a CRP test?

Your risk of developing heart disease in the next 10 years is measured by your Framingham risk score and additional risk factor assessment. CRP testing is usually not necessary for healthy low-risk individuals. However, CRP can be a tiebreaker test for people with an intermediate 10-year risk (10% to 20%) when it’s not clear if they need medication to control their risk factors (such as borderline high cholesterol or high blood pressure).

CRP is one of the numbers used in calculating your Reynolds Risk Score, a measure of 10-year heart disease risk that may be more accurate than the Framingham score in women at intermediate risk. People with heart disease or those at high-risk should ask their doctor if a CRP test is likely to change their treatment. A low CRP level does not mean that you can ignore other risk factors for heart disease.

What does the test involve?

There is no special preparation for a CRP test. A blood sample will be taken from a vein in your arm. The test takes less than a minute and you can go home immediately after.

What do the results mean?

If your CRP is high, you have a higher risk of developing heart disease. A low CRP level does not mean that you can ignore other risk factors for heart disease. A very high reading (more than 10 mg/L) indicates that you have an infection of some sort. The test should be repeated in about 2 weeks after the infection has cleared.

What are the risks and limitations of this test?

The CRP test is a simple blood test that carries no risks. Your CRP level can be affected by medications and other factors. hormone therapy, pregnancy, birth control pills, and intrauterine devices (IUDs) can raise CRP levels. Cholesterol lowering statin drugs, anti-inflammatories (such as aspirin, Advil, Motrin, and naproxen) may lower CRP levels. If you have chronic inflammation (such as arthritis) or have recently been ill, your CRP level will be high.

Why is CRP testing controversial?

There is an ongoing debate about how useful CRP really is. Some scientists argue that it doesn’t provide any more information about your risk for heart disease than a thorough assessment of established heart disease risk factors. The early studies showing that CRP helped predict heart disease risk took some, but not all, of the established risk factors into account.

In the third National Health and Nutrition Examination Survey of more than 15,000 people 18 years and older (53% were women), only 4% of men and 10% of women had high CRP without having a borderline or abnormal heart disease risk factor. The risk factors that were measured included cholesterol levels, blood sugar, blood pressure, smoking, and overweight (using body mass index, BMI). Other studies have also shown no additional benefit for CRP testing. It is also unclear whether knowing your CRP level will change how you are treated.

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