What is C-Reactive Protein?
C-reactive protein (CRP) is a substance produced by the body in response to inflammation—the process by which the body responds to injury. Physicians now believe that atherosclerosis, the buildup of fatty plaque on the walls of the arteries, is an inflammatory process. By measuring the amount of CRP in a woman's blood, doctors can tell how much inflammation is occurring in her body and get an idea of how much damage is being done to her blood vessels. When added to traditional risk factors, CRP measurement can help doctors better understand a woman's risk of future blood vessel problems.
While most of the research on CRP has been done in the context of heart attack and stroke, Peripheral Artery Disease (PAD) is caused by the same inflammatory process as other forms of blood vessel disease. It is hoped that CRP can help identify women who are at high risk for future PAD problems in time to take steps to prevent them.
CRP is most often used as a "marker" of inflammation, but CRP itself may also contribute to blood vessel problems by encouraging the buildup of plaque on the artery walls and reducing the vessel's ability to heal itself.1 However, it has not been proven that lowering CRP levels with medications can reduce the risk of future problems.
Does CRP affect my PAD risk?
Women with high CRP levels have a higher risk of having a heart attack and dying of heart disease than women with low levels.2 Recent studies have found that women with high CRP levels are twice as likely to develop PAD in the legs compared with women with normal or low CRP levels.3,4 The higher a woman's CRP level, the higher her risk.5
CRP increases your risk of PAD elsewhere in your body as well.6 One study of 773 patients (53% were women) found that those with the highest CRP levels had a 90% higher risk of carotid artery disease (disease in the arteries in the neck) and a 70% increased risk of aortic disease (disease of the large artery that carries blood from the heart to the rest of the body) compared to those with the lowest CRP levels.7
In addition to increasing the risk of developing blood vessel disease, women with PAD and high CRP tend to have worse outcomes than those with low CRP levels.1 In one study of 601 patients (41% were women) 55 and older with PAD, those with high CRP levels had worse overall physical functioning—shorter 6-minute walk distance, slower walking speed, less balance, and more difficulty standing up from sitting.8 Some research also indicates that the inflammation marked by CRP can directly damage the muscles in the legs and reduce muscle mass and strength.1
High CRP levels also predict higher death rates and more heart problems in patients who undergo procedures to treat PAD in the legs9,10 or carotid artery disease in the neck11 (although none of these studies examined women's results separately). You may want to speak with your doctor about your CRP levels if you are considering undergoing a procedure, especially carotid stenting. See also: CRP & Stroke Risk
Should I have my CRP level tested?
CRP levels are measured using a test called the high-sensitivity CRP test (hs-CRP). Whether you would benefit from a CRP test depends on your overall risk of heart and blood vessel disease:
- If your overall risk is low (less than a 10% chance of developing heart or blood vessel disease in the next 10 years) no test is needed.
- If your risk is intermediate (10% to 20% risk), you may benefit from a CRP test to better understand your risk. Intermediate-risk patients with high CRP may benefit from more aggressive treatment to control their risk factors.
- If your risk is high (more than 20% in 10 years), or if you have already has been diagnosed with PAD, heart disease, or stroke, you should be treated aggressively regardless of your CRP level, so no test is needed.
What do my CRP numbers mean?
|CRP Risk Levels|
|Risk Category||CRP (mg/L)|
|Low||Less than 1.0|
|Average||1.0 to 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 mostly white populations. When these cutoffs were developed, it was assumed that CRP levels were similar in women and men. However, since then studies have shown that average CRP levels are almost twice as high in women as in men (3.3 vs. 1.8 mg/L). Even after accounting for other factors that affect CRP levels, women are 60% to 70% more likely to have high CRP than men.12 Further studies are needed to determine if CRP cutoffs should be different for women.
Because CRP only detects inflammation in general, its levels can be affected by many factors in addition to gender. Black women tend to have higher CRP levels than Hispanic and white women, while Asians tend to have lower levels.13 CRP levels are also elevated by other medical conditions including arthritis, diabetes, high blood pressure, bacterial and viral infections, sleep disturbances, too much or too little physical activity, drinking too much alcohol, and depression. Some drugs, such as hormone replacement therapy, can affect CRP.
Will lowering CRP lower my PAD risk?
CRP has been more strongly linked to heart disease and its outcomes than PAD. However, it has still not been proven that lowering your CRP levels can prevent heart disease.14 Some small studies have found that lowering CRP levels can make a woman less likely to develop PAD. However, this has not yet been proven in a large randomized clinical trial (the gold standard way to determine if a treatment is effective). Until a large study is done, it is not recommended that women take medication to lower CRP (such as blood thinners or cholesterol-lowering statin drugs) to reduce their PAD risk.1
A few observational studies have found that lowering CRP with statin drugs is beneficial in patients with PAD. One study looked at 515 patients with PAD (43% were women) and found that those with high CRP benefited most from statin drugs. Patients with low CRP when the study began did not benefit from statin therapy, while those with high CRP cut their risk of dying or having a heart attack in half.15 However, it has not been proven that statins cut your risk by lowering CRP levels, rather than simply by lowering cholesterol.
Diabetes, smoking, and being overweight or obese are associated with increased levels of markers of inflammation, including CRP.16 If you are concerned about the effect of CRP on your risk of PAD, quitting smoking, maintaining a healthy weight, and controlling diabetes (if you have it) are proven ways to reduce inflammation that also reduce your risk of developing PAD. See Preventing PAD: The Basics for more ways to lower your risk of developing PAD.
- McDermott MM, Lloyd-Jones DM. The role of biomarkers and genetics in peripheral arterial disease. J Am Coll Cardiol. Sep 29 2009;54(14):1228-1237.
- Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation. Jan 28 2003;107(3):363-369.
- Wildman RP, Muntner P, Chen J, Sutton-Tyrrell K, He J. Relation of inflammation to peripheral arterial disease in the national health and nutrition examination survey, 1999-2002. Am J Cardiol. Dec 1 2005;96(11):1579-1583.
- Pradhan AD, Shrivastava S, Cook NR, Rifai N, Creager MA, Ridker PM. Symptomatic peripheral arterial disease in women: nontraditional biomarkers of elevated risk. Circulation. Feb 12 2008;117(6):823-831.
- Shankar A, Li J, Nieto FJ, Klein BE, Klein R. Association between C-reactive protein level and peripheral arterial disease among US adults without cardiovascular disease, diabetes, or hypertension. Am Heart J. Sep 2007;154(3):495-501.
- Sasaki S, Yasuda K, Takigami K, Yamauchi H, Shiiya N, Sakuma M. Inflammatory abdominal aortic aneurysms and atherosclerotic abdominal aortic aneurysms--comparisons of clinical features and long-term results. Jpn Circ J. Mar 1997;61(3):231-235.
- Van Der Meer IM, De Maat MP, Hak AE, et al. C-reactive protein predicts progression of atherosclerosis measured at various sites in the arterial tree: the Rotterdam Study. Stroke. Dec 2002;33(12):2750-2755.
- McDermott MM, Greenland P, Green D, et al. D-dimer, inflammatory markers, and lower extremity functioning in patients with and without peripheral arterial disease. Circulation. Jul 1 2003;107(25):3191-3198.
- Owens CD, Ridker PM, Belkin M, et al. Elevated C-reactive protein levels are associated with postoperative events in patients undergoing lower extremity vein bypass surgery. J Vasc Surg. Jan 2007;45(1):2-9.
- Rossi ML, Merlini PA, Ardissino D. Percutaneous coronary revascularisation in women. Thromb Res. Sep 30 2001;103 Suppl 1:S105-111.
- Schillinger M, Exner M, Mlekusch W, et al. Inflammation and Carotid Artery--Risk for Atherosclerosis Study (ICARAS). Circulation. May 3 2005;111(17):2203-2209.
- Khera A, McGuire DK, Murphy SA, et al. Race and gender differences in C-reactive protein levels. J Am Coll Cardiol. Aug 2 2005;46(3):464-469.
- Albert MA, Glynn RJ, Buring J, Ridker PM. C-reactive protein levels among women of various ethnic groups living in the United States (from the Women's Health Study). Am J Cardiol. May 15 2004;93(10):1238-1242.
- Helfand M, Buckley DI, Freeman M, et al. Emerging risk factors for coronary heart disease: a summary of systematic reviews conducted for the U.S. Preventive Services Task Force. Ann Intern Med. Oct 6 2009;151(7):496-507.
- Schillinger M, Exner M, Mlekusch W, et al. Statin therapy improves cardiovascular outcome of patients with peripheral artery disease. Eur Heart J. May 2004;25(9):742-748.
- Ridker PM, Silvertown JD. Inflammation, C-reactive protein, and atherothrombosis. J Periodontol. Aug 2008;79(8 Suppl):1544-1551.