American College of Surgeons 90th Annual Clinical Congress

NEW ORLEANS—Surgeons from Madigan Army Medical Center, Tacoma, WA, have reported a link between a common blood test for inflammation and carotid stenosis (narrowing of the blood vessels leading to the brain from the neck), which can lead to a stroke. In a study presented at the 2004 annual Clinical Congress of the American College of Surgeons, the surgeons noted that elevated blood levels of C-reactive protein (CRP) were more predictive of stenosis than cholesterol levels and other risk factors for cardiovascular disease. Their findings support similar results reported by other research groups.

After analyzing risk factors, including low-density lipoprotein (LDL), serum triglycerides, family history, and long-term glucose control, in 58 patients, the surgeons found that only CRP was associated with carotid stenosis. The surgeons are now expanding the study to more than 500 patients. These patients will be evaluated for the next three years to determine whether individuals with elevated CRP levels go on to have a transient ischemic attack (a stroke that lasts only a few minutes) or a full-blown stroke. "We will be following these patients every three to six months and tracking who has an adverse neurologic event related to carotid disease. It will be interesting to see if patients with an elevated CRP have an increased risk down the road of an adverse neurologic outcome," Philip S. Mullenix, MD, a resident in vascular surgery, said.

Dr. Mullenix acknowledged that his research is raising more questions than it is answering. However, if CRP does predict neurologic disease due to atherosclerosis (hardening of the arteries), monitoring CRP levels could lead to a whole new way of identifying patients who may need treatment to prevent brain attack.

At the present time, patients with high levels of LDL receive statin drugs to reduce the chance they may develop atherosclerotic disease. Statins also reduce CRP levels. However, patients with low LDL but elevated CRP are not currently placed on statin therapy. If elevated CRP is a danger sign for stroke, patients might be started on a statin even if their LDL is low, Dr. Mullenix suggested.

CRP also might be used to help prioritize patients for carotid surgery. The standard way of determining whether a patient needs carotid endarterectomy (a procedure that removes plaque from the lining of blood vessels) is based on the velocity of blood flow through the carotid arteries. However, velocity is a surrogate measure of buildup of plaque on the walls of blood vessels. "What we're really interested in is plaque that has a propensity to cause a stroke. It's thought that elevated CRP is associated with plaque that has ulcerated or thrombotic [blood clot] components and therefore is unstable," Dr. Mullenix explained. Unstable or vulnerable plaque can break off and become lodged in blood vessels downstream, blocking blood supply to the brain and causing a stroke. "CRP might change the frequency of surveillance of patients with carotid disease. Patients with high CRPs might be assessed every six months instead of every year. In an adjunctive way, along with other factors, it might tip the balance toward surgery for those patients we're on the fence about in terms of our clinical impression," Dr. Mullenix said.

CRP is a general, systemic marker for inflammation. It is increased in patients with rheumatoid arthritis, chronic inflammation, infection, and malignancy. Because atherosclerosis is a systemic inflammatory disease, in the last few years, CRP has been tested as a predictor of future acute atherosclerotic coronary events. Until Dr. Mullenix's study, investigators have not studied how carotid disease may contribute to elevations in CRP.

In his study, Dr. Mullenix and his colleagues measured serum CRP and LDL in 58 men who were suspected of having carotid stenosis and compared how well each of the two tests predicted carotid disease. CRP was statistically correlated (p<0.001) with carotid stenosis, but LDL was not. Average CRP levels were higher in patients with stenosis than in those who did not have carotid disease. LDL levels were similar in both groups of patients. When compared with other risk factors for carotid stenosis, such as age, history of smoking, diabetes, hypertension, and coronary artery disease, CRP was independently associated with stenosis, while LDL was not. Finally, CRP independently predicted stenosis, while LDL did not.

"If future studies indeed show that elevated CRP—even when you control for other cardiovascular disease risk factors—is a marker of the stroke potential for a carotid lesion, vascular surgeons, physicians who treat vascular disease, and patients would be very concerned about it," Dr. Mullenix concluded.

Dr. Mullenix's research colleagues include Scott Steele, MD; Matthew Martin, MD; Benjamin Starnes, MD; and Charles Andersen, MD, FACS.

News from the 2004 Clinical Congress