NEW YORK — The predictive value of the Framingham risk score could change substantially if serum C-reactive protein levels were included in the calculation.

An analysis of data collected on more than 15,000 women in the Women's Health Study showed that incorporating C-reactive protein (CRP) levels into the Framingham risk score significantly alters the risk estimate for nearly a third of women whose 10-year risk of a coronary event was 5%–9.9% without CRP in the risk equation. Among women whose baseline risk without CRP predicted a 10%–19.9% risk of a coronary event, adding CRP information significantly changed the risk for 42% of these women, Paul M. Ridker, M.D., said at an international symposium on triglycerides and HDL.

The redefined risk level can move either up or down, said Dr. Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital in Boston.

For example, among the women whose risk of coronary disease over the next 10 years was 5%–9.9% using the standard Framingham risk score, addition of CRP level into the risk calculation caused some of the women to have a risk of less than 5%, and some women to have a risk of 10% or higher. A total of 32% of these women had their risk estimate placed outside of the 5%–9.9% range by adding their CRP level into the risk calculation. This impact of CRP could potentially have an immediate effect on patient management and provides a rationale for immediately adding CRP to the traditional risk factors—such as age, gender, smoking status, blood pressure, and serum lipid levels, etc.—that make up the Framingham risk score.

“The issue is lifestyle change,” said Dr. Ridker at the symposium, sponsored by the Giovanni Lorenzini Medical Foundation. CRP levels may be able to get primary care physicians to say to patients that they need to lose weight, watch their diet, and exercise more because patients with a high serum level of CRP may have a higher risk than their LDL-cholesterol level indicates.

“These new data show that you can refine your estimates of who to treat and who not to treat,” commented Steven E. Nissen, M.D., medical director of the Cardiovascular Coordinating Center at the Cleveland Clinic Foundation.

Risk estimates that incorporate CRP levels would “do a better job of getting drug treatment to the people who would benefit from it the most,” he said. Using CRP levels to help determine who needs treatment with, for example, a statin, may cut unneeded treatment from low-risk patients and may better target treatment to higher risk patients, he said.

The Framingham risk score is used to determine which patients, who do not have established coronary disease, should start statin and aspirin therapy.

According to the Adult Treatment Panel III guidelines of the National Cholesterol Education Program, people with a 10-year risk of a coronary event of 10% or more, as calculated by the Framingham risk score, should start statin therapy if their serum level of LDL cholesterol is at least 130 mg/dL.

If their risk score is less than 10%, then statin therapy is not recommended unless their serum LDL cholesterol is 160 mg/dL or higher.

Guidelines from the U.S. Preventive Services Task Force say that people without proven coronary disease who have a 5-year risk of 3% or more should start daily treatment with aspirin.

The Women's Health Study enrolled 15,632 healthy women with an average age of 54 into a placebo-controlled trial that assessed the efficacy of treatment with aspirin and vitamin E.

During an average follow-up of 10 years, 464 women developed a first-ever, confirmed cardiovascular end point. Among the parameters collected at baseline were serum CRP levels.

On the basis of these data, Dr. Ridker and his associates calculated that the 20% of women with the highest CRP levels at baseline (at least 4.19 mg/dL) had a nearly threefold increased risk of a cardiovascular event during the next 10 years, compared with the 20% of women with the lowest CRP levels (less than 0.5 mg/dL).

This threefold increased risk of an event was calculated in a risk model that adjusted for all of the existing components of the Framingham risk score, showing that CRP was a significant predictor of risk, independent of the factors currently in the risk score, said Dr. Ridker, who is also a professor of medicine at Harvard University in Boston.

The analysis also showed that the ratio of total cholesterol to HDL cholesterol was at least as good for predicting the risk of the ocurrence of cardiovascular events as was the ratio of apolipoprotein B-100 to HDL lipoprotein cholesterol (JAMA 2005;294:326–33).

The finding showed that “we get all the information that we need from the ratio of total cholesterol to HDL cholesterol and … don't need fancy, more expensive lipid measures like apo B-100,” Dr. Ridker told this newspaper.

Dr. Ridker is a coinventor on patents held by Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease.

C-Reactive Protein May Alter Women's Framingham Risk Score