NEW ORLEANS — A new formula for calculating the cardiovascular disease risk of men and women, the Reynolds Risk Score, is an opportunity, according to proponents, to move beyond the Framingham Risk Score, the standard formula currently recommended for primary prevention assessment in the United States.
The Reynolds Risk Score calculates an individual's cardiovascular risk using the same six risk factors as in the Framingham Risk Score: age, smoking, diabetes, systolic blood pressure, total cholesterol, and HDL cholesterol. In addition, it incorporates two additional risk factors: high-sensitivity C-reactive protein (hsCRP), and parental history of a myocardial infarction before age 60.
But to critics, the Reynolds Risk Scores for women and for men are not yet adequately validated, rely on the controversial risk marker hsCRP, and offer at best a modest improvement over the Framingham Risk Score.
The role of hsCRP as a new measure of cardiovascular risk in people without a history of clinical disease was in the spotlight twice at the annual scientific sessions of the American Heart Association. Once was when the Reynolds Risk Score for men was unveiled in a report at the meeting by one of its developers, Dr. Paul M. Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital in Boston. It also was the key enrollment criterion in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) study, the results of which showed that people with high hsCRP levels but normal serum levels of LDL cholesterol had a marked benefit when put on statin treatment.
The Reynolds Risk Score for women was introduced nearly 2 years ago, in a February 2007 journal report (JAMA 2007; 297:611-9).
“The Reynolds Risk Score for men confirms in a second major cohort that the addition of the same two risk factors—hsCRP, representing inflammation, and family history, representing genetics, improves our overall ability to predict risk when compared to the covariates used in Framingham,” Dr. Ridker said in an interview.
The Reynolds Risk Score was derived for women using a randomly selected, 16,400-person subgroup from the 24,558 women who were enrolled in the Women's Health Study and were followed for a median of about 10 years.
In validity tests involving the remaining 8,158 women, predicted outcomes were compared with actual rates. In this analysis, the Reynolds Risk Score accurately reclassified about half of these women, compared with their classification using the Framingham Risk Score. On the basis of this evidence, Dr. Ridker and his associates made the Reynolds Risk Score for women available online in 2007 at www.reynoldsriskscore.org.
“We have been quite pleased with the widespread positive reception it has gotten from many within the prevention community,” Dr. Ridker said.
But other experts say that the Reynolds Risk Score for women has not caught on, in part because of its limited validation, in part because of its reliance on hsCRP levels.
“The Reynolds Risk Score was not very well validated,” in contrast to the Framingham Risk Score, which underwent validation in 2001, commented Dr. Peter W.F. Wilson, a cardiology epidemiologist and professor of medicine at Emory University, Atlanta. Most people say wait until we see a validation before using the Reynolds Risk Score, he said in an interview.
“The Reynolds Risk Score requires getting a hsCRP, and it's not currently recommended to universally screen for this,” commented Dr. Lori Mosca, a professor of medicine at Columbia University and director of preventive cardiology at New York-Presbyterian Hospital in New York. Measuring hsCRP in a lot of people “could greatly increase the cost of risk assessment, and it has not yet been shown to improve clinical outcomes compared with the Framingham Risk Score.” What's needed is a study to prove that getting a Reynolds Risk Score leads to better outcomes, she said in an interview.
A hsCRP test is currently reimbursed at about $18, nearly the same amount as a standard lipid panel.
The Reynolds Risk Scores “need validation in a lot of other settings before they are as robust as the Framingham Risk Score,” commented Dr. Donald Lloyd-Jones, a cardiologist at Northwestern University, Chicago.
In defense of the Reynolds Risk Score, Nancy R. Cook, Sc.D., noted that “the Reynolds Risk Score for women was internally validated. This is a higher standard than that faced by the Framingham models.” In addition, “the model for men serves as a type of external validation,” said Dr. Cook, a biostatistician at Brigham and Women's Hospital and a codeveloper of the Reynolds Risk Score.
After publication of the Reynolds Risk Score for women, the score was tested in men using data on 10,724 initially healthy, American, nondiabetic men aged 50 or older in the Physician's Health Study, who were followed for a median of 10.8 years.
When risk assessment by the Reynolds Risk Score was compared with the Framingham Risk Score, about 19% of all the men, and about 20% of those with an intermediate risk were reclassified by the Reynolds formula. The reclassifications were correct (based on actual outcomes) for 90% of all men, and for 100% of the intermediate-risk men, Dr. Ridker reported at the meeting. This analysis was published simultaneously with his talk (Circulation 2008;118:2243-51).
Dr. Ridker cautioned that the Reynolds score for men had been tested in a cohort of physicians, who have a relatively high socioeconomic status and generally excellent access to health care. This group was also predominantly white, with low numbers of African Americans, Hispanics, and Asians.
Dr. Ridker is listed as a coinventor on patents held by Brigham and Women's Hospital that relate to the hsCRP test, and he has received research support from AstraZeneca The company sponsored JUPITER and markets rosuvastatin (Crestor), the statin used in that study.
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