A team of Brigham and Women’s Hospital (BWH) researchers led by cardiologist Paul M. Ridker, MD, MPH, Director, Cardiovascular Disease Prevention, has developed and validated a new global cardiovascular risk assessment algorithm, the Reynolds Risk Score, that more accurately predicts a woman’s short- and long-term risk of heart attack and other adverse events. The study appeared in the February 14, 2007 issue of the Journal of the American Medical Association (JAMA).
Women and heart disease
Dr. Ridker says, “The biology and symptoms of heart disease are different in men and women, but the current guidelines for predicting risk do not reflect that reality. Approximately 20 percent of women who have heart attacks have none of the traditional risk factors, and about half have normal cholesterol levels. Clearly, we were missing some important predictive information, and so along with my colleagues Drs. Julie Buring and Nancy Cook, we decided to do something unique, to not only objectively derive a new scoring system, but also to validate it against currently measured factors.”
NHLBI-funded research study
The researchers studied 24,558 initially healthy women 45 or older enrolled in the National Heart, Lung, and Blood Institute’s Women’s Health Study. The women were prospectively followed for an average of 10.2 years for cardiovascular events including myocardial infarction, ischemic stroke, coronary revascularization, and cardiovascular death.
The women were randomized to a derivation cohort, comprising about two-thirds of the original group, and a validation cohort. In the derivation cohort, the researchers considered 35 potential variables and the interactions among them. Variables included:
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Alternative lipid measures;
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Inflammatory markers;
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Markers of glycemic control;
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Creatinine and homocysteine levels;
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and the traditional risk determinants.
New risk scoring algorithm
From these, they derived the Reynolds Risk Score and tested it in the validation cohort against the Framingham risk score, the current gold standard in risk assessment. Dr. Ridker noted, “We were looking to develop the most parsimonious model, that is, that model that would offer the maximum predictive impact with the fewest factors. The final Reynolds Risk Score includes seven simple variables – age, systolic blood pressure, smoking, total cholesterol, HDL cholesterol, high-sensitivity C-reactive protein (hsCRP), and parental history of myocardial infarction before age 60.
The Reynolds Risk Score includes two factors – hsCRP and parental history of heart attack before age 60 – that were not measured by the Framingham risk score or the
Adult Treatment Panel III (ATP-III). When these new factors were added into women’s cardiac risk assessment, between 40 and 50 percent of the women who had been classified as being at intermediate risk were reclassified into either lower- or higher-risk categories with 98 percent accuracy.
According to Dr. Ridker, “The Reynolds Risk Score brings the new biology of genetics and inflammation to the bedside in the same way that measuring cholesterol brought the then-new biology of lipids to clinical practice 30 years ago.”
The fact that risk factors such as obesity, exercise, homocysteine, and lipoprotein(a) did not make it into the Reynolds Risk Score does not mean they are not important, but rather that the mechanisms by which they affect risk they must be mediated through other factors.
Changing risk assessment
These findings have significant implications for clinical practice. First, all the Framingham risk factors have been validated. In addition, Dr. Ridker says, “We identified two new factors – hsCRP and family history – that substantially improve clinicians’ ability to predict cardiovascular risk for individual women, and even more important, allow us to more accurately target preventive therapies including aspirin and statins.”
“If the Reynolds Risk Score were adopted as the standard for assessing risk, 20 to 25 percent of women currently classified at intermediate risk over the next ten years would be reclassified to a lower risk category and could be spared the toxicity of unnecessary medications. A similar number would be deemed to be at higher risk and offered preventive therapy. This is a win for everyone.” Dr. Ridker and his team have already begun work to validate these findings and develop a new cardiovascular risk scoring system for men.
Access the Reynolds Risk Score: www.reynoldsriskscore.org.
Referrals and Information
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Donald W. Reynolds Cardiovascular Clinical Research Center
The Donald W. Reynolds Cardiovascular Clinical Research Center at Harvard Medical School and Brigham and Women’s Hospital is funded by a major grant from the Donald W. Reynolds Foundation and is dedicated to cardiovascular disease research, identifying new targets for therapy and new predictors of risk for atherosclerosis.
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