Improved Cardiovascular Risk Prediction Paves the Way to Better Cardiovascular Care for Women

Led by cardiologist Paul M. Ridker, MD, MPH, Director of the Brigham and Women’s Hospital Center for Cardiovascular Disease Prevention, a team of researchers has developed and validated the Reynolds Risk Score, a new global cardiovascular risk assessment algorithm designed to more accurately predict a woman’s short- and long-term risk of heart attack and other cardiovascular events.

The current guidelines for predicting cardiovascular risk do not fully reflect biological and symptomatic differences between men and women. Approximately 20 percent of women who experience heart attacks have none of the traditional risk factors, and about half have normal cholesterol levels.

The study, which appeared in the February 14, 2007 issue of the Journal of the American Medical Association (JAMA), included 24,558 initially healthy women age 45 or older who were 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 — including alternative lipid measures, inflammatory markers like high sensitivity C-reactive protein (hsCRP), markers of glycemic control, and creatinine and homocysteine levels — as well as the traditional risk determinants — and the interactions among them. From these, the researchers derived the Reynolds Risk Score (www.reynoldsriskscore.org) and tested it in the validation cohort against the Framingham risk score, the gold standard for risk assessment. The final Reynolds Risk Score includes seven simple variables:

• Age;
• Systolic blood pressure;
• Smoking;
• Total cholesterol;
• HDL cholesterol;
• High-sensitivity C-reactive protein (hsCRP);
• Parental history of myocardial
• infarction before age 60.

New Risk Factors
The Reynolds Risk Score includes two factors — hsCRP and parental history of heart attack before age 60 — that are not included in 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. While risk factors, such as obesity, exercise, homocysteine, and lipoprotein (a), are not part of the Reynolds Risk Score, they are still important. Themechanisms by which they affect risk, however, must be mediated through other factors.

The Study’s Implications
These findings have significant implications for clinical practice. First, the new data validates all of the traditional Framingham risk factors. In addition, two new factors have been identified reflecting inflammation and genetics that substantially improve clinicians’ ability to predict cardiovascular risk for individual women and more accurately target preventive therapies, including aspirin and statins.

If adopted as the standard for assessing risk, the Reynolds Risk Score would reclassify 20 to 25 percent of women currently deemed at inter-mediate risk over the next 10 years to a lower risk category. These women could be spared the toxicity of unnecessary medications. A similar number of women would be deemed to be at higher risk and offered preventive therapy. Dr. Ridker and collaborators Drs. Julie Buring and Nancy Cook have also begun work to develop a new cardiovascular risk scoring system for men.

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