Development and Validation of Improved Algorithms for the Assessment of Global Cardiovascular Risk in Women

IN THE DECADE BETWEEN 1956 AND 1966, investigators in Framingham, Mass, defined age, hypertension, smoking, diabetes, and hyperlipidemia as major determinants of coronary heart disease and coined the term coronary risk factors. Over time, these markers were codified into global risk scores for assessment of cardiovascular risk. However, for women, up to 20% of all coronary events occur in the absence of these major risk factors, whereas many women with traditional risk factors do not experience coronary events. Furthermore, over the past halfcentury, understanding of the biological processes underlying atherothrombosis has markedly shifted to encompass the complex biology of hemostasis, thrombosis, inflammation, endothelial dysfunction, and plaque instability. Despite this changing view of pathophysiology, variables included in currentriskalgorithmsforwomenarelargely unchanged fromthose recommended40 years ago. Additional risk markers that have been proposed include alternative lipid measures, such as apolipoproteins A-I and B-100, non–high-density lipoprotein cholesterol (HDL-C), and lipoprotein(a); inflammatory biomarkers such as high-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule 1 (sICAM-1), and fibrinogen; markers of glycemic control such as glycatedhemoglobinA1c; andplasmacreatinine and homocysteine levels. However, data are scant evaluating whether improved risk prediction algorithms can be developed that use these markers. We assayed all of these novel biomarkers as well as a large number of tradiFor editorial comment see p 641. Author Affiliations: Donald W. Reynolds Center for Cardiovascular Research and the Center for Cardiovascular Disease Prevention (Drs Ridker, Cook, and Buring), Division of Preventive Medicine (Drs Ridker, Buring, and Cook), and the Division of Cardiovascular Diseases (Dr Ridker), Brigham and Women’s Hospital, Boston, Mass, and the Department of Laboratory Medicine, Children’s Hospital, Boston, Mass (Dr Rifai). Corresponding Author: Paul M Ridker, MD, MPH, Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, 900 Commonwealth Ave E, Boston, MA 02215 (pridker@partners.org). Context Despite improved understanding of atherothrombosis, cardiovascular prediction algorithms for women have largely relied on traditional risk factors.