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Although physical activity and physical fitness are inversely and causally associated with coronary heart disease (CHD) morbidity and mortality, available equations for estimating CHD risk do not include scores for activity or fitness. Therefore, this study evaluated the association of physical fitness and moderate-intensity physical activity with the 10-year Framingham CHD risk estimate.Cross-sectional analyses were performed on data from 137 healthy middle-aged women (53.9±9.9 yr; 28.3±6.0 kg/m2). Health histories, body composition, blood pressure, and blood samples were obtained from a clinical examination. Levels of moderate (3-6 METS) intensity physical activity, expressed as MET-minutes/day of energy expenditure, were derived from multiple 24-hour physical activity records. Physical fitness was quantified as duration of a symptom-limited maximal treadmill exercise test.After adjustment for race, body mass index (BMI), and hormone replacement status, a graded reduction in the Framingham risk score was observed across low (5.8%), moderate (4.0%), and high (3.6%) fitness levels (P for trend=0.009). Women in both the moderate and high fitness categories had a lower (P<0.01) risk score compared with their low fit counterparts. Significant differences in risk were not seen among low (3.9%), moderate (4.9%), and high (4.4%) physical activity groups. The lack of association between the risk score by physical activity may have been due to the homogeneity of activity levels among participants. Our findings reinforce existing data that show enhanced levels of fitness are associated with lower risk for CHD.