OBJECTIVES: An ongoing population-based cohort study was used to assess the prevalence of risk factors, signs of inflammation based on the degree of high sensitive C-reactive protein (hs-CRP) and subclinical atherosclerosis using electron beam computed tomography for detection of coronary artery calcification (CAC). We evaluated the sex related cardiovascular risk stratification based on quantification of subclinical atherosclerosis and inflammation. BACKGROUND: The National Cholesterol Education Program in Adult Treatment Panel III (NCEP ATP III) suggests using CAC and hs-CRP in individuals at intermediate risk. The effect on risk stratification was not yet tested in the general population. METHODS: In the Heinz Nixdorf Recall study 4066 (93.2%) subjects without and 280 (6.8%) of 4345 subjects with coronary artery disease (CAD) (age 45-75years) were screened in whom data for CAC, hs-CRP, and all risk factors for calculating the Framingham risk score (FRS) were available. This subset of participants was representative to the overall population. Age-adjusted prevalence rate ratios (RR) for prevalence of CAD in relation to risk factors were determined. Framingham risk score groups and NCEP ATP III-based risk categories were calculated. Alterations in risk classification were analyzed using three CAC and hs-CRP categories each: (1) CAC<100, 100-399 and >/=400 or >75th percentile, respectively, (2) hs-CRP3mg/L, and (3) a combined CAC and hs-CRP score. RESULTS: Highest RRs of CAD were found for high CAC versus low CAC in men (RR=18.2, 95% CI=10.6-31.3) and for the combined CAC+hs-CRP index in women (RR=11.0, 95% CI=5.1-23.6, both p<0.0001). For high versus low hs-CRP-values a significant RR was found for women only (RR=2.5, 95% CI=1.3-4.6, p<0.01). RRs for other risk factors like hyperlipidemia, HDL, smoking, BMI>30kg/m(2) were much smaller showing sex differences as well. Thirty percent males and 71% females were classified as low NCEP ATP III risk, 38% and 20% as intermediate and 31% and 9% as high risk. Adding CAC and hs-CRP to NCEP ATP risk categories changed distribution of risk categories considerably with strong differences between sexes. This sex dependence in the magnitude of change in risk categories nearly vanishes, when the combined index of CAC and hs-CRP was used. CONCLUSIONS: NCEP ATP III risk categories are significantly and sex-dependently altered using CAC and hs-CRP. CAC is suggested to be of highest value in men. hs-CRP seems to be of complementary value only in women. Measuring atherosclerotic inflammation may improve sex-related risk prediction in a general population.