Factors Associated With Presence and Extent of Coronary Calcium in Those Predicted to Be at Low Risk According to Framingham Risk Score (from the Multi-Ethnic Study of Atherosclerosis)

Even among asymptomatic persons at low risk (<10%) according to the Framingham risk score, high coronary artery calcium (CAC) scores signify a greater predicted risk of coronary heart disease events. We sought to determine the noninvasive factors (without radiation exposure) significantly associated with CAC in low-risk, asymptomatic persons. In a cross-sectional analysis, we studied 3,046 participants from the Multi-Ethnic Study of Atherosclerosis at a low 10-year predicted risk (Framingham risk score <10%) of coronary heart disease events. Multivariate logistic regression analysis was used to assess the association of novel markers with the presence of any CAC (CAC >0) and advanced CAC (CAC ≥300). A CAC level of >0 and of ≥300 was present in 30% and 3.5% of participants, respectively. Factor VIIIc, fibrinogen, and soluble intercellular adhesion molecule were each associated with the presence of CAC (p ≤0.02), and C-reactive protein, D-dimer, and the carotid intima-media thickness with advanced CAC (p ≤0.03). The base model combining the traditional risk factors had excellent discrimination for advanced CAC (C-statistic 0.808). The addition of the 2 best-fit models combining the biomarkers with or without carotid intima-media thickness improved the c-statistic to 0.822 and 0.820, respectively. All 3 models calibrated well but were similar in estimating the individual risk probabilities for advanced CAC (prevalence 9.97%, 10.63%, and 10.10% in the greatest quartiles of predicted probabilities vs 0.26%, 0.26%, and 0.26% in the lowest quartiles, respectively). In conclusion, in low-risk persons, the traditional risk factors alone predicted advanced CAC with high discrimination and calibration. The biomarker combinations with and without carotid intima-media thickness were also significantly associated with advanced CAC; however, the improvement in the prediction and estimation of the clinical risk were modest compared to the traditional risk factors alone.