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ATIENTS WITH TYPE 2 DIABETES mellitus (DM) have a marked increase in the risk of myocardial infarction (MI), and a substantially worse prognosis after MI compared with patients without diabetes. [1][2][3] In recent years, it has become apparent that optimal control of blood pressure and low-density lipoprotein cholesterol (LDL-C) level can substantially reduce excess cardiovascular risk in patients with diabetes. 4-6 However, even with optimal control of these potent cardiovascular risk factors, incremental risk for cardiovascular events remains high compared with individuals without diabetes. 2,3,6 New approaches are, therefore, needed to further reduce cardiovascular risk in patients with diabetes.Emerging evidence suggests that thiazolidinediones could be useful for reducing cardiovascular risk. In isolated vessel-wall cells, troglitazone, pioglitazone, and rosiglitazone have been shown to modulate gene expression in a manner that would be predicted to be atheroprotective in vivo. 7,8 In hu-mans, these agents have been shown to have beneficial effects on systemic inflammatory and coagulation markers, lipoprotein profile, and endothelial cell function. 9-12 Some of these beneficial ef-Author Affiliations are listed at the end of this article.

Background The presence and extent of coronary artery calcium (CAC) correlates with the overall magnitude of coronary atherosclerotic plaque burden and with the development of subsequent coronary events. In this study we aim to establish whether age-gender specific percentiles of CAC predict cardiovascular outcomes better than the actual (absolute) CAC score. Methods MESA is a prospective cohort study of asymptomatic 6814 participants, followed for coronary heart disease (CHD) events including myocardial infarction, angina, resuscitated cardiac arrest, or CHD death. Time to incident CHD was modeled using Cox regression, and we compared models using percentiles based on age, gender and/or race/ethnicity to categories commonly used(0, 1-100, 101-400, 400+ Agatston units). Results There were 163(2.4%) incident CHD events (median follow-up 3.75 years). Expressing CAC in terms of age and gender specific percentiles had significantly lower area under the ROC curve(AUC) than using absolute scores (women: AUC 0.73 versus 0.76,p=0.044; men: AUC 0.73 versus 0.77,p<0.001). Akaike’s information criterion (AIC) indicated better model fit using the overall score. Both methods robustly predicted events(>90th percentile associated with a hazard ratio(HR) of 16.4(95% c.i. 9.30,28.9), and score >400 associated with HR of 20.6(95% c.i. 11.8, 36.0). Within groups based on age/gender/race/ethnicity specific percentiles there remains a clear trend of increasing risk across levels of the absolute CAC groups. In contrast, once absolute CAC category is fixed, there is no increasing trend across levels of age/gender/race/ethnicity specific categories. Patients with low absolute scores are low risk, regardless of age-gender-ethnicity percentile rank. Persons with an absolute CAC score of >400 are high risk, regardless of percentile rank. Conclusion Using absolute CAC in standard groups performed better than age-gender-ethnicity percentiles in terms of model fit and discrimination. We recommend using cut-points based on the absolute CAC amount and the common CAC cutpoints of 100 and 400 appear to perform well.

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