Absence of Coronary Artery Calcium Identifies Asymptomatic Diabetic Individuals at Low Near-Term But Not Long-Term Risk of Mortality

Diabetes mellitus is a prominent cause of death in the United States, with the presence of coronary artery disease (CAD) and cerebrovascular events contributing to a substantial portion of mortality among diabetic patients. Further, diabetes is considered to be a CAD equivalent, and the risk of incident adverse clinical events for diabetic individuals is estimated to be similar to nondiabetic individuals considered high-risk by clinical prediction models. Coronary artery calcium (CAC) scoring by noncontrast computed tomography (CT) is a well-validated tool for the detection of CAD in asymptomatic individuals. Prior studies have observed the presence, extent, and progression of CAC to enable prediction of adverse clinical events among asymptomatic individuals. Notably, the absence of CAC in asymptomatic individuals—including those with diabetes mellitus—has been associated with a salutary prognosis, although these investigations have been limited to near-term follow-up periods extending to only 5 years. Background—Data regarding coronary artery calcification (CAC) prognosis in diabetic individuals are limited to 5-years follow-up. We investigated the long-term risk stratification of CAC among diabetic compared with nondiabetic individuals. Methods and Results—Nine thousand seven hundred and fifteen asymptomatic individuals undergoing CAC scoring were followed for a median (interquartile range) of 14.7 (13.9–15.6) years. The incidence density rate and hazard ratios with 95% confidence intervals were used to calculate all-cause mortality. Incremental prognostic utility of CAC was evaluated using the area under the receiver operator characteristic curve and net reclassification improvement. Diabetics (54.7±10.8 years; 59.4% male) comprised 8.3% of the cohort (n=810), of which 188 (23.2%) died. For CAC=0, the rate of mortality was similar between diabetic and nondiabetic individuals for the first 5 years (P>0.05), with a nonlinear increased risk of mortality for diabetics after 5 years (P<0.05). The adjusted risk of death for those in the highest (CAC>400) versus the lowest (CAC=0) category of CAC increased by a hazards of 4.64 (95% confidence interval =3.74–5.76) and 3.41 (95% confidence interval =2.22–5.22) for nondiabetic and diabetic individuals, respectively. The presence of CAC improved discrimination (area under the receiver operator characteristic curve range: 0.73–0.74; P<0.01) and reclassification (category-free net reclassification improvement range: 0.53–0.50; P<0.001) beyond conventional risk factors in nondiabetic and diabetic individuals, respectively. Conclusions—CAC=0 is associated with a favorable 5-year prognosis for asymptomatic diabetic and nondiabetic individuals. After 5 years, the risk of mortality increases significantly for diabetic individuals even in the presence of a baseline CAC=0. (Circ Cardiovasc Imaging. 2016;9:e003528. DOI: 10.1161/CIRCIMAGING.115.003528.)