CAC Score for Risk Classification in Diabetes and Metabolic Syndrome

Study Questions:

What is the value of long-term prognostication of incident coronary heart disease (CHD) and atherosclerotic cardiovascular disease (ASCVD) using coronary artery calcium (CAC) scores among those with type 2 diabetes, metabolic syndrome (MetS), or neither condition?


This study included participants from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of 6,814 men and women aged 45-84 years without known CVD from four race/ethnicity groups (white [38.5%], African American [27.5%], Hispanic [22.1%], and Chinese [11.9%]) recruited from July 2000-August 2002. Follow-up for each participant extended to the first occurrence of an incident event, other death, loss to follow-up, or the last follow-up call through December 31, 2013. Data analysis was performed from June 1, 2016, to September 12, 2017. Cox proportional hazards regression models were used to estimate hazard ratios (HRs). The CAC score was log-transformed (lnCACscore) as ln(CAC+1) to maintain the normality of CAC measures. CAC scores were also categorized as 0, 1-99, 100-399, and ≥400 and dichotomized as 0 or >0. Area under the receiver operator characteristic curve and net reclassification improvement were used to compare incremental contributions of CAC score when added to the Framingham risk score (FRS), ethnicity/race, and socioeconomic status. The 10-year risk estimates were categorized as <5% (low risk), 5% to <7.5% (intermediate risk), and ≥7.5% (high risk) for CHD events and ASCVD events.


Of 6,814 MESA participants, 6,751 had complete risk factor and follow-up data and were included (mean [standard deviation] age, 62.2 [10.2] years; 47.2 male). A total of 881 (13.0%) had diabetes, 1,738 (25.7%) had MetS, and 4,132 (61.2%) had neither condition. After 11.1 mean years of follow-up, CHD events occurred in 84 participants with diabetes (135 ASCVD events), 115 with MetS (175 ASCVD events), and 157 with neither (250 ASCVD events). The CAC score was significantly and independently associated with incident CHD in multivariable analyses in those with diabetes (HR, 1.30), MetS (HR, 1.30), and neither condition (HR, 1.37). For incident CHD, net reclassification improvement with addition of CAC score was 0.23 in those with diabetes, 0.22 in those with MetS, and 0.25 in those with neither condition. For those with diabetes but no CAC, the CHD event rate was very low at 3.7 per 1,000 person-years (3.7% 10-year risk). Among those with diabetes and the highest FRS category of >20%, the CHD event rate was not high if the participant had a CAC score of 0 (4.7 per 1,000 person-years). Compared with those with a CAC score of 0, the HRs for CHD and ASCVD events increased progressively with higher CAC categories; those with CAC scores of ≥400 had the highest HRs for CHD events (HR, 5.60). The CAC score was also a prognostic indicator of CHD and ASCVD after controlling for diabetes duration of ≥10 years at baseline, insulin use, and glycemic control.


In a large multiethnic cohort, the addition of CAC score to global risk assessment was associated with significantly improved risk classification in those with MetS and diabetes, even if diabetes duration was longer than a decade, suggesting a role for the CAC score in risk assessment in such patients.


The MESA cohort identifies persons for whom a CAC score can improve risk stratification beyond ACC/AHA and Reynolds risk scores and the decision for statins and aspirin. While diabetes has been considered a coronary disease risk equivalent, particularly if for >10 years, the MESA study demonstrates that a significant number may be relatively low risk. As the authors concluded, future studies should examine whether newer antidiabetic medications, such as sodium glucose cotransporter-2 inhibitors or glucagon-like peptide-1 receptor agonists, that benefit patients with known ASCVD could be considered for those at increased risk based on extent of CAC or other measures of subclinical atherosclerosis.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Atherosclerotic Disease (CAD/PAD), Nonstatins, Novel Agents, Statins

Keywords: Aspirin, Atherosclerosis, Coronary Artery Disease, Diabetes Mellitus, Type 2, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypoglycemic Agents, Insulins, Metabolic Syndrome X, Plaque, Atherosclerotic, Primary Prevention, Risk Factors

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