Risk Classification by CAC Score in Diabetes and Metabolic Syndrome
What is the value of the coronary artery calcium (CAC) score for long-term prognostication of incident coronary heart disease (CHD) and atherosclerotic cardiovascular disease (ASCVD) among those with diabetes, metabolic syndrome (MetS), or neither?
Study participants were from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of 6,814 males and females aged 45-84 years without known CVD from four race/ethnicity groups recruited from six US communities 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. Cox proportional hazards regression models were used to estimate hazard ratios (HRs). 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, ethnicity/race, and socioeconomic status. Any detectable calcium was defined as a CAC score >0. The CAC score was log transformed to maintain the normality of CAC measures, and the scores were also categorized as 0, 1–99, 100–399, and ≥400, and dichotomized as 0 or >0.
A total of 6,751 MESA participants had complete risk factor and follow-up data: mean age, 62.2 [10.2] years; 47.2% male; 13.0% had diabetes, 25.7% had MetS, and 61.2% had neither condition. Among the study participants, 37.3% of those with diabetes (similar in those with or without MetS), 44.8% of those with MetS, and 55.0% of those with neither diabetes nor MetS had a CAC score of 0. After 11.1 mean years of follow-up, CHD events occurred in 5.3% and ASCVD events in 8.3%. CHD events occurred in 84 (9.5%) participants with diabetes (135 ASCVD events), 115 (6.6%) with MetS (175 ASCVD events), and 157 (3.8%) with neither (250 ASCVD events). In each group, a stepwise increase in observed CHD and ASCVD events was seen with increasing severity of CAC score categories. For those with diabetes but no CAC, the CHD event rate was 3.7 per 1,000 person-years. The CAC score was independently and significantly 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. The CAC score of zero was also a prognostic indicator of CHD and ASCVD after controlling for diabetes duration of 10 years or longer 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.
Considering the long-term follow-up of >10 years, the study refutes the conclusion that diabetes is a coronary risk equivalent (≥20% 10-year risk of CHD). Amongst those with diabetes and the highest Framingham risk score 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). While important, they do not support the conclusion that a CAC score be obtained in all persons with diabetes and the MetS.
Keywords: Atherosclerosis, Coronary Artery Disease, Coronary Vessels, Diabetes Mellitus, Type 2, Insulin, Metabolic Syndrome X, Plaque, Atherosclerotic, Primary Prevention, Risk Assessment, Risk Factors, Tomography, X-Ray Computed
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