Coronary Artery Calcium and Multisite Atherosclerosis: Role in Risk Refinement

The 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease was recently released, providing another important step forward toward strategies to prevent atherosclerotic cardiovascular disease (ASCVD).1 It was encouraging to see that coronary artery calcium (CAC) scanning has now been given a class IIa recommendation for guiding lipid lowering treatments if decision-making is inconclusive among patients without a history of clinical ASCVD but with intermediate 10-year ASCVD risk (≥7.5%-≤20%).

The data from Multi-Ethnic Study of Atherosclerosis (MESA) continues to support the power for CAC assessment, where Budoff et al. showed that over 10 years of follow-up, all participants with CAC >100 were estimated to have >7.5% risk regardless of demographic subset. For each doubling of CAC, they estimated a 14% relative increment in ASCVD risk while holding all other risk factors constant. This association was not significantly modified by age, sex, race/ethnicity or baseline lipid-lowering use.2 Such reclassification by CAC can be important, as overestimation of ASCVD risk by the pooled cohort equation (PCE) score has been reported.3

It is well known that patients with metabolic syndrome (MetS) and diabetes have higher risk than those without; however, we have new understanding that within patients with diabetes there can exist various levels of risk.4,5 Another recent analysis from MESA showed that 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.6

Persons with atherosclerosis documented in multiple sites can be also considered at high risk for future CVD events. However, non-invasive assessments in atherosclerosis other than CAC, such as abdominal aortic calcium (AAC), ankle brachial index (ABI) and carotid intimal-medial thickness (CIMT), have not been documented as an effective marker to evaluate ASCVD risk in the current guidelines.1,7 For the perspective of primary prevention, risk assessment utilizing multiple measures for atherosclerosis from different sites of the body have not been well described. In another recent publication from MESA, Zhao et al. have elegantly investigated whether the extent and severity of multisite atherosclerosis predict CVD and coronary heart disease (CHD) events.8 In the study, the number of atherosclerosis sites by CAC, AAC, ABI and CIMT and their severity score improved the prediction of CHD and CVD events over CIMT and ABI; however, this trend no longer existed once CAC was taken in account. The strength of this study was that it compared the different imaging modalities, and CAC seemed to be best modality to predict events among patients with MetS or diabetes.

In the latest guideline, for certain patients with intermediate risk (≥7.5% - ≤20%) and CAC score of zero, there is option of 'de-risking' and therefore not considering or delaying initiation of a statin. Although currently this is not applicable to patients with diabetes, there is accumulating data that that the prognostic value of CAC among patients with diabetes is excellent over time and those with CAC of zero were shown to be at low risk of all-cause death for 5 years.9 This again points to heterogeneity of cardiovascular risk among patients with diabetes.10 In the study by Zhao et al., they have nicely demonstrated that patients without CAC experienced less atherosclerosis in other vascular beds. Such findings suggested that the evaluation of CAC has a potential for further risk refinement in predicting future cardiovascular risk even among patients with MetS and diabetes.1,8


  1. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol 2018. [Epub ahead of print]
  2. Budoff MJ, Yougn R, Burke G, et al. Ten-year association of coronary artery calcium with atheroscleortic cardiovascular disease (ASCVD) events: the multi-ethnic study of atheroslcerosis (MESA). Eur Heart J 2018;39:2401-8.
  3. Rana JS, Tabada GH, Solomon MD, et al. Accuracy of the atherosclerotic cardiovascualr risk equation in a large contemporary, multiethnic population. J Am Coll Cardiol 2016;67:2118-30.
  4. Rana JS, Liu JY, Moffet HH, Jaffe M, Karter AJ. Diabetes and prior coronary heart disease are not necessarily risk equivalent for future coronary heart disease events. J Gen Intern Med 2016;31:387-93.
  5. Rana JS, Blankstein R. Are all individuals with diabetes equal, or some more equal than others? JACC Cardiovasc Imaging 2016;9:1289-91.
  6. Malik S, Zhao Y, Budoff M, et al. Coronary artery calcium score for long-term risk classification in individuals with type 2 diabetes and metabolic syndrome from the Multi-Ethnic Study of Atherosclerosis. JAMA Cardiol 2017;2:1332-40.
  7. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. J Am Coll Cardiol 2014;63:2935-59.
  8. Zhao Y, Evans MA, Allison MA, et al. Multisite atheroslcerosis in subjects with metabolic syndrome and diabetes and relation to cardiovascular events: the Mutli-Ethnic Study of Atherosclerosis. Atherosclerosis 2019;282:202-9.
  9. Valenti V, Hartaigh BO, Cho I, et al. Absence of coronary artery calcium identifies asymptomatic diabetic individuals at low near-term but not long-term risk of mortality: a 15-year follow-up study of 9715 patients. Circ Cardiovasc Imaging 2016;9:e003528.
  10. Budoff MJ, Raggi P, Beller GA, et al. Noninvasive cardiovascular risk assessment of the asymptomatic diabetic patient: the Imaging Council of the American College of Cardiology. JACC Cardiovasc Imaging 2016;9:176-92.

Keywords: Diabetes Mellitus, Risk Factors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Metabolic Syndrome, Ankle Brachial Index, Calcium, Coronary Vessels, Cardiovascular Diseases, Risk Assessment, Atherosclerosis, Coronary Disease, Primary Prevention, Demography, Lipids

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