Left Main CAC and Diabetes Confer Very High Risk With CAC ≥1,000

Quick Takes

  • When coronary artery calcium (CAC) score is used in primary prevention to assess ASCVD risk, a CAC score ≥1,000 is considered high risk or very high risk.
  • In the presence of diabetes or left main disease (site specific ≥300 or ≥25% of total CAC), it should be considered very high risk for ASCVD mortality as equated to ≥2 major ASCVD events or 1 major event and ≥2 high-risk conditions (1.4 per 100 person-years).
  • Over a median follow-up of 11 years, a CAC score ≥1,000 had about a two-fold incremental risk of ASCVD mortality in diabetes and left main disease, and seven-fold with both present. The risk would be considerably higher if it included all ASCVD events.

Study Questions:

Does coronary artery calcium (CAC) score ≥1,000 (Agatston units) in persons with one or more atherosclerotic cardiovascular disease (ASCVD) risk factors warrant treatment as very high risk requiring more intense lipid lowering and other medical therapy?


The authors from the CAC Consortium studied 2,246 asymptomatic patients with CAC score ≥1,000 and no prior ASCVD events. Cox proportional hazards regression modeling was performed for ASCVD mortality during a median follow-up of 11.3 years. Crude ASCVD mortality rates were compared to those reported for secondary prevention trial patients classified as very high risk defined by ≥2 major ASCVD events or 1 major event and ≥2 high-risk conditions (1.4 per 100 person-years) without a prior ASCVD event. Percentage of left main CAC burden was calculated by dividing the left main CAC by the total CAC Agatston score. Severe left main CAC was defined as >25% of total CAC in the coronary arteries, or an absolute left main CAC score of ≥300.


The mean age was 66.6 years, 14% were female, 10% were nonwhite, and the median 10-year ASCVD risk was 16.7 % with an 8% ASCVD mortality over the 11.3-year follow-up. Median CAC score was 1,592 and 6% had severe left main CAC. Diabetes (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.47-2.83) and severe left main CAC (HR, 2.32; 95% CI, 1.51-3.55) were associated with ASCVD mortality. The ASCVD mortality per 100 person-years for all patients was 0.8 (95% CI, 0.7-0.9), though higher rates were observed for diabetes (HR, 1.4; 95% CI, 0.8-1.9), severe left main CAC (HR, 1.3; 95% CI, 0.6-2.0), and both diabetes and severe left main CAC (HR, 7.1; 95% confidence interval [CI], 3.4-10.8). There was a stepwise higher ASCVD mortality rate across increasing left main CAC; scores ≥100 and ≥300 conferred 1.6- to 2.4-fold higher risk of ASCVD mortality, independent of traditional risk factors and total CAC score. There was no difference in lipid-lowering therapy for those with and without ASCVD mortality.


Among asymptomatic patients with CAC score ≥1,000 without a prior index event, diabetes and severe left main CAC define very-high-risk ASCVD, identifying individuals who may benefit from more intensive prevention therapies across several domains, including low-density lipoprotein cholesterol (LDL-C) lowering.


Primary prevention patients with CAC scores ≥1,000 who had severe left main CAC and diabetes experienced a five-fold higher crude ASCVD mortality rate compared to mortality rates previously reported for secondary prevention patients meeting guideline-defined very-high-risk status. This suggests an LDL-C goal of <55 mg/dL based on US expert consensus and <40 mg/dL for European guidelines and intensifying other medical therapy. Relative risk for ASCVD event rate would have been much higher if it included acute coronary syndromes, ischemic stroke, and revascularization for which the CAC score may have influenced the decision.

Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention

Keywords: Diabetes Mellitus, Plaque, Atherosclerotic

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