By Michael H. Crawford, MD
Professor of Medicine, Lucy Stern Chair in Cardiology, University of California, San Francisco
SYNOPSIS: A large registry study of individuals without known cardiovascular disease but with known coronary artery computed tomography calcium scores showed those with an Agatston score higher than 300 are at risk of experiencing major cardiac events similar to patients with known cardiovascular disease over five years.
SOURCE: Budoff MJ, Kinninger A, Gransar H, et al. When does a calcium score equate to secondary prevention? JACC Cardiovasc Imaging 2023;16:1181-1189.
Coronary artery calcium (CAC) scores by computed tomography (CT) scans are recommended for decisions regarding initiation of primary prevention measures in asymptomatic individuals.1 A score of 100 Agatston units or higher has been proposed as the point where primary prevention measures, such as statin therapy, are reasonable.2 However, some asymptomatic individuals without prior cardiovascular (CV) events record much higher CAC scores. Thus, the question has arisen: At which point does a CAC score indicate clinicians should introduce more aggressive secondary prevention measures?
To answer this question, investigators from the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry assessed whether there was a level of CAC score that was associated with an atherosclerotic CV disease (ASCVD) event rate similar to patients who have experienced an ASCVD event. Patients with complete follow-up for events were divided into those without known ASCVD and those with established ASCVD.
The resulting study population of 4,949 patients had a mean age of 58 years and 56% were men. Patients were followed for a median of 4.7 years. The primary endpoint was a composite of major adverse CV events (MACE), which included all-cause death, myocardial infarction (MI), hospitalization for unstable angina, and target vessel revascularization after longer than 90 days. Death occurred in 5%, as did MI. The overall MACE rate was 9%, and MACE plus late revascularization was 12%. Most subjects (4,511) reported no history of ASCVD, but 438 did (299 of whom had experienced a MI). In the no prior ASCVD group, age and ASCVD risk factor incidence increased as the CAC score increased. At a CAC score higher than 300, the frequency of risk factors equaled that of those with a history of an ASCVD event. Also, the highest rate of ASCVD events in the no prior event group was seen in those with CAC scores greater than 300 (20%), which was the same rate as observed in the prior ASCVD event group. ASCVD event rates were not statistically different in those with a CAC score higher than 300 compared to those with established ASCVD.
The authors concluded individuals without known ASCVD and a CAC score higher than 300 are at the same risk of a MACE over five years as those with established ASCVD. This information may be of value for deciding on the intensity of risk factor control in patients without a history of ASCVD.
COMMENTARY
The 2018 cholesterol treatment guidelines recommend considering therapies beyond statins, such as ezetimibe, bempedoic acid, or PCSK9 inhibitors, to help those at high risk of ASCVD events reach target LDL cholesterol levels.2 Also, many publications have suggested that a CAC score higher than 300 is high risk, but largely in the context of patients with known ASCVD.
The Budoff et al study is the first to establish the level of CAC at which the risk of an ASCVD event in persons without known ASCVD rises to the risk level of patients with known ASCVD. Interestingly, it was the same (300 Agatston units). This means instead of the ideal LDL cholesterol target of lower than 100 mg/dL for primary prevention, we need to help the patient without known ASCVD and a CAC score lower than 300 reach the secondary prevention target, an LDL cholesterol level lower than 70 mg/dL (or perhaps lower). Notably, in the Budoff et al study, the presence of diabetes alone did not elevate the no known ASCVD individual to the event risk level of a known ASCVD patient.
There were several limitations to the Budoff et al study. The authors did not provide any information on therapy and other risk factors in their subjects. The endpoints were not adjudicated independently. Researchers used non-contrast CT only, so non-calcified plaque was not considered. Many believe that non-calcified plaque is more prone to rupturing than calcified plaque.3 The Budoff et al study population was referred for CT CAC score determination and may not represent the general primary prevention population. Those without known ASCVD might decide to obtain CT CAC scores to help decide if they should try to achieve LDL cholesterol levels less than 100 mg/dL by taking statins. Knowing they are high risk for ASCVD events if their CAC score is higher than 300 Agatston units is important information that may justify more aggressive pharmacologic therapy.
REFERENCES
- Greenland P, Blaha MJ, Budoff MJ, et al. Coronary calcium score and cardiovascular risk. J Am Coll Cardiol 2018;72:434-447.
- 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: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;139:e1046-e1081.
- Khan A, Arbab-Zadeh A, Kiani AN, et al. Progression of noncalcified and calcified coronary plaque by CT angiography in SLE. Rheumatol Int 2017;37:59-65.
