Coronary artery calcium scoring associated with significant improvements in atherosclerotic cardiovascular disease reclassification when guiding statin therapy

1. The use of coronary artery calcium scoring was associated with significant improvements in the reclassification and discrimination of incident atherosclerotic cardiovascular disease.

2. Coronary artery calcium scoring may be beneficial as an adjunct to risk-enhancing factor assessment when identifying individuals at intermediate risk of atherosclerotic cardiovascular disease who would benefit from statin therapy.

Evidence Rating Level: 4 (Below Average)

Study Rundown: In its most recent guidelines on the management of blood cholesterol from 2018, the American Heart Association/American College of Cardiology (AHA/ACC) recommended the use of risk-enhancing factor assessment and the selective use of coronary artery calcium (CAC) scoring to guide statin therapy in patients with an intermediate risk of atherosclerotic cardiovascular disease (ASCVD). However, the guidelines also recognized the challenges and difficulties in the objective assessment of the extent to which a single risk-enhancing factor may quantitatively modify the 10-year risk estimate for an individual patient. Furthermore, the presence of risk-enhancing factors despite a CAC score of 0 is not uncommon and its prevalence in cardiovascular patients remains unknown. Given these conditions, the Multi-Ethnic Study of Atherosclerosis sought to evaluate the association of risk-enhancing factors and clinically relevant CAC categories with incident ASCVD events based on the recommendations of the 2018 AHA/ACC cholesterol guidelines. The main outcome and measure of the analysis was incident ASCVD over a median follow-up of 12.0 years. From 1,688 adult patients at intermediate risk of ASCVD, the presence of CAC was associated with ASCVD event rates of 7.5 or more events per 1000 person-years, exceeding the threshold used to initiate statin therapy as per the AHA/ACC guidelines. Comparatively, ASCVD event rates were less than 7.5 per 1000 person-years when CAC scores were 0 except among individuals with low ankle-brachial index (ABI) where ASCVD event rates were 7.5 or more per 1000 person-years, even in the absence of CAC. These results suggested that the use of CAC scoring was associated with significant improvements in the reclassification and discrimination of incident ASCVD and may be beneficial as an adjunct to risk-enhancing factor assessment when identifying individuals at intermediate risk of ASCVD who would benefit from statin therapy. A limitation of this study was the relatively small cohort size that may have led to low statistical power in the analysis and explain the lack of association between risk enhancing factors and ASCVD outcomes observed in this cross-sectional study.

Click to read the study in JAMA Cardiology

Relevant Reading: Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA)

In-Depth [cross-sectional study]: The Multi-Ethnic Study of Atherosclerosis was a multicenter population-based prospective cross-sectional study conducted in the US that enrolled a total of 1,688 participants (mean [SD] age, 65 [6] years; 976 men [57.8%]; 648 [38.4%] White participants, 562 [33.3%] Black, 305 [18.1%] Hispanic, 173 [10.2%] Chinese American). Data was collected between July 2000 and July 2002 with follow-up through to August 2015 (median [IQR] follow-up, 12.0 [11.5-12.6] years). Inclusion criteria included individuals aged 45 to 75 years with no clinical ASCVD or diabetes at baseline, at intermediate risk of ASCVD (7.5%to <20.0%), and with a low-density lipoprotein cholesterol (LDL-C) level of 70 to 189 mg/dL. Exposures to participants included a family history of premature ASCVD, premature menopause, metabolic syndrome, chronic kidney disease, lipid and inflammatory biomarkers, and low ABI. In total, 722 participants (42.8%) had a CAC score of 0 where the prevalence of a CAC score of 0 among those with 1 to 2 risk-enhancing factors vs those with 3 or more was 45.7% and 40.3%, respectively. Furthermore, the unadjusted incidence rate of ASCVD among those with a CAC score of 0 through follow-up was less than 7.5 events per 1000 person-years for all individual and combinations of risk-enhancing factors (except for ABI, where the incidence rate was 10.4 events per 1000 person-years [95%CI, 1.5-73.5]). Lastly, although individual and composite addition of risk-enhancing factors to traditional risk factors was associated with improvement in the area under the receiver operating curve, the use of CAC scoring was associated with the greatest improvement in C statistic (0.633 vs 0.678) for ASCVD events. For incident ASCVD, the net reclassification improvement for CAC was 0.067.

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