Coronary Artery Calcium Score, Risk Factors, and Clinical Outcomes in Nonobstructive Coronary Artery Disease: A Long-Term Follow-Up Study

Abstract

Abstract Background: The prognostic value of coronary artery calcium (CAC) score in nonobstructive coronary artery disease (NObCAD; stenosis < 50%) remains insufficiently characterized. Objectives: To investigate the association between CAC score, cardiovascular risk factors, and clinical outcomes in patients with NObCAD. Methods: A total of 2,509 patients underwent coronary computed tomography angiography (CTA) and were followed for 8.9 ± 2.6 years. Plaque burden was classified according to CAD-RADS™ 2.0 into none, mild, moderate, and high/highest. The primary endpoint (PEP) was a composite of all-cause mortality, acute coronary syndrome/acute myocardial infarction, and stroke. Statistical significance was set at 5%. Results: CAC score was 0 in 45.4% of patients, 1-99 in 36.6%, and ≥ 100 in 18.0%. Correspondingly, 38.3% of patients had no coronary lesions, 38.5% had mild lesions, 14.1% had moderate lesions, and 9.2% had high/highest lesions. Among patients with CAC = 0, the absence of coronary lesions predominated (81.2%), whereas it was rare among those with CAC ≥ 100. The PEP occurred in 4.9% of patients, predominantly driven by all-cause mortality. Among the 396 patients with serial coronary CTA (mean interval: 6.5 ± 2.6 years), CAC progression (> 2.5 increase based on the square root method) was observed in 41.9%. Plaque burden increased in parallel. CAC score showed a positive association with plaque burden and cardiovascular risk factors. Conclusions: In NObCAD, CAC is present in more than half of patients and is associated with both plaque burden and cardiovascular risk factors. The incidence of PEP increases in proportion to risk factor burden and CAC levels. CAC and plaque burden progress concurrently over time, supporting the role of CAC as a surrogate marker of subclinical atherosclerosis progression.