Med J Malaysia. 2026 Jul;81(4):447-454.
ABSTRACT
INTRODUCTION: The Agatston coronary artery calcium (CAC) score is a widely used screening tool. However, its negative predictive value (NPV) in the Southeast Asian population, prone to premature non-calcified atherosclerosis, is not well defined.
MATERIALS AND METHODS: We analysed paired data from 5,375 asymptomatic patients who underwent concurrent CAC scoring and Coronary CT Angiography (CCTA) at a tertiary center in Kuala Lumpur over 20 years. This cohort was selected to study plaque missed by CAC. A validated automated pipeline (weighted Cohen's Kappa = 0.978) was used to determine stenosis severity.
RESULTS: Zero CAC yielded a negative predictive value of 76.1% for any plaque; 23.9% of calcium-negative patients harboured hidden atherosclerosis, including 3.5% with obstructive disease. While odds increased linearly with age (OR 1.22 per decade, p=0.004), missed disease peaked in males aged 40-44 and peri-menopausal women aged 55-59. These age groups represent a window during which lipidrich plaques accumulate before calcifying.
CONCLUSION: Zero CAC can mask a "pre-calcific window" of active, radiolucent atheroma accumulation. Rather than a state of biological protection, this Zero CAC cohort harbours hidden risk driven by the same demographic engines as calcified disease, simply operating at an earlier phenotypic stage. Confirmatory CCTA is critical for high-risk younger males and peri-menopausal women to bridge this inherent diagnostic blind spot.
PMID:42584430