Global cardiac microcalcification activity and the risk of cardiovascular events

Abstract Background 18F­-NaF­-PET­-CT (Positron emission tomography computed tomography with 18F sodium fluoride) detects active microcalcification. The global cardiac microcalcification activity has been associated with a high burden of cardiovascular (CV) risk factors. Purpose We aimed to investigate whether high cardiac microcalcification burden is associated with CV events. Methods Patient-level outcomes analysis of the ROPPET-NAF trial (Rosuvastatin Effect on Atherosclerotic Plaque Metabolism – a Subclinical Atherosclerosis Imaging Study With 18F–NaF PET-CT) and its pilot study. The primary cardiac microcalcification activity measure was the global molecular calcification score (GMCS). The primary endpoint was defined as the composite of CV death, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization, or unplanned arterial revascularization procedure. Results Between May 2014 and December 2021, a total of 57 participants were enrolled. Median age was 65 years, 63% were male, most had hypertension (96%) and diabetes (82%). The median predicted 10-year risk of atherosclerotic CV disease was 12% per the PREVENT-ASCVD equation and 10% according to SCORE2. Median baseline GMCS was 221 (145, 318). Over a median of 4.3 years (IQR: 3.1-9.8), 9 participants (16%) experienced the composite primary end point nonfatal stroke (n=4), heart failure hospitalization (n= 3), nonfatal myocardial infarction (n=1) and unplanned arterial revascularization (n=1). GMCS was associated with higher risk of the primary endpoint (HR 1.007; 95% CI: 1.002-1.013; p = 0.008), albeit with a very modest effect size. This association remained significant after multivariate adjustment (HR 1.013; 95% CI: 1.003-1.023; p = 0.011). Of note, in this cohort, GMCS outperformed the SCORE2 and PREVENT risk tools (AUC 0.797 versus 0.598 versus 0.660, respectively). Conclusion In this high-risk population, cardiac microcalcification burden had a modest association with cardiovascular events. As we shift from the "vulnerable plaque" to the "vulnerable patient" paradigm, GMCS may be a promising CV risk stratification tool.