Identification of different lipid profiles in patients with zero calcium score with or without plaques after coronary computed tomography: a prospective registry to refine primary prevention

Background/Introduction Coronary artery calcium (CAC) scoring via computed tomography is a widely utilized tool for cardiovascular risk stratification, with a zero score indicating low risk. However, it does not fully exclude coronary artery disease (CAD), as non-calcified, lipid-rich plaques prone to rupture and cause acute coronary syndrome. Traditional lipid markers like LDL-C and HDL-C play a central role in risk evaluation, but they may not fully capture CAD risk in CAC-zero patients. Emerging biomarkers such as lipoprotein(a), apolipoprotein B, and the ApoB/ApoA-1 ratio offer potential for improved risk prediction, though their clinical use remains limited. Purpose This study examines the association between lipid profiles and CAD in low-risk patients with a zero CAC score. It aims to identify lipid plaque predictors to enhance risk stratification, optimize CCTA use, and improve primary prevention strategies. Methods This ongoing single-center study at University Hospital Galway and University of Galway (C.A.2792) aims to enhance risk stratification in low-risk patients undergoing coronary CCTA. CAC scores were assessed using non-contrast scans, and blood samples for lipid analysis were collected pre-scan. Results Among 434 patients, 201 (46.3%) were female, with a mean age of 56.5±10 years. A total of 215 participants had a CAC score ≥1, while 219 patients (50.5%) had a CAC score of zero. Despite having a zero CAC score, CAD was identified in 32 participants, including 19 with CAD-RADS 1 (8.6%), 9 with CAD-RADS 2 (4.1%), 3 with CAD-RADS 3 (1.4%), and 1 with CAD-RADS 4 (0.5%). Overall, 5.9% of CAC-zero patients had non-calcified plaques exceeding 25% stenosis. Compared to those with CAC ≥1, CAC-zero patients were younger (53±10 vs. 61±9 years, p<0.001), had a lower prevalence of diabetes (7.3% vs. 15.2%, p=0.015) and hypertension (35% vs. 48%, p=0.033), and included a higher proportion of females (57% vs. 36%, p<0.001). In the CAC-zero cohort, Lp(a) levels were significantly associated with the presence of plaques >25% (p=0.009), whereas no significant association was observed in the CAC ≥1 cohort (p=0.222). Conversely, a higher ApoB/ApoA1 ratio was significantly associated with plaques >25% only in patients with CAC ≥1 (OR 8.272, 95% CI 1.147–59.650, p=0.036) and not in those with CAC=0 (OR 2.173, 95% CI 0.164–28.774, p=0.556). A threshold Lp(a) level of >126 mg/dl was identified as the optimal cutoff value for detecting non-calcified plaques in CAC-zero patients. Conclusion While CAC scoring is a valuable tool for assessing atherosclerotic risk, a zero score does not rule out CAD, as non-calcified plaques may still be present. High-risk lipid markers could improve risk stratification, especially in cases with imaging limitations or contrast contraindications.