New atherosclerotic plaque formation by coronary CTA in suspected coronary artery disease patients: Results from the PARADIGM Registry

Background The natural history of new atherosclerotic lesion formation in humans has not been described morphologically in primary prevention populations by direct anatomical visualization. Purpose To compare new atherosclerotic plaque formation prevalence and characteristics among patients with and without prior plaque by coronary CTA (CCTA). Methods We performed a sub-analysis of the PARADIGM registry which consecutively enrolled 2252 patients with suspected CAD undergoing serial CCTA at a scan interval of ≥2 years. Patients were excluded for noninterpretable scans, prior CAD, and interval major adverse cardiac events. Quantitative CCTA was performed and patients with and without plaque at baseline scan were compared for presence of new lesions (NLs) and differences in plaque characteristics including location, percent diameter stenosis (%DS) severity, total and compositional plaque volume and presence of high-risk plaque (HRP) on follow-up. Results Of 1343 patients (age 60.4±9.4 years, 42.8% females), 334 (24.9%) patients had no baseline plaque (BP). Over 3.3 years (IQR 2.6, 4.8), NLs developed in 35% of patients without and 46.7% of patients with BP (p=0.0003). New obstructive lesions ≥50% were rare, observed in 3(0.9%) in those without and 7(0.7%) in those with BP. Among patients with NLs (n=588), those developing in patients without BP had higher %DS (median=17.2% (IQR 11.3, 25.7) vs. 15.8% (IQR 8.8, 23.2), p=0.013), higher PV (21.8mm3 (IQR 9.54, 41.7) vs. 16.1mm3 (IQR 6.70, 31.5), p=0.008), higher fibrofatty composition of 30-130 HU (10.7% (IQR 1, 29.9) vs. 3.1% (IQR 0.04, 17.4), p<0.001) and lower calcific composition (14.2% (IQR 0.6, 46.4) vs. 29.6% (IQR 9.2, 61.8), p<0.001), comparing to patients with BP. New HRP occurred in 105 (18%) patients with NLs with no significant difference among both groups, however, positive remodeling was more in patients with BP (OR = 2.04 (95% CI 1- 4.03), p=0.044). The most common site of NLs was the left anterior descending artery (60%) in absence of BP and right coronary artery (47%) in presence of BP. Adjusting for covariates and CT interval, the presence of BP (OR 1.84; 95%CI 1.38, 2.46, p<0.001), diabetes (OR 1.38; 95%CI 1.03, 1.85) and higher body mass index (OR 1.04 per kg/m2; 95%CI 1.01, 1.08) increased the likelihood of NL formation. Conclusions Over the intermediate term, new lesions can be observed by CCTA in over 1/3 of patients without and nearly 1/2 of patients with baseline plaque, although new obstructive lesions are infrequent. Adjusting for covariates, baseline plaque presence was associated with an increased likelihood of new lesions formation, however, patients without any baseline plaque tended to have higher degree of stenosis, larger total and low attenuation compositional plaque volumes with less calcification and same prevalence of HRP occurrence to patients with baseline plaque. New lesions development was higher in diabetic patients and with higher BMI.