Discriminating established cardiovascular disease using a novel multiterritory ultrasound plaque burden measure (wTPT): findings from the P-SONAR study

OBJECTIVE: Ultrasound-imaging of subclinical atherosclerosis may refine cardiovascular (CV) risk assessment, but quantification methods vary and often include carotid arteries only. Because atherosclerosis is multiterritory, global (carotid–femoral) plaque quantification may better reflect systemic burden. We examined whether a novel multiterritory measure, weighted total plaque thickness (wTPT), better discriminates established CV disease than traditional risk factors and plaque measures. METHODS: In 5 418 participants (59.8 ± 8.1 years; 53.0% women) from the Prospective Screening Of Non-invasive Atherosclerosis Risk study, plaque burden was assessed across 12 carotid and femoral segments using wTPT, maximal plaque thickness (MPT), plaque count, and number of arteries with plaque. Discrimination of prior CV disease was evaluated using c-statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: Global wTPT showed the strongest discrimination of established CV disease (c-statistic 0.85 [95% CI: 0.83–0.87]), outperforming alternative plaque measures (p < 0.001). Adding global wTPT to risk factors improved discrimination from 0.84 to 0.89 (95% CI: 0.87–0.91), NRI 0.71 (95% CI: 0.57–0.84) and IDI 0.058 (95% CI: 0.004–0.071). Femoral wTPT outperformed carotid wTPT (p < 0.001), and global wTPT exceeded both (p = 0.014). Across wTPT quartiles, odds of prior CV disease increased stepwise: 2.0 (95% CI: 0.89–4.4), 4.2 (95% CI: 2.0–8.6), and 10.0 (95% CI: 5.0–20.1) versus the lowest quartile. CONCLUSION: Global wTPT showed superior discrimination of established CV disease and added substantial incremental discriminative value beyond standard risk factors. These findings support wTPT as a marker of systemic atherosclerosis and a strong candidate for future outcome-based risk refinement. If prospectively validated, wTPT may contribute to improved risk stratification by identifying individuals with a high systemic atherosclerotic burden. TRIAL REGISTRATION: Clinicaltrials.gov. Identifier: NCT06933745. Registered 22 april 2025.