The worst quartile of Vascular Proximity Coverage (VPC-AUC), a novel CT-based marker, was associated with a 42% increased risk of 10-year mortality in COPD (HR 1.42; 95% CI 1.22-1.65; P<0.001).
Cohort (n=7,878)
Does Vascular Proximity Coverage (VPC) on CT imaging predict mortality and functional outcomes in patients with COPD independent of total vessel volume?
Vascular Proximity Coverage (VPC) is a novel CT-based metric that captures functional pulmonary vascular morphology and identifies high-risk COPD phenotypes with increased mortality despite preserved overall vessel volume.
Effect estimate: HR 1.42 (95% CI 1.22-1.65)
p-value: p=<0.001
Abstract Rationale Conventional CT-derived pulmonary vascular metrics, including BV5 (vessel volume from vessels with cross-sectional area of 5mm²) and total vessel volume, quantify vascular mass but do not assess the functional morphology of the pulmonary vascular tree. In COPD, peripheral microvascular pruning frequently co-exists with compensatory enlargement of central vessels, which paradoxically increases overall vessel volume while simultaneously reducing effective vascular penetration into the lung parenchyma. We developed Vascular Proximity Coverage (VPC), a novel distance-based CT biomarker to quantify the spatial efficiency of pulmonary vascular distribution. Methods This retrospective analysis included 7,878 COPDGene participants with vascular segmentation. Vascular proximity coverage (VPC-AUC0-10) was computed by measuring the Euclidean distance from each lung voxel to its nearest vessel and integrating the coverage curve C(r)—the cumulative proportion of tissue within distance r—from 0 to 10mm, where higher values indicate efficient vascular distribution and lower values indicate greater tissue-vessel separation (Figure 1). Multivariable analyses adjusted for age, sex, race, BMI, smoking status, pack-years, emphysema, scanner type and BV5 evaluated associations with cross-sectional outcomes (FEV₁, FEV₁/FVC, 6MWD, SGRQ, and 10-year mortality. We performed combined phenotype analysis by dichotomizing participants at median BV5 and VPC-AUC values, creating four phenotypes: high BV5/high VPC (optimal), high BV5/low VPC (preserved volume/impaired distribution), low BV5/high VPC (reduced volume/preserved distribution), and low BV5/low VPC (globally impaired). Results VPC-AUC declined significantly across GOLD stages (5.9 in non-smokers to 5.3 in GOLD4, p 0.001). Among GOLD0 individuals, current smokers showed reduced VPC-AUC versus never-smokers (5.5 vs. 5.9, p 0.001). Each standard deviation increase in VPC-AUC independently associated with higher FEV₁ (β = 55ml, 95% CI: 28-81ml), greater 6MWD (β = 26m, 95% CI: 22-30m), and better SGRQ scores (β=-2.5, 95% CI: -3.2 to -1.8; all p 0.001). Combined phenotype analysis demonstrated VPC-AUC’s substantial independence from vessel volume (BV5 correlation r = 0.15). Compared to optimal phenotype (high BV5/high VPC), Low BV5/high VPC showed intermediate risk (HR = 1.20, p = 0.022), the high BV5/low VPC phenotype, representing central vessel dilation masking peripheral loss, showed 25% increased mortality (HR = 1.25, 95% CI: 1.08-1.44, p = 0.003) despite preserved vessel volume, and globally impaired low BV5/low VPC had highest mortality (HR = 1.30, p 0.001). Quartile analysis demonstrated the worst VPC-AUC quartile showing 42% increased mortality (HR = 1.42, 95% CI: 1.22-1.65, p 0.001) with moderate discrimination (C-index=0.74). Conclusion VPC-AUC captures functional vascular morphology independent of vessel volume, identifying high-risk phenotypes with preserved volumetric metrics but impaired vascular distribution. This enables earlier risk stratification and may guide targeted therapeutic interventions in COPD. This abstract is funded by: This work was supported by NHLBI R01 HL151421 (SPB & AN), NHLBI K01HL163249 (SB), NHLBI U01 HL089897 and U01 HL089856. COPDGene is also supported by the COPD Foundation through contributions made to an Industry Advisory Board that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Sunovion.
Aguilera et al. (Fri,) conducted a cohort in COPD (n=7,878). Vascular Proximity Coverage (VPC-AUC0-10) vs. Higher VPC-AUC quartiles was evaluated on 10-year mortality (HR 1.42, 95% CI 1.22-1.65, p=<0.001). The worst quartile of Vascular Proximity Coverage (VPC-AUC), a novel CT-based marker, was associated with a 42% increased risk of 10-year mortality in COPD (HR 1.42; 95% CI 1.22-1.65; P<0.001).
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