Comprehensive coronary computed tomography angiography assessment in high-altitude diabetic populations: integrating plaque characteristics, pericoronary inflammation, and coronary function

Background Coronary computed tomography angiography (CCTA) provides complementary anatomical, inflammatory, calcific, and functional biomarkers, but their interpretation under chronic high-altitude exposure remains uncertain. We characterized CCTA phenotypes according to altitude and type 2 diabetes and explored associations with major adverse cardiovascular events (MACE). Methods This retrospective matched cohort with prospective outcome ascertainment included adults undergoing clinically indicated CCTA for suspected coronary artery disease. Participants were classified by high-altitude residence (≥2,500 m for ≥5 years) or low-altitude residence (<500 m) and by diabetes status, forming four groups. Propensity score matching was performed separately within diabetes strata using age, sex, body mass index, and hypertension, yielding 174 participants in 87 matched pairs. CCTA assessment included pericoronary adipose tissue (PCAT) attenuation, plaque characteristics, coronary artery calcium (CAC), coronary stenosis, and vessel-specific CT-derived fractional flow reserve (CT-FFR). Primary models evaluated altitude, diabetes, and their interaction with adjustment for age, sex, body mass index, and hypertension. Associations with MACE were explored using univariable Cox models among participants with follow-up. Results In primary covariate-adjusted analyses, diabetes was associated with higher PCAT attenuation, CAC, total plaque volume, plaque burden, and maximum stenosis and with lower left anterior descending (LAD) CT-FFR (all q ≤ 0.018). Compared with the low-altitude Han group, the high-altitude Tibetan group had higher LAD and right coronary artery CT-FFR and lower CAC and plaque burden (all q ≤ 0.037). Among 13 interaction tests, only the altitude × diabetes interaction for LAD-PCAT remained significant after false discovery rate correction (−6.62 HU; 95% CI, −10.32 to −2.91; raw P < 0.001; q = 0.008). Among 119 participants with follow-up, 20 MACE occurred over a median of 28 months. Exploratory univariable analyses showed large but imprecise associations of diabetes and high-risk plaque with MACE, whereas altitude was not statistically associated with MACE ( P = 0.557). Conclusion Diabetes was associated with a more adverse coronary CCTA phenotype, whereas the high-altitude Tibetan group showed lower CAC and plaque burden and higher vessel-specific CT-FFR than the low-altitude Han group. The association between diabetes and LAD-PCAT attenuation differed between these groups. These findings warrant validation in larger, ethnically comparable longitudinal cohorts.