Results:

Between 2005 and 2009, 1,872 participants in the derivation cohort underwent coronary CTA (median age, 62 years [range 17–89]). Between 2008 and 2016, 2,040 patients in the validation cohort had coronary CTA (median age, 53 years [range 19–87]). Median follow-up was 72 months (range 51–109) in the derivation cohort and 54 months (range 4–105) in the validation cohort. In both cohorts, high perivascular FAI values around the proximal right coronary artery and left anterior descending artery (but not around the left circumflex artery) were predictive of all-cause and cardiac mortality and correlated strongly with each other. Therefore, the perivascular FAI measured around the right coronary artery was used as a representative biomarker of global coronary inflammation (for prediction of cardiac mortality, hazard ratio [HR], 2.15; 95% confidence interval [CI], 1.33–3.48; p = 0.0017 in the derivation cohort, and 2.06, 1.50–2.83; p < 0,0001 in the validation cohort). The optimum cutoff for the perivascular FAI, above which there is a steep increase in cardiac mortality, was ascertained as –70.1 Hounsfield units (HU) or higher in the derivation cohort (HR, 9.04; 95% CI, 3.35–24.40; p < 0.0001 for cardiac mortality; 2.55, 1.65–3.92; p < 0.0001 for all-cause mortality). This cutoff was confirmed in the validation cohort (HR, 5.62; 95% CI, 2.90–10.88; p < 0.0001 for cardiac mortality; 3.69, 2.26–6.02; p < 0.0001 for all-cause mortality). Perivascular FAI improved risk discrimination in both cohorts, leading to significant reclassification for all-cause and cardiac mortality.