Association of Physiological Discordance Between Fractional Flow Reserve and Nonhyperemic Pressure Ratios With Lipid-Rich Plaque Burden

Abstract Aims Fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs) frequently yield discordant results in clinical practice, yet the mechanisms underlying this mismatch remain uncertain. Plaque composition has been suggested to influence FFR, raising the possibility that discordance reflects the features of lipid-rich plaque (LRP). To investigate whether physiological discordance between FFR and NHPR is associated with increased lipid burden. Methods and Results We retrospectively analyzed 217 intermediate coronary lesions from 189 patients who underwent FFR, NHPR, and near-infrared spectroscopy with intravascular ultrasound imaging. Lesions were classified using established cutoffs for FFR (0.80) and NHPR (0.89). Lipid burden was quantified by the maximum lipid core burden index within any 4-mm segment (maxLCBI4mm). LRP was defined as maxLCBI4mm >400. The clinical endpoint was 3-year target vessel failure (TVF). Physiological discordance occurred in 24.0% of lesions, predominantly as an FFR+/NHPR− pattern (19.8%). FFR was independently associated with maxLCBI4mm (β, 65.2; 95%CI, 29.0–101.5; P < 0.001), whereas NHPR was not (β, 16.5; 95%CI, −15.9–49.0; P = 0.316). The FFR+/NHPR− group demonstrated the highest maxLCBI4mm (525 ± 201) and the greatest prevalence of LRP (65.1%; both P < 0.001). In multivariable analysis, the FFR+/NHPR− pattern independently predicted LRP (adjusted OR, 6.12; 95%C, : 1.20–31.28; P = 0.030). TVF occurrences did not differ significantly across physiological groups. Conclusion FFR+/NHPR− lesions exhibit markedly greater lipid burden, suggesting that hyperemia-based indices better capture plaque vulnerability than resting physiology. This pattern may serve as a marker of plaque vulnerability, suggesting that deferral of FFR+/NHPR− lesions could warrant caution given their higher lipid burden. (250/250 words)