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The aim of this study was to explore the evolution of coronary lesions which had repeated physiologic evaluation by FFR as an endpoint, describe the clinical significance of longitudinal FFR change (ΔFFR=FFRfollow-up-FFRbaseline) and its correlation with angiographic indices, and identify predictors of FFRfollow-up.A retrospective, single-centre analysis of 414 stenoses (331 patients) with consecutive FFR measurements at least six months apart was performed (median time interval: 24 [17, 37] months). The change in percent diameter stenosis was 2% (-5%, 11%). FFR values at baseline and follow-up were 0.86 (0.82, 0.90) and 0.83 (0.79, 0.90), respectively (0.0001). The median ΔFFR was -0.007 (-0.028, 0.010) per year. Worsening FFR (ΔFFR-0.05) was observed in 105 (25%) stenoses, stable FFR (-0.05 ≤ΔFFR ≤0.05) in 276 (67%) and improving FFR (ΔFFR0.05) in 33 (8%) stenoses. The number of haemodynamically significant stenoses (FFR ≤0.80) was higher at follow-up compared to baseline (33% versus 17%, p0.0001); ΔFFR correlated weakly with delta diameter stenosis (Δ%DS, ρ=-0.111, p=0.024). In mixed effects repeated measures analysis, only lesion location had an independent correlation with FFR values after adjusting for multiple confounders. In ROC analysis, FFRbaseline values predicted future clinically significant values (c-statistic: 0.736 [95% CI: 0.682-0.783]).FFR values decrease slowly over a two-year follow-up. FFRbaseline, but not angiographic indices, is a predictor of significant functional atherosclerosis progression, predicting which stenoses will require revascularisation.