Inflammation and Coronary Flow Reserve in Chronic Stable Coronary Artery Disease: Evidence for a Long Standing Interplay

Funding Acknowledgements Type of funding sources: None. Background Low grade inflammation is involved in pathogenesis of ischemia and outcome in coronary artery disease (CAD). Dobutamine stress echo (DSE) and coronary flow reserve (CFR) are both related with incident CAD and respective outcome as well. Purpose To evaluate the potential relationship between inflammation, evaluated by high-sensitivity C-reactive protein as surrogate, and DSE outcome/left anterior descending artery (LAD) CFR in stable chronic CAD. Methods We studied 132 consecutive pts (age 58±12years, 18 females, 33 diabetics) with stable CAD, by DSE with concomitant evaluation of LAD CFR. A cut off 3 mg/dL was used to define high and low CRP groups (CRPH/30pts, CRPL/92pts). CRP distribution was positive skewed (median 1.7mg/l) and CRP was then normalized by log transformation (CRP 0.72±0.9, logCRP 3.2±3.3). Sixty-three out of 132 pts had a follow up DSE with a concomitant reevaluation of CFR at 98±74 months. Absolute and % changes of CFR were estimated. Results CRPH and CRPL groups had similar baseline: CFR (CRPH: 2.3±0.6, CRPL: 2.4±0.6mg/dl), creatinine (1.0±0.2 vs 1.1±0.4mg/dl), HbA1c (5.4±1.0 vs 5.6±1.3%) and LDL (109±46 vs 102±35mg/dl). CRPH and CRPL groups had also similar hemodynamic burden at DSE and incidence of positive DSE. dCFR and %dCFR were lower in CRPL (0.20±0.70 vs 0.69±0.92, p = 0.02 and 0.13±0.33 vs 0.46±0.67 p = 0.01). Further clustering based on optimal CAD treatment achieved at baseline (guidelines defined optimal resting heart rate and LDL) did not change the findings. CFR was inversely related with logCRP (figure 1: r=-0.21, p = 0.04) and creatinine (r=-0.18 p = 0.05). Moreover, during follow up the improvement in CFR (%dCFR) was related with baseline logCRP (figure 2: r=0.30 p = 0.03). In stepwise logistic regression analysis for prediction of a CFR>2, including categorical classification of CRP (>3), diabetes, LDL (>80), Lpa(>50) and resting heart rate, then only CRP>3 classification was finally selected (exp(B)=0.38, p = 0.01). Conclusion Inflammation activity evaluated by CRP in stable CAD is related with the estimated LAD CFR irrespectively from the DSE outcome, both at baseline evaluation as well as dynamically during a long term follow up. The relationship is independent from LDL, Lpa levels and diabetic substrate, thus implying a strong pathophysiological interplay.