Association And Effect Of Aspirin And LDL-C On Coronary Blood Flow In Subjects With Angiographic Normal Coronary Artery

Part I Effect of Aspirin on Coronary Blood Flow in Subjects with Angiographic Normal Coronary ArteryBackground:Impaired endothelial function and platelet function disorder are known as the major mechanism responsible for slow coronary flow (SCF). Aspirin can inhibits aggregation of platelet and has beneficial pharmacological basis for vascular endothelium, which regulate coronary vascular tone, but the effect of aspirin on coronary blood flow has not been clarified. The aim of this study is to evaluate the effect of aspirin on coronary blood flow in subjects with angiographic normal coronary artery.Methods:Five hundred and sixty-three subjects with angiographic normal coronary artery were enrolled from the angiography registry database of the Second Affiliated Hospital, Zhejiang University School of Medicine, and classified into two groups according to aspirin taken or not before the procedure. Thrombolysis in Myocardial Infarction (TIMI) frame counts (TFC) was used as an index for epicardial coronary blood flow. After using stepwise individual matching, propensity score matching and regression models to adjust the confounders, and comparation between two groups, we confirmed the effect of aspirin to coronary flow in subjects with angiographic normal coronary artery.Results:Basic clincal characteristics have no difference between two groups, except for age, hypertension, LDL-C, Prothrombin Time (PT), ACEI/ARB、 CCB and Statin usage. Whether matching or not, mean TFC is lower in Aspirin group than in non Aspirin group (before matching:29.61±5.12vs31.64±7.91; after matching age:29.28±5.20vs31.12±7.49; after matching age&LDL-C:29.15±5.60vs31.55±7.89; matching propensity score:29.11±5.52vs31.61±8.71; P<0.05for all). In sub-group analysis, the diiference of mean TCF between Asiprin and non Aspirin group was decresed in Statin sub-group. The association between Aspirin and mean TFC was significant (β:-2.641;95%CI:-4.059～-1.223) and did not change after adjustment for Age, Hypertension, ACEI/ARB, CCB, Statins, LDL and PT, which still can be observed after adjustment for confounders either in age-matching(P:-1.599;95%CI:-3.091～-0.108) or in age&LDL-C-matching group(β:-2.025;95%CI:-3.938～-0.112).Conclusions:Although many factors especially Statins may interfere the effect of Aspirin on the coronary blood flow, Aspirin is independently and negatively associated with mean TFC, suggesting that aspirin can improve the cornary folw in subjects with angiographic normal coronary artery, and could be used for the treatment of slow coronary flow phenomenon. Part II Assess the Association Between LDL-C and Coronary Blood Flow in Subjects with Angiographic Normal Coronary ArteryBackground:Impaired microvascular endothelial function is known as the major mechanism responsible for slow coronary flow (SCF). As far as we know, low-density lipoprotein cholesterol (LDL-C) impaired endothelial cell function is clear, although the mechanisms are complicated. LDL-C could play an adverse role in coronary blood flow. However, no study has ever evaluated the relationship between LDL-C and coronary blood flow in Subjects with angiographic normal coronary artery. The aim of this study is to assess the relationship between LDL-C and coronary blood flow after taking full consideration of other interferences, especially the oral lipid-lowering drug Statins.Methods:Five hundred and sixty-three subjects with angiographic normal coronary artery were enrolled from the angiography registry database of the Second Affiliated Hospital, Zhejiang University School of Medicine, and divided into low and high LDL-C group according to LDL-C level less or more than2.6mmol/l.Thrombolysis in Myocardial Infarction (TIMI) frame counts (TFC) was used as an index for epicardial coronary blood flow. After using regression models to adjust the confounders, we compared between two groups in total and in sub-groups (Statins-taken/non-Statins-taken). We explored the relationship between LDL-C and TFC and assessed the role of Statins involved in this relationship in subjects with angiographic normal coronary artery.Results:Basic clincal characteristics have no difference between two groups, except for age, BMI, TQ Aspirin and Statin usage. Either single or mean coronary TFC is lower in low LDL-C group than in high LDL-C group (LAD:33.39±9.14vs 35.99±10.00; LCX:27.19±7.40vs28.87±7.51; RCA:28.75±8.39vs30.63±8.56; Mean:29.78±6.72vs31.83±7.36; P<0.05for all). LDL-C is Person positively correlated with either single or mean coronary TFC, but the Partial correlation score is decreased after adjustment the unbalanced parameter including Age, BMI, TG, Aspirin and Statin usage. Curve fitting found a non-completely linear correlation (inverse "S" curve) between LDL-C and TFC. In sub-group analysis, although Statins have a reductive effect to the relationship of LDL-C and TFC, it can not be reversed by Statins. The association between LDL-C and mean TFC was significant (β:1.099;95%CI:0.240～-1.958) and did not change after adjustment for Age,BMI,TG,Asiprin and Statins, which still can be observed after adjustment for confounders in non-Statin subgroup (β:1.337;95%CI:0.271～2.402)but not in Statin subgroup (β:1.38;95%CI:-0.157～2.916).Conclusions:LDL-C is associated with TFC, but the association is not completely linear, which can be reduced but not revered by Statins. This suggested that LDL-C has a negative effect on coronary blood flow, and Statin treatment may be benefitial to the coronary blood flow improvement, especially in patients with higher serum LDL-C concentration.