| Research Background:In recent years,as the population ages and people’s material living conditions improve greatly,the incidence of coronary heart disease in China has increased year by year due to the lagging behind of popularization of healthy lifestyle.According to WHO,the total number of patients with coronary heart disease in China has been ranked second in the world.Prevention of coronary heart disease is an important measure to reduce human mortality.A large number of epidemiological and genetic studies have proven that coronary heart disease is a chronic polygenic epidemic disease,and multiple genetic and environmental factors contribute to the occurrence of coronary heart disease.Therefore,early detection of the relevant high-risk clinical factors of coronary heart disease is the focus of prevention of coronary heart disease.It is now clear that the major risk factors related to cardiovascular disease are smoking,hypertension,diabetes mellitus,hypercholesterolemia and so on.However,a large number of clinical facts have shown that some people still cannot reduce the prevalence of coronary heart disease or improve clinical prognosis after the full intervention of traditional risk factors,indicating that there are other non-traditional risk factors for some patients with coronary heart disease.Therefore,it is of great significance to find new risk factors of coronary heart disease and take appropriate intervention measures for the early control of cardiovascular disease incidence.In recent years,a large number of studies have shown that homocysteine can also cause atherosclerosis.Hcy can lead to increased clinical events in stroke,which has been recognized by international experts.In recent years,many reports say that Hcy is also an important risk factor for coronary atherosclerosis,but this view is challenged by a lot of experts.Some studies show that Hcy is not directly related to the incidence of coronary heart disease,and reducing the plasma Hcy level does not significantly improve the incidence of myocardial infarction,cerebral infarction and other diseases.Therefore,some experts believe that HHcy is only the associated factor of coronary heart disease.By comparing the incidence of coronary heart disease and degree of coronary artery lesions between patients with HHcy and without HHcy,and detecting the expression of peripheral blood homocysteine among different types of coronary heart diseases and coronary artery lesions,this study explores the relationship between HHcy and coronary atherosclerotic lesions in patients with coronary heart disease,so as to provide a basis for early identification,diagnosis and treatment of patients with coronary heart disease.Objective:To observe the relationship between hyperhomocysteinemia and morphology of coronary lesion.Study population:A total of 236 patients who were clinically suspected coronary artery disease in department of cardiology of the 2nd Affiliated Hospital of Wenzhou Medical University from March,2016 to June,2017 were chosen in.All the patients underwent conventional coronary angiography in hospital.Methods:The study compared the incidence of coronary artery disease,degree of coronary lesion and severity of coronary diseases in patients with HHcy and without HHcy(Taking the homocysteine level 10 umol/L as the critical value)on the one hand,and on the other hand evaluated the effect of HHcy on morphology of coronary lesion by comparing the Hey level of different types of coronary artery diseases and coronary artery lesions.Results:1.To be compared with normal plasma Hey level group,the HHcy group has a significant higher incidence rate of coronary disease(69.0%vs 47.7%,P<0.05),and also a significant higher incidence rate of triple-vessel coronary disease(24.0%vs 7.7%,P<0.05),high score of Gensini(19.9%vs 6.2%,P<0.05)and ACS(43.9%vs 21.5%,P<0.05).2.There is a significant association between plasma Hey level and coronary heart disease diagnosed by coronary angiography(OR=1.191,95%CI:1.089～1.302,P<0.001).3.The Gensini score is positively related to age(r=0.342,P<0.001),diabetes mellitus(r=0.314,P<0.001),hypertension(r=0.399,P<0.001),smoking history(r=0.489,P<0.001),chronic kidney disease history(r=0.448,P<0.001),hypercholesterol(r=0.229,P<0.001),Hcy(r=0.589,P<0.001),whereas uncorrelated with high BMI(r=0.005,P=0.953)and gender(r=0.114,P=0.136).The Gensini score is independently correlated with age(β=0.448,95%CI:0.180～0.716,P<0.001),diabetesmellitus(β=6.500,95%CI:0.835～12.164,P=0.026),smoking history(β=14.182,95%CI:8.021～20.344,P<0.001),hypertension(β=8.325,95%CI:2.292～14.358,P=0,008),chronic kidney disease history(β=13.919,95%CI:5.978～21.859,P<0.001),and Hcy(β=1.534,95%CI:1.133～1.935,P<0.001).4.There is a significant difference for the incidence rate of HHcybetween CHD group and non-CHD group(P=0.002,Chi-square values 9.192),118 patients with HHcy in CHD group(79.2%)and 53 patients with HHcy in non-CHD group(60.9%).5.The CHD group is assigned to three groups according to the clinical manifestation:chronic coronary disease(61 patients),unstable angina(50 patients),acute myocardial infraction(38 patients).The difference between groups has a statistical" significance with ANOVA(F=26.958,P<0.01),and the plasma Hey level in different CHD groups has a significant difference(P<0.05)except between the AMI group and unstable angina groupvia LSD,showing that the plasma Hey level is rising with the severity of patient’s clinical condition.6.The CHD group is assigned to three groups according the amount of main vessel withcoronary lesion:one-vessel lesion group(61 patients),double-vessel lesion group(42 patients),triple-vessel lesion group(46 patients).The difference among four groups has a statistical significance with one way ANOVA(F=35.522,P<0.01),and the plasma Hcy level in different groups has a significant difference(11.2±5.1 μmol/L vs 14.8 ± 6.7 μmol/L vs 18.8 ±6.9 μmol/L vs 22.7 ±7.8 μmol/L,P<0.05)via LSD,showing that the plasma Hcy level is rising with amount of main vessel which has coronary lesions.7.The CHD group is assigned to three groups according the Gensini score:low score group(52 patients),medium score group(59 patients),high score group(38 patients).The difference among four groups has a statistical significance with one way ANOVA(F=32.353,P<0.01),and the plasma Hcy level in different CHD groups has a significant difference(P<0.05)except between medium score group and high score group,showing that the plasma Hey level is rising with the severity of coronary lesion.8.When unitary linearity regression was performed between the Hey level and the Gensini score,it was seen that Hey level was positively related to the Gensini score(r=0.527,P<0.01).The result had a significant difference via F-test(F=56.564,P=0.000),and established regressive equation Y=15.474+1.602X.Conclusion:1.Hyperhomocysteinemia is an independent risk factor for coronary heart disease and Gensini score.2.The plasma Hey level is rising with the severity of patient’s clinical condition,the amount of vessel with coronary lesion increasing and the Gensini score increasing.3.The plasma Hey level is colsely related to the severity of coronary lesion morphology.Research Background:Coronary microcirculation plays an important role in maintaining the physiological function of normal human heart,and the mechanism for regulating the vascular lumen in the microcirculation is very complex.This mechanism is often referred to as coronary microcirculation dysfunction.The IMR value obtained by pressure guidewire is a new detection method used to evaluate the relative independence of coronary microcirculation in recent years.The method has high reproducibility and high reliability.The occurrence of slow blood flow found in coronary angiography has been shown to be closely related to elevated coronary artery microcirculation resistance,while coronary slow flow is an important factor affecting the prognosis of coronary heart disease.In recent years,studies have shown that its occurrence may be related to increased plasma Hcy levels,which plays an important role in the pathogenesis of coronary slow blood flow and is an independent predictor of coronary slow blood flow phenomenon.More studies have found that acute HHcy caused by short-tem intake of a large number of methionine can lead to obvious coronary microcirculation dysfunction.It is still controversial about various explanations on the pathogenesis of increase of coronary microcirculation resistance,including vascular endothelial dysfunction,smooth muscle cell dysfunction,autonomic nerve dysfunction,vascular institutional changes,extravascular compression,inflammatory response and other factors.Among these,inflammatory response can damage coronary microvascular function in many ways.Hofmann et al.found that HHcy may activate the immune system and inflammatory response in susceptible animals,and that high-sensitivity C-reactive protein(hs-CRP)is an indicator of vascular inflammation in the body and is considered to be an effective predictor of high-risk cardiovascular events.The increase of the concentration of Hcy and the concentration of hs-CRP in plasma can provide the theoretical basis for the early diagnosis and treatment of coronary heart disease.There exist a lot of clinical studies on how HHcy leads to myocardial ischemia by changing the area of epicardial coronary artery.However,the correlation between HHcy and coronary microcirculation function has not been studied at home and abroad,and the mechanism has not been elucidated.This study innovatively introduces the concept of IMR,deepening the understanding of the influence of HHcy on coronary microcirculation through the coronary artery pressure wire detection technology.Objective:The aim of this study was to investigate the impact of hyperhomocysteinemia on coronary microcirculation in patients who have been referred for elective coronary angiography.Study population:This study included 79 consecutive participants who were referred for elective coronary angiography due to suspected myocardial ischemia at The Second Hospital of Wenzhou Medical University from May 2014 to December 2015.Methods:The index of microvascular resistance(IMR),coronary flow reserve(CFR),and fractional flow reserve(FFR)were measured in coronary arteries with intermediate stenoses.Blood samples were collected to determine homocysteine and high-sensitivity C-reactive protein(hs-CRP)levels.All participants were categorized into two groups according to the plasma homocysteine cutoff value of 10 μmoI/L.Results:1.Participants in the high-level homocysteine group had higher IMR(35±8 vs 24±5,P<0.05)and lower FFR(0.78±0.13 vs 0.84±0.10,P<0.05)and CFR(1.87±0.38 vs2.09±0.55,P<0.05)during hyperemia compared to participants in the normal-level homocysteine group.2.Linear regression analysis revealed that homocysteine levels were positively correlated with IMR(r=0.550,P<0.01)and negatively correlated with FFR(r=-0.173,P<0.01).However,homocysteine levels had no correlation with CFR(r=-0.058,P=0.611).3.Serum hs-CRP levels were positively correlated with IMR(r=0.699,P<0.01).4.Multiple regression analysis indicated that homocysteine was an independent predictor of IMR(beta coefficient=0.50,95%confidence interval:0.16-0.85,P=0.005)and Serum hs-CRP levels was also an independent predictor of IMR(beta coefficient=3.13,95%confidence interval:2.14～4.11,P<0.001)Conclusion:Patients with hyperhomocysteinemia were characterized by elevated hs-CRP serum levels,higher IMR,and lower FFR.Elevated Hey levels can result in increased resistance of coronary microcirculation and increased inflammatory response.Hyperhomo-cysteinemia may cause coronary microcirculatory dysfunction partly by promoting inflammatory responses involving hs-CRP-related mechanisms. |
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