| Coronary heart disease refers to ischemic heart disease mainly caused by stenosis of coronary artery which can lead to myocardial hypoxia.At present,the incidence of premature coronary artery disease(PCAD)is getting higher with continuous development of economy and improvement of living standard,and PCAD is becoming more popular in Asian countries.However,little is known about its clinical features and prognosis.Therefore,patients with PCAD were selected in this study,aiming to analyze the risk factors of major adverse cardiovascular events(MACE)and provide basis for secondary prevention.In addition,basic research and drug intervention were carried out to elucidate the mechanism of atherosclerosis and provide evidence for clinical treatment.Part One Analysis of risk factors for major adverse cardiovascular-events in patients with premature coronary artery diseaseObjective: Risk factors of MACE in PCAD patients were analyzed to provide basis for secondary prevention of these patients.Methods:1.Patients diagnosed as acute coronary syndrome(ACS)and undergoing coronary angiography in the first hospital of Hebei Medical University from March 1,2014 to December 31,2017 were selected as the primary study subjects.A total of 2,847 patients with premature ACS were enrolled.These patients were excluded: 10 patients with hypertrophic cardiomyopathy,14 patients with severe valvular disease required surgery,3 patients with malignant tumor,8 patients with immune system diseases,12 patients with severe renal insufficiency,and 94 patients with incomplete clinical data.A total of 2,706 patients were included for follow-up study.Clinical data and coronary intervention data were obtained from inpatient records.All baseline clinical data were collected.2.The patients were followed up by telephone or outpatient and the contents were MACE and medication after enrollment.The patients were followed up until December 31,2018.Results:1.277 patients were lost to follow-up,with a loss rate of 10.24%.A total of 2,429 patients diagnosed with premature ACS were finally followed up for statistical analysis.The incidence of ACS in males was higher than that in females.60.68% of the patients had hypertension and 26.60% had diabetes.The coronary artery lesions were mainly single branch lesions and the anterior descending branch lesions were the most common.Aspirin and statins had the highest rates of medicine therapy.2.A total of 224 MACE occurred during the follow-up period,with an incidence of 9.22%,including 189(7.47%)patients with unstable angina(UA),25(1.03%)patients with acute myocardial infarction(AMI),6(0.25%)patients with UA and AMI,and 4(0.16%)patients with cardiac death.There were 224 patients in the MACE group and 2,205 patients in the non-MACE group.The age,proportion of female,hypertension,diabetes,and previous coronary heart disease in the MACE group were higher than that in the non-MACE group.The level of homocysteine(Hcy)in the MACE group were higher than in the non-MACE group.The proportion of single coronary artery lesions in the MACE was lower than that in the non-MACE group.The proportion of medicine therapy alone was lower in the MACE group than in the non-MACE group,while the rate of percutaneous coronary intervention(PCI)was higher in the non-MACE group.The proportion of nitrate and clopidogrel applications in the MACE group were higher than those in the non-MACE group.3.Univariate Cox proportional hazard model analysis showed that female,hypertension,diabetes,a history of old myocardial infarction,a history of PCI,a history of coronary artery bypass grafting(CABG),identified as NSTEMI,hyperhomocysteine,and PCI were risk factors for MACE in premature ACS patient.Further multivariate Cox proportional hazard model analysis showed that female,a history of myocardial infarction,identified as non-ST-segment elevation myocardial infarction(NSTEMI)and Hcy were independent risk factors for predicting MACE in premature ACS patients.Conclusions:1.The proportion of male patients with premature ACS was higher than that of female patients.However,the incidence of MACE in female patients was significantly higher than that in male patients once premature ACS occurs.Female was an independent risk factor for MACE in premature ACS patients.2.Hcy was an independent risk factor for MACE in premature ACS patients.3.The long-term prognosis of patients with NSTEMI is worse than that of patients with ST-segment elevation myocardial infarction(STEMI).NSTEMI is an independent risk factor for long-term MACE risk in patients with PCAD.Part Two Association of homocysteine with the risk of major adverse cardiovascular events in female with premature acute coronary syndromeObjective: To investigate the correlation between Hcy level and the clinical characteristics of premature ACS in female,and the predictive value of Hcy level on the risk of MACE,so as to provide basis for the secondary prevention of premature ACS in female.Methods:1.Female patients diagnosed as ACS and undergoing coronary angiography in the first hospital of Hebei Medical University from March 1,2014 to December 31,2017 were selected as the primary study subjects.A total of 1,299 patients were enrolled.These patients were excluded: 3 patients with hypertrophic cardiomyopathy,5 patients with severe valvular disease required surgery,1 patients with malignant tumor,6 patients with immune system diseases,5 patients with severe renal insufficiency,and 49 patients with incomplete clinical data.A total of 1,230 patients were included for follow-up study.Clinical data and coronary intervention data were obtained from inpatient records.All baseline clinical data were collected.2.The patients were followed up by telephone or outpatient and the contents were MACE and medication after enrollment.The patients were followed up until December 31,2018.Results:1.128 patients were lost to follow-up.A total of 1,102 patients diagnosed with premature ACS were finally followed up for statistical analysis,with an average age of 51.46 ± 3.68 years.Among them,UA(83.1%),NSTEMI(12.4%)and STEMI(4.5%)were diagnosed.2.Patients were divided into three groups according to Hcy level: low homocysteine group(Hcy?9.1?mol /L);moderate homocysteine group(Hcy:9.2-11.6?mol/L);high homocysteine group(Hcy>11.6?mol/L).The age of low homocysteine group was lower than the other two groups.Creatinine and uric acid levels increased,while fasting glucose levels decreased with the increase of Hcy.3.A total of 118 MACE occurred,with an incidence of 10.7%.The Hcy level of the MACE group was significantly higher than that of the non-MACE group.4.The area under ROC curve was 0.789.The sensitivity was 51.7%.The specificity was 95.0%,and the optimal boundary value of Hcy level was16.85?mol/L.5.Kaplan-Meier analysis showed that the increased Hcy level was associated with MACE in female patients with premature ACS.The MACE-free survival rate was significantly reduced with the increase of Hcy level.Cox proportional hazard regression model analysis showed that high Hcy level was an independent risk factor of MACE risk in female patients with premature ACS.Conclusions: Elevated Hcy level was associated with poor prognosi s in female patients with premature ACS.Hcy was an independent risk factor of MACE risk in female patients with premature ACS.Therefore,serum Hcy level can be used as an appropriate indicator for female pa tients at high risk of premature ACS.Part Three Atorvastatin antagonizes inflammatory response induced by homocysteine in vascular smooth muscle cellsObjective: To investigate the mechanism of Hcy caused atherosclerosis.And whether atorvastatin can antagonize the inflammatory response of vascular smooth muscle cells induced by Hcy through inhibiting inflammatory response.Methods:1.The thoracic and abdominal aorta were dissected from male SD rats,and the vascular smooth muscle cells(VSMCs)were cultured.Experiments were done with cells from three to five generations.2.Four flask cells with the same growth state and density were divided into control group,Hcy group,Hcy + atorvastatin group and atorvastatin group,respectively.The expressions of transcription factor nuclear factor-?B(NF-?B),C-reactive protein(CRP),interleukin-1?(IL-1?)and interleukin-6(IL-6)in different groups were detected by Western blot.3.RNA was extracted from vascular smooth muscle cells by Trizol method,and the total RNA was reverse transcripted.The expressions of NF-?B,CRP,IL-6 and IL-1? in different groups were detected by PT-PCR.Results:1.The expression of NF-?B in rat VSMCs was up-regulated by Hcy,while atorvastatin can down-regulated the expression of NF-?B induced by high Hcy.2.The expression of CRP in rat VSMCs was up-regulated by Hcy,while atorvastatin can down-regulated the expression of CRP induced by high Hcy.3.The expression of IL-1? in rat VSMCs was up-regulated by Hcy,while atorvastatin can down-regulated the expression of IL-1? induced by high Hcy.4.The expression of IL-6 in rat VSMCs was up-regulated by Hcy,while atorvastatin can down-regulated the expression of IL-6 induced by high Hcy.Conclusions: High Hcy can induce the expression of inflammatory cytokines CRP,IL-1? and IL-6,thus promoting the occurrence of atherosclerosis.Atorvastatin can antagonize Hcy-induced endothelial cell inflammation by inhibiting the activation of NF-?B,and down-regulating the expression of cytokines CRP,IL-6 and IL-1?. |
PDF Full Text Request