Factors determining clinical effectiveness of clopidogrel and prognosis of patients with stable ischemic heart disease

Aim of the study was to elucidate genetic and drug factors affecting efficacy of clopidogrel in patients with ischemic heart disease - inhabitants of central region of Russian Federation. We included 399 patients with IHD (79% men, mean age 58.3+/-9 years) receiving long term therapy with clopidogrel 75 mg/day (during stable manifestations of the disease) or 75-150 mg/day in combination with aspirin (in relation with recent elective percutaneous interventions). We studied carriage of polymorphisms of genes controlling intestinal absorption of clopidogrel (ABCB1 C3435T), activation of clopidogrel in the liver (CYP2C19 *1 *2), and also registered concomitant administration of proton pump inhibitors (PPI). Then we determined relationship of these factors to development of vascular complications (vascular death/myocardial infarction/requirement in revascularization) during 18 months followup. Among studied genetic factors carriage of allele variants CYP2C19 *1/*2 and *2/* (found in 25.5 and 1.8% of patients, respectively), possessed prognostic significance. In the group of clopidogrel monotherapy carriage of at least one *2 allele was associated with increased rate of vascular complications (33.3% vs. 11.3%) including thrombotic complications (27.7% vs. 3.2%; =0.01). In patients receiving 75 mg/day of clopidogrel in combination with aspirin total rate of thrombotic complications as well as of all adverse unfavorable outcomes was higher in *2 carriers compared with wild type homozygotes (14.0% vs.8.7% and 21.0% vs. 15.8%, respectively). In patients receiving double dose clopidogrel in combination with aspirin we found no worsening of outcomes associated with CYP2C19*2 carriage. In the multifactorial risk model independent predictors of vascular complications turned out to be CYP2C19 *2/*2 homozygosity (RR 4.9; =0.02) and concomitant PPI administration ( 1.8; p=0.05).     

Results of a 5-year prospective observation of ischemic heart disease patients with stable stenocardia due to stenosing coronary arteriosclerosis

A prospective five-year study and medicinal treatment were conducted in 317 coronary patients with stable angina in the absence of any signs of heart failure, and stenosing coronary arterial atherosclerosis as evidenced by selective coronary angiography. Total mortality was 2.8%, and the incidence of documented non-fatal myocardial infarction was 3.8% per year. The mortality was mostly dependent on the severity of angina's functional class and the number of affected major coronary arteries (narrowed by more than 70%). A group of patients with unfavorable prognosis was identified (functional class III to IV, low physical stress tolerance, the involvement of two or three major coronary arteries). The results demonstrate the efficiency of long-term medication in coronary patients with stable angina due to stenosing coronary atherosclerosis.     

Heredity and coronary artery lesions in patients with ischemic heart disease (clinico-coronarographic comparisons)

The effect of aggravated heredity for coronary heart disease on the extent of coronary arterial damage and the course of the disease was studied in 575 coronary patients. An information system based on the findings was treated on a third-generation computer M-4030. Coronary patients with aggravated heredity showed high rates of coronary arteries narrowing, more severe course of the disease and frequent large-focal myocardial infarctions with aneurysms of the heart.     

Plasma lipids oxidation in patients with occlusive atherosclerosis of lower extremities and ischemic heart disease

Dynamics of lipoprotein oxidation in blood plasma was studied by Cu-induced plasma oxidation in 114 patients with atherosclerosis of lower extremities of various severity with and without ischemic heart disease. Preparedness of plasma lipoproteins to oxidation in patients was higher than in healthy subjects. Degree of oxidizeability increased with increase of severity and extent of atherosclerosis and was highest in patients with atherosclerosis of lower extremities and ischemic heart disease. There were no significant differences between groups of patients with various severity and extent of atherosclerosis in levels of total cholesterol and triglycerides as well as in other parameters of lipid spectrum. Correlation analysis revealed no relationship between age of patients and degree of plasma oxidizeability.     

Experience with 5 years of drug therapy of ischemic heart disease patients with stable angina and stenosing atherosclerosis of the coronary arteries

The results of 5-year pharmacologic treatment of 234 coronary patients with stable angina of varying functional classes are reported. Coronarography detected stenosis of major coronary arteries in all cases; ventriculography demonstrated no disorders of left-ventricular contractility. Clinical improvement and stabilization occurred in 75.2% of patients, deterioration, in 24.8%. Of the latter group, nonfatal myocardial infarction occurred in 13.7%, and signs of heart failure developed in 9.8%. Repeat bicycle ergometry demonstrated increased or unchanged physical stress tolerance in 67.1%. Working capacity was intact after five years in 61.1%. Therefore, long-term medication of coronary patients with stable angina and normal left-ventricular contractility has proved efficient.     

Assessment of aortic atherosclerosis and carotid atherosclerosis in coronary artery disease

The present study investigated the relationship between aortic atherosclerosis and carotid atherosclerosis, and studied the effects of coronary risk factors for these arteries. The subjects consisted of 78 patients with coronary artery disease (CAD) and 69 patients without CAD. All subjects underwent enhanced computed tomography and B-mode ultrasonography within a short time period to determine the extent of aorta and carotid atherosclerosis. Significant correlations between maximal aortic wall thickness (MAWT) and aortic wall volume (AWV) with carotid intima-media thickness (IMT) were demonstrated. MAWT, AWV and IMT were significantly higher in patients with CAD compared with controls (p=0.009, p=0.024, p=0.001, respectively). Furthermore, there were significant differences in MAWT, AWV and IMT among groups classified by the number of coronary artery stenoses, and no significant differences among groups classified by risk factors, but it was shown that MAWT, AWV and IMT increased gradually as the risk factors increased in number. MAWT, AWV and IMT had positive correlations with age, systolic blood pressure and triglyceride, and a negative correlation with high density lipoprotein-cholesterol. This study demonstrated that both aortic atherosclerosis and carotid atherosclerosis are closely correlated with coronary atherosclerosis, and that the atherosclerosis indices are independently associated with age and hyperlipidemia.     

Progression of coronary artery disease in randomized medical and surgical patients over a 5-year angiographic follow-up

Progression of coronary artery disease (CAD) was assessed prospectively in a randomized series of 36 medically treated and 42 surgically treated patients with angina pectoris. The medical patients were reexamined after 5 years and the surgical patients 3 weeks, 1 year and 5 years after operation. Sixtyseven percent of the medical patients and 69% of the surgical patients had progression. The frequency of new lesions in initially normal segments after 5 years in the medical group was 6.7%, versus 4.1% in ungrafted normal segments in the surgical group (p = 0.05 < 0.010). The frequency of progression in abnormal arteries was 24.1% in the medical group, versus 22.6% in the ungrafted arteries of the surgical group (p = 0.90 < 0.95). The rate of progression of obstructed segments proximal to the graft over 5 years was 43%, versus 27% of the corresponding segments in the medical group (p < 0.01). Progression took place in 11.6% of normal segments proximal to the graft, versus 2% of the corresponding segments in the medical group (p < 0.05); 69% of progression occurring In segments proximal to the graft had reached total occlusion, versus 38% of the corresponding segments in the medical group (p < 0.01). Progression developed in 3.9% of segments distal to the graft, versus 3.1% of the corresponding segments in the medical group.Progression takes place at identical rates in medically treated patients and in ungrafted arteries and segments distal to the graft in surgical patients. Proximal to the graft the rates differ and total occlusions appear as early as 3 weeks after operation.     

Increasing prevalence of peripheral artery occlusive disease in hemodialysis patients: a 2-year follow-up

IntroductionPeripheral artery occlusive disease (PAOD) has been reported to be prevalent in hemodialysis patients and influence their mortality. Ankle-brachial index (ABI) < 0.9 is a reliable marker for PAOD. The aims of the 2-year longitudinal study were to assess whether there was a progression in PAOD and to find out the determinants of ABI progression in hemodialysis patients.MethodsThis study enrolled 237 routine hemodialysis patients and 154 patients completed the 2-year follow-up. The ABI was measured by an ABI-form device at baseline and at the first and second year follow-up. The change in ABI (ΔABI) was defined as ABI measured at the second year followup minus ABI measured at baseline.ResultsThe prevalence of ABI < 0.9 increased yearly (10.4%, 22.7% and 27.9%, respectively; P < 0.001) and the values of ABI decreased yearly (1.11 ± 0.16, 0.97 ± 0.17 and 0.96 ± 0.19, respectively; P < 0.001) in the 154 follow-up patients. Multiple stepwise analysis identified fasting glucose level, calcium-phosphorous product, high-sensitivity C-reactive protein and homocysteine level as independent determinants of ΔABI.ConclusionsOur results demonstrated the prevalence of PAOD increased and the values of ABI decreased yearly in hemodialysis patients. The ABI progression was associated with high fasting glucose level, high calcium-phosphorous product, high-sensitivity C-reactive protein and low homocysteine levels.     

Results of a 10-year prospective study of patients with ischemic heart disease

The paper analyses the results of a 10-year prospective study of 396 patients with coronary heart disease concurrent with stable angina pectoris of different functional classes without serious concomitant diseases. In all the patients. coronary angiography revealed stenosis of one-to-three great coronary arteries and ventriculography showed no severe abnormalities in left ventricular contractility. A long-term drug therapy promoted not only improvement of the clinical status in most patients, but maintenance of work capacity and increase of their lifespan. The annual mortality rate was 3.0%, the incidence of nonfatal myocardial infarction was 5.9%. Repeated coronary angiography indicated that progression of coronary atherosclerosis was accompanied by a clinical deterioration in the patients' health and a decrease in exercise tolerance.     

Genetics of ischemic (coronary) heart disease

On the basis of the medical history and clinical examination of members of families of 133 practically healthy probands and probands suffering from ischemic heart disease and comparison of the frequency of this disease among: (1) husbands and wives and relatives of brother-sisters of probands with ischemic heart disease; (2) husbands and wives, living together for a long time, one of whom had a favourable heredity while the heredity of the other is aggravated by vascular and metabolic diseases; (3) step-borthers and step-sisters born of remarriage of a healthy person to another healthy person in one case and to a sick person in another; (4) persons related in different extent to a sick proband, the authors conclude that genetic factors are very important in the development of coronary atherosclerosis and ischemic heart disease.     

外周血管动脉粥样硬化对年轻冠心病患者的预测意义

目的探讨外周血管颈动脉、股动脉粥样硬化对年轻冠状动脉性心脏病（冠心病）的预测作用。方法根据冠状动脉造影结果将58例≤40岁的患者分为冠心病组（37例）和非冠心病组（21例）,采用高分辨彩色多普勒超声同时检查颈动脉、股动脉,分别测量颈动脉内膜-中层厚度（carotid intima media thickness,CIMT）、股动脉内膜-中层厚度（femoral intima media thickness．FIMT）,以内膜-中层厚度（intima media thickness,IMT）≥1．2mm为粥样硬化斑块。比较两组的CIMT、FIMT及斑块检出率．计算斑块对年轻冠心病的预测值。结果冠心病组CIMT、FIMT高于非冠心病组[（1．36±0．51）mm比（0．84±0．38）mm,P〈0．05：（1．48±0．84）mm比（0.74±0．26）mm．P〈0．05]．冠心病组颈动脉、股动脉粥样硬化斑块形成检m牢均明显高于非冠心病组．差异有统计意义i62ck（23／37）比9．5％（2／21）．P〈0．05;57％（21／37）比14％（3／21）,P〈0．05]。颈动脉、股动脉粥样硬化斑块预测年轻冠心病的敏感性分别为62％、57％,特异性为90％、86％,阳性预测值分别为92％、88％,阴性预测值为58％、53％：颈动脉、股动脉联合检测未见明显提高预测值。结论外周血管颈动脉、股动脉粥样硬化与年轻冠心病相关,颈动脉、股动脉粥样硬化斑块对年轻冠心病患者均有预测作用,其特异性、阳性预测值均较高．     

Prevalence and clinical significance of multifocal atherosclerosis in patients with ischemic heart disease

This review is devoted to the problem of detection of multifocal atherosclerosis (MFA) in patients with acute and chronic forms of ischemic heart disease (IHD). According to different sources rate of detection of MFA varies between 13.5 and 94%. According to register study conducted in the Kemerovo cardiological center it has been proved that isolated involvement of coronary vascular bed is an exemption and that some degree of MFA is found in most patients with ST-elevation myocardial infarction. It is considered that estimating thickness of carotid artery intima-media complex, degree of stenosis of extracoronary arteries one can not only predict severity of coronary atherosclerosis but also assess total risk of development of vascular catastrophes. According to results of our studies it has been shown that in patients with ST-elevation myocardial infarction and even hemodynamically insignificant stenoses in extracoronary vascular beds 12 month prognosis is substantially worse than in patients with MI without signs of MFA. In this connection it is necessary to include into routine practice of physicians observing patients with pathology of any vascular bed active detection and monitoring of involvement of other vascular beds in order to make timely decision on the use of effective methods of treatment and prevention of ischemic events.     

冠心病预后与冠状动脉侧支循环的关系

目的：研究冠心病（CHD）预后与冠状动脉侧支循环的关系。方法：依据冠状动脉造影结果98例患者被分为CHD无侧支循环组（62例）、CHD有侧支循环组（20例）、正常对照组（16例）,分析各组患者的临床资料。结果：CHD组（无论有无侧支循环）与正常对照组相比,除糖尿病发病率较高外（P〈0.01）,其他CHD易患因素差异均无显著性（P〉0.05）;有侧支循环与无侧支循环CHD患者相比,主要CHD易患因素、不稳定型心绞痛的发生率差异均无显著性（P〉0.05）;但无侧支循环患者左室射血分数〈50%患者比率（29.0%比10.0%）,心肌梗死（61.3%比30.0%）、室壁瘤（22.6%比0）的发生率较有侧支循环患者显著增加（P〈0.01）。结论：侧支循环存在与否与冠心病患者预后有关。     

Factors determining prognosis of patients with stable ischemic heart disease (results of a five years prospective study)

Risk stratification seems to be very important in patients with stable coronary artery disease (CAD). However, the prognostic scales are now available only for the early risk assessment in patients with acute coronary syndromes and in patients undergoing percutaneous coronary interventions. Aim of the study was to assess the frequency of cardiovascular events (CVE) during 5 years of follow-up in patients with stable CAD and to construct a long-term risk prediction model for these patients. 503 patients (mean age 59.4 years) were included in the study. The follow-up period ranged between 3.0 and 7.5 years (mean 5.0 years). Main end points were fatal and non-fatal cardiovascular events: cardiovascular death, acute coronary syndromes, ischemic stroke, transient ischemic attack, peripheral arterial thrombosis, and need for revascularization in any affected vascular area. Total frequency of events was 31.0% (5.7/100 patient years). Independent predictors of events were: severity of angina, three vessel coronary disease, previous myocardial infarction, previous stroke/ transient ischemic attack, peripheral arterial disease, obesity, chronic kidney disease and history of erosive gastritis. The presence of more or equal 3 risk factors was significantly associated with increased frequency of CVE.     

Results of stenting and surgical treatment in patients with ischemic heart disease and multivessel coronary artery involvement

Efficacy of surgical and endovascular (with the use of stents) methods of treatment was assessed in 56 patients with ischemic heart disease and double and triple vessel involvement. Coronary artery bypass grafting (CABG) was carried out in 31, implantation of stents - in 25 patients. Clinical factors used for assessment of efficacy of treatment were development of events (deaths, myocardial infarctions), presence of angina, changes of exercise capacity. In immediate postoperative period there were 2 myocardial infarctions (1 in each group, i.e. 4 and 3.2% after stenting and CABG, respectively) and no deaths. Absence of clinical effect (persistence of angina) more often occurred after stenting (12%) that after CABG (6.5%). Length of hospital stay was shorter after stenting (13-/+8 days) than after CABG (24-/+10 days). Increment of exercise tolerance was higher after stenting than after CABG (62-/+10 and 54-/+8 W, respectively). During 1 year of follow-up 1 myocardial infarction developed (after stenting). In a year after procedure angina recurred in 24 and 12.9% of patients subjected to stenting and CABG, respectively; increments of exercise tolerance were 53-/+8 and 49-/+7 W after stenting and CABG, respectively. These results are indicative of high efficacy of surgical and endovascular (with implantation of stents) treatment of multivessel coronary artery disease.     

Extracoronary atherosclerosis in patients with chronic ischemic heart disease: relationship with risk factors and the severity of coronary artery disease.

AIM: The aim of the present study was to investigate the prevalence of carotid and/or peripheral atherosclerotic lesions in patients with chronic ischemic heart disease (previous acute myocardial infarction [AMI] or stable angina). METHODS: We studied 248 patients (168 male and 80 female), mean age 63+/-10 years, which were investigated for traditional risk factors. Systolic blood pressure, body mass index, lipid profile, fasting glucose and plasma fibrinogen were also measured. We assessed the prevalence of atherosclerotic lesions in carotid and lower limb arteries, by ultrasound duplex scanning (UDS). RESULTS: Angina was present in 33% of the patients, a previous AMI in 67%, a previous transient ischemic attack in 4% and a previous ischemic stroke in 6% of patients. A total of 195 patients underwent coronary angiography: 1 vessel was involved in 48% of patients, 2 vessels in 33%, and 3 vessels in 19%. Detecting peripheral atherosclerotic lesions by UDS, increased intima-media thickness (IMT) or plaques in carotid arteries were found in 232 patients (94%) and carotid stenosis >70% in 13 patients (5%). In lower limb arteries, IMT or plaques were present in 202 patients (82%) and a stenosis >70% in 18 patients (7%). Severity of coronary artery disease (CAD) was correlated to extracoronary atherosclerosis: carotid and lower limb arterial atherosclerosis was detected in 73% of patients with 1 vessel, in 83% of patients with 2 vessel, in 87% of those with 3 vessel CAD. CONCLUSION: Our study suggests that in patients with CAD, it is useful to screen the peripheral circulation by non-invasive tests, such as UDS. Patients with the diagnosis of ischemic heart disease and combined extracoronary atherosclerosis need a careful follow-up and a more aggressive therapy for secondary prevention.     

冠心病患者冠状动脉粥样硬化程度与颈动脉粥样硬化的相关性研究

目的 探讨冠心病患者颈动脉粥样硬化与冠状动脉硬化程度之间的关系.方法 选取2012年1月至2013年6月河北大学附属医院心内科治疗的冠心病患者350例,依据冠状动脉造影结果将患者分为冠心病组和非冠心病组,其中冠心病组260例,非冠心病组90例;依据造影结果将冠心病组患者进行再次分组,其中单支病变组113例,双支病变组89例,三支病变组58例.比较冠心病组及非冠心病组间及不同冠状动脉病变支数三组间的颈动脉内-中膜厚度（IMT）、斑块积分及Gensini评分;统计分析冠状动脉病变支数与以上观察指标的相关性.结果 冠心病组的颈动脉IMT、斑块积分、Gensini积分分别为（1.37±0.23）、（5.37±3.98）、（23.32±7.33）,均高于非冠心病组,两组间比较差异有统计学意义（P＜0.05）.双支病变组和三支病变组的斑块检出率为79.8％和81.0％,双支病变组及三支病变组患者颈动脉IMT分别为（1.31±0.21）mm和（1.37±0.27）mm,双支病变组和三支病变组患者的斑块检出率与颈动脉IMT值均高于单支病变组,三组间比较差异有统计学意义（P＜0.05）.冠状动脉病变支数与IMT、颈动脉斑块积分呈显著正相关;Gensini评分与IMT及颈动脉斑块积分呈显著正相关.结论 冠状动脉的粥样硬化程度随着患者的颈动脉粥样硬化程度的升高而加重,冠心病的严重程度可以通过颈动脉超声检测反映出来.