Fibrinogen, factor VII clotting activity and coronary artery disease severity

To asses the relationship between fibrinogen, factor VII coagulant (VIIc) activity and extent of coronary artery disease, we studied 43 white males shown to have greater than 50% stenosis of at least one major coronary artery. Thirty six had a definite history of myocardial infarction at least 3 months earlier and were classified as having 1, 2 or 3 vessel disease while 7 had 2 or 3 vessel disease, but no prior infarction. Groups were similar with regard to age, body mass index and blood pressure. In those with documented prior infarction, there was a significant relationship between the extent of atheroma and coagulation variables factor VIIc and fibrinogen. However, given a similar degree of atheroma, patients with prior infarction had significantly higher levels of factor VIIc activity compared with patients without such a history. These results corroborate those from prospective studies confirming a significant role for the coagulation system in the clinical manifestation of coronary artery disease.     

Analysis of polymorphisms Leiden Factor V G1691A and prothrombin G20210A as risk factors for acute myocardial infarction

Thrombotic risk increases in elderly, therefore, the understanding of the genetic predisposition of hypercoagulability could make the difference in the prevention of venous and/or arterial thrombotic events. Laboratory evaluation of hyperfibrinogenemia, increased Factor VII levels, antiphospholipid antibodies presence and hyperhomocysteinemia are considered to have a consistent high predictivity for arterial thrombophilic diseases. Anyway, a large debate exists on the validity of testing Leiden Factor V (FV) G1691A and/or prothrombin (FII) G20210A polymorphisms in patients affected by arterial thrombotic diseases, despite of the several observations described. Here we report data strongly suggesting that at least the FII G20210A polymorphism might be considered an important risk factor for acute myocardial infarction in aged patients (55–80 years old). On the other hand, in spite of a not different genotypic and allelic distribution for the Leiden FV G1691A mutation, the presence of one or both the two polymorphisms is significantly higher among cases than in controls. In conclusion, our data suggest that FII G20210A and/or Leiden FV might be involved as risk factor for arterial disorders in about 5% of old subjects, justifying the opportunity of a genetic screening and an eventual preventive treatment, in particular in old subjects in which other and major risk factors, as hypertension and atherosclerosis, are detected.     

Mean platelet volume is an independent risk factor for myocardial infarction but not for coronary artery disease

After rupture of an arteriosclerotic plaque in a coronary artery, platelets play a crucial role in the subsequent thrombus formation, leading to myocardial infarction. An increased mean platelet volume (MPV), as an indicator of larger, more reactive platelets, may represent a risk factor for myocardial infarction. However, this hypothesis is still controversial and most studies addressing the role of MPV were performed comparing patients suffering from myocardial infarction with healthy controls. We intended to identify patients at high risk of suffering myocardial infarction in a group of patients with known coronary artery disease. One hundred and eighty-five consecutive patients with stable coronary artery disease were compared with 188 individuals who had suffered myocardial infarction. Patients within the highest quintile of MPV (> or = 11.6 fl) had a significantly higher risk of experiencing a myocardial infarction compared with patients within the lowest quintile (OR = 2.6, 95% CI 1.3-5.1) in a multivariate analysis that included sex, age, body mass index, hyperlipidaemia, hypertension, smoking and diabetes mellitus. Our results indicate that patients with pre-existing coronary artery disease and an increased MPV (> or = 11.6 fl) are at higher risk of myocardial infarction. These patients can be easily identified during routine haematological analysis and could possibly benefit from preventive treatment.     

The prothrombin 20210A allele and the factor V Leiden are associated with venous thrombosis but not with early coronary artery disease.

This study was performed in order to establish the role of the prothrombin 20210 G/A and factor V Leiden (R506Q) polymorphisms in the susceptibility to develop venous thromboembolism and early coronary artery disease (CAD). These polymorphisms were determined in 82 consecutive patients with venous thromboembolism, 175 male patients with early CAD, and 200 healthy controls from the same Caucasian population (Asturias, Northern Spain). DNA was amplified using polymerase chain reactions and digested with the appropriate restriction enzymes in order to define the prothrombin and factor V genotypes. The prevalence of the heterozygous for the prothrombin A allele was 3.5% in the general population and 15.8% in patients with venous thrombosis (P = 0.0007); the frequency was 4% in patients with early CAD. No sex-related differences in the prevalence of the A allele were observed, and the average age at the first venous thromboembolic event was similar between GG and AG patients. The frequency of carriers of the factor V Leiden polymorphism was 9.75% among patients with venous thromboembolism, compared with 3.5% among controls, and 3.4% in the patients with CAD. Our data showed an association between venous thromboembolism and the AG genotype at the prothrombin 20210 G/A polymorphism. This polymorphism was not related to an increased risk for early CAD in our population of male patients.     

Factor V Leiden, prothrombin G20210A and MTHFR gene mutations in inflammatory bowel disease.

BACKGROUND/AIMS: Thromboembolic events are more common in patients with inflammatory bowel disease than in the normal population; however, the reason for the increased prevalence is not clear. The aim of this study was to evaluate the prevalence of factor V Leiden, prothrombin G20210A and methylene tetrahydrofolate reductase (MTHFR) gene mutations in IBD patients followed in our outpatient clinic. METHODS: Thirty-four patients with ulcerative colitis and 28 patients with Crohn's disease and 80 healthy controls were included in the study. No patient had a history of previous thromboembolism. Factor V Leiden, prothrombin G20210A and MTHFR gene mutations were studied. RESULTS: Heterozygote factor V Leiden mutation was found in five (6.25%) control patients and in two (3.2%) IBD patients. Heterozygote MTHFR mutation was obtained in seven (11.3%) IBD patients and in five (6.25%) controls. Heterozygote prothrombin G20210A mutation was found in two (2.5%) and homozygote MTHFR mutation in one (1.25%) control patient. There was no statistical difference between the IBD group and healthy controls. CONCLUSIONS: Genetic mutations that could increase the thrombosis risk were not found to be different in IBD versus the normal population in our study.     

Two common genetic thrombotic risk factors: factor V Leiden and prothrombin G20210A in adult Turkish patients with thrombosis

The prevalence of genetic risk factors for thrombosis varies greatly in different parts of the world, both in patients with thrombosis and in the general population. Factor V Leiden (FVL) and prothrombin G20210A (PT G20210A) mutations are the most common genetic defects leading to thrombosis. We have previously reported that those two thrombotic risk alleles are frequently found in Turkish children with thrombosis. The aim of the present study was to investigate the frequency of FVL and PT G20210A and their clinical manifestations in adult Turkish patients with thrombosis. Between January 1997 and February 2000, 146 patients with documented thrombosis were investigated in our center for the presence of the FVL and PT G20210A mutations. Forty-five of 146 patients with thrombosis (30.8%) were detected to have FVL mutation. Among those cases with the FVL mutation, seven (4.8%) had homozygote and 38 (26%) had heterozygote mutation. The PT G20210A mutation was detected in 10 of the 146 patients with thrombosis (6.8%). Another six cases (4.1%) had both FVL and PT G20210A mutations. The overall frequency of these two common risk alleles in our adult population with thrombosis was 41.6%. Our findings reveal that FVL and PT G20210A mutations are significant genetic risk factors contributing to the pathophysiology of thrombosis in the Turkish population.     

Prevalence of genetic prothrombotic factors (factor V Leiden and II20210 prothrombin mutation) in glomerular nephropathies with or without thrombosis

The presence of genetic prothrombotic factors (factor V Leiden and the prothrombin II20210 mutation) was investigated in 38 patients with glomerulonephritis with or without a history of thrombotic events and/or nephrotic syndrome. We found an increased prevalence (36%) of heterozygous factor V Leiden in those patients with a history of thrombotic events. This is ten times the prevalence in the normal Spanish population. Carrier status for this mutation may be a determining factor in the development of thrombotic events along with the acquired disorders of coagulation to which these patients are prone. We found only one patient who was a carrier of the G-A II20210 mutation of the prothrombin gene; this patient had no history of venous thrombosis or embolism. Our findings suggest the need to measure activated protein C resistance and to look for the most frequent genotype causing it, Factor V Leiden, in patients with glomerulonephritis to identify those at risk who may benefit from prophylaxis against thrombosis.     

Family history of myocardial infarction as an independent risk factor for coronary heart disease

The hypothesis that a family history of heart attack before the age of 60 years is an independent risk factor for coronary heart disease was examined in a random sample of 1044 men aged 40-70. Data on personal and family history, smoking, weight, height, plasma lipid and lipoprotein concentrations, blood pressure, and resting and exercise electrocardiograms were collected according to the standard Lipid Research Clinics protocol. A history of heart attack in first degree relatives was ascertained by interviewing the participants. Evidence of coronary heart disease was found in 123 men (reported heart attack in 20, electrocardiographic findings of ischaemic heart disease at rest in 40, and electrocardiographic findings during heart rate limited exercise in 63). Subjects with coronary heart disease had considerably higher concentrations of total cholesterol, higher blood pressures, and lower concentrations of high density lipoprotein cholesterol than those without. Twenty nine per cent of the subjects with coronary heart disease reported a history of heart attack in a first degree relative before 60 years of age compared with 19% of those without. In a multivariate logistic model, the coefficients for age, cholesterol concentrations, and hypertension were all positive and statistically significant. The coefficient for HDL cholesterol concentration was negative and significant. A family history of heart attack showed a significant positive association, indicating a relation with coronary heart disease that is independent of the other variables in the model. The relation persisted in apparently asymptomatic patients with coronary heart disease.     

The venous thrombosis risk factor 20210 A allele of the prothrombin gene is not a major risk factor for arterial thrombotic disease

A nucleotide change (G to A transition) at position 20210 has recently been demonstrated to be a risk factor for venous thrombosis. The relevance of this polymorphism to thrombotic disease was investigated by genotypic identification in three prospective case–control studies: 101 case patients with acute coronary heart disease (CHD), 104 patients with acute cerebrovascular disease (CVD), 82 patients with a confirmed diagnosis of deep venous thrombosis (DVT), and one control age- and sex-matched for each patient. The prevalence of the genetic variation was significantly associated with the occurrence of DVT, but did not differ in patients with CHD or CVD from that in controls, suggesting that this allele should not be considered a major risk factor for arterial thrombotic disease.     

主动脉脉搏波传导速度升高与冠心病发病的相关性

目的:探讨脉搏波传导速度(PWV)对冠心病(CHD)的预测价值。方法:患者分为非CHD组(97例)和CHD组(114例)。比较2组患者CHD危险因素以及各动脉段PWV的差异,采用Logistic回归分析比较上述危险因素在CHD发病中的作用。结果:CHD组患者的性别构成、年龄、高血压、糖尿病、血脂异常、吸烟等显著多于非CHD组(P<0.05),CHD组踝肱指数显著低于非CHD组。CHD组患者的心-左右股动脉段PWV和心-左右桡动脉段PWV显著大于非CHD组(P<0.01),而左右股-踝动脉段PWV在CHD组和非CHD组差异无统计学意义。Logistic回归分析发现,患高血压、糖尿病、血脂异常、吸烟以及心-股动脉段PWV升高、踝肱指数降低等与CHD的发生显著相关(P<0.05)。结论:同高血压、糖尿病、血脂异常、吸烟一样,心-右股动脉段PWV显著增高以及踝肱指数降低也是CHD发病的危险因素。     

血尿酸不是冠心病的独立危险因素

目的探讨血尿酸浓度升高是否为冠心病的独立预测因子。方法对上海交通大学附属第六人民医院心内科2003-09~2004-03住院患者临床资料进行回顾性分析,选择经冠状动脉造影证实的连续性冠心病患者118例(稳定型心绞痛36例,不稳定型心绞痛28例,急性心肌梗死54例),年龄66(65·79±10·03)岁,其中男94例、女24例;同期冠脉造影正常的连续性入院患者67例作为对照组,年龄61(60·75±11·98)岁,其中男43例、女24例。入院第2天清晨取空腹12h抽取静脉血进行血尿酸、血脂等各种生化检查,详细询问包括吸烟、高血压等病史。入院期间行冠脉造影检查。结果冠心病组血尿酸浓度高于对照组[(372·31±100·28)mmol/L对(340·08±81·58)mmol/L,P=0·028],冠心病组之间血尿酸浓度差异并无显著性。但Logistic回归分析显示血尿酸并非冠心病的独立危险因素。结论血尿酸浓度升高可能只是动脉粥样硬化的一个标志,而非冠心病的独立危险因素。     

Family history of myocardial infarction as an independent risk factor for coronary heart disease.

The hypothesis that a family history of heart attack before the age of 60 years is an independent risk factor for coronary heart disease was examined in a random sample of 1044 men aged 40-70. Data on personal and family history, smoking, weight, height, plasma lipid and lipoprotein concentrations, blood pressure, and resting and exercise electrocardiograms were collected according to the standard Lipid Research Clinics protocol. A history of heart attack in first degree relatives was ascertained by interviewing the participants. Evidence of coronary heart disease was found in 123 men (reported heart attack in 20, electrocardiographic findings of ischaemic heart disease at rest in 40, and electrocardiographic findings during heart rate limited exercise in 63). Subjects with coronary heart disease had considerably higher concentrations of total cholesterol, higher blood pressures, and lower concentrations of high density lipoprotein cholesterol than those without. Twenty nine per cent of the subjects with coronary heart disease reported a history of heart attack in a first degree relative before 60 years of age compared with 19% of those without. In a multivariate logistic model, the coefficients for age, cholesterol concentrations, and hypertension were all positive and statistically significant. The coefficient for HDL cholesterol concentration was negative and significant. A family history of heart attack showed a significant positive association, indicating a relation with coronary heart disease that is independent of the other variables in the model. The relation persisted in apparently asymptomatic patients with coronary heart disease.     

Arterial thrombosis and acute myocardial infarction with angiographically normal coronary arteries in a woman heterozygous for both factor V Leiden and prothrombin mutation

Thirteen years after her last thrombotic event, anticoagulation was discontinued in a patient with combined thrombophilia involving mutation in factor V and G20210A polymorphism of the prothrombin gene. The only history was of arterial thrombosis. Three months later she presented a transmural myocardial infarction caused by coronary thrombosis.