[Show abstract][Hide abstract] ABSTRACT: To evaluate the relationship between haemostatic and rheological factors and cardiovascular outcome in subjects with angina pectoris in the general population.
Two hundred and seven men and women aged 55-74 had evidence of angina at baseline. Sixty-seven (32.3%) had a fatal or non-fatal cardiovascular event during follow-up. Median levels of tissue plasminogen activator antigen and leucocyte elastase were higher in the event group compared with the no event group (10.0 ng. ml(-1)vs 7.2 ng. ml(-1);P</=0.001, and 40.3 ng. ml(-1)vs 31.0 ng. ml(-1);P</=0.01, respectively). Whole blood viscosity was also significantly higher in the event group than in the no event group (3.80 mPa.s vs 3.53 mPa.s;P</=0.05). After adjusting for age and sex, unit increases in both tissue plasminogen activator antigen and leucocyte elastase levels were significantly associated with an increased risk of a cardiovascular event. These associations remained after further adjusting for cardiovascular risk factors and baseline myocardial infarction. The relative risks were 2.07 (95% CI, 1.30-3.45;P</=0.01) for tissue plasminogen activator antigen and 1. 95 (95% CI, 1.12-3.50;P</=0.05) for leucocyte elastase.
Disturbed fibrinolysis and activation of leucocytes may be implicated in the development of thrombotic cardiovascular events in subjects with angina pectoris in the general population.
European Heart Journal 10/2000; 21(19):1607-13. · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hyperhomocysteinaemia and reduced nitric oxide synthesis may each result in endothelial dysfunction predisposing to atherogenesis. Genetic variants of methylene tetrahydrofolate reductase (MTHFR) and endothelial nitric oxide synthase (ecNOS) influence homocysteine metabolism and nitric oxide synthesis, respectively and might thus be determinants of the risk of atherosclerotic disease. The aim of our study was to identify, in a general population sample, the risks of peripheral arterial disease and of coronary heart disease related to MTHFR (175;198) and ecNOS (4;5) polymorphisms. In the Edinburgh Artery Study, which is a population based cohort study, 940 men and women aged 60-79 years, who had previously been selected at random from the general population, had DNA extracted from a venous blood sample. Based on a clinical examination at baseline and follow up investigations, three groups of subjects were identified: those with peripheral arterial disease (n=80), those with coronary heart disease (n=137), and healthy controls who had no evidence of cardiovascular disease (n=300). The distributions of the ecNOS and MTHFR genotypes did not differ significantly between the groups with and without cardiovascular disease. However, the ecNOS-4 allele (frequency 0.13) was related to the occurrence of coronary heart disease in non smokers, OR=2.47 (95% CI [1.42, 4.34], P=0.02). No association was found with peripheral arterial disease. The MTHFR-175 allele (frequency 0.31) was not related to coronary heart disease, but was associated with a reduced risk of peripheral arterial disease, OR=0.54 (95% CI [0.32, 0.90], P=0.02). Neither the ecNOS-4 allele or MTHFR-175 allele was related to the ankle brachial pressure index in the whole study population. In conclusion, the ecNOS-4 allele was associated with a slightly increased risk of coronary heart disease in non-smokers, but otherwise the MTHFR and ecNOS genotypes appeared to have little influence on the risks of peripheral arterial disease and coronary heart disease in this older population.
[Show abstract][Hide abstract] ABSTRACT: The role of fibrinogen and other haemostatic factors in prediction of peripheral arterial disease (PAD) has not been established. We examined the associations of plasma fibrinogen, von Willebrand Factor (vWF), tissue plasminogen activator (t-PA) antigen, fibrin D-dimer, and factor VII with the development and clinical progression of PAD. In the Edinburgh Artery Study, 1592 men and women, aged between 55 and 74 years, were followed prospectively over 5 years to detect the onset of PAD, and the deterioration of established PAD. At baseline, 418 individuals had evidence of PAD and 60 (14.4%) subsequently deteriorated. 1080 subjects had no baseline disease, but 59 (5.5%) developed PAD during follow-up. Median levels of fibrinogen and vWF were higher in the group developing disease compared with the group which did not (2.78 g/l versus 2.57 g/l, P< or =0.01; 116 IU/dl versus 104 IU/dl, P< or =0.05; respectively). After adjusting for age and sex, fibrinogen (P< or =0.01) and vWF (P< or =0.05) were significantly associated with the risk of developing PAD. The association between fibrinogen and development of disease remained after adjusting for cardiovascular risk factors and baseline ischaemic heart disease (relative risk, 1.35, 95% confidence interval, 1.05, 1.73; P< or =0.05). None of the haemostatic factors were significantly associated with progression of PAD. In conclusion, plasma fibrinogen levels are related to the future onset of PAD, providing further evidence of a possible role of elevated fibrinogen in the development of atherosclerotic disease.
Blood Coagulation and Fibrinolysis 01/2000; 11(1):43-50. · 1.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The relationship between haematological factors and peripheral arterial disease (PAD) among diabetics has not been widely examined. 1592 men and women aged 55-74 years were selected from the general population. They underwent an assessment for PAD and a glucose tolerance test. 288 subjects (18.7%) were identified as having diabetes or impaired glucose tolerance (IGT). Among the diabetes/IGT group, median levels of fibrinogen, von Willebrand factor (VWF), tissue plasminogen activator (t-PA), fibrin D-dimer and plasma viscosity were higher in subjects with PAD than those without PAD (P </= 0.05). The prevalence of PAD was higher in those with diabetes/IGT (20.6%) compared to those with normal glucose tolerance (12.5%) (odds ratio 1.64; 95% CI 1.17, 2.31). After separate adjustment for fibrinogen, VWF, t-PA, fibrin D-dimer, leucocyte elastase, plasma viscosity and haematocrit, those with diabetes/IGT no longer had a significantly higher risk of PAD compared to those with a normal glucose tolerance test. Simultaneous adjustment for the first four of these haematological factors reduced the risk of PAD among subjects with diabetes/IGT to 1.11 (95% CI 0.76, 1.63). Increased levels of haemostatic factors may partly explain the higher prevalence of PAD in diabetic/IGT subjects compared to normal glucose-tolerant subjects. Future randomized controlled trials involving the indirect lowering of levels of haematological factors should help to explain whether the associations reported here are of causal significance.
British Journal of Haematology 07/1999; 105(3):648-54. · 4.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the risk factors for peripheral arterial disease (PAD) in a diabetic population and to examine whether different levels of these risk factors might explain why diabetic subjects have an increased risk of PAD compared with normal glucose tolerance subjects.
There were 1,592 men and women aged 55-74 years selected at random from the age-sex registers of 11 general practices in Edinburgh, Scotland. Subjects underwent a comprehensive medical examination, including assessment for PAD (intermittent claudication on World Health Organization questionnaire or major asymptomatic disease on noninvasive testing) and a glucose tolerance test.
Of the subjects, 288 (18.7%) were found to have diabetes or impaired glucose tolerance (IGT). The prevalence of PAD was greater in those with diabetes/IGT (20.6%) compared with those with normal glucose tolerance (12.5%) (odds ratio [OR] 1.64, 95% CI 1.17-2.31). Among the diabetes/IGT group, mean levels of smoking, systolic blood pressure, and triglycerides were higher in subjects with PAD than in those without PAD (P < or = 0.05). Mean levels of systolic blood pressure and plasma triglycerides were also higher in diabetic subjects than in nondiabetic subjects with PAD (P < or = 0.05). In multivariate analysis, those with diabetes/IGT no longer had a significantly higher risk of PAD after adjusting separately for systolic blood pressure (OR 1.22, 95% CI 0.85-1.73) and plasma triglycerides (OR 1.26, 95% CI 0.89-1.79). Simultaneous adjustment for both systolic blood pressure and triglycerides reduced the risk of PAD among diabetic subjects to 1.11 (95% CI 0.78-1.58).
Increased mean levels of triglycerides and systolic blood pressure may help to explain the higher prevalence of PAD in diabetic subjects compared with that in normal glucose tolerance subjects.
Diabetes Care 04/1999; 22(3):453-8. · 8.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: To determine the relationship between varicose veins and duration of menstrual life, age of menopause, pregnancy, oral contraceptive use and hormone replacement therapy (HRT).