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ABSTRACT: The purpose of the present study was to determine the relationship between fiber intake, constipation, and clinical venous disease in the general population. The Edinburgh Vein Study was comprised of 1566 men and women aged 18-64 years who were selected at random from the age-sex registers of 12 general practices. Fiber intake, intestinal transit time, defecation frequency and the prevalence of straining at stool were all found to be significantly different between the sexes. Men who reported that they strained to start passing a motion showed a higher prevalence of mild and severe trunk varices compared to men who did not strain. After adjustment for social class, BMI and mobility at work, this group of men showed a significantly elevated risk of having severe trunk varices (OR 2.76, 95% CI 1.16, 6.58). In contrast, no consistent relationships were seen among women. Overall, within this Western general population, an association between dietary fiber, constipation and the presence or severity of varicose veins was not supported.
Journal of Clinical Epidemiology 05/2001; 54(4):423-9. · 4.27 Impact Factor
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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. · 10.48 Impact Factor
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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.
Atherosclerosis 06/2000; 150(1):179-85. · 3.79 Impact Factor
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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. · 1.24 Impact Factor
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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. · 4.94 Impact Factor
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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. · 8.09 Impact Factor
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ABSTRACT: The efficiency of individualisation using nonisotopic chemiluminescent- enhanced probes (NICE) was investigated by analysing DNA fingerprints obtained from 190 unrelated Caucasians. Novel analysis of the scoring procedure enabled us to include the comparison of 585 pairs of samples for each of two probes. When the results of NICE probes 33.6 and 33.15 were combined, the mean percentage band share between two unrelated individuals was 16.8% and the mean number of bands identified in an individual DNA fingerprint was 54.8. Results were compared with those obtained using isotopically labelled probes and suggest that the two labelling systems gave similar efficiencies for differentiating between individuals. Analysis of DNA fingerprints from 37 family trios (mother, child and father groups) gave a mutation rate of 0.10% when using NICE probes. The two labelling systems compared were equally efficient in establishing family relationships.
Electrophoresis 11/1997; 18(11):1916-22. · 3.30 Impact Factor
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ABSTRACT: The relationship of small-bowel dysmotility to dietary intake in irritable bowel syndrome (IBS) is obscure.
This study evaluated postprandial jejunal motility in IBS patients classified as constipation-predominant (n = 25) or diarrhoea-predominant (n = 35) and compared results against 18 volunteers. Twenty-four-hour ambulatory jejunal manometry was carried out in all subjects, and recordings were analysed by microcomputer and visual assessment.
By means of analysis of variance (fitting factors for channels, meals, and time periods) postprandial contraction frequency was greater in both patient groups compared with normal (constipation-predominant versus normal, diarrhoea-predominant versus normal; P < 0.001). In the constipation-predominant cohort, contraction amplitudes were lower (constipation-predominant versus normal; P < 0.002). Discrete cluster contractions occurred with similar frequency and duration in both patient and volunteer groups.
Quantitative differences of postprandial jejunal contraction characteristics have been shown between patients with IBS and healthy volunteers. Contraction frequency is greater than normal in both diarrhoea- and constipation-predominant categories, whereas contraction amplitudes are lower in constipation-predominant patients.
Scandinavian Journal of Gastroenterology 02/1997; 32(1):39-47. · 2.02 Impact Factor
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ABSTRACT: The initial cause of the bovine spongiform encephalopathy (BSE) epidemic is generally accepted to have been the feeding of infected animal protein to cattle. The proportion of animals affected in any year in a particular herd has generally been low. This suggests either considerable variation in the extent of challenge of the individual animals or variation in their susceptibility to challenge or both. There is known to be genetic variation in susceptibility in other spongiform encephalopathies, such as scrapie in sheep. However, earlier indications that there may be associations between the incidence of BSE in cattle and polymorphisms and mutations in the PrP gene have not been confirmed (Hunter et al. 1994). Here, we attempt to model the likely extent of challenge of the individual animals in five Holstein Friesian pedigree herds and also the distribution of incubation times to the date of clinical onset. By studying the incidence of the disease in related animals we first found that single locus genetic models fitted the data much better than a non-genetic model. This was the first statistical evidence found of genetic variation in susceptibility to BSE. A check on the model in which individual animals were randomly allocated to 'parents' showed that the result was due to the lack of allowance in the non-genetic model for those animals insufficiently challenged or, for non-genetic reasons, resistant to their level of challenge. Thus there is still no evidence, molecular or statistical, for genetic variation in susceptibility. The importance of checking the attribution of genetic effects in complex models by the random allocation of progeny to parents is clear.
Philosophical Transactions of The Royal Society B Biological Sciences 08/1996; 351(1342):913-20. · 6.40 Impact Factor
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ABSTRACT: Case control study techniques were used to compare the incidence of bovine spongiform encephalopathy (BSE) in the progeny of two affected sires and 110 affected dams with the incidence of BSE in the progeny of animals known to be unaffected at the last record. All the progeny were born before the ban on ruminant-derived protein in feedstuffs issued in July 1988. The results provide little, if any, evidence of differences between the incidence in the progeny of the affected animals and the incidence in the progeny of the presumed unaffected animals. Data from five herds were used in a logistic regression analysis to study the effects of the disease status of the dam and the age of the dam at the birth of the calf on the incidence of BSE. The disease status of the dam did not significantly affect the disease status of its progeny, after allowance had been made for the effects of herd, year and the age at last record of the progeny. The difficulty of establishing maternal transmission if a high proportion of the dams are incubating the disease and transmission can occur early in the incubation period is discussed.
The Veterinary record 05/1996; 138(17):407-8. · 1.25 Impact Factor
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ABSTRACT: Choroid plexus (CP) cysts are commonly detected on routine mid-trimester ultrasound scan. When associated anomalies are detected, the risk is sufficient to justify an invasive diagnostic test such as amniocentesis. However, the risk when no associated anomalies are detected is much less well defined. This information is required to determine the appropriate management in cases of apparently isolated CP cysts. We thought the only way to resolve the difficulties in counselling prospective parents was to conduct a prospective study in a large unselected population. A registry of fetal CP cysts detected over 3 years in the Yorkshire Region was compiled and we identified 524 CP cysts. These cases were then amalgamated and analysed with 1361 cases from prospective studies reported in the world English literature and a further 71 unpublished cases identified from a 2 year prospective series from Ninewells Hospital, Dundee. The risk of chromosomal abnormalities was 1 in 150 (95% CI 1 in 85, 1 in 261) when no fetal anatomic abnormalities, apart from the CP cysts themselves, were detected antenatally. The risk increased to approximately 1 in 3 if any other associated ultrasound abnormalities were detected antenatally. The risk did not appear to be related to whether or not cyst size diminished as gestation progresses, whether they were unilateral or bilateral, and whether they were small or large in size (60-80% < 10 mm). 76% of aneuploidic cases were trisomy 18 and 17% were trisomy 21. The risk of Down's syndrome in fetuses with CP cysts but no other anomalies detected antenatally is 1 in 880. The probability of a chromosomal abnormality is high when CP cysts are associated with any other antenatally detected anomaly, indicating a clear need to offering amniocentesis. The predictive value is much lower when no other anomalies are detected. In such cases, it is probably advisable to regard CP cysts as an indication for detailed ultrasound assessment, rather than invasive testing.
The Lancet 09/1995; 346(8977):724-9. · 38.28 Impact Factor
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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 less than or equal to 0.01; 116 IU/dl versus 104 IU/dl, P less than or equal to 0.05; respectively). After adjusting for age and sex, fibrinogen (P less than or equal to 0.01) and vWF (P less than or equal to 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 less than or equal to 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.
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ABSTRACT: Aims
To evaluate the relationship between haemostatic and rheological factors and cardiovascular outcome in subjects with angina pectoris in the general population.
Methods and Results
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 less than or equal to 0.001, and 40.3 ng . ml(-1) vs 31.0 ng . ml(-1); P less than or equal to 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 less than or equal to 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 less than or equal to 0.01) for tissue plasminogen activator antigen and 1.95 (95% CI, 1.12-3.50; P less than or equal to 0.05) for leucocyte elastase.
Conclusion
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.
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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.
