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Biomedical subjects

A Rumley

Publications and source records attributed to A Rumley.

At least 19 recordsLinked to original sources
PubMed2006

Effects of older age on fibrin D-dimer, C-reactive protein, and other hemostatic and inflammatory variables in men aged 60-79 years.

BACKGROUND: Previous studies have suggested that several hemostatic and inflammatory variables, which are risk predictors for arterial or venous thrombosis, increase with age. However, there is a lack of data from large population studies for reliable estimates of reference ranges. OBJECTIVES: To establish reliable reference ranges of hemostatic and inflammatory variables for 5-year age groups in older men and their implications for pathogenesis and diagnosis. PATIENTS AND METHODS: A total of 3861 men aged 60-79 years at the 20 years follow-up of the British Regional Heart Study. RESULTS: Several variables increased with age. The greatest median increases between 60-64 and 75-79 years age groups were observed for fibrin D-dimer (91%) and C-reactive protein (CRP) (57%). Significant median increases were also observed for von Willebrand factor antigen (23%), tissue plasminogen activator antigen (11%), factor VIII (10%), and fibrinogen (8%). In contrast, levels of classical cardiovascular risk factors neither decreased nor increased substantially with age, with the exception of systolic blood pressure (median increase 10%). CONCLUSIONS: The exponential increases in risk of arterial and venous thrombotic events in men between age 60 and 79 years (when most such events occur) may be related in part to increasing activation of blood coagulation, fibrinolysis, and inflammation; possibly related to the increasing inflammatory burden of both atherosclerotic and non-vascular disease. These increases also have implications for diagnosis of suspected acute venous thromboembolism (D-dimer), and recently proposed screening for prediction of coronary heart disease risk and detection of occult disease (CRP).

Aged↗
PubMed2005

Are atrial fibrillation guidelines altering management? A community based study.

BACKGROUND AND AIMS: We wanted to determine the prevalence of atrial fibrillation (AF) in a community based cross sectional study in greater Glasgow and how current anti-thrombotic management compares to published guidelines. METHODS: 1466 patients with AF were identified in General Practices in our community and 1008 consented to take part. Their demographic details and medical history were recorded. RESULTS: 1466 patients (mean age 73.4; 55% female) with AF were identified, in our community, giving a prevalence of 1%. 53% of patients were on warfarin therapy. Of those not receiving warfarin, only one third had a putative contra-indication. The proportion ofAF patients on warfarin increased with increasing stroke risk, and over the period of the study. CONCLUSIONS: Prevalence of AF was in keeping with previous estimates. The proportion of patients with AF receiving warfarin therapy appears to be increasing. In the moderate risk group, there was a tendency to use more warfarin in the younger age groups compared to the elderly. It was in the moderate and low risk groups that there was still evidence of deviation from published guidelines.

Aged↗
PubMed2004

Insulin resistance, haemostatic and inflammatory markers and coronary heart disease risk factors in Type 2 diabetic men with and without coronary heart disease.

AIMS/HYPOTHESIS: We have examined markers of haemostasis and inflammation in men with diabetes, coronary heart disease (CHD) or both, and assessed their associations with insulin resistance in men with Type 2 diabetes. METHODS: The study was carried out in 4066 British men aged 60 to 79 years who were not on warfarin or insulin, of whom there were 426 men with prevalent Type 2 diabetes and 842 with prevalent CHD. RESULTS: Men with Type 2 diabetes were more likely to have multiple risk factors and higher levels of haemostatic and inflammatory markers than men without, irrespective of CHD status. Compared with men with CHD only, men with diabetes only showed increased levels of tissue plasminogen activator antigen, increased plasma and blood viscosity, and increased levels of coagulation factors VII, VIII and IX. They also had dyslipidaemia. In men with diabetes, increased insulin resistance (homeostasis model assessment, HOMA) was associated with increased levels of haemostatic markers and dyslipidaemia. The prevalence of CHD increased significantly with increasing tertiles of HOMA (adjusted odds ratio 1.32 [95% CI: 0.72-2.42] in the second, and 1.70 [95% CI: 0.92-3.44] in the third tertile; p=0.04 for trend). CONCLUSIONS/INTERPRETATION: Increased insulin resistance among men with Type 2 diabetes is associated with increased prevalence of CHD and of activated haemostasis and dyslipidaemia. Reducing insulin resistance in men with diabetes may reduce their tendency to develop thrombosis and hence CHD risk.

Adult↗
PubMed2004

C-reactive protein, fibrin D-dimer, and risk of ischemic heart disease: the Caerphilly and Speedwell studies.

BACKGROUND: There is increasing interest in the predictive value of C-reactive protein (CRP) and fibrin D-dimer in the prediction of ischemic heart disease (IHD). We assessed their joint and independent associations with IHD in a large combined analysis of 2 population cohorts. METHODS AND RESULTS: Men aged 49 to 66 years from the general populations of Caerphilly and Speedwell were studied between 1982 and 1988 and re-examined for new IHD events at fixed intervals of approximately 105 months (Caerphilly) and 75 months (Speedwell). 3213 men had CRP and D-dimer measured at baseline and 351 (11%) had a new IHD event. Mean levels of CRP and D-dimer were significantly higher among men in whom IHD developed. The relative odds of IHD in men in the top 20% of the distribution of CRP was 2.97 (95% CI, 2.04, 4.32) and for D-dimer was 2.40 (95% CI, 1.69, 3.40); CRP and D-dimer had additive effects on risk of IHD. Multivariate analysis reduced the size of the relative odds, which remained significant for D-dimer. CONCLUSIONS: Both inflammatory and thrombogenic markers are important (and potentially additive) predictors of coronary risk.

Aged↗
PubMed2004

Tissue plasminogen activator antigen and coronary heart disease. Prospective study and meta-analysis.

AIMS: To determine whether circulating tissue plasminogen activator (t-PA) antigen concentrations are prospectively related to risk of coronary heart disease (CHD) in the general population. METHODS AND RESULTS: We measured baseline concentrations of t-PA antigen in the stored serum samples of 606 CHD cases and 1227 controls 'nested' in a prospective cohort of 5661 men monitored for 16 years, and conducted a meta-analysis of previous relevant studies to place our findings in context. Tissue plasminogen activator antigen values were strongly correlated with several vascular risk factors, including serum lipids, body mass index, alcohol consumption, and markers of systemic inflammation. In a comparison of men in the top third compared with those in the bottom third of baseline t-PA antigen values, the odds ratio for CHD was 2.20 (95% confidence interval (CI) 1.70-2.85) after adjustment for age and town only, but this fell to 1.48 (1.09-2.01) after further adjustment. Analysis of t-PA as a continuous variable gave similar results. Similarly, when published information on all seven available prospective cohort studies in general populations (2119 cases and 8832 controls in total) was synthesized, the combined odds ratio was 2.18 (1.77-2.69) after adjustment for age and sex only, and this fell to 1.47 (1.19-1.81) after further adjustment. CONCLUSION: Although there is a statistically significant association between circulating concentrations of t-PA antigen and subsequent CHD, additional studies are needed to determine to what extent this is independent from more established risk factors.

Adult↗
PubMed2004

Plasma lipid peroxides: relationships to cardiovascular risk factors and prevalent cardiovascular disease.

BACKGROUND: The epidemiology of plasma lipid peroxides, which may play a role in atherogenesis, has not been well defined. AIM: To study the relationships of plasma lipid peroxides to cardiovascular risk factors in a random population sample. DESIGN: Random, age- and sex-stratified population sample. METHODS: We studied 739 men and women aged 25-74 years. Lipid peroxides were assayed by the thiobarbituric acid (TBA) assay for malondialdehyde (MDA) in stored plasma samples. RESULTS: Lipid peroxide levels increased with age. In men, lipid peroxides were significantly associated with smoking habit. Lipid peroxides correlated with non-fasting serum triglycerides (r = 0.33; p < 0.0001) in both sexes. Weaker associations were observed for cholesterol, high-density lipoprotein cholesterol (inversely), body mass index, fibrinogen and white cell count; as well as an inverse association with serum vitamin C in men. DISCUSSION: These findings clarify the relationships of plasma lipid peroxides to cardiovascular risk factors; and are consistent with the hypothesis that lipid peroxidation may be one mechanism through which several risk factors may promote cardiovascular disease.

Adult↗
PubMed2004

Dementia in subjects with atrial fibrillation: hemostatic function and the role of anticoagulation.

BACKGROUND: Atrial fibrillation (AF) is associated with cognitive impairment and dementia, perhaps through encouraging a prothrombotic state and cardioembolism. OBJECTIVES: We wished to test the hypotheses that hemostatic function is altered in subjects with AF who develop dementia, and that long-term warfarin anticoagulation is protective against this complication. PATIENTS AND METHODS: Recruitment was from an observational cohort study of AF. Baseline assessment included measurement of plasma fibrinogen, fibrin D-dimer, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complexes (TAT), von Willebrand factor and tissue plasminogen activator. We assessed cognitive function after 3 years' follow-up using the 13-item modified Telephone Interview for Cognitive Status (TICSm) and the short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS: Of the 218 subjects assessed, 145 (66%) were prescribed warfarin. Forty-nine (22%) met TICSm/IQCODE criteria for dementia. D-dimer, F1+2 and TAT levels were higher in AF subjects with dementia compared with those without (medians 81 vs. 60 ng mL(-1), P = 0.008; 0.76 vs. 0.49 nmol L(-1), P = 0.006; and 1.78 vs. 1.44 microg L(-1), P = 0.003, respectively). These associations became of borderline statistical significance following adjustment for age. Logistic regression showed a trend towards warfarin use being independently associated with reduced prevalence of dementia (odds ratio 0.52, P = 0.08). CONCLUSIONS: We found evidence of increased thrombin generation and fibrin turnover in subjects with AF and dementia compared with those without dementia. Long-term warfarin use may be protective against the development of dementia in subjects with AF.

Aged↗
PubMed2004

A randomized comparison of the effects of aspirin and clopidogrel on thrombotic risk factors and C-reactive protein following myocardial infarction: the CADET trial.

A randomized, double-blind multicenter trial-the Clopidogrel and Aspirin: Determination of the Effects on Thrombogenicity (CADET) trial-was carried out to compare the effects of clopidogrel vs. aspirin on thrombotic variables and C-reactive protein (CRP), over a 6-month period of treatment, in patients with an acute myocardial infarction within the previous 3-7 days, who were not scheduled for major surgery including coronary artery bypass grafting. Patients (n = 184) were randomly allocated to aspirin (75 mg day(-1)) or clopidogrel (75 mg day(-1)). Blood samples were taken at baseline and then at clinic visits at 1, 3 and 6 months. By 1 month, clottable and immunonephelometric fibrinogen, D-dimer, von Willebrand factor, factor VIII and CRP were significantly (P < 0.05) reduced from baseline values in both treatment groups; as well as tissue plasminogen activator antigen in the aspirin group only. At 6 months, there were no differences between treatment groups (P > 0.05) for any of the variables, whether or not potential confounding variables were adjusted for. Similarly, there were no differences between treatments in the difference between baseline and final values for any of the variables. Aspirin and clopidogrel were thus found to have similar effects on thrombotic variables and CRP in this patient population.

Aged↗
PubMed2003

Human CRP gene polymorphism influences CRP levels: implications for the prediction and pathogenesis of coronary heart disease.

OBJECTIVE: C-reactive protein (CRP) concentrations are predictive of cardiovascular disease, and levels are heritable, in part. We identified novel polymorphisms in the CRP gene and assessed their influence on CRP level. METHODS AND RESULTS: CRP was measured in 250 male army recruits before and after strenuous exercise and perioperatively in 193 coronary artery bypass graft (CABG) patients. Two novel polymorphisms were identified in the CRP gene, -717G>A in the promoter and +1444C>T in the 3'UTR. Among army recruits, CRP was higher in +1444TT homozygotes than +1444 C-allele carriers at baseline (1.04+/-0.38 versus 0.55+/-0.06, P=0.014) and at all time points after exercise (2.35+/-0.68 versus 1.07+/-0.12, 2.11+/-0.53 versus 0.88+/-0.09, and 1.77+/-0.44 versus 0.71+/-0.09, P=0.034, P=0.007, and P=0.013, at 2, 48, and 96 hours after exercise, respectively). In the CABG patients, mean CRP (mg/L) rose from 1.97+/-0.36 at baseline to 167.2+/-5.0 72 hours postoperatively. Genotype did not influence CRP at baseline; however, peak post-CABG CRP levels were higher in +1444TT homozygotes compared with +1444C-allele carriers (198+/-17 versus 164+/-5, P=0.03). CONCLUSIONS: The CRP gene +1444C>T variant influences basal and stimulated CRP level. These findings have implications both for the prediction and pathogenesis of coronary heart disease.

Acute-Phase Reaction↗
PubMed2003

Associations of plasma fibrinogen assays, C-reactive protein and interleukin-6 with previous myocardial infarction.

BACKGROUND: The association of plasma fibrinogen with myocardial infarction (MI) may (like that of C-reactive protein, CRP) be a marker of subclinical inflammation, mediated by cytokines such as interleukin-6 (IL-6). There are well-recognized discrepancies between commonly performed fibrinogen assays. Increased ratio of clottable fibrinogen to intact fibrinogen (measured by a recently developed immunoassay) has been proposed as a measure of hyperfunctional fibrinogen, and is elevated in acute MI. OBJECTIVE: To compare the associations of intact fibrinogen and four routine fibrinogen assays (two von Clauss assays; one prothrombin-time derived; and one immunonephelometric) in a case-control study of previous MI. PATIENTS/METHODS: Cases (n=399) were recruited 3-9 months after their event; 413 controls were age- and sex- matched from the case-control study local population. Intact fibrinogen was measured in 50% of subjects. RESULTS: All routine fibrinogen assays showed high intercorrelations (r=0.82-0.93) and significant (P<0.0001) increased mean levels in cases vs. controls. These four routine assays correlated only moderately with intact fibrinogen (r=0.45-0.62), while intact fibrinogen showed only a small, nonsignificant increase in cases vs. controls. Consequently, the ratio of each of the four routine assays to the intact fibrinogen assay was significantly higher (P<0.0003) in cases vs. controls. Each fibrinogen assay correlated with plasma levels of CRP and IL-6 (which were also elevated in cases vs. controls). Each routine fibrinogen assay remained significantly elevated in cases vs. controls after further adjustment for C-reactive protein and interleukin-6. CONCLUSIONS: These data provide evidence for acquired, increased hyperfunctional plasma fibrinogen in MI survivors, which is not associated with markers of inflammatory reactions. The causes and significance of these results remain to be established in prospective studies.

Biomarkers↗
PubMed2002

Adrenocortical, autonomic, and inflammatory causes of the metabolic syndrome: nested case-control study.

BACKGROUND: The causes of metabolic syndrome (MS), which may be a precursor of coronary disease, are uncertain. We hypothesize that disturbances in neuroendocrine and cardiac autonomic activity (CAA) contribute to development of MS. We examine reversibility and the power of psychosocial and behavioral factors to explain the neuroendocrine adaptations that accompany MS. METHODS AND RESULTS: This was a double-blind case-control study of working men aged 45 to 63 years drawn from the Whitehall II cohort. MS cases (n=30) were compared with healthy controls (n=153). Cortisol secretion, sensitivity, and 24-hour cortisol metabolite and catecholamine output were measured over 2 days. CAA was obtained from power spectral analysis of heart rate variability (HRV) recordings. Twenty-four-hour cortisol metabolite and normetanephrine (3-methoxynorepinephrine) outputs were higher among cases than controls (+ 0.49, +0.45 SD, respectively). HRV and total power were lower among cases (both -0.72 SD). Serum interleukin-6, plasma C-reactive protein, and viscosity were higher among cases (+0.89, +0.51, and +0.72 SD). Lower HRV was associated with higher normetanephrine output (r=-0.19; P=0.03). Among former cases (MS 5 years previously, n=23), cortisol output, heart rate, and interleukin-6 were at the level of controls. Psychosocial factors accounted for 37% of the link between MS and normetanephrine output, and 7% to 19% for CAA. Health-related behaviors accounted for 5% to 18% of neuroendocrine differences. CONCLUSIONS: Neuroendocrine stress axes are activated in MS. There is relative cardiac sympathetic predominance. The neuroendocrine changes may be reversible. This case-control study provides the first evidence that chronic stress may be a cause of MS. Confirmatory prospective studies are required.

Adrenal Cortex↗
PubMed2002

Effects of moderate weight loss on anginal symptoms and indices of coagulation and fibrinolysis in overweight patients with angina pectoris.

OBJECTIVE: To evaluate the effects of moderate weight loss, in overweight patients with angina, on plasma coagulation, fibrinolytic indicies and pain frequency. DESIGN: Single-stranded 12-week dietary intervention, an individualised eating plan with quantitative advice delivered by a dietitian. Target weight loss of 0.5 kg per week. SETTING: Outpatient research clinic. SUBJECTS: Fifty-four volunteers with angina pectoris were recruited. Five subjects withdrew, so 27 males, 22 females, mean body mass index (BMI) 29.3 (s.d. 4.3) kg/m(2) and age 60.3 (s.d. 6.5) y completed the intervention. MEASUREMENTS: Body weight and frequency of anginal pain. Plasma fibrinogen, red cell aggregation (RCA), viscosity, factor VII activity, plasminogen activator inhibitor (PAI) activity, tissue plasminogen activator antigen (t-PA), plasma cholesterol, triglyceride and insulin. RESULTS: After the 12-week dietary intervention period, mean body weight fell by 3.5 (s.d. 2.6) kg or 4.3% (P=0.0001), range -11.7 to +1.7 kg. Mean angina frequency fell by 1.8 (s.d. 3.6) from 3.2 to 1.4 episodes/week (P=0.009) and plasma cholesterol by 0.4 (s.d. 0.7) from 6.3 to 5.9 mmol/l (P=0.0001). HDL cholesterol and triglyceride were unchanged. Of the coagulation and fibrinolytic factors, factor VII activity and RCA were significantly reduced by 5 (s.d. 20), IU/dl (P=0.04) and 1.3 (s.d. 1.3) arbitrary units (P=0.014), respectively. CONCLUSIONS: A conventional dietetic intervention, resulting in 4% weight loss, offers the potential to reduce atherosclerotic and thrombotic risk, and to reduce pain frequency, in angina patients. Given the importance of this result in a public health context, these results indicate that this may be a fruitful area for future nutrition research.

Angina Pectoris↗
PubMed2002

Hormonal replacement therapy, prothrombotic mutations and the risk of venous thrombosis.

Hormone replacement therapy (HRT) increases the risk of venous thrombosis. We investigated whether this risk is affected by carriership of hereditary prothrombotic abnormalities. Therefore, we determined the two most common prothrombotic mutations, factor V Leiden and prothrombin 20210A in women who participated in a case-control study on venous thrombosis. Relative risks were expressed as odds ratios (OR) with 95% confidence intervals (CI95). Among 77 women aged 45-64 years with a first venous thrombosis, 51% were receiving HRT at the time of thrombosis, compared with 24% of control women (OR = 3.3, CI95 1.8-5.8). Among the patients, 23% had a prothrombotic defect, versus 7% among the control women (OR = 3.8, CI95 1.7-8.5). Women who had factor V Leiden and used HRT had a 15-fold increased risk (OR = 15.5, CI95 3.1-77), which exceeded the expected joint odds ratio of 6.1 (under an additive model). We conclude that the thrombotic risk of HRT may particularly affect women with prothrombotic mutations. Efforts to avoid HRT in women with increased risk of thrombosis are advisable.

Case-Control Studies↗
PubMed2002

von Willebrand factor and coronary heart disease: prospective study and meta-analysis.

AIMS: To determine whether circulating von Willebrand factor concentrations are prospectively related to risk of coronary heart disease in the general population. METHODS AND RESULTS: We measured baseline von Willebrand factor values in the stored serum samples of 625 men with major coronary events and in 1266 controls 'nested' in a prospective study of 5661 men aged 40-59 years, recruited from general practices in 18 British towns in 1978-1980 and followed up for 16 years for fatal coronary heart disease and non-fatal myocardial infarction. We conducted a meta-analysis of previous relevant studies to place our results in context. Men in the top third of baseline von Willebrand factor values (tertile cutoff >126 IU.dl(-1)) had an odds ratio for coronary heart disease of 1.83 (95% confidence interval 1.43-2.35; 2P <0.0001) compared with those in the bottom third (tertile cutoff <90 IU.dl(-1)), after adjustments for age and town. The odds ratio was little changed after further adjustment for risk factors (1.82, 95% CI 1.37-2.41), and was not significantly different in an analysis restricted to the 404 cases and 1007 controls without baseline evidence of coronary heart disease (odds ratio 1.53, 95% CI 1.10-2.12). A meta-analysis of all relevant population-based prospective studies (including the present study) yielded a combined odds ratio of 1.5 (95% CI 1.1-2.0). von Willebrand factor values were strongly correlated with Helicobacter pylori seropositivity and circulating concentrations of C-reactive protein (2 P<0.0001 for each), but not with smoking, blood lipids, or most other measured risk factors. CONCLUSION: Though circulating von Willebrand factor concentrations may be associated with incident coronary heart disease, further studies are needed to determine the extent to which this is causal.

Adult↗
PubMed2002

Impact of angiotensin converting enzyme inhibition on post-coronary artery bypass interleukin 6 release.

BACKGROUND: Angiotensin 1 converting enzyme (ACE) inhibitors reduce morbidity and mortality after coronary artery bypass graft surgery (CABG). This benefit may result from an anti-inflammatory action. OBJECTIVE: To examine the effect of ACE inhibition on interleukin 6 (IL-6) concentrations after CABG. PATIENTS AND METHODS: 161 patients undergoing elective first time CABG were recruited, of whom 41 (25%) were receiving ACE inhibitor treatment; 21 patients with confounding postoperative complications were excluded. After these exclusions there were 33 patients (24%) on ACE inhibitor treatment. Plasma IL-6 was measured preoperatively and again six hours after CABG. RESULTS: Baseline IL-6 concentrations (geometric mean (SEM)) were non-significantly lower among the patients receiving ACE inhibitors (3.7 (0.1) v 4.3 (0.1) pg/ml, p = 0.12). Overall, post-CABG IL-6 concentrations increased significantly (mean rise 177 (12) pg/ml, p < 0.0005). This response was blunted among ACE inhibitor treated patients. Median increases in IL-6 concentrations were 117 v 193 pg/ml, for treated v non-treated patients, respectively (Kruskal-Wallis, p = 0.02), with peak postoperative IL-6 concentrations lower among the subjects receiving ACE inhibitors than in untreated subjects (142 (19) v 196 (13) pg/ml, p = 0.02). The effect of ACE inhibitors remained significant after multivariate analysis (p = 0.018). CONCLUSIONS: ACE inhibitor treatment is associated with a reduction in IL-6 response to CABG. The data suggest that this class of drug may have a direct anti-inflammatory effect, which could explain some of its clinical benefit.

Acute-Phase Reaction↗