Anticoagulation with warfarin downregulates inflammation.
Explore the source record for details and available documents.
Administration, Oral↗
Biomedical subjects
G D Lowe
Publications and source records attributed to G D Lowe.
Length of docked tail and the incidence of rectal prolapse in lambs.
A multistate cooperative study was conducted to study the current issue of tail length in docked lambs and its relationship to incidence of rectal prolapse. A total of 1,227 lambs at six locations were randomly allocated to two or three tail dock treatments: 1) short--tail was removed as close to the body as possible, 2) medium--tail was removed at a location midway between the attachment of the tail to the body and the attachment of the caudal folds to the tail, and 3) long--tail was removed at the attachment of the caudal folds to the tail. Short-docked lambs had a greater (P < 0.05) incidence of rectal prolapse (7.8%) than lambs with a medium (4.0%) or a long (1.8%) dock. Female lambs had a higher (P < 0.05) incidence of rectal prolapse than male lambs. At two stations, lambs were finished either in a feedlot on a high-concentrate diet or on pasture with no grain supplementation. At one station, with a very low incidence of rectal prolapse, there was no difference in incidence between lambs finished in the feedlot or on pasture; however, at the station with a relatively high incidence of rectal prolapse, lambs in the feedlot had a higher (P < 0.05) incidence than lambs on pasture. The half-sib estimate of heritability for the incidence of rectal prolapse was low (0.14). The results of this study strongly implicate short dock length as a cause of rectal prolapse in lambs finished on high-concentrate diets. Furthermore, the results of this study and the only other study known conducted on this issue strongly suggest that docking lambs at the site of the attachment of the caudal folds to the tail will result in a negligible incidence of rectal prolapse.
Animal Husbandry↗
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↗
Statin therapy and the acute inflammatory response after coronary artery bypass grafting.
Explore the source record for details and available documents.
Aged↗
Fibrin D-dimer and coronary heart disease: prospective study and meta-analysis.
BACKGROUND: It is unknown whether modest increases of fibrin D-dimer, a circulating marker of fibrin turnover, are relevant to coronary heart disease (CHD) in the general population. METHODS AND RESULTS: We measured serum concentrations of D-dimer antigen in the stored baseline blood samples of 630 CHD cases and 1269 controls "nested" in a prospective cohort of 5661 men who were monitored for 16 years, and we conducted a meta-analysis of previous relevant studies to place our findings in context. In a comparison of men in the top third compared with those in the bottom third of baseline fibrin D-dimer values (tertile cutoffs, >94 versus <49 ng/mL), the odds ratio for CHD was 1.67 (95% CI, 1.31 to 2.13; P<0.0001) after adjustments for age and town. The odds ratio increased slightly after further adjustment for smoking, other classic risk factors, and indicators of socioeconomic status (1.79; 95% CI, 1.36 to 2.36). Strong correlations were observed of fibrin D-dimer values with circulating concentrations of C-reactive protein and serum amyloid A protein but not with smoking, blood lipids, blood pressure, and other risk factors. CONCLUSION: Although there may be an association between circulating D-dimer values and CHD, further studies are needed to determine the extent to which this is causal.
Adult↗
Lipoprotein (a) and development of intermittent claudication and major cardiovascular events in men and women: the Edinburgh Artery Study.
Lipoprotein (a) may be an important risk factor for atherosclerosis. It is widely accepted that lipoprotein (a) levels are raised in patients with coronary heart disease, but there is some doubt about the causality of the relationship. In addition, little is known about the relationship between lipoprotein (a) and either stroke or peripheral arterial disease, nor about the role of lipoprotein (a) in women. Subjects aged 55-74 years (n=1592) were selected at random from 11 general practices in Edinburgh, Scotland and followed up for 5 years. The incidences of myocardial infarction, intermittent claudication and stroke were 13.4, 9.4 and 3.7%, respectively. Raised lipoprotein (a) levels at baseline were associated with an increased risk (95% confidence interval) of myocardial infarction RR 1.15 (1.00, 1.32), intermittent claudication RR 1.32 (1.10, 1.57) but not significantly for stroke RR 1.24 (0.93, 1.64). This increased risk persisted for intermittent claudication after adjustment for baseline cardiovascular disease and other risk factors RR 1.20 (1.00, 1.43), but for myocardial infarction became non-significant RR 1.06 (0.91, 1.23). The risk of disease associated with raised lipoprotein (a) was slightly higher in women than in men, especially for intermittent claudication (men RR 1.09 (0.87, 1.36) compared to women RR 1.37 (1.01, 1.87)). In conclusion, we found that lipoprotein (a) was an independent predictor of cardiovascular events in both sexes. The association between lipoprotein (a) and cardiovascular events may have been stronger in women than in men, and for peripheral arterial disease than myocardial infarction and stroke.
Aged↗
Combined prednisolone and intravenous immunoglobulin treatment for acquired factor VIII inhibitors: a 2-year review.
Acquired inhibitors to factor VIII (FVIII) are rare, but life-threatening in up to 22% of cases. The optimal therapy for suppression of these inhibitors remains unclear. Prednisolone is the mainstay of therapy, producing responses in approximately 30% of cases. Intravenous immunoglobulin (IVIg) has a similar response rate, but a more rapid effect. We report the results of prednisolone 1 mg kg(-1) combined with IVIg 2 g kg(-1) in divided doses as first-line therapy in seven consecutive patients with acquired FVIII inhibitors. All patients were bleeding at the time of diagnosis with prolonged activated partial thromboplastin time. There were four complete responses, one partial response, one nonresponse and one with an inadequate follow-up for assessment of response, giving an overall response rate of 71%. In all complete responders the inhibitor declined rapidly and was undetectable by day 21 from start of treatment. Therapy was well tolerated and responses have been maintained off treatment for 2-8 months. This is a safe, well-tolerated rapidly acting regimen with good response rates.
Aged↗
Skin microvascular vasodilatory capacity in offspring of two parents with Type 2 diabetes.
AIMS: Microvascular dysfunction occurs in Type 2 diabetes and in subjects with fasting hyperglycaemia. It is unclear whether this dysfunction relates to dysglycaemia. This study investigated in normogylcaemic individuals whether a genetic predisposition to diabetes, or indices of insulin resistance including endothelial markers, were associated with impaired microvascular function. METHODS: Maximum microvascular hyperaemia to local heating of the skin was measured using laser Doppler flowmetry in 21 normoglycaemic subjects with no family history of diabetes (Group 1) and 21 normoglycaemic age, sex and body mass index-matched offspring of two parents with Type 2 diabetes (Group 2). RESULTS: Although Group 2 had normal fasting plasma glucose and glucose tolerance tests, the 120-min glucose values were significantly higher at 6.4 (5.3-6.6) mmol/l (median (25th - 75th centile)) than the control group at 4.9 (4.6-5.9) mmol/l (P = 0.005) and the insulinogenic index was lower at 97.1 (60.9-130.8) vs. 124.0 (97.2-177.7) (P = 0.027). Skin maximum microvascular hyperaemia (Group 1: 1.56 (1.39-1.80) vs. Group 2: 1.53 (1.30-1.98) V, P = 0.99) and minimum microvascular resistance which normalizes the hyperaemia data for blood pressure (Group 1: 52.0 (43.2-67.4) vs. Group 2: 56.0 (43.7-69.6) mmHg/V, P = 0.70) did not differ in the two groups. Significant positive associations occurred between minimum microvascular resistance and indices of the insulin resistance syndrome; plasminogen activator inhibitor type 1 (R(s) = 0.46, P = 0.003), t-PA (R(s) = 0.36, P = 0.03), total cholesterol (R(s) = 0.35, P = 0.02), and triglyceride concentration (R(s) = 0.35, P = 0.02), and an inverse association with insulin sensitivity (R(s) = -0.33, P = 0.03). CONCLUSIONS: In normoglycaemic adults cutaneous microvascular vasodilatory capacity is associated with features of insulin resistance syndrome, particularly with plasminogen activator inhibitor type 1. A strong family history of Type 2 diabetes alone does not result in impairment in the maximum hyperaemic response. Diabet. Med. 18, 541-545 (2001)
Adult↗
The role of myocardial perfusion scanning, heart rate variability and D-dimers in predicting the risk of perioperative cardiac complications after peripheral vascular surgery.
OBJECTIVES: To study the value of a number of proposed prognostic factors in prediction of the risk of perioperative cardiac events after vascular surgery. DESIGN AND METHODS: Two hundred and ninety-seven patients undergoing peripheral vascular surgery were prospectively studied. Patients underwent preoperative 24 h ambulatory electrocardiography, measurement of haemostatic variables, myocardial assessment of perfusion by dipyridamole-thallium scintigraphy and radionuclide ventriculography. The primary endpoint was cardiac death or nonfatal myocardial infarction within 30 days of surgery. A combined endpoint included the primary endpoint plus occurrence of cardiac failure, unstable angina or serious arrhythmias. RESULTS: The primary endpoint occurred in 21 (7%), and the combined endpoint in 41 (14%) of patients. On multivariate analysis, increased age, previous myocardial infarction, aortic surgery, impaired heart rate variability and a positive thallium scan were independent predictors of primary end-points. Preoperative atrial fibrillation and increased fibrin D-dimer were additional predictors of the combined endpoint. Construction of receiver-operator characteristic curves to examine the incremental value of predictive models showed that sensitivity and specificity of clinical data alone for primary endpoints was 71% and 72% respectively, while for the full model (incorporating heart rate variability and thallium data) this rose to 84% and 80% (p=0.0001). CONCLUSIONS: Preliminary screening using clinical data has limited value in risk assessment prior to vascular surgery but preoperative heart rate variability, D-dimers and thallium scanning provide modest incremental predictive value.
Aged↗
Is sticky blood a treatable determinant of cognitive decline and of dementia?
Explore the source record for details and available documents.
Aged↗
The prevalence of prophylaxis for deep vein thrombosis in acute hospital trusts.
OBJECTIVE: The effectiveness of activities to promote routine prophylaxis to prevent thromboembolism is difficult to assess because information about the prevalence of prophylaxis is sparse. The aim of this study was to assess the prevalence of deep vein thrombosis (DVT) prophylaxis for patients at risk in general medicine, general surgery, orthopaedics and gynaecology in Scotland and the North of England. DESIGN: Retrospective case note review of a random sample of episodes of care in a stratified random sample of directorates in Scotland and a convenience sample in England. SETTING: Twenty acute hospital directorates in Scotland and eight in the North of England. PARTICIPANTS: Case notes of patients at risk of thrombosis and discharged from the selected directorates in a 12-month period (n = 742). MAIN OUTCOME MEASURES: The proportion of patients receiving prophylaxis in each directorate. RESULTS: Overall, 469/526 (89%) of patients in Scotland and 199/216 (92%) in England received prophylaxis. The proportion varied from 71% in general medicine to 100% in orthopaedics. The frequency of use of different forms of prophylaxis varied between directorates. Approximately 60% of the patients who received prophylaxis received more than one form. CONCLUSIONS: Prophylaxis for DVT is well established for procedures and conditions that are known to increase the risk of thrombosis and for which there are no contraindications. Additional efforts to promote prophylaxis for these conditions are unlikely to be cost effective. Further research is needed to establish whether rates are equally high in other conditions, and whether the high prophylaxis rates are due to clinical effectiveness initiatives.
Anticoagulants↗
Cardiovascular risk factors, including thrombotic variables, in a population with rheumatoid arthritis.
OBJECTIVE: To compare prevalent cardiovascular disease, conventional cardiovascular risk factors and thrombotic variables in a cohort with well-controlled rheumatoid arthritis (RA) and in population controls. METHODS: Seventy-six RA patients and 641 controls, randomly sampled from the local population in the North Glasgow MONICA study. Conventional cardiovascular risk factors (blood pressure, smoking, cholesterol) and thrombotic variables [fibrinogen, von Willebrand factor (vWF), tissue plasminogen activator antigen (t-PA), fibrin D-dimer, plasminogen activator inhibitor (PAI-1), plasma viscosity] were measured by standard procedures. RESULTS: RA patients had a significantly higher prevalence of angina pectoris (P=0.03). Stroke also tended to be more common in the RA group, but the difference did not reach statistical significance (P=0.08). Diastolic blood pressure was significantly higher and serum cholesterol significantly lower in the RA group than in controls. Current smoking habits and exercise history were similar in the two groups, although RA patients were more likely to have previously smoked. Significant elevations in several thrombotic predictors of cardiovascular disease (fibrinogen, vWF, t-PA antigen and fibrin D-dimer) were found in the RA group. CONCLUSIONS: In this RA patient population, diastolic blood pressure was higher than in controls and thrombotic variables were elevated compared with controls. These features are identified as potential additional cardiovascular risk factors in the RA patients studied. Prospective studies of risk modification may permit the identification of factors which could lead to a reduction in the known increased cardiovascular risk in RA.
Adult↗
Haemostasis in ischaemic stroke and vascular dementia.
Abnormalities of coagulation and fibrinolysis may play an important role in the pathogenesis of ischaemic stroke and vascular dementia. We aimed to determine whether haemostatic function is altered in acute recent-onset or chronic ischaemic cerebrovascular disease. We studied consecutive patients with ischaemic stroke (n = 74) and vascular dementia (n = 42) compared with healthy controls (n = 40) in a case-control study. The ischaemic stroke group was assessed twice, 3-10 days after the acute stroke and at 1-3 months. Fibrinogen, fibrin D-dimer (marker of fibrin turnover) and von Willebrand factor (vWF) (marker of endothelial disturbance) were elevated acutely (P < 0.0001) and in the convalescent phase after ischaemic stroke (P < 0.0001, P < 0.0001, and P < 0.01 respectively, compared with controls). Similar results were seen in the vascular dementia group. Stepwise multivariate regression analyses showed that cerebrovascular disease correlated independently with fibrinogen (P < 0.001) and fibrin D-dimer levels (P < 0.001), while vWF correlated independently with electrocardiograph evidence of ischaemic heart disease (P = 0.004). Changes between acute and convalescent phases in ischaemic stroke were slightly inconsistent. However, in the acute stage there were tendencies for fibrinogen, D-dimer and vWF to be increased, and factor VIII was significantly higher. Abnormalities of haemostasis, including increased fibrin turnover and endothelial disturbance, are found in both acute and chronic cerebral ischaemia. Many of these patients have co-existent ischaemic heart disease and this may contribute to some of these changes. Acute ischaemic stroke is associated with transient changes in haemostatic factors; however, most abnormalities persist into the convalescent phase, and are also demonstrable in subjects with vascular dementia.
Acute-Phase Reaction↗
Lifestyle factors and coagulation activation markers: the Caerphilly Study.
Coagulation activation markers are being investigated as risk factors for cardiovascular disease; we examined the contribution of several lifestyle factors to variation in plasma levels of several activation markers measured in a population-based study of 1947 men. Smoking, alcohol, body mass index (BMI), leisure and work activity, social class, and use of prescribed medicines were each examined in turn. Specific assays of fibrin D-dimer and von Willebrand factor (vWF) activity showed similar relationships to lifestyle variables as we observed previously for less specific assays of D-dimer and vWF antigen. D-dimer levels increased with age, in smokers and in men taking prescribed medication, and were negatively associated with leisure time activity. vWF activity increased with age and showed a U-shaped distribution with BMI. Factors VIIc and VIIIc and thrombin-antithrombin complexes were associated with BMI, factor VIIIc and prothrombin fragments 1 + 2 (F1 + 2) were associated with age, activated partial thromboplastin time (aPTT) and F1 + 2 were associated with smoking, and aPTT showed a small negative association with alcohol consumption. We conclude that lifestyle modification has the possibility of favourably influencing several of these risk markers. In particular, cigarette smoking has a possibly reversible effect on coagulation activation (measured by F1 + 2 and D-dimer).
Aged↗
Fibrinogen and its degradation products as thrombotic risk factors.
Recent meta-analyses of prospective studies have shown that plasma levels of both fibrinogen and fibrin D-dimer are independent predictors of ischemic heart disease. Although at present reported studies using different assays do not show heterogeneity, there is a need for prospective comparison of different assays, as well as for development of standards. Collaborative development of the clinical use of these risk predictors is also required. Finally, the causal significance of the associations of fibrinogen and D-dimer with thrombotic events remains to be established by randomized controlled trials of reduction in their plasma levels.
Fibrin Fibrinogen Degradation Products↗
Who should take aspirin for primary prophylaxis of coronary heart disease?
Explore the source record for details and available documents.
Aspirin↗
C-reactive protein, fibrin D-dimer, and incident ischemic heart disease in the Speedwell study: are inflammation and fibrin turnover linked in pathogenesis?
Plasma levels of C-reactive protein (CRP, a marker of the reactant plasma protein component of the inflammatory response) and of fibrin D-dimer (a marker of cross-linked fibrin turnover) have each been associated in recent studies with the risk of future ischemic heart disease (IHD). Previous experimental studies have shown that fibrin degradation products, including D-dimer, have effects on inflammatory processes and acute-phase protein responses. In the Speedwell Prospective Study, we therefore measured CRP and D-dimer levels in stored plasma samples from 1690 men aged 49 to 67 years who were followed-up for incident IHD for an average of 75+/-4 months (mean+/-SD) and studied their associations with each other, with baseline and incident IHD, and with IHD risk factors. CRP and D-dimer levels were each associated with age, plasma fibrinogen, smoking habit, and baseline evidence of IHD. CRP was associated with D-dimer (r=0.21, P<0.00001). On univariate analyses, both CRP and D-dimer were associated with incident IHD. The incidence of IHD increased with CRP independently of the level of D-dimer (P=0.0002) and also increased with D-dimer independently of the level of CRP (P=0.048). In multivariate analyses, inclusion of D-dimer and conventional risk factors reduced the strength of the association between CRP and incident IHD; likewise, inclusion of CRP and conventional risk factors reduced the strength of the association between D-dimer and incident IHD. We conclude that although these respective markers of inflammation and fibrin turnover show modest association with each other in middle-aged men, they may have additive associations with risk of incident IHD. Further larger studies are required to test this hypothesis.
Acute-Phase Proteins↗