Bleeding complications during warfarin treatment in primary healthcare centres compared with anticoagulation clinics

Objectives. To examine determinants of bleeding complications during warfarin treatment in an unselected patient population and evaluate possible differences in safety between specialized anticoagulation clinics and primary healthcare centres. Design. Prospective cohort study. Data were collected with an admission form and medical records were scrutinized in order to pursue all adverse events. Differences between groups were estimated with a t-test and chi-squared test, and univariate and multivariate Cox regression analysis. Setting. All patients treated and monitored with oral anticoagulation in primary healthcare centres and specialized anticoagulation clinics in the Sundsvall and Skellefteå region (northern Sweden) during a five-year period. Subjects. A total of 2731 patients corresponding to 5044 treatment years. Main outcome measures. Bleedings were classified as fatal or major. Major bleedings were defined as an event causing admission, prolonged in-hospital care or death. Results. In total 195 major bleedings occurred corresponding to 3.9% per treatment year, including 34 fatal events (0.67% per treatment year). Patients monitored at the two specialized anticoagulation clinics combined had a major bleeding frequency of 4.1% as compared with 3.9% at primary healthcare units. The frequency of fatal haemorrhage was 0.57% and 0.76%, respectively. The rate of major and fatal bleeding was age related with an increase of 4% and 5%, respectively, per year. Conclusions. There was no difference in bleeding complications between patients monitored at primary healthcare centres and specialized anticoagulation clinics. Age was continuously and independently associated with bleeding risk. These study data indicate the need to exercise caution in treatment of the elderly.     

Comparison of soluble thrombomodulin, von Willebrand factor, tPA/PAI-1 complex, and high-sensitivity CRP concentrations in serum, EDTA plasma, citrated plasma, and acidified citrated plasma (Stabilyte) stored at -70 degrees C for 8-11 years

The aim was to define the most suitable specimen collection tubes for measurements of soluble Thrombomodulin (sTM), von Willebrand factor (vWF), and tPA/PAI-1 complex concentrations, and in particular whether the strongly acidic citrate additive in Stabilyte plasma would give significantly improved long-term stability of any of these analytes. We measured these analytes in paired specimens from 34 subjects, sampled 8-11 years before analysis, in serum, EDTA plasma, citrated plasma, and acidified citrated plasma (Stabilyte). Results were evaluated by regression analysis and Bland-Altman plots. All associations were linear across a wide assay range. Soluble TM was found to be highly unstable in serum as well as in EDTA plasma and to some extent even in ordinary citrate plasma: acidified citrate plasma is necessary to preserve sTM immunoreactivity in long-term storage. For hsCRP the slopes were not significantly different from that predicted by the dilution effect (0.83-0.86) of the citrate additive and there was no appreciable intercept. vWF values were comparable in citrate and acidified citrate plasma but serum and EDTA plasma samples yielded lower than expected results. For tPA/PAI-1 complex, Stabilyte tubes gave systematically lower results than the other tubes, with serum and EDTA plasma scoring the highest values, suggesting that in vitro increase in complex levels takes places upon blood collection and/or storage. We conclude that Stabilyte plasma is the specimen collection tube of choice for biobank projects aiming to measure fibrinolytic factors as well as several other analytes in the clotting system, such as soluble thrombomodulin and von Willebrand factor, in addition to the inflammatory marker hs-CRP. Indeed, using acidified Stabilyte plasma as the single medium would substantially simplify sampling for many epidemiological studies.     

Quantitative measurement of carotid atherosclerosis in relation to levels of von Willebrand factor and fibrinolytic variables in plasma--a 2-year follow-up study

BACKGROUND: It has been proposed that the mechanism of action of the new risk factors for myocardial infarction and stroke, von Willebrand factor (vWF), tissue plasminogen activator (tPA) and tissue plasminogen activator inhibitor-1 (PAI-1) could possibly be mediated via a primary effect on atherogenesis but there is little data to substantiate this. DESIGN: A prospective single-centre cohort study of progression of atherosclerosis. METHODS: Carotid plaque area was quantitated by two-dimensional (2D) ultrasound in 258 subjects at entry and after 1 and 2 years. Plasma and serum samples were drawn at baseline and serum lipids and plasma levels of haemostatic factors were measured. RESULTS: The traditional risk factors, smoking, total cholesterol, hypertension and male gender explained 51% of the variance in plaque area at baseline and 48% at 1-year follow-up. There were small positive associations of plaque area with vWF, tPA and tPA/PAI-1 complex and a tendency to negative associations with PAI-1 levels, independent from the traditional risk factors. The additional explanatory power of the haemostatic factors did not exceed 3%. CONCLUSION: The data accord with a marginal role in atherogenesis of vWF and tPA, and underline the major impact of smoking, hypertension and cholesterol on carotid plaque area progression.     

Fish intake, mercury, long-chain n-3 polyunsaturated fatty acids and risk of stroke in northern Sweden

Results of previous studies on fish intake and stroke risk have been inconclusive. Different stroke types have often not been separated. Our aim was to elucidate whether intake of fish, Hg or the sum of proportions of fatty acids EPA (20 : 5n-3) and DHA (22 : 6n-3) influence the risk of haemorrhagic or ischaemic stroke. Within a population-based cohort from a community intervention programme, 369 stroke cases and 738 matched controls were identified and included in the present nested case-control study. Information on fish intake had been recorded at recruitment, i.e. before diagnosis. Hg levels were determined in erythrocyte membranes, also collected at recruitment, and the relative content of fatty acids was measured in erythrocyte membranes or plasma phospholipids. The results showed that in women there was a non-significant decrease in stroke risk with increasing fish intake (OR 0.90 (95 % CI 0.73, 1.11) per meal per week). The risk in women differed significantly (P = 0.03) from that in men, in whom the OR for stroke rose with increasing fish intake (OR 1.24 (95 % CI 1.01, 1.51) per meal per week). The corresponding risk in men for Hg was 0.99 (95 % CI 0.93, 1.06), and for the sum of proportions of EPA and DHA 1.08 (95 % CI 0.92, 1.28). We conclude that the relationship between stroke risk and fish intake seems to be different in men and women. Increased levels of EPA and DHA do not decrease the risk for stroke and there is no association between stroke risk and Hg at these low levels.     

Haemostatic and inflammatory markers are independently associated with myocardial infarction in men and women

Introduction

Previous studies have shown that plasma levels of haemostatic and inflammatory markers are associated with risk of coronary heart disease (CHD). As haemostatic markers are also acute-phase reactants, it is not clear if their association with CHD is independent of inflammatory markers and established cardiovascular risk factors.

Materials and Methods

We used a prospective incident case-control study design nested in two cohorts from Sweden. Baseline measurements of a panel of cardiovascular risk factors and eight established markers of haemostasis or inflammation were assessed in 469 first-ever myocardial infarction (MI) cases and 895 matched controls.

Results

After adjustment for baseline values of established risk factors, von Willebrand factor appeared to have the strongest association with MI among the haemostatic markers assayed, with an odds ratio of 2.52 (95% CI, 1.72-3.67) for a comparison of individuals in extreme thirds of baseline levels. For a similar comparison, after adjustment for established risk factors and haemostatic markers, odds ratios for IL-6 and CRP were 1.67 (95% CI, 1.08-2.60) and 1.58 (95% CI, 1.03-2.41), respectively. The relative predictive ability of the individual markers over and above established risk factors was modest according to comparisons of Area under the Receiver Operating Characteristic (AUROC) curves. However, when all eight markers were combined in a single model, the AUROC curve was significantly increased to 0.820 (95% CI, 0.795-0.846) compared to 0.762 (95% CI, 0.732-0.791) for established risk factors only.

Conclusions

These findings suggest that haemostasis and inflammation have at least partially separate roles in risk of myocardial infarction.     

Prevalence of systemic immunoreactivity to <Emphasis Type="Italic">Aggregatibacter actinomycetemcomitans</Emphasis> leukotoxin in relation to the incidence of myocardial infarction

Background  

Chronic infections and associated inflammatory markers are suggested risk factors for cardiovascular disease (CVD). The proinflammatory cytokine, interleukin (IL)-1β, is suggested to play a role in the regulation of local inflammatory responses in both CVD and periodontitis. The leukotoxin from the periodontal pathogen Aggregatibacter actinomycetemcomitans has recently been shown to cause abundant secretion of IL-1β from macrophages. The aim of the present study was to compare the prevalence of systemic immunoreactivity to A. actinomycetemcomitans leukotoxin in myocardial infarction (MI) cases (n = 532) and matched controls (n = 1,000) in a population-based case and referents study in northern Sweden.     

Bleeding complications during warfarin treatment in primary healthcare centres compared with anticoagulation clinics

Objectives

To examine determinants of bleeding complications during warfarin treatment in an unselected patient population and evaluate possible differences in safety between specialized anticoagulation clinics and primary healthcare centres.

Design

Prospective cohort study. Data were collected with an admission form and medical records were scrutinized in order to pursue all adverse events. Differences between groups were estimated with a t-test and chi-squared test, and univariate and multivariate Cox regression analysis.

Setting

All patients treated and monitored with oral anticoagulation in primary healthcare centres and specialized anticoagulation clinics in the Sundsvall and Skellefteå region (northern Sweden) during a five-year period.

Subjects

A total of 2731 patients corresponding to 5044 treatment years.

Main outcome measures

Bleedings were classified as fatal or major. Major bleedings were defined as an event causing admission, prolonged in-hospital care or death.

Results

In total 195 major bleedings occurred corresponding to 3.9% per treatment year, including 34 fatal events (0.67% per treatment year). Patients monitored at the two specialized anticoagulation clinics combined had a major bleeding frequency of 4.1% as compared with 3.9% at primary healthcare units. The frequency of fatal haemorrhage was 0.57% and 0.76%, respectively. The rate of major and fatal bleeding was age related with an increase of 4% and 5%, respectively, per year.

Conclusions

There was no difference in bleeding complications between patients monitored at primary healthcare centres and specialized anticoagulation clinics. Age was continuously and independently associated with bleeding risk. These study data indicate the need to exercise caution in treatment of the elderly.     

The effects of commuting activity and occupational and leisure time physical activity on risk of myocardial infarction.

BACKGROUND: Risk reduction of myocardial infarction has been shown for leisure time physical activity. The results of studies on occupational physical activity and risk of myocardial infarction are incongruous and studies on commuting activity are scarce. The aim of this study was to investigate how commuting activity, occupational physical activity and leisure time physical activity were associated with risk of future first myocardial infarction. DESIGN: We used a prospective incident case-referent study design nested in V?sterbotten Intervention Program and the Northern Sweden MONICA study. METHODS: Commuting habits, occupational physical activity, leisure time physical activity and cardiovascular risk factors were assessed at baseline screening and compared in 583 cases (20% women) with a first myocardial infarction and 2098 matched referents. RESULTS: Regular car commuting was associated with increased risk of myocardial infarction versus commuting by bus, cycling or walking [odds ratio (OR) 1.74; 95% confidence interval (CI), 1.20-2.52] after multivariate adjustment. High versus low leisure time physical activity was associated with reduced risk of myocardial infarction (OR 0.69; 95% CI, 0.50-0.95) after adjustment for occupational physical activity and commuting activity, but the association was not statistically significant after further multivariate adjustment. After multivariate adjustment we observed a reduced risk for myocardial infarction in men with moderate (OR 0.70; 95% CI, 0.50-0.98) or high (OR 0.67; 95% CI, 0.42-1.08) versus low occupational physical activity. CONCLUSIONS: We found a clear association between car commuting and a first myocardial infarction and a corresponding inverse association with leisure time physical activity, while the impact of occupational physical activity on the risk of myocardial infarction was weaker.