| 1. |
- Boman, Kurt, et al.
(författare)
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Effects of atenolol or losartan on fibrinolysis and von Willebrand factor in hypertensive patients with left ventricular hypertrophy.
- 2010
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Ingår i: Clinical and applied thrombosis/hemostasis. - : SAGE Publications. - 1076-0296 .- 1938-2723. ; 16:2, s. 146-152
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To compare the effects of the beta-blocker atenolol with the angiotensin receptor blocker (ARB) losartan on plasma tissue-type plasminogen activator (tPA) activity and mass concentration, plasminogen activator inhibitor-1 (PAI-1) activity, tPA/PAI-1 complex, and von Willebrand factor (VWF). DESIGN: A prespecified, explorative substudy in 22 patients with hypertension and left ventricular hypertrophy (LVH) performed within randomized multicenter, double-blind prospective study. RESULTS: After a median of 36 weeks of treatment, there were significant differences between the treatment groups, atenolol versus losartan, in plasma median levels of tPA mass (11.9 vs 7.3 ng/mL, P = .019), PAI-1 activity (20.7 vs 4.8 IU/mL, P = .030), and tPA/PAI-1 complex (7.1 vs 2.5 ng/mL, P = .015). In patients treated with atenolol, median levels of tPA mass (8.9-11.9 ng/mL, P = .021) and VWF (113.5%-134.3%, P = .021) increased significantly, indicating a change toward a more prothrombotic state. No significant changes occurred in the losartan group. CONCLUSION: Losartan treatment was associated with preserved fibrinolytic balance compared to a more prothrombotic fibrinolytic and hemostatic state in the atenolol group. These findings suggest different fibrinolytic and hemostatic responses to treatment in hypertensive patients with LVH.
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| 2. |
- Rautio, Aslak, et al.
(författare)
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The effect of basal insulin glargine on the fibrinolytic system and von Willebrand factor in people with dysglycaemia and high risk for cardiovascular events : Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial
- 2017
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Ingår i: Diabetes & Vascular Disease Research. - : Sage Publications. - 1479-1641 .- 1752-8984. ; 14:4, s. 345-352
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Fibrinolytic factors, plasminogen activator inhibitor-1, tissue plasminogen activator, tissue plasminogen activator/plasminogen activator-complex and the haemostatic factor von Willebrand factor are known markers of cardiovascular disease. Their plasma levels are adversely affected in patients with dysglycaemia, and glucose normalization with insulin glargine might improve the levels of these factors. Methods: Prespecified Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial (ClinicalTrials.gov number, NCT00069784). Tissue plasminogen activator activity, tissue plasminogen activator antigen, plasminogen activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor were analysed at study start, after 2 years and at the end of the study (median follow-up of 6.2 years). Results: Of 129 patients (mean age of 64 ± 7 years, females: 19%), 68 (53%) and 61 (47%) were randomized to the insulin glargine and standard care group, respectively. Allocation to insulin glargine did not significantly affect the studied fibrinolytic markers or von Willebrand factor compared to standard care. Likewise, there were no significant differences in plasminogen activator inhibitor-1, tissue plasminogen activator antigen and von Willebrand factor. During the whole study period, the within-group analysis revealed a curvilinear pattern and significant changes for tissue plasminogen activator/plasminogen activator inhibitor-1 complex, tissue plasminogen activator antigen and von Willebrand factor in the insulin glargine but not in the standard care group. Conclusion: In people with dysglycaemia and other cardiovascular risk factors, basal insulin does not improve the levels of markers of fibrinolysis or von Willebrand factor compared to standard glucose-lowering treatments.
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| 3. |
- Hernestål Boman, Jenny, 1980-
(författare)
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Fibrinolytic factors in relation to anthropometry and incident type 2 diabetes.
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Fibrinolytic imbalance is associated with cardiovascular disease and its risk factors. The longitudinal changes in the fibrinolytic factors tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and tPA/PAI-1 complex have been inadequately studied in the general population and in relation to incident type 2 diabetes mellitus (T2DM). The measurements, questionnaires and blood samples prospectively collected in the World Health Organisation-project MONItoring trends and determinants in CArdiovascular disease (MONICA) and in the Västerbotten Intervention Programme (VIP) enable such studies. The samples have been stored since 1985, at the Northern Sweden Medical Research Biobank. However, it is unknown how these factors are affected by long-term storage.The aims of this thesis were to evaluate the effects of long-term storage on fibrinolytic factors, and to determine how these factors are related to incident T2DM, how these factors change over time and how these factors are related to changes in anthropometric measurements.Storage time was shown to have a negligible impact on plasma antigen levels of fibrinolytic factors. After adjustments for traditional diabetic and cardiovascular risk markers the fibrinolytic factors tPA, PAI-1 and tPA/PAI-1 complex were associated with incident T2DM. PAI-1 was associated with incident T2DM in subjects with normal fasting and 2-hour plasma glucose levels. In MONICA-Västerbotten, tPA, PAI-1 and tPA/PAI-1 complex increased over 9 years in both men and women. PAI-1 appears to interact in a complex manner with anthropometric, inflammatory, glycaemic and lipidemic measurements, but the pattern of components correlating with the changes in PAI-1 differed markedly between the sexes.In conclusion, PAI-1 is a potential risk marker of incident T2DM. PAI-1 increased markedly over nine years, but the pathophysiological background to these findings needs to be further investigated, separately for each sex.
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| 4. |
- Hernestål-Boman, Jenny, 1980-, et al.
(författare)
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Individual changes in fibrinolytic factors, von Willebrand factor, and C-reactive protein over a nine-year period.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Intra-individual changes in haemostatic factor concentrations over time are unknown, in the general population.Objective: To describe intra-individual longitudinal changes in tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), tPA/PAI-1 complex, von Willebrand factor (VWF), and C-reactive protein (CRP) over nine years, in different age groups, stratified for sex.Methods: The MONICA survey in 1990 examined randomly selected men and women in four age groups (25–64 years) who were re-examined in 1999. A total of 309 individuals donated venous blood samples in Stabilyte tubes for both surveys during the morning hours, after an overnight fast. We analysed tPA activity and antigens of tPA, PAI-1, tPA/PAI-1 complex, VWF, and CRP.Results: Over nine years, in both men and women, we found significant intra-individual increases in the antigen levels of tPA, PAI-1, tPA/PAI-1 complex, VWF, and CRP (P < 0.001). PAI-1 antigen levels increased by 75% for men and 95% for women. Compared to men, women had a significantly higher CRP increase (0.92 vs. 0.22 mg/L; P = 0.044). The P for trend for mean Δ1999–1990 across age groups showed a significant linear trend for VWF (P = 0.001 for men; P < 0.001 for women), but not for the other studied variables.Conclusions: There were intra-individual longitudinal increases in the antigen levels of tPA, PAI-1, tPA/PAI-1 complex, VWF, and CRP over nine years in both men and women, with PAI-1 showing the highest relative increase. VWF increased significantly across age groups; however, fibrinolytic variables did not.
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| 5. |
- Hernestål-Boman, Jenny, 1980-, et al.
(författare)
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Individual PAI-1 increase over nine years relates differently in men and women to changes in anthropometric, glycaemic, inflammatory and lipid markers.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Levels of plasminogen activator inhibitor-1 (PAI-1) is known to correlate to factors related to the metabolic syndrome. We have previously shown that PAI-1 antigen increased by 75% in men and 95% in women over nine years.Objective: The aim of this study was to explore relationships between intra-individual changes in PAI-1 and changes in anthropometric measurements, blood pressure, glycaemic, lipid and inflammatory markers, separately for men and women.Method: In northern Sweden, 125 men and 116 women were examined first in 1990 and re-examined in 1999 during the morning hours. Changes over time (Δ) were calculated as the value at 1999 minus the value at 1990.Results: In men, ΔPAI-1 was significantly correlated to ΔBMI (r =0.33), ΔCRP (r =0.25), Δtriglycerides (r =0.39), Δfasting plasma glucose (r =0.41) and Δ2-hour plasma glucose (r =0.29). In women, ΔPAI-1 was significantly correlated to ΔBMI (r =0.36), Δwaist circumference (r =0.38), Δhip circumference (r =0.27), ΔCRP (r =0.27) and Δtotal cholesterol (r =0.19). The multivariate linear regression analysis showed that ΔPAI-1 was significantly related to Δfasting plasma glucose and ΔCRP in men (R2 for the complete model was 0.31). In women, ΔPAI-1 was significantly related to Δwaist circumference (R2 for the complete model was 0.17).Conclusion: We expected that changes in anthropometric, glycaemic, inflammatory and lipid markers would explain a large part of the observed PAI-1 increase. However, the multivariate analysis explained only 20% of the variation in ΔPAI-1 in women and 30% in men. Interestingly, the patterns of components correlating with the changes in PAI-1 differed between sexes.
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| 6. |
- Hernestål-Boman, Jenny, et al.
(författare)
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Long-term stability of fibrinolytic factors stored at-80 degrees C
- 2010
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 125:5, s. 451-456
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Blood samples in epidemiological studies are often stored for several years and analysed at different occasions. The reagent kits are continually modified for better precision and accuracy. Our hypothesis was that epidemiological studies are affected by long-term storage and/or modifications of reagent kits. Materials and Methods: Plasma samples stored at -80 degrees C from two populations were used: A case-referent study with samples collected from 1985 to 2000 and analysed 2005 (n=1598) were used to study influence of long-term storage. A cross-sectional study analysed 1990 (n=1558) and re-analysed 2001 (n=78) and 2005 (n=828) was used to study influence of reagent kit modifications. Fibrinolytic analyses included immunoassays of tPA, PAI-1 and tPA-PAI-1 complex and chromogenic substrate assays of the activities of tPA and PAI-1. Results: Long-term storage for a median time of 11.6 years (range 5 to 20) showed an effect of time on tPA antigen R-2=0.01, PAI-1 antigen R-2=0.01 and tPA-PAI-1 complex R-2=0.02. Modifications in reagent kits affected the levels of fibrinolytic factors; for tPA antigen the slope coefficients were between 0.72 and 0.95 (R-2 0.47-0.75), whereas tPA activity showed an agreement with slope coefficients 1.06 to 1.09 (R-2 0.67-0.93). Conclusions: This study showed that long-term storage affects fibrinolytic variables to a negligible extent, but modifications in reagent kits introduced an element of bias. We conclude that analysis of samples on a single occasion is preferable to multiple occasions, as storage has negligible effect. (C) 2009 Elsevier Ltd. All rights reserved.
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| 7. |
- Hernestål-Boman, Jenny, et al.
(författare)
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Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study
- 2012
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Ingår i: Cardiovascular Diabetology. - : BioMed Central. - 1475-2840. ; 11, s. 152-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diabetic patients experience stimulated coagulation and dysfibrinolysis, which is associated with an increased risk of cardiovascular events. This imbalance may precede the manifest diagnosis. We investigated whether elevated antigen levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), the tPA/PAI-1 complex, or von Willebrand Factor (VWF) precede type 2 diabetes mellitus (T2DM) diagnosis, and whether this elevation occurs before increased fasting plasma glucose (FPG) or 2-hour plasma glucose (2hPG) in individuals who later develop T2DM.Methods: We conducted a prospective incident case-referent study within the Vasterbotten Intervention Programme. Cardiovascular risk factor data as well as FPG and 2hPG and blood samples for future research were collected at a baseline health examination between 1989 and 2000, (n= 28 736). During follow-up in January 2001, 157 cases had developed T2DM. Referents without T2DM were matched for sex, age, and year of participation (n=277). Subgroup analysis was performed for cases with normal baseline glucose levels (FPG <6.1 mmol/L and 2hPG < 8.9 mmol/L) and cases with elevated levels (FPG 6.1-6.9 mmol/L and/or 2hPG 8.9-12.1 mmol/L).Results: After adjusting for BMI, family history of diabetes, physical activity, smoking, systolic blood pressure and levels of C-reactive protein and triglycerides, independent associations were found between incident T2DM and elevated levels of tPA (OR=1.54, 95% CI 1.06-2.23), PAI-1 (OR=1.61, 95% CI 1.14-2.28), and tPA/PAI-1 complex (OR=2.45, 95% CI 1.56-3.84). In participants with normal glucose levels, PAI-1 (OR=2.06, 95% CI 1.10 - 3.86) exhibited an independent relationship with incident T2DM after the adjustments.Conclusions: Elevated levels of fibrinolytic variables precede the manifestation of T2DM after adjusting for metabolic and cardiovascular risk factors and can be detected several years before changes in glucose tolerance.
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| 8. |
- Wennberg, Patrik, et al.
(författare)
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Acute effects of breaking up prolonged sitting on fatigue and cognition : a pilot study
- 2016
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare the acute effects of uninterrupted sitting with sitting interrupted by brief bouts of light-intensity walking on self-reported fatigue, cognition, neuroendocrine biomarkers and cardiometabolic risk markers in overweight/obese adults.Design: Randomised two-condition crossover trial.Setting: Laboratory study conducted in Melbourne, Australia.Participants: 19 overweight/obese adults (45–75 years).Interventions: After an initial 2 h period seated, participants consumed a meal-replacement beverage and completed (on 2 days separated by a 6-day washout period) each condition over the next 5 h: uninterrupted sitting (sedentary condition) or sitting with 3 min bouts of light-intensity walking every 30 min (active condition).Primary outcome measures: Self-reported fatigue, executive function and episodic memory at 0 h, 4 h and 7 h.Secondary outcome measures: Neuroendocrine biomarkers and cardiometabolic risk markers (blood collections at 0 h, 4 h and 7 h, blood pressure and heart rate measured hourly and interstitial glucose measured using a continuous glucose monitoring system).Results: During the active condition, fatigue levels were lower at 4 h (−13.32 (95% CI −23.48 to −3.16)) and at 7 h (−10.73 (95% CI −20.89 to −0.58)) compared to the sedentary condition. Heart rate was higher at 4 h (4.47 (95% CI 8.37 to 0.58)) and at 7 h (4.32 (95% CI 8.21 to 0.42)) during the active condition compared to the sedentary condition. There were no significant differences between conditions by time for other variables. In the sedentary condition, changes in fatigue scores over time correlated with a decrease in heart rate and plasma dihydroxyphenylalanine (DOPA) and an increase in plasma dihydroxyphenylglycol (DHPG).Conclusions: Interrupting prolonged sitting with light-intensity walking breaks may be an effective fatigue countermeasure acutely. Fatigue levels corresponded with the heart rate and neuroendocrine biomarker changes in uninterrupted sitting in this pilot study. Further research is needed to identify potential implications, particularly for the occupational health context.
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