| 1. |
- 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 .- 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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| 2. |
- Carrasquilla, Germán D, et al.
(författare)
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Postmenopausal hormone therapy and risk of stroke : A pooled analysis of data from population-based cohort studies.
- 2017
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 14:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent research indicates a favourable influence of postmenopausal hormone therapy (HT) if initiated early, but not late, on subclinical atherosclerosis. However, the clinical relevance of timing of HT initiation for hard end points such as stroke remains to be determined. Further, no previous research has considered the timing of initiation of HT in relation to haemorrhagic stroke risk. The importance of the route of administration, type, active ingredient, and duration of HT for stroke risk is also unclear. We aimed to assess the association between HT and risk of stroke, considering the timing of initiation, route of administration, type, active ingredient, and duration of HT.METHODS AND FINDINGS: Data on HT use reported by the participants in 5 population-based Swedish cohort studies, with baseline investigations performed during the period 1987-2002, were combined in this observational study. In total, 88,914 postmenopausal women who reported data on HT use and had no previous cardiovascular disease diagnosis were included. Incident events of stroke (ischaemic, haemorrhagic, or unspecified) and haemorrhagic stroke were identified from national population registers. Laplace regression was employed to assess crude and multivariable-adjusted associations between HT and stroke risk by estimating percentile differences (PDs) with 95% confidence intervals (CIs). The fifth and first PDs were calculated for stroke and haemorrhagic stroke, respectively. Crude models were adjusted for age at baseline only. The final adjusted models included age at baseline, level of education, smoking status, body mass index, level of physical activity, and age at menopause onset. Additional variables evaluated for potential confounding were type of menopause, parity, use of oral contraceptives, alcohol consumption, hypertension, dyslipidaemia, diabetes, family history of cardiovascular disease, and cohort. During a median follow-up of 14.3 years, 6,371 first-time stroke events were recorded; of these, 1,080 were haemorrhagic. Following multivariable adjustment, early initiation (<5 years since menopause onset) of HT was associated with a longer stroke-free period than never use (fifth PD, 1.00 years; 95% CI 0.42 to 1.57), but there was no significant extension to the time period free of haemorrhagic stroke (first PD, 1.52 years; 95% CI -0.32 to 3.37). When considering timing as a continuous variable, the stroke-free and the haemorrhagic stroke-free periods were maximal if HT was initiated approximately 0-5 years from the onset of menopause. If single conjugated equine oestrogen HT was used, late initiation of HT was associated with a shorter stroke-free (fifth PD, -4.41 years; 95% CI -7.14 to -1.68) and haemorrhagic stroke-free (first PD, -9.51 years; 95% CI -12.77 to -6.24) period than never use. Combined HT when initiated late was significantly associated with a shorter haemorrhagic stroke-free period (first PD, -1.97 years; 95% CI -3.81 to -0.13), but not with a shorter stroke-free period (fifth PD, -1.21 years; 95% CI -3.11 to 0.68) than never use. Given the observational nature of this study, the possibility of uncontrolled confounding cannot be excluded. Further, immortal time bias, also related to the observational design, cannot be ruled out.CONCLUSIONS: When initiated early in relation to menopause onset, HT was not associated with increased risk of incident stroke, regardless of the route of administration, type of HT, active ingredient, and duration. Generally, these findings held also for haemorrhagic stroke. Our results suggest that the initiation of HT 0-5 years after menopause onset, as compared to never use, is associated with a decreased risk of stroke and haemorrhagic stroke. Late initiation was associated with elevated risks of stroke and haemorrhagic stroke when conjugated equine oestrogen was used as single therapy. Late initiation of combined HT was associated with haemorrhagic stroke risk.
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| 3. |
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| 4. |
- Eliasson, Mats, et al.
(författare)
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The disparity between long-term survival in patients with and without diabetes following a first myocardial infarction did not change between 1989 and 2006 : an analysis of 6,776 patients in the Northern Sweden MONICA Study
- 2011
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Ingår i: Diabetologia. - : SpringerLink. - 0012-186X .- 1432-0428. ; 54:10, s. 2538-2543
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Long-term survival after myocardial infarction(MI) has improved in the population, but data ondiabetic patients is lacking. We analysed survival for up to18 years after a first MI in patients with or without diabetesMethods: The Northern Sweden MONICA MyocardialInfarction Registry was linked to the Cause-of-DeathRegistry for a total of 6,776 patients, 25–64 years of age,with a first MI during 1989–2006. Prehospital deaths wereincluded. Follow-up ended on 30 August 2008.Results: Sixteen per cent had diabetes. Median follow-uptime was 6.8 years, and the study included 50,667 patientyears.One third of the non-diabetic patients died vs half ofthe diabetic patients. Median survival for non-diabetic menwas 227 months and for diabetic men 123 months.Corresponding figures for the non-diabetic and diabeticwomen were 222 and 81 months respectively. Men withdiabetes had an age-adjusted HR for all-cause mortality of 1.56 (95% CI 1.39, 1.79) vs men without diabetes. Mortality risk was higher among diabetic women, HR1.97 (1.62, 2.39) (diabetes × sex interaction, p=0.03). Survival increased for three consecutive cohorts and washigher in non-diabetic patients for all durations of follow-upand in all three cohorts. The interaction of diabetes x cohortwas not significant over time (p=0.5) and HRs did notdiffer either.Conclusions/interpretation Long-term survival after a firstMI is markedly lower in diabetic patients, especially amongwomen, over an 18-year observation time. Althoughsurvival has improved in diabetic patients, the effect ofdiabetes upon mortality has not diminished.
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| 5. |
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| 6. |
- Eriksson, Marie, et al.
(författare)
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Greater decreases in cholesterol levels among individuals with high cardiovascular risk than among the general population : the northern Sweden MONICA study 1994 to 2014
- 2016
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 37:25, s. 1985-1992
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Decreasing cholesterol levels in Western populations is the main reason for decreasing mortality due to coronary heart disease. Our aim was to analyze trends in cholesterol levels in the population during a period of 20 years in relation to previous cardiovascular disease (CVD), other cardiovascular risk factors, and socioeconomic status.METHODS AND RESULTS: A total of 4546 women and 4349 men aged 25-74 years participated in five population-based surveys in the Northern Sweden MONICA Study between 1994 and 2014 (participation rate 76.8-62.5%). Total cholesterol levels decreased from 6.2 mmol/L (95% confidence interval, CI, 6.1-6.2) in 1994 to 5.5 mmol/L (CI 5.4-5.5) in 2014. The decrease was more pronounced in elderly vs. younger participants (1.0 vs. 0.5 mmol/L). In 2014, participants with previous CVD, diabetes, or hypertension had lower cholesterol levels than the general population, whereas their levels were higher or similar to the general population in 1994. The use of lipid-lowering drugs increased markedly and was used by 14.3% in 2014. Previously described differences in cholesterol levels between participants with obesity and normal weight, and between those with and without university education, diminished, or vanished over time.CONCLUSION: Cholesterol levels decreased by 0.7 mmol/L over 20 years with no sign of abating. The improvement occurred in all age and gender groups but more prominently among those at high risk of ischaemic heart disease.
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| 7. |
- Eriksson, Marie, et al.
(författare)
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Large improvements in major cardiovascular risk factors in the population of northern Sweden : the MONICA study 1986–2009
- 2011
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 269:2, s. 219-231
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. The incidence of cardiovascular disease has declined rapidly in Sweden since the 1980s. We explored changes in major cardiovascular risk factors in northern Sweden between 1986 and 2009.Design. Since 1986, six population surveys have been carried out in northern Sweden using procedures of the World Health Organization MONICA project. The population age range was 25–64 years in 1986 and 1990, and 25–74 years from 1994. Trends were analysed using generalized linear models.Results. A total of 10 586 subjects were included in the surveys. Blood pressure decreased by 4.9/3.9 mmHg in women and 1.8/1.5 mmHg in men aged 25–64 years between 1986 and 2009. In men and women aged 65–74 years, the decrease was 12.6/6.1 mmHg between 1994 and 2009. From 1994, the use of blood pressure‐lowering drugs increased, particularly among the older subgroup. The prevalence of smoking halved between 1986 and 2009; 11% of women and 9% of men were smokers in 2009. Cholesterol levels decreased by 0.9 mmol L−1 in the younger age group (25–64 years), and the use of lipid‐lowering agents increased from 1994. Among subjects aged 25–64 years, one in five was obese in 2009, which was twice as many as in 1986, and body mass index (BMI) increased by 1.5 kg m−2, corresponding to an increase in weight of 4 kg. There was no further increase in BMI from 2004. The prevalence of diabetes did not change between 1986 and 2009. The proportion that received a university education increased markedly in all age groups, especially in women, during the study period.Conclusions. Significant improvements were observed in major cardiovascular risk factors in northern Sweden between 1986 and 2009.
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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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