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- Andersson, Jonas, 1977-
(author)
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Inflammation and lifestyle in cardiovascular medicine
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Despite major advances in the treatment and prevention of atherosclerosis the last several decades, cardiovascular disease still accounts for the majority of deaths in Sweden. With the population getting older, more obese and with rising numbers of diabetics, the cardiovascular disease burden may increase further in the future. The focus in cardiovascular disease has shifted with time from calcification and narrowing of arteries to the biological processes within the atherosclerotic plaque. C-reactive protein (CRP) has emerged as one of many proteins that reflect a low grade systemic inflammation and is suitable for analysis as it is more stable and easily measured than most other inflammatory markers. Several large prospective studies have shown that CRP is not only an inflammatory marker, but even a predictive marker for cardiovascular disease. C-reactive protein is associated with several other risk factors for cardiovascular disease including obesity and the metabolic syndrome. Our study of twenty healthy men during a two week endurance cross country skiing tour demonstrated a decline in already low baseline CRP levels immediately after the tour and six weeks later. In a study of 200 obese individuals with impaired glucose tolerance randomised to a counselling session at their health care centre or a one month stay at a wellness centre, we found decreased levels of CRP in subjects admitted to the wellness centre. The effect remained at one, but not after three years of follow-up. In a prospective, nested, case-referent study with 308 ischemic strokes, 61 intracerebral haemorrhages and 735 matched referents, CRP was associated with ischemic stroke in both uni- and multivariate analyses. No association was found with intracerebral haemorrhages. When classifying ischemic stroke according to TOAST criteria, CRP was associated with small vessel disease. The CRP 1444 (CC/CT vs. TT) polymorphism was associated with plasma levels of CRP, but neither with ischemic stroke nor with intracerebral haemorrhage. A study on 129 patients with atrial fibrillation was used to evaluate whether inflammation sensitive fibrinolytic variables adjusted for CRP could predict recurrence of atrial fibrillation after electrical cardioversion. In multivariate iv models, lower PAI-1 mass was associated with sinus rhythm even after adjusting for CRP and markers of the metabolic syndrome. In conclusion, lifestyle intervention can be used to reduce CRP levels, but it remains a challenge to maintain this effect. CRP is a marker of ischemic stroke, but there are no significant associations between the CRP1444 polymorphism and any stroke subtype, suggesting that the CRP relationship with ischemic stroke is not causal. The fibrinolytic variable, PAI-1, is associated with the risk of recurrence of atrial fibrillation after electrical cardioversion after adjustment for CRP. Our findings suggest a pathophysiological link between atrial fibrillation and PAI-1, but the relation to inflammation remains unclear.
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- Byhamre, Marja Lisa, 1981-
(author)
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Snus use and mortality : associations, potential mechanisms, and socioeconomic aspects
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Snus is a smokeless tobacco product made of a moist powder of ground tobacco. It is used mainly in the Nordic countries, although increasingly popular internationally. The Swedish snus tradition dates back to the seventeenth century, and it is now used daily by about 23% of the male and 6% of the female population. Snus contains high levels of nicotine as well as carcinogenic substances and microorganisms that could potentially cause adverse health effects. The physiological effects of snus use include acutely raised blood pressure and heart rate, and increased cardiac oxygen demand, while the psychological response results in alertness and anxiety reduction. The high nicotine content causes rapid onset of addiction. Previous research on snus use and health is largely inconclusive, but indicates increased risks of all-cause, cardiovascular and cancer mortality. This thesis aimed to further investigate the health effects of snus use, with a focus on mortality, potential underlying mechanisms, and the impact of socioeconomic factors. Four original papers form the base of this thesis. The first study was performed on a pooled dataset of eight Swedish cohorts (The Swedish Collaboration on Health Effects of Snus use), including over 169 000 men. We found an increased risk of all-cause (HR 1.28, 95% CI 1.20; 1.35), cardiovascular, and other cause mortality, and indications of raised cancer mortality. The second study was set within an interventional program in northern Sweden (Västerbotten Intervention Programme) and included 46 000 men and women. It showed increased mortality overall (estimates similar to first study), from cardiovascular diseases, and external causes (e.g., accidents and suicide) that remained after controlling for socioeconomic status. We found these associations in groups of varying socioeconomic background (e.g., both basic education and high-income groups), suggesting that increased mortality risks among snus users are not restricted to certain socioeconomic groups. Studies three and four investigated potential underlying mechanisms that might contribute to increased mortality among snus users, including established cardiometabolic risk factors in study three (the metabolic syndrome and its components: obesity, hypertension, type 2-diabetes and abnormal blood lipids) and more novel risk factors in study four (low-grade inflammation, low vitamin D-concentrations, and altered iii testosterone levels). The analytical samples were drawn from a long- term follow-up study of around 900 16-year-olds in a municipality in northern Sweden (Northern Sweden Cohort, study three) and more than 6 000 participants in another population-based cohort (the Northern Sweden MONICA study, study four). We found no associations between snus use and established cardiometabolic risk factors, but there was evidence of lower concentrations of inflammatory and vitamin D-status biomarkers in both men and women, and higher testosterone concentrations in men who were currently using snus. We conclude that snus use is associated with increased all-cause and cardiovascular mortality, and to death by other causes, that may be restricted to external causes. Cancer mortality may also be increased among snus users. The associations cannot be fully explained by differences in socioeconomic status among snus users and non-users. Established cardiometabolic risk factors do not seem to be the main mechanisms behind these associations. Lower inflammatory biomarker levels among snus users may serve as a protective factor, while lower vitamin D-concentrations and increased testosterone levels may be part of an underlying mechanism linking snus use to increased mortality. Future research should focus on the health consequences of snus use among women, on other possible links between snus use and death, and on mortality in different cancers among users of snus. The health consequences of dual use of snus and cigarettes should also be assessed.
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- Hernestål Boman, Jenny, 1980-
(author)
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Fibrinolytic factors in relation to anthropometry and incident type 2 diabetes.
- 2014
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Doctoral thesis (other academic/artistic)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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- Hernestål-Boman, Jenny, 1980-, et al.
(author)
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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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Other publication (other academic/artistic)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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- Hernestål-Boman, Jenny, 1980-, et al.
(author)
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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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Other publication (other academic/artistic)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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