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- Andersson, Jonas, 1977-
(författare)
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Inflammation and lifestyle in cardiovascular medicine
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 2. |
- 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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| 3. |
- Johansson, Lars, 1961-
(författare)
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Teenager fatalities : epidemiology and implications for prevention
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A significant number of teenagers are killed each year by unintentional or intentional injuries. A teenager is in a vulnerable phase of her/his life, going from being a child to adult. This transition often includes testing the limits of their capabilities, which can include, e.g., high speed driving, testing alcohol and other drugs, including drinking and driving. The development from child to adult includes different psychological stress factors, such as, e.g., school problems, broken love affairs and bullying. The demands – perceived or real – also increases over time and vulnerable individuals can turn to self-harm and in the most extreme case suicide.The aim of this thesis was to investigate teenager fatalities in the northern half of Sweden and to suggest preventive measures.A survey of teenager fatalities during a twenty-year period revealed that the incidence of unintentional (n=248) deaths decreased, while intentional (n=102) deaths were unaffected over time. Most unintentional deaths were transportation related (n=204) while most of the intentional deaths were suicides (n=88). Twenty-eight percent of the decedents were test-positive for alcohol at autopsy.In a series of three studies, teenager suicides were investigated in depth, firstly through an interview study with the investigating police officer in charge of the investigation of a teenager suicide. Most of the suicides occurred in rural and depopulated areas despite the fact that most teenagers live in the larger cities along the coastline. A majority of the suicides appeared to be planned. Females, contrary to males, often had a psychiatric history. One of the conclusions was that police officers provide essential information concerning the circumstances around a teenager suicide.Parents who had lost a child through suicide, and in some cases siblings, were interviewed 15-25 months after the suicide. It was striking how the life of the surviving family members were still affected by the devastating trauma of the suicide; most parents testified that they were still struggling with the question “why?” and that they were thinking of their lost child every day. Post suicide support was often badly timed and insufficient, especially for the younger siblings. The family doctor has an important role as a co-ordinator of a long-term individually formulated support scheme for the bereaved.Evidence of suicide contagion and suicide cluster formation, i.e., one teenager suicide led to another suicide, was found in these studies, and two suicide clusters were identified, with links between the victims in each cluster. Both clusters occurred within a geographical and timely proximity. Everyone involved in the well-being of the young should be aware of the risk of contagion and suicide cluster formation.The fifth study concerned 12,812 teenagers who visited the Emergency Room at Umeå University Hospital due to an injury during 1993 through 2006. Sixty-one of these were found dead through 2007, 49 by unnatural (of which 38 were included) and 12 by natural causes. The standard mortality rate for unnatural death was calculated to 1.44 (1.02-1.98), confirming an increased risk of premature death. In many of these deaths, alcohol and drugs may have contributed. By increasing the awareness among health professionals that injury can predict a premature death - primarily among those who develop substance abuse - some premature deaths may be prevented by early intervention.This thesis confirms that most teenagers die from unnatural causes, mostly in transportation-related events and by suicide. By studying these deaths, preventive measures that could save lives have been suggested.
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| 4. |
- Lind, Marcus, 1975-
(författare)
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Determinants of adverse events during oral anticoagulant treatment
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Treament with oral anticoagulation is highly effective in reducing the burden of thromboembolic complications in several clinical conditions. The number of patients receiving oral anticoagulation is growing steadily. InSwedenabout 1.5 percent of the population receives treatment. Although the treatment is highly effective in preventing thromboembolic complications, it is also associated with a substantial increase in the risk of bleeding. In clinical practice every physician has to balance the potential benefit of treatment against the risk of bleeding complications in the individual patient. To aid in this decision making, risk scores addressing the likelihood of thromboembolic events, as well as the risk of bleeding complications, have been developed. These scores are imperfect and, to some degree limited by the fact that the risk factors predictive of thromboembolic events are also often associated with bleeding complications. The addition of biomarkers has the potential to increase the predictive ability of risk scores and further enhance the net benefit of oral anticoagulant treatment in the individual patient. In this thesis several potential biomarkers for thromoboembolic and haemorrhagic complications of anticoagulant therapy have been investigated in a longitudinal cohort study of 719 patients with a median follow-up time of 4.2 years. Thrombomodulin is a key component in the generation of activated protein C and hence, a coagulation inhibitor. Conversely, it is also a key component in the inhibition of fibrinolysis by activation of trombin-activated fibrinolysis inhibitor. In warfarin-treated patients we demonstrate that thrombomodulin predicts an increased risk of bleeding complications, but not cardiovascular events. Thus, thrombomodulin has potential as a biomarker specifically for bleeding complications. Von Willebrand factor plays a central and intricate role in the aggregation of platelets and low levels of VWF have been associated with bleeding as a manifestation of von Willebrand’s disease. In our study we noted that high levels of von Willebrand factor predict an increased risk of cardiovascular as well as all-cause mortality, possibly as an expression of endothelial dysfunction. We also noted that high levels of WVF seem to be associated with serious bleeding complications. Decreased renal function is usually measured by an increase in the levels of creatinine and cystatin C, or a decrease in the calculated glomerular filtration rate. A decrease in kidney function is regarded as a marker of an increased risk of bleeding complications. We investigated all the mentioned markers of kidney function and no association with bleeding complications became apparent. However, a clear association between a decrease in kidney function and mortality was noted. Our findings indicate that the emphasis on impaired kidney function as a risk marker needs to be shifted from bleeding complications toward thromboembolic events. Fibrinolysis is important in containing coagulation and several constituents of the fibrinolytic pathway have been shown to predict cardiovascular events and mortality. We found that fibrinolytic factors seem to predict cardiovascular events in patients with oral anticoagulation and that D-dimer also predicts bleeding complications. In conclusion, we have found several biomarkers which exhibit different predictive abilities in patients with oral anticoagulation. It is likely that biomarkers, either alone, in combination, or as ancillary components of risk scores, can contribute to improved risk stratification in patients with oral anticoagulation.
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