| 1. |
- Lundberg, Christina, 1972-
(författare)
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Screening for Atherosclerosis with Magnetic Resonance Imaging and Ultrasound
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atherosclerosis is a major cause of death and disability worldwide. Although traditional risk factors can identify the healthy or severely affected individuals, sudden lethal outcome is still frequent in those suggested as intermediate in risk for cardiovascular events (CVE). Adding imaging to the traditional scoring systems might improve risk stratification.This thesis investigates whether the addition of magnetic resonance imaging (MRI) and ultrasound (US) to traditional risk factors might render atherosclerosis suitable for mass screening, selective screening or screening in research settings.In paper I the carotid arteries were assessed in six different manners (carotid intima media thickness (CIMT) in two different locations, presence of plaque, number of plaques, plaque size and plaque composition) using US. More than 800 Caucasian subjects were assessed at ages 70 and 75, and outcome examined at 80 years of age. Plaques with an area exceeding 10mm2 in the bulb were found to be most closely related to CVE.Paper II established that carotid plaque volume measured with MRI did not correlate with carotid plaque area assessed with US. MRI reached the highest levels of reproducibility of the two methods.Paper III used the previously created total atherosclerotic score (TAS), a scoring system based on whole body magnetic resonance angiography (WBMRA) that assesses global atherosclerosis. TAS was found to predict CVE in 305 PIVUS-subjects at age 70 years during 5 years of follow-up. The risk for CVE was found to be eightfold with TAS>0.In paper IV CIMT was assessed with US at ages 70 and 75 years. CIMT at baseline, but not the change in CIMT over five years, was significantly related to TAS, thus suggesting carotid changes to correlate with atherosclerosis throughout the body.In conclusion, in research settings WBMRA and MRI, as well as US, can be used for screening and following up of atherosclerotic changes, as their predictive values and reproducibility are good. US might be feasible in selective screening but none of these methods are as of now suitable for mass screening.
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| 2. |
- Mani, Kevin, 1975-
(författare)
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Abdominal Aortic Aneurysm : Epidemiological and Health Economic Aspects
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abdominal aortic aneurysm (AAA) is a common disease that is life threatening when rupture occurs. The aims of this thesis were to study (I) the long-term survival after AAA repair, (II) the cost of repair with open (OR) and endovascular (EVAR) technique, (III) the effect of different statistical methods on interpretation of cost data, (IV) the prevalence of the disease among patients with suspected arterial disease referred to the vascular laboratory, and (V) the cost-effectiveness of selective high-risk screening. Analyses of data from the Swedish vascular registry (Swedvasc), local patient registries, patient records and hospital cost registries form the basis of this thesis. Short- and long-term survival after intact AAA repair improved over the past two decades, despite increasing patient age and rate of comorbidities over time. Compared to a general population adjusted for age, sex and calendar year, the relative 5-year survival was 90% among those surviving repair. While short-term survival improved over time after ruptured repair, relative long-term survival was stable. Despite differences in patient selection and cost structure, the total cost of AAA repair with EVAR and OR was similar in a population based setting (€28,193). There was lack of consistency in the methods used in cost-analysis in the current literature, and p-values were highly dependent on test method. The practice of selective (non-population-based) screening for AAA among patients referred to the vascular laboratory was studied. The prevalence of AAA was 4.2% among male and 1.5% among female patients. AAA was associated with high age and prevalence of arterial stenosis. Of AAAs detected through selective screening, 21.5% had undergone elective repair at 7.5 years follow-up. In a health-economic evaluation, the incremental cost-effectiveness ratio of selective screening was €11,084 per life year gained. In conclusion, survival after intact AAA repair has improved over time, despite changes in case-mix. Results of health economic reports on cost of AAA repair can be highly dependent on patient selection as well as presentation of data and the statistical methods used. Selective screening for AAA among patients referred to the vascular laboratory is cost-effective.
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| 3. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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| 4. |
- Ersryd, Samuel
(författare)
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Abdominal compartment syndrome and colonic ischaemia after abdominal aortic aneurysm repair in the endovascular era
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abdominal Compartment Syndrome (ACS) and colonic ischaemia (CI) are serious and potentially lethal complications after open (OSR) and endovascular repair (EVAR) of ruptured (rAAA) and intact (iAAA) abdominal aortic aneurysms. The aims of this thesis were to investigate the incidence, outcome, and risk factors associated with ACS (Papers I-III) and to evaluate extraluminal colonic tonometry for postoperative surveillance of colonic perfusion (Paper IV).Papers I-III combined data from the nationwide Swedish vascular registry (Swedvasc) (2008-2015) with case records and radiologic imaging. Paper I investigated incidence and outcome of ACS. The incidence was approximately 7% for both EVAR and OSR after rAAA and 1.6% after OSR and 0.5% after EVAR for iAAA. ACS was associated with a more than two-fold (59% vs 27%) 90-day mortality after rAAA and six-fold (19% vs 3%) after iAAA. Paper II investigated risk factors and outcome among subgroups. Risk of death could not be attributed to a specific main pathology of ACS: CI, postoperative bleeding and general oedema, nor to timing of decompressive laparotomy in relation to AAA surgery. However, the duration of intra-abdominal hypertension (IAH) predicted the need for renal replacement therapy. Paper III investigated risk factors after EVAR for rAAA. ACS was rare without pronounced pre- or intraoperative physiologic derangement associated with circulatory instability. Aortic morphology did not impact ACS development, nor did presence of a patent inferior mesenteric and lumbar arteries, known risk factors for type II endoleak. Paper IV studied patients operated on for iAAA/rAAA (n=27), and demonstrated extraluminal colonic tonometry safe, reliable and indicative of CI among all affected patients (n=4).In conclusion, ACS was common after rAAA repair, with poor outcome irrespective of AAA repair technique and indication for repair. Outcome did not differ depending on the main pathophysiological finding associated with ACS development, while a longer duration of IAH increased the risk of renal replacement therapy. ACS after EVAR for rAAA was largely associated with pre- and intraoperative physiologic factors. These findings highlight the importance of vigilant intra-abdominal pressure measurement after rAAA repair and in case of haemodynamic instability, as well as timely interventions to treat IAH. Extraluminal colonic tonometry appears promising for surveillance of postoperative colonic perfusion.
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| 5. |
- Hager, Jakob, 1967-
(författare)
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Abdominal Aortic Aneurysm : Aspects on how to affect mortality from rupture
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abdominal Aortic Aneurysm (AAA) is a disease that mainly affects elderly men, and ruptured AAA (rAAA) is associated with a mortality of > 80%. AAA seldom gives any symptoms prior to rupture.The aims of this thesis were to investigate different aspects of how to affect mortality from rAAA.In Study I, we identified 849 patients treated for rAAA during 1987-2004, and studied the 30-day survival after surgery, depending on whether they came directly to the treating hospital (one-stop) or were transferred via another hospital (two-stop). A two-stop referral pattern resulted in a 27% lower population-based survival rate for patients 65-74 years of age. However, the consequences would be small even if a one-stop referral pattern could be generally accomplished, due to the huge over-all mortality related to rAAA, hence an argument to find and treat AAA before rupture, e.g. by screening.In Study II, we examined the AAA-prevalence and the risk factors for AAA among 70-year-old men. The screening-detected AAA-prevalence was 2.3%, thus less than half the predicted. The most important risk factor was smoking.In Study III, we compared the screening-detected AAA-prevalence, the attendance rate, and the rate of opportunistic detection of AAA, between almost 8000 65- and 6000 70-year-old men. There was no difference in the screening-detected prevalence; probably due to the fact that almost 40% of the AAAs among the 70-year-old were already known prior to screening, compared to roughly 25% in the 65-year-old. The attendance rate was higher among the 65-year-old men, 85.7% compared 84.0% in the 70-year-old. Thus, there is no benefit of screening for AAA among 70- instead of 65-year-old men.In Study IV, a cost-effectiveness analysis, we found that screening for AAA still appears to be cost-effective, despite profound changes in disease pattern and AAA-management.In conclusion, we found that mortality from rAAA is not affected in any substantial way by different referral patterns and hence centralisation of services for AAA/rAAA is not a solution. A better alternative is to prevent rupture through early detection by screening. Screening 65-year-old men for AAA still appears to be cost-effective, despite profound changes in disease pattern and AAA-management during the last decade. Screening 70- instead of 65-year-old men will not increase the efficacy of screening.
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| 6. |
- Holsti, Mari, 1963-
(författare)
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Vascular remodelling and circulating basement membrane fragments in abdominal aortic aneurysm
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An abdominal aortic aneurysm (AAA) is a degenerative disease, characterized by advanced inflammation and extracellular matrix (ECM) remodelling. Enhanced protease activity mediated by cytokines results in the degradation of ECM proteins, leading to the generation of different bioactive fragments. Some of these generated fragments are released from the vascular basement membrane (VBM), a highly specialized ECM. VBM provides mechanical and structural stability and regulates many important cellular functions of the vascular system. Type IV and XVIII collagens are two structural proteins in VBM, with crucial roles in maintaining of the VBM integrity and vascular architecture. Circulating levels of type IV and XVIII collagen fragments are found physiologically, but have also been associated with many diseases. Remodelling of VBM and expression of its components has not been as well studied in AAA as that of the interstitial ECM.Here we investigate these VBM collagens, their expression and possible association with aortic diameter and expansion rate in individuals with an AAA in comparison with different control groups. Further we study whether there is a link between the circulating VBM collagen fragments and several inflammatory markers, all highly involved in AAA pathogenesis. Lastly, we study the impact of surgical intervention on plasma levels of VBM collagens in patients treated by either open surgical repair (OSR) or endovascular aortic aneurysm repair (EVAR).Methods: Circulating levels of type IV and XVIII collagen fragments were analysed in individuals with an AAA and compared with healthy controls and patients with peripheral artery disease (paper I). A possible association between VBM collagen fragments and the aortic diameter and expansion was studied in a large population-based cohort of 615 men stratified into three aortic diameter groups based on initial maximum aortic diameter (paper II). Furthermore, 159 individuals were followed up over time with repeated measurements of aortic diameter and blood samples. The follow up cohort were divided into two subgroups based on expansion rate of AAA. Moreover, the location of VBM collagens in tissue from aortic wall in individuals with an AAA was characterized and the expression pattern was compared with normal aorta (paper II). In paper III, the association between the plasma levels of VBM collagens and inflammatory markers; IL-1 (IL-1α and IL-1β), IL-6, IL-8, TNF-α INF-γ and hs-CRP were studied in same cohort as paper II. Finally, the effect of surgical intervention on circulating levels of VBM collagen fragments was investigated in AAA patients who had undegone either OSR or EVAR by comparison of plasma levels before and after AAA repair.Ultrasound technique was used for measurements of aortic diameter (paper I, II, III and IV). Analysis of circulating VBM collagens and inflammatory markers were performed by ELISA-assay (Paper I, II, III and IV) and Multiplex-assays, respectively (paper III). Aortic wall tissues were analysed by haematoxylin and eosin (H&E) and immunofluorescence staining (Paper II).Results: There were significantly increased plasma levels of VBM collagen fragments in individuals with an AAA, compared with healthy controls and individulas with a peripheral artery disease (PAD), (Paper I). The levels of type IV collagen in AAA patients did not differ from the group with PAD, and there were no significant differences between the control groups regarding plasma levels of both VBM collagen fragments (Paper I). The increased levels of VBM collagen fragments were significantly associated with aortic diameter with highest levels in the group with an AAA (Paper II). Altered expression of the VBM collagens and fragmentation of elastic fibres were observed in tissue from AAA patients (Paper II). A significant association between the levels of pro-inflammatory cytokines IL-6 and IL-8, and VBM collagens was found. Additionally, there were a significant association between the plasma levels of IL-8, TNF-α and hs-CRP and an AAA (Paper III). Aneurysms with faster expansion rate had significantly higher levels of IL-6, IL-1β, and type XVIII/endostatin collagen. Additionally, IL-6, type XVIII/endostatin collagen and baseline-aortic diameter were significantly associated with expansion rate (Paper III). AAA repair was associated with changes in plasma levels of VBM collagens (Paper IV).Conclusion: Circulating levels of VBM collagens were increased in patients with an AAA, and significantly associated with aortic diameter and expansion rate. The expression of VBM collagens was altered in AAA tissue compared with normal aorta. In addition, plasma levels of several inflammatory markers were associated as with VBM collagens, aortic diameter and expansion rate. The levels of both VBM collagens were altered at short and long time after AAA repair.
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| 7. |
- Högberg, Dominika
(författare)
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Screening for asymptomatic carotid atherosclerosis
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ischemic stroke is the most common cause of handicap in adults and the third most common cause of death in Sweden. Internal carotid artery atherosclerosis is an important cause and accounts for 20% of ischemic strokes. Screening for carotid atherosclerosis has been debated over the past two decades.The aims of this thesis were (I) to study the prevalence of and risk factors associated with carotid artery atherosclerosis among 65 year old men, (II) to evaluate a simplified ultrasound protocol (the grayscale/mosaic method) for the exclusion of significant carotid artery stenosis for screening purpose, (III) to evaluate the required effect of primary preventive therapy in reducing risk of stroke among patients with asymptomatic carotid disease in order for screening to be cost-effective and (IV) to study natural history of carotid atherosclerosis and outcome five years after screening in 65-year old men.The prevalence of atherosclerotic plaques was high (25%), while the prevalence of >50% stenosis was relatively low (2.0%). Smoking, hypertension, diabetes mellitus and coronary artery disease were independent risk factors and individuals with several risk factors had a higher prevalence of stenosis. Most of those at risk were not on any preventive medication. A simplified grayscale/mosaic method was found to have a high negative predictive value for significant carotid stenosis. The minimum stroke risk reduction effect required for preventive intervention to be cost effective was 22%. Carotid atherosclerotic plaque and stenosis 50-79% has a relatively benign development during five years if treated with BMT and risk factor adjustment. Very few progressed to symptomatic disease. More severe stenosis (80-99%) had higher rate of neurological events, and may benefit from additional intervention.In conclusion, prevalence of silent atherosclerotic disease in carotid arteries was common among 65-year-old men. Most of those at risk had no secondary prevention. There is a simple DUS method that could be used for screening purpose. Screening for carotid disease is only cost-effective if the preventive strategy lowers the risk of stroke by 22%. Men with plaques and moderate stenosis have a good prognosis, but among those with severe stenosis there is a need for further intervention.
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| 8. |
- Lyttkens, Linda
(författare)
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Health Related Quality of Life in patients with screening detected Sub-Aneurysmal aorta and Abdominal Aortic Aneurysm
- 2023
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objective Paper I: Most screening and opportunistically detected abdominal aortic aneurysms (AAA) are small and kept under surveillance for several years before preventive surgery. Living with the diagnosis of an AAA may have an influence on the patient’s life. The aim was to review systematically review the current knowledge of the effect on health related quality of life (HRQoL) and patients’ experiences of living with an AAA while under surveillance.Paper II: To investigate HRQoL and comorbidity in men with screening detected AAA, Sub-Aneurysmal aorta (SAA) and Controls at baseline screening and after long-term follow-up.Methods Paper I: A systematic literature review of quantitative and qualitative studies, which were quality assessed according to the GRADE system, was carried out. PubMed, Cochrane, Embase, CINAHL, PsycINFO, and MEDLINE were searched. Narrative synthesis and meta-analysis were performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.Paper II: Between 2006 and 2015, 16 689 sixty-five-year old men participated in the aortic screening program in the county of Uppsala in Sweden. All 539 men diagnosed with an SAA or AAA were invited to participate in the study UpAAA and 324 accepted. Baseline questionnaires was distributed after screening, and at 5-year follow-up. For each year a control group of approx. 50 men, participating in the screening program with normal aorta, were included. ResultsPaper I: Synthesis and meta-analyses of studies based on the Short Form-36 demonstrated that patients with an AAA consistently rated their general health lower than controls and conveyed no significant negative impact for patients with an AAA when assessed at follow up and compared with pre-screening. Analysis of HRQoL estimates of mental health, anxiety, and depression demonstrated no significant differences for patients with AAA compared with controls, or within the AAA group. Qualitative studies revealed that patients with an AAA felt safe being under surveillance and receiving a diagnosis of AAA set thoughts and feelings in motion regarding health, ageing, and mortality. Patients’ lack of knowledge about the disease, its progression, and future planning can cause insecurity and worries.Paper II: AAA and SAA group both has impairment in the physical dimensions of HRQOL and a higher prevalence of co-morbidity at baseline, compared to controls. At 5-year follow-up, the similarities between AAA and SAA group remained with no difference in HRQOL but a higher prevalence of CVD, hypertension and diabetes in men with AAA. Compared with controls both AAA and SAA had significantly higher impairment in HRQoL, and prevalence of co-morbidity and the AAA group was most affected.
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| 9. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Rationale for a Swedish cohort consortium
- 2019
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Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis Group. - 0300-9734 .- 2000-1967. ; 124:1, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.
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| 10. |
- Sörelius, Karl, 1981-
(författare)
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Aortic infections : The Nadir of Vascular Surgery
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aortic infections are rare, life-threatening and constitute a major challenge in surgical management. This thesis aims to evaluate short – and long-term outcome of endovascular aortic repair (EVAR) for mycotic aortic aneurysms (MAA) and the subsequent risk of recurrent infections, changes in surgical practice over time for abdominal MAAs in Sweden and outcome for different treatment modalities, as well as the risk of secondary vascular infection after treatment with Open abdomen after aortic surgery.Paper I, a retrospective single centre study of patients with MAA treated with EVAR, demonstrated a good short-term outcome, 91% survival at 30-days, and acceptable mid-term survival, 73% at 1-year.Paper II, a retrospective international multicentre study of patients treated with EVAR for MAA, confirmed the results in paper I, and showed that EVAR is feasible and for most MAA patients a durable treatment option, 5-year survival was 55% and 10-year 41%. A total of 19% died from an infection-related complication, mostly during the first postoperative year. Non-Salmonella-positive culture was a predictor for late infection–related death.Paper III, a population-based cohort study on all abdominal MAAs operated on between 1994-2014 in Sweden. Overall survival was 86% at 3-months, 79% at 1-year and 59% at 5-years. The survival was significantly better after endovascular compared to open repair up to 1-year without increasing recurrence of infection or reoperation, thereafter there was no difference. After 2001 EVAR constituted 60 % of all repairs, thus indicating a paradigm shift in treatment for abdominal MAAs in Sweden.Paper IV, a prospective multicentre study of patients treated with open abdomen after aortic surgery. Infectious complications, such as graft infections, occurred after intestinal ischaemia and prolonged OA-treatment, and were often fatal.
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