| 1. |
- Hellström Ängerud, Karin, 1967-
(författare)
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Symptoms and care seeking behaviour during myocardial infarction in patients with diabetes
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: In Myocardial infarction (MI) it is well established that timely diagnosis and treatment may reduce mortality and improve the prognosis. Therefore it is important that patients with MI seek medical care as soon as possible. Patients with diabetes have a higher risk for MI and worse prognosis compared to patients without diabetes. Previous research is inconclusive regarding symptoms and pre-hospital delay times in MI among patients with diabetes and there is lack of research in how patients with diabetes perceive, interpret and respond to MI symptoms. Aim: The overall aim of this thesis was to explore symptoms and care seeking behaviour during MI in patients with diabetes. Methods: This thesis comprises four studies. Studies I and II were based on data from the Northern Sweden MONICA myocardial infarction registry to describe symptoms in 4028 patients (I) and pre-hospital delay and factors associated with pre-hospital delay of ≥ 2 h in 4266 patients (II). Study III included 694 patients, at five hospitals in Sweden. The patients answered a questionnaire about symptoms, response to symptoms and delay times in MI. In study IV data were collected through interviews about experiences of getting MI and the decision to seek medical care. Results: Study I showed that typical MI symptoms according to MONICA criteria were common in both men and women, both with and without diabetes, and no differences between the groups were found. Study II showed that more patients with diabetes had pre-hospital delay times of ≥ 2 h compared to patients without diabetes. In Study III, chest pain was the most common self-reported MI symptom in patients with and without diabetes and there were no differences between the groups. Shoulder pain/discomfort, shortness of breath and tiredness were more common in patients with diabetes whereas cold sweat was less common compared to patients without diabetes. Less than 40 % of patients with diabetes called the emergency medical services (EMS) as their first medical contact (FMC) and about 60 % initially contacted a spouse after symptom onset. Patients with diabetes reported longer patient delay than patients without diabetes, but after age and gender adjustments the results were not significant. Pain, pressure or discomfort in the stomach, anxiety, symptoms that come and go and thoughts that the symptoms would disappear were associated with longer patient delay in patients with diabetes. In study IV, the analysis revealed the core category “Becoming ready to act” and the categories perceiving symptoms, becoming aware of illness, feeling endangered, and acting on illness experience. Patients with diabetes described a variety of different MI symptoms, the onsets of MI varied and it was sometimes difficult to interpret symptoms as related to MI. The decision to seek medical care for MI was complex with several barriers for timely care seeking. Conclusion: Chest pain was common in patients with diabetes and in contrast to our hypothesis chest pain was equally common in both patients with and without diabetes. There were more similarities than differences in MI symptoms between patients with and without diabetes. However, patients with diabetes were more likely to have pre-hospital delay for 2 hours or more compared to those without diabetes and there seems to be an underutilization of the use of emergency medical services as first medical contact. The process to seek care for MI was complex, initiated by perceiving symptoms, followed by illness awareness, feelings of being endangered and finally acting on the illness experience.
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| 2. |
- Andersson, Anne, 1966-
(författare)
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Long-term side effects after treatment of Hodgkin's lymphoma
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Long-term side effects associated with the treatment of Hodgkin’s lymphoma (HL) have frequently been reported during the last decades. Studies have shown increased mortality in HL survivors. Following Hodgkin’s lymphoma, second malignancies (SM) and cardiovascular disease (CVD) are the most common causes of death in individuals treated for HL. This study investigates the incidence of side effects such as SM, CVD and infections in a cohort diagnosed with HL in Sweden between 1965 and 1995. In addition, this study identifies covariate risk factors for late side effects in order to develop strategies that prevent morbidity and mortality in HL survivors. Methods Using the Swedish Cancer Registry (SCR) at the National Board of Health and Welfare and the Multi-Generation Registry at Statistics (MGR) Sweden, we identified 6946 individuals diagnosed with HL between the years 1965 and 1995, and their first degree relatives (FDR) (n=17 858). In addition we identified the malignancies and inpatient care for CVD and infections for the HL cohort and their FDR. The standard incidence ratio (SIR) was calculated for the risk of SM, CVD and infections. For SM and CVD the risk also was stratified and calculated for family history of disease. The Swedish Hodgkin Intervention and Prevention study (SHIP), a prospective study, invited 702 individuals treated for HL at the age of 45 years or younger and who were treated in the region of Skåne, Uppsala or Umeå. The participants completed a questionnaire and were invited to an out-patient visit to an oncologist with clinical examination and blood tests. Any pathological findings were referred for further investigation. Results An increased risk for SM in HL long-term survivors was observed and seems to increase with the number of FDRs with cancer. There was also an increased risk for inpatient care due to congestive heart failure (CHF) and coronary artery disease (CAD). A family history of CHF and CAD further increased the risk for these diseases. The risk for inpatient care due to infections was increased and remained increased after 20 years or longer. The risk for infections was associated with splenectomy and hypothyroidism. Radiotherapy was an independent risk factor for cardiovascular disease in the cohort of the prospective study. ConclusionLong-term survivors from HL have an increased risk for developing late side effects such as SM, CVD and infections. Since many HL patients are young and the cure rate from the disease is high, it is of great importance to offer focused surveillance programs to selected individuals who are at high risk, e.g. individuals who received radiotherapy as part of their treatment and who have other known risk factors for cardiovascular disease such as hypertension, hypercholesterolemia, family history and smoking.
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| 3. |
- Holmgren, Anders, 1956-
(författare)
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Metabolic risk markers and relative survival in patients with aortic stenosis requiring surgery
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Aortic stenosis (AS) is the most common valve disorder requiring surgery in developed countries. The etiology of AS is only partly known. Identification of new biomarkers in prospective studies could lead to novel insights in the etiology of AS, and possibly lead to improved clinical management. Long term observed survival after aortic valve surgery has improved over the last decades despite an ageing population presenting with more comorbidities. Whether this is reflected in improved relative survival is not known. We evaluated if biomarkers associated prospectively with AS requiring surgery, and if these associations differed between genders, time to surgery and the presence of coronary artery disease (CAD). We also assessed long term observed and relative survival after aortic valve surgery with and without concomitant coronary artery by-pass surgery (CABG).Methods and results: Study I: We prospectively studied the impact of lipoprotein (a)(Lp[a]) and apolipoproteins (Apo) in subgroups of AS. During a 20-year period, 336 patients with prior participation in large population-based surveys in northern Sweden were operated due to AS plus CABG when indicated. For each case two referents were matched. Data from the baseline survey were collected and included data on cardiovascular risk factors, health history, measurements of anthropometry, blood pressure, blood glucose and blood lipid levels were retrieved. Data from pre- and perioperative assessments were also collected. The presence of CAD was determined from the coronary angiogram. Elevated levels of Lp(a) and an elevated Apo B/Apo A 1 ratio were independently associated with future surgery for AS, but only in patients with concomitant CAD (OR 1.29, 95 % CI 1.07-1.55 and 1.43, 95 % CI 1.16-1.76 respectively). Study II: The same patient cohort as in study I was used. A panel of 92 cardiovascular candidate proteins were analysed with the multiplex proximity extension assay in samples obtained at baseline. Six circulating proteins (growth differentiation factor 15[GDF-15], galectin-4, von Willebrand factor [vWF], interleukin 17 receptor A, transferrin receptor protein 1, and proprotein convertase subtilisin/kexin type 9, [PCSK9]) were associated with future surgery for AS in patients with concurrent CAD (ORs ranged from 1.25 to 1.37 per SD increase in the protein signal). In the validation study with 106 additional cases, the association of all but one, (interleukin 17 receptor A), of these proteins were replicated in patients with AS and concurrent CAD but not in those without concurrent CAD. Study III: In the same patient cohort as in study I and II we evaluated if troponin T (TnT) and C-reactive protein (CRP) associated prospectively with future surgery for AS. TnT was independently associated with surgery for AS in patients both with (OR 1.22, 95 % CI 1.02-1.46) and without concomitant CAD (1.39, 95% CI 1.05-1.84). CRP was not associated with surgery for AS (OR 1.06, 95 % CI 0.92-1.23). Study IV: 4970 patients between 2005 and 2016 from three Swedish heart surgery centres, undergoing aortic valve replacement (AVR) due to either AS or aortic regurgitation in conjunction with CABG when indicated, were followed up. All-cause mortality, as well as both observed and relative survival, was analysed with focus on age, sex, type of valve prosthesis and the impact of concomitant CABG. Median follow-up was 4.7 years (2.3-7.6). 30-day mortality was 2.3 %. Long-term survival with 30-day mortality excluded was 96.6 %, 82.7 %, 57.6 % after 1, 5 and 10 years respectively. Relative survival rates (adjusting for the background mortality in the general Swedish population based on age, sex and year) were 99.6 %, 99.5 % and 90.6 % after 1, 5 and 10 years respectively. Age had a negative influence on observed survival (p<0.001) but was associated with better relative survival (relative mortality rate [RMR] 0.74, 95 % CI 0.71 - 0.77). Women had a lower observed mortality than men (p<0.001) but a lower relative survival (RMR 1.17, 95 % CI 1.02-1.35). Combined surgery (AVR+CABG) was not significantly associated with higher mortality (p=0.43) in a multivariable adjusted analysis. The presence of bicuspid morphology was associated with lower observed mortality compared with tricuspid valve, and a relative survival matching that in the general population.Conclusion: I. Plasma levels of Lp(a) and the Apo B/Apo A 1 ratio were independently associated with future surgery for AS but only in patients with concomitant CAD. This finding suggests that patients with AS have different phenotypes and may open a new avenue of research on targeted risk factor interventions in this population. II. Five circulating proteins – GDF-15, galectin-4, vWF, transferrin receptor protein 1, and PCSK9 – were associated with the need for aortic valve surgery several years later. The role of these proteins should be investigated in future studies. III. Elevated plasma levels of TnT were independently associated with future surgery for AS, irrespective of the presence of concomitant CAD, which could indicate that the myocardium is subject to mechanical stress already in the subclinical stage of AS. This may be used as a clinical tool for identification of patients with subclinical AS who could benefit from early intervention. Elevated CRP levels did not associate with future AVR. IV. Relative survival following AVR was particularly good in the elderly matching that in the general population underlining the benefits of aortic valve surgery in properly selected patients. Women had decreased relative survival compared to men. This should be explored in future studies. Adding CABG to an AVR procedure was not associated with increased risk. Bicuspid valve morphology was associated with lower observed mortality compared with tricuspid valve morphology, and with a relative survival matching that of the general population.
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| 4. |
- Nyman, Emma, 1990-
(författare)
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Ultrasound measurements of subclinical carotid atherosclerosis : methodological and clinical studies
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ultrasound measurements of subclinical carotid atherosclerosis have been evaluated as an additional parameter in risk evaluation of cardiovascular diseases (CVD). The overall aim of this thesis was to increase knowledge regarding ultrasound measurements of subclinical carotid atherosclerosis. This included methodological studies of the reproducibility in commonly applied measurements and evaluation of subclinical carotid atherosclerotic progression. All studies within this thesis are based on material from the population based, randomized control trial VIPVIZA. Enrolled from a routine CVD prevention programme, all participants had an additional carotid ultrasound examination including measurements of carotid intima media thickness (cIMT) and carotid plaque detection. The group randomised to the intervention received a pictorial presentation which illustrating their individually measured subclinical atherosclerotic burden. At the 3-year follow-up the same measurements were repeated.Variability, defined by variation of coefficient (CV) of measurements, of plaque risk markers including echogenicity and plaque area were evaluated throughout the cardiac cycle. Additionally, the inter-observer reproducibility of plaque detection was evaluated, and the intervention effect on the 3-year cIMT and plaque progression was compared between intervention (n: 1575) and control group (n: 1579). Lastly, association of baseline carotid wall echogenicity and the 3-year progression of cIMT was evaluated. Small and echolucent plaques had higher CV in measurements of area and echogenicity, respectively. Cardiac cycle variations caused reclassification of up to one in four of the analysed plaques. Small carotid plaques contributed to decreased inter-sonographer reproducibility as compared to large plaques. In the 3-year follow-up the intervention group showed decreased progression of cIMT in the left carotid compared to the control group. No difference was found for in plaque related variables. The echogenicity of the carotid wall associated with the progression of cIMT over the 3-year follow-up period, where echolucent carotid wall had a higher rate of progression bilaterally.Variability of plaque risk markers and the reproducibility of plaque detection should be considered in analysis of subclinical carotid atherosclerosis by ultrasound. Progression of left cIMT was decreased by the intervention, which indicates that increased preventive actions were taken by the intervention group. The echogenicity of the carotid wall may contribute new insights regarding identification of progressive atherosclerotic diseases.
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| 5. |
- Häggmark, Sören, 1949-
(författare)
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Detection of myocardial ischemia : clinical and experimental studies with focus on vectorcardiography, heart rate and perioperative conditions.
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction. Multiple clinical methods for detecting myocardial ischemia are utilised in the hospital setting each day, but there is uncertainty about their diagnostic accuracy. In the operating room, multiple methods may be employed, while in the CCU advanced electrophysiological (ECG) techniques for myocardial ischemia detection, and in particular, ST segment analysis, are common. Vectorcardiography (VCG) is one form of ECG. Several conditions other than ischemia may cause marked ST changes, which can impair the process of diagnosis of clinical ischemia. Elevated HR is one of these factors, which is studied here. The hypotheses were about concordance of different methods to detect ischemia, and relation of ECG ST levels to HR with and without myocardial ischemia. Methods. Study I. Anesthetised vascular surgical patients with coronary artery disease were studied during the start of anesthesia and surgery: ECG, hemodynamic, mechanical, and metabolic parameters were measured and categorised as positive or negative with reference to a specific definition of myocardial ischemia. Study II. Awake patients with no ischemic heart disease were paced in graded steps, and VCG ST analyses were performed. Study III. Anesthetised pigs were studied for local metabolic and VCG ST changes related to controlled HR levels and transient coronary occlusion. Study IV. Thirty five anesthetised coronary artery disease (CAD) patients and ten non-CAD patients were paced at controlled levels, and great coronary artery vein (GCV) lactate measurement was used to determine presence or absence of myocardial ischemia. The CAD patients were paced up to HR levels where myocardial ischemia could be confirmed. The relation of HR-related VCG ST levels to presence or absence of ischemia was analysed. In Studies II,, III, and IV the ST vector magnitude (ST-VM), the change from baseline in ST-VM (STC-VM), and the vector angle change from baseline (STC-VA) were analysed for each step. Results. Study I. Poor concordance was demonstrated for positive events (presumed myocardial ischemia) between the hemodynamic, ECG, mechanical, and metabolic detection methods. Study II. STC-VM but not ST-VM levels demonstrated HR-related increases in the presumed absence of myocardial ischemia in 18 awake subjects. J point time to ST measurement did not affect the response of VCG ST to HR. Study III. STC-VM levels showed HR-related increases in the absence of ischemia (tested by local metabolic observations). VCG ST parameters responded positively to transient regional ischemia. Study IV. CAD patients, which demonstrated a clear pattern of onset and progress of ischemia during pacing, were further analysed for the relation of VCG ST level to ischemia. Sensitivity and specificity of STC-VM levels were described by ROC analysis for a range of STC-VM levels. Conclusions. Concordance of different measures for detection of onset of myocardial ischemia is difficult to assess in the absence of a very reliable reference method. The contribution of HR and ischemia to VCG ST levels were estimated in study subjects. HR-related increases in STC-VM occur in the absence of ischemia. HR levels need to be considered when interpreting STC-VM as a diagnostic test for ischemia. Further study is needed to establish criteria that take into account multiple clinical factors in order to improve the predictive value of our tests for myocardial ischemia.
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| 6. |
- Nilsson Sommar, Johan, et al.
(författare)
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Long-term exposure to particulate air pollution and presence and progression of carotid artery plaques : A northern Sweden VIPVIZA cohort study
- 2022
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 211
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To estimate the association between long-term exposure to particulate air pollution and sub-clinical atherosclerosis based on the existence of plaque and the carotid intima-media thickness (cIMT).METHODS: Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA) is a randomised controlled trial integrated within the Västerbotten Intervention Programme, an ongoing population-based cardiovascular disease (CVD) prevention programme in northern Sweden. Individuals aged 40, 50, or 60 years with one or more conventional CVD risk factors in Umeå municipality were eligible to participate. The 1425 participants underwent an ultrasound assessment of cIMT and plaque formation during the period 2013-2016 and at 3-year follow-up. Source-specific annual mean concentrations of particulate matter with aerodynamic diameter ≤10 μm (PM10) and ≤2.5 μm (PM2.5), and black carbon (BC) at the individual's residential address were modelled for the calendar years 1990, 2001 and 2011. Poisson regression was used to estimate prevalence ratios for presence of carotid artery plaques, and linear regression for cIMT.RESULTS: The plaque prevalence was 43% at baseline and 47% at follow-up. An interquartile range (IQR) increase in PM10 (range in year 2011: 7.1-13.5 μg/m3) was associated with a prevalence ratio at baseline ultrasound of 1.11 (95% CI 0.99-1.25), 1.08 (95% CI 0.99-1.17), and 1.00 (95% CI 0.93-1.08) for lag 23, 12 and 2 years, and at follow-up 1.04 (95% CI 0.95-1.14), 1.08 (95% CI 1.00-1.16), and 1.01 (95% CI 0.95-1.08). Similar prevalence ratios per IQR were found for PM2.5 and BC, but with somewhat lower precision for the later. Particle concentrations were however not associated with the progression of plaque. No cross-sectional or longitudinal associations of change were found for cIMT.CONCLUSIONS: This study of individuals with low/moderate risk for CVD give some additional support for an effect of long-term air pollution in early subclinical atherosclerosis.
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| 7. |
- Näslund, Ulf, et al.
(författare)
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Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA) : a pragmatic, open-label, randomised controlled trial
- 2019
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 393:10167, s. 133-142
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Primary prevention of cardiovascular disease often fails because of poor adherence among practitioners and individuals to prevention guidelines. We aimed to investigate whether ultrasound-based pictorial information about subclinical carotid atherosclerosis, targeting both primary care physicians and individuals, improves prevention.METHODS: Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention (VIPVIZA) is a pragmatic, open-label, randomised controlled trial that was integrated within the Västerbotten Intervention Programme, an ongoing population-based cardiovascular disease prevention programme in northern Sweden. Individuals aged 40, 50, or 60 years with one or more conventional risk factors were eligible to participate. Participants underwent clinical examination, blood sampling, and ultrasound assessment of carotid intima media wall thickness and plaque formation. Participants were randomly assigned 1:1 with a computer-generated randomisation list to an intervention group (pictorial representation of carotid ultrasound plus a nurse phone call to confirm understanding) or a control group (not informed). The primary outcomes, Framingham risk score (FRS) and European systematic coronary risk evaluation (SCORE), were assessed after 1 year among participants who were followed up. This study is registered with ClinicalTrials.gov, number NCT01849575.FINDINGS: 3532 individuals were enrolled between April 29, 2013, and June 7, 2016, of which 1783 were randomly assigned to the control group and 1749 were assigned to the intervention group. 3175 participants completed the 1-year follow-up. At the 1-year follow-up, FRS and SCORE differed significantly between groups (FRS 1·07 [95% CI 0·11 to 2·03, p=0·0017] and SCORE 0·16 [0·02 to 0·30, p=0·0010]). FRS decreased from baseline to the 1-year follow-up in the intervention group and increased in the control group (-0·58 [95% CI -0·86 to -0·30] vs 0·35 [0·08 to 0·63]). SCORE increased in both groups (0·13 [95% CI 0·09 to 0·18] vs 0·27 [0·23 to 0·30]).INTERPRETATION: This study provides evidence of the contributory role of pictorial presentation of silent atherosclerosis for prevention of cardiovascular disease. It supports further development of methods to reduce the major problem of low adherence to medication and lifestyle modification.
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