| 1. |
- Eriksson [Engvall], Gunilla, 1976-
(författare)
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The intelligence discourse : the Swedish military intelligence (MUST) as a producer of knowledge
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Swedish Military Intelligence and Security Directorate (MUST) is a producer of knowledge, a knowledge that is fundamental for decisionmaking in foreign and security policy. The intelligence knowledge production is often held as objective, value neutral, and with the intention of ‘speaking truth onto power’. However, this study holds that such a perspective on intelligence knowledge production calls for a revision. Hence, the overall purpose of this study is to examine the characteristics of knowledge in intelligence analysis and also to investigate how that knowledge is affected by the social context of its production, the military intelligence service. The source material is of three kinds; first texts and documents, second interviews with intelligence analysts and managers, and third observations of seminars and meetings during the production process of estimates.The results are that there is a strong presence of an implicit interpretive framework that continuously influences and guides the knowledge production and thereby makes the knowledge dependent on one specific perspective contrary to the intentional objectivity within the intelligence service. Further, the study reveals that the social and discursive practices for intelligence knowledge production include a ‘logic of appropriateness’ suggesting the presence of a structured Denkkollektiv with a structured Denkstil. The actions and choices of the individuals are transformed to create conformity to the norms within the social discursive practices. Thus, the inherited frame of interpretation, as well as the socialised norm of staying within the existing accepted frames ofthinking and acting ends up to the stability and duration of the not always accurate and fruitful Denkstil.At the core of political science resides the question of how policy is shaped. Even though this study has focused merely on one organisation in a specific policy field in one country it brings insights to the knowledge and policy nexus.
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| 2. |
- Karlsson, Jerker, 1967-
(författare)
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Abdominal Aortic Wall Mechanics - Stress, Strain and Stiffness in A Medical Perspective : An Experimental Study in Man
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The stiffness of the abdominal aorta is considered a significant factor affecting the morbidity and mortality of cardiovascular disease. Estimating vascular stiffness is an integral part in cardiovascular risk assessment. Wall stress of the abdominal aorta appears to be a crucial factor in the remodeling of the arterial wall and the growth of aneurysms. Consequently, arterial mechanics plays a vital role in the function of the cardiovascular system. Therefore, there is a need for comprehensive studies of mechanical forces in the vessel wall to better understand the mechanisms behind normal and pathological changes that are significant for hypertension, atherosclerosis, and the development of arterial aneurysms. The aim of this study was to explore the blood pressure-induced forces in the aortic wall using a computational mechanical model, with particular attention to the effects of age, sex, and blood pressure on the remodeling process of the vessel wall. Methods: A computational model, comprising a solid mechanical model and a parameter identification process known as the Parameter Identification Method for Mechanical Parameters (PIMMP), was used to investigate the mechanical properties of the abdominal aortic vessel wall. Data for the model were obtained from the human abdominal aorta of volunteers: 30 healthy individuals, females (n=15) and males, divided into three age groups with an equal number of females and males (n=5 in each age group). Invasive blood pressure, measured via catheter, and diameter variation in the abdominal aorta, measured via ultrasound, were acquired to be used as input data for PIMMP. This dataset was utilized in Papers I, III, and IV. In Paper II, 24 datasets were generated, based on model parameters presented in the scientific literature. Results: Paper I reveals that elderly males exhibit both higher aortic wall stress and higher isotropic stress component, than females. With age, males show an increase in isotropic load-bearing fraction and a decrease in anisotropic load-bearing fraction, a trend not observed in females. Paper II validates an in silico aortic model against a computerized membrane model of an abdominal aorta. The membrane model accurately predicts stress states as well as the load-bearing fraction of anisotropic material across all blood pressure levels, independent of the transmural stress gradient. However, the model’s accuracy is limited due to insufficient in vivo axial loading information. Paper III demonstrates that changes in circumferential stretch have a more pronounced effect on longitudinal stress than the other way around. Both circumferential and longitudinal stiffnesses increase with age, irrespective of sex. However, sex-based differences in stiffness are observed when comparing younger and older groups. Paper IV investigates pulse wave velocity (PWV) calculations using the Moens-Korteweg equation and the Bramwell-Hill equation. PWV shows a positive association with both isotropic and anisotropic material properties, with a transition zone observed between diastolic and systolic blood pressures, to a positive association with anisotropic properties at systolic blood pressure. Furthermore, an increase in PWV with age, with no significant difference between sexes, is observed. The Extra Material suggests a deficiency in age-related wall stress regulation in males, potentially due to insufficient stiffness of anisotropic materials such as collagen. In contrast, females show an age-related increase in abdominal aortic wall thickness and anisotropic material stiffness, indicating adequate wall stress regulation. Conclusions: This doctoral dissertation focused on the effects of age and sex on the abdominal aortic wall. Overall, the findings suggest potential alterations in the collagen and elastin content during the remodeling of the abdominal aorta, which may differ between sexes. These alterations could be induced chemically or mechanically. The model has shown potential in identifying healthy individuals within a population. These insights may contribute to the understanding of cardiovascular health and disease progression.
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| 3. |
- Sandstedt, Mårten, 1972-
(författare)
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Computed Tomography of the Coronary Arteries : Developmental and Prognostic Investigations
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Computed tomography (CT) is an increasingly used modality for investigations of patients with suspected coronary artery disease (CAD). Technical advances could improve diagnostic accuracy and lead to clinical workflow improvements. Also, more prognostic information can optimize clinical follow-up strategies and treatments.The general aim of this thesis was to explore the use of CT for CAD investigations. Three studies aimed to examine new technologies, including the evaluation of an on-site, computed tomography-based fractional flow reserve (CT-FFR) software (study I), the evaluation of an AI-based, calcium scoring computed tomography (CSCT) software (study III), and the evaluation of an photon-counting detector (PCD)-CT (study IV). One study aimed to evaluate the long-term prognostic value of coronary computed tomography angiography (CCTA) in symptomatic patients with no history of CAD (study II).The software evaluation studies (study I and III) and the prognostic study (study II) utilized CT data from clinical patients, while the PCD-CT evaluation study (study IV) used CT data from cadaveric specimens. The performances of both software programs were compared with standard references, being represented by fractional flow reserve (FFR) measurements (study I), and coronary artery calcification (CAC) scores from a semi-automatic software (study III), respectively. The PCD-CT performance on CAC quantification was compared with corresponding results from an energy integrating detector (EID)-CT, using micro-CT as the standard reference (study IV). The prognostic study merged registries to identify major adverse cardiac events (MACE), having a follow-up time of up to 7.5 years (study II).The CT-FFR and CSCT software correlation and agreement to corresponding standard references were good and excellent, respectively. Also, both software programs had time-saving potential (study I and III). The CAC quantification was more accurate using PCD-CT than EID-CT (study IV). The prognosis was excellent in patients with normal coronary arteries, and progressively impaired in non-obstructive and obstructive CAD (study II).The results in this thesis convey developmental, technical CT technology advances for CAD investigations. In addition, prognostic follow-up data is communicated. The results may benefit patients by an increased accuracy in the CT evaluation of CAD and can contribute to improve clinical follow-up strategies. Furthermore, the results suggest possibilities to improve the workflow in clinical radiology, which potentially could impact health care costs.
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| 4. |
- De Geer, Jakob, 1970-
(författare)
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On the use of computed tomography in cardiac imaging
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundCardiac Computed Tomography Angiography (CCTA) is becoming increasingly useful in the work‐up of coronary artery disease (CAD). Several potential methods for increasing the diagnostic yield of cardiac CT are available.Purpose Study I: To investigate whether the use of a 2‐D, non‐linear adaptive noise reduction filter can improve CCTA image quality.Study II: To evaluate the variation in adenosine stress dynamic CT perfusion (CTP) blood flow as compared to stress 99mTc SPECT. Secondly, to compare the perfusion results from manual and automatic myocardial CTP segmentation.Study III: To evaluate the accuracy of non‐invasive, CCTA‐derived Fractional Flow Reserve (cFFR).Study IV: To evaluate the prognostic value of CCTA in terms of major adverse cardiac events (MACE).Materials and methodsStudy I: Single images from 36 consecutive CCTA exams performed with two different dose levels were used. Image quality in full dose, low‐dose and noise‐reduced low‐dose images was graded using visual grading analysis. Image noise was measured.Study II: CTP and SPECT were performed in 17 patients, and the variation in per AHA‐segment blood flow was evaluated and compared. CTP results from manual and automated image segmentation were compared.Study III: CCTA datasets from 21 patients were processed using cFFR software and the results compared to the corresponding invasively measured FFR (invFFR).Study IV: 1205 consecutive patients with chest pain of unknown origin underwent CCTA. Baseline data and data on subsequent MACE were retrieved from relevant registries. Survival, hazard ratios and the three‐year incidence of cardiac events and readmissions were calculated.Results Study I: There was significant improvement in perceived image quality for all criteria when the filter was applied, and a significant decrease in image noise.Study II: The correlation coefficients for CTP vs. SPECT were 0.38 and 0.41 (p<0.001, for manual and automated segmentation respectively. Mean per patient CTP blood flow in normal segments varied between 94‐183 ml/100 ml tissue/min for manual segmentation, and 104‐196 ml/100 ml tissue/min for automated segmentation. The Spearman rank correlation coefficient for manual vs. automated segmentation CTP was ρ = 0.88 (p<0.001) and the Intraclass Correlation Coefficient (ICC) was 0.93 (p<0.001).Study III: The Spearman rank correlation coefficient for cFFR vs. invFFR was ρ = 0.77 (p<0.001) and the ICC was 0.73 (p<0.001). Sensitivity, specificity, positive predictive value and negative predictive value for significant stenosis (FFR<0.80, per vessel) were 0.83, 0.76, 0.56 and 0.93 respectively.Study IV: The hazard ratio for non‐obstructive CAD vs. normal coronary arteries was 5.13 (95% C.I 1.03‐25.43, p<0.05), and 151.40 (95% C.I 37.03‐619.08, p<0.001) for obstructive CAD vs. normal coronary arteries. The three‐year incidence of MACE was 1.1% for patients with normal vessels on CCTA, 2.5% for patients with non‐obstructive CAD and 42.7% for patients with obstructive CAD (p<0.001).Conclusions:Study I: Image quality and noise levels of low dose images were significantly improved with the filter, even though the improvement was small compared to the image quality of the corresponding diastolic full‐dose images.Study II: Correlation between dynamic CTP and SPECT was positive but weak. There were large variations in CTP blood flow in normal segments on SPECT, rendering the definition of an absolute cut‐off value for normal vs. ischemic myocardium difficult. Manual and automatic segmentation were equally useful.Study III: The correlation between cFFR and invFFR was good, indicating that noninvasively estimated cFFR performs on a similar level as invasively measure FFR. Study IV: The long‐term risk for MACE was very low in patients without obstructive CAD on CCTA, though there seemed to be a substantial increase in the risk for MACE even in patients with non‐obstructive CAD as compared to normal coronary arteries. In addition, even patients with normal coronary arteries or non‐obstructive CAD continued to have a substantial number of readmissions for chest pain or angina pectoris.
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| 5. |
- De Geer, Lina
(författare)
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Cardiac dysfunction in septic shock : Observational studies on characteristics and outcome
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Cardiac dysfunction is a well-known complication of sepsis, but its characteristics and consequences, especially on a longer term, remain unclear. The aim of this thesis was to study the characteristics and the implications of cardiac dysfunction for outcome in intensive care unit (ICU) patients with septic shock.Purpose: First, to assess the ability of a cardiac biomarker to predict outcome in ICU patients. Second, to characterise cardiac dysfunction in septic shock using speckle tracking echocardiography. Third, to investigate the reliability of echocardiographic methods used to describe cardiac dysfunction in septic shock. Fourth, to study long-term cardiac outcome in severe sepsis and septic shock patients.Materials and methods: The cardiac biomarker amino-terminal pro-brain natriuretic peptide (NTproBNP) was collected in 481 patients on ICU admission and its ability to predict death was assessed. In 50 patients with septic shock, echocardiography was performed on ICU admission and was repeated during and after ICU stay. Measurements of cardiac strain using speckle tracking echocardiography were assessed in relation to other echocardiographic function parameters, NT-proBNP and severity of illness scores, and their change over time was analysed. Echocardiograms from patients with septic shock were independently evaluated by two physicians and the results analysed regarding measurement variability. A nationwide-registry-based open cohort of 9,520 severe sepsis and septic shock ICU patients discharged alive from the ICU was analysed together with a non-septic control group matched for age, sex and severity of illness. In patients who died after ICU discharge, information on causes of death was collected.Results: A discriminatory level of significance of NT-proBNP on ICU admission was identified at ≥1,380 ng/L, above which NT-proBNP was an independent predictor of death. With increasing levels of NT-proBNP, patients were more severely ill, had a longer ICU stay and were more often admitted with septic shock. Cardiac strain was frequently impaired in septic shock patients but was not superior to other echocardiographic measurements in detecting cardiac dysfunction. Cardiac strain correlated with other echocardiographic function parameters and with NT-proBNP, and was the least user-dependent echocardiographic parameter in septic shock patients. Cardiac strain remained unchanged over time, did not differ between survivors and non-survivors and could not predict an increased risk of death. During a follow-up of up to nearly 6 years after ICU discharge, 3,954 (42%) of sepsis patients died, 654 (17%) with cardiac failure as the cause of death. With increasing severity of illness on admission, the risk of death with cardiac failure as the cause of death after ICU discharge increased. In comparison to other ICU patients with similar severity of illness, however, the risk of death due to cardiac was not increased in patients with severe sepsis or septic shock.Conclusions: Laboratory or echocardiographic signs of cardiac dysfunction are commonly seen in ICU patients in general and in septic shock patients in particular. The assessment of cardiac dysfunction in patients with septic shock is, however, complicated by pre-existing comorbidities, by treatment given in the ICU and by critical illness in itself. Signs of cardiac dysfunction, and the increasing risk of death related to cardiac failure seen after remission of sepsis, may therefore be reflections of critical illness per se, rather than of sepsis.
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| 6. |
- Calcutteea, Avin, 1978-
(författare)
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New insights in the assessment of right ventricular function : an echocardiographic study
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The right ventricle (RV) is multi-compartmental in orientation with a complex structural geometry. However, assessment of this part of the heart has remained an elusive clinical challenge. As a matter of fact, its importance has been underestimated in the past, especially its role as a determinant of cardiac symptoms, exercise capacity in chronic heart failure and survival in patients with valvular disease of the left heart. Evidence also exists that pulmonary hypertension (PH) affects primarily the right ventricular function. On the other hand, previous literature suggested that severe aortic stenosis (AS) affects left ventricular (LV) structure and function which partially recover after aortic valve replacement (AVR). However, the impact of that on RV global and segmental function remains undetermined. Objectives: We sought to gain more insight into the RV physiology using 3D technology, Speckle tracking as well as already applicable echocardiographic measures. Our first aim was to assess the normal differential function of the RV inflow tract (IT), apical and outflow tract (OT) compartments, also their interrelations and the response to pulmonary hypertension. We also investigated the extent of RV dysfunction in severe AS and its response to AVR. Lastly, we studied the extent of global and regional right ventricular dysfunction in patients with pulmonary hypertension of different aetiologies and normal LV function.Methods: The studies were performed on three different groups; (1) left sided heart failure with (Group 1) and without (Group 2) secondary pulmonary hypertension, (2) severe aortic stenosis and six months post AVR and (3) pulmonary hypertension of different aetiologies and normal left ventricular function. We used 3D, speckle tracking echocardiography and conventionally available Doppler echocardiographic transthoracic techniques including M-mode, 2D and myocardial tissue Doppler. All patients’ measurements were compared with healthy subjects (controls). Statistics were performed using a commercially available SPSS software.Results:1- Our RV 3D tripartite model was validated with 2D measures and eventually showed strong correlations between RV inflow diameter (2D) and end diastolic volume (3D) (r=0.69, p<0.001) and between tricuspid annular systolic excursion (TAPSE) and RV ejection fraction (3D) (r=0.71, p<0.001). In patients (group 1 & 2) we found that the apical ejection fraction (EF) was less than the inflow and outflow (controls: p<0.01 & p<0.01, Group 1: p<0.05 & p<0.01 and Group 2: p<0.05 & p<0.01, respectively). Ejection fraction (EF) was reduced in both patient groups (p<0.05 for all compartments). Whilst in controls, the inflow compartment reached the minimum volume 20 ms before the outflow and apex, in Group 2 it was virtually simultaneous. Both patient groups showed prolonged isovolumic contraction (IVC) and relaxation (IVR) times (p<0.05 for all). Also, in controls, the outflow tract was the only compartment where the rate of volume fall correlated with the time to peak RV ejection (r = 0.62, p = 0.03). In Group 1, this relationship was lost and became with the inflow compartment (r = 0.61, p = 0.01). In Group 2, the highest correlation was with the apex (r=0.60, p<0.05), but not with the outflow tract.2- In patients with severe aortic stenosis, time to peak RV ejection correlated with the basal cavity segment (r = 0.72, p<0.001) but not with the RVOT. The same pattern of disturbance remained after 6 months of AVR (r = 0.71, p<0.001). In contrast to the pre-operative and post-operative patients, time to RV peak ejection correlated with the time to peak outflow tract strain rate (r = 0.7, p<0.001), but not with basal cavity function. Finally in patients, RVOT strain rate (SR) did not change after AVR but basal cavity SR fell (p=0.04).3- In patients with pulmonary hypertension of different aetiologies and normal LV function, RV inflow and outflow tracts were dilated (p<0.001 for both). Furthermore, TAPSE (p<0.001), inflow velocities (p<0.001), basal and mid-cavity strain rate (SR) and longitudinal displacement (p<0.001 for all) were all reduced. The time to peak systolic SR at basal, mid-cavity (p<0.001 for both) and RVOT (p=0.007) was short as was that to peak displacement (p<0.001 for all). The time to peak pulmonary ejection correlated with time to peak SR at RVOT (r=0.7, p<0.001) in controls, but with that of the mid cavity in patients (r=0.71, p<0.001). Finally, pulmonary ejection acceleration (PAc) was faster (p=0.001) and RV filling time shorter in patients (p=0.03) with respect to controls.Conclusion: RV has distinct features for the inflow, apical and outflow tract compartments, with different extent of contribution to the overall systolic function. In PH, RV becomes one dyssynchronous compartment which itself may have perpetual effect on overall cardiac dysfunction. In addition, critical aortic stenosis results in RV configuration changes with the inflow tract, rather than outflow tract, determining peak ejection. This pattern of disturbance remains six month after valve replacement, which confirms that once RV physiology is disturbed it does not fully recover. The findings of this study suggest an organised RV remodelling which might explain the known limited exercise capacity in such patients. Furthermore, in patients with PH of different aetiologies and normal LV function, there is a similar pattern of RV disturbance. Therefore, we can conclude that early identification of such changes might help in identifying patients who need more aggressive therapy early on in the disease process.
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| 7. |
- Kvernby, Sofia, 1987-
(författare)
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Myocardial Tissue Characterization Using Magnetic Resonance Imaging
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In cardiovascular disease, which is the most common cause of death in the world, early diagnosis is crucial for disease outcome. Diagnosis of cardiovascular disease can be challenging, though. Quantification of myocardial T1 and T2 relaxation times with MRI has demonstrated to be a promising method for characterizing myocardial tissue, but long measurement times have hampered clinical use. The overall aim of this doctoral thesis was to develop, validate and, in patient studies, evaluate a very fast three-dimensional method for simultaneous quantification of myocardial T1 and T2 relaxation times with whole coverage of the left ventricle.The 3D-QALAS method is presented in Paper I of this thesis. It is a method that simultaneous measures both T1 and T2 relaxation times in a three-dimensional volume of the heart. The method requires 15 heartbeats, to produce 13 short-axis slices of the left ventricle with voxelwise information of both T1 and T2 relaxation times. The 3D-QALAS method was validated in phantoms and in 10 healthy volunteers by comparing the method with reference methods and demonstrated good accuracy and robustness both in-vitro and in-vivo.In Paper II, the 3D-QALAS method was carefully validated in-vivo by investigating accuracy and precision in 10 healthy volunteers, while the clinical feasibility of the method was investigated in 23 patients with various cardiac pathologies. Repeated independent and dependent scans together with the intra-scan repeatability, demonstrated all a very good precision for the 3D-QALAS method in healthy volunteers.In Paper III and IV, the 3D-QALAS method was applied and evaluated in patient cohorts where the heart muscle alters over time. In Paper III, patients with severe aortic stenosis underwent MRI examinations with 3D-QALAS before, 3 months after and 12 months after aortic valve surgery. Changes in T1 and T2 were observed, which might be used as markers of myocardial changes with respect to edema and fibrosis, which may develop due to increased workload over a long period of time.In study IV, 3D-QALAS was used to investigate 10 breast cancer patients treated with radiation therapy prior to treatment, 2-3 weeks into treatment, and one and 6 months after completion of treatment, to investigate any changes in T1 and T2 and further if they can be correlated to unwanted irradiation of the heart during radiation therapy.
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| 8. |
- Nicoll, Rachel, 1955-
(författare)
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Insights into the relationship between coronary calcification and atherosclerosis risk factors
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction Coronary artery disease (CAD) is the most common cause of death in Europe and North America and early detection of atherosclerosis is a clinical priority. Diagnosis of CAD remains conventional angiography, although recent technology has introduced non-invasive imaging of coronary arteries using computed tomographic coronary angiography (CTCA), which enables the detection and quantification of coronary artery calcification (CAC). CAC forms within the arterial wall and is usually found in or adjacent to atherosclerotic plaques and is consequently known as sub-clinical atherosclerosis. The conventional cardiovascular (CV) risk factors used to quantify the estimated 10-year coronary event risk comprise dyslipidaemia, hypertension, diabetes mellitus, obesity, smoking and family history of CAD. Nevertheless, their relationship with significant (>50%) stenosis, their interaction with the CAC score and their predictive ability for CAC presence and extent has not been fully determined in symptomatic patients. Methods For Papers 1-4 we took patients from the Euro-CCAD cohort, an international study established in 2009 in Umeå, Sweden. The study data gave us the CAC score and the CV risk factor profile in 6309 patients, together with angiography results for a reduced cohort of 5515 patients. In Papers 1 and 2 we assessed the risk factors for significant stenosis, including CAC as a risk factor. Paper 2 carried out this analysis by geographical region: Europe vs USA and northern vs southern Europe. Paper 3 investigated the CV risk factors for CAC presence, stratified by age and gender, while Paper 4 assessed the CV risk factors for CAC extent, stratified by gender. In paper 5 we carried out a systematic review and meta-analysis of all studies of the risk factor predictors of CAC presence, extent and progression in symptomatic patients. From a total of 884 studies, we identified 10 which fitted our inclusion criteria, providing us with a total of 15,769 symptomatic patients. All 10 were entered in the systematic review and 7 were also eligible for the meta-analysis. ResultsPaper 1: Among risk factors alone, the most powerful predictors of significant coronary stenosis were male gender followed by diabetes, smoking, hypercholesterolaemia, hypertension, family history of CAD and age; only obesity was not predictive. When including the log transformed CAC score as a risk factor, this proved the most powerful predictor of >50% stenosis, but hypercholesterolaemia and hypertension lost their predictive ability. The conventional risk factors alone were 70% accurate in predicting significant stenosis, the log transformed CAC score alone was 82% accurate but the combination was 84% accurate and improved both sensitivity and specificity. Paper 2: Despite some striking differences in profiles between Europe and the USA, the most important risk factors for >50% stenosis in both groups were male gender followed by diabetes. When the log CAC score was included as a risk factor, it became by far the most important predictor of >50% stenosis in both continents, followed by male gender. In the northern vs southern Europe comparison the result was similar, with the log CAC score being the most important predictor of >50% stenosis in both regions, followed by male gender. Paper 3: Independent predictors of CAC presence in males and females were age, dyslipidaemia, hypertension, diabetes and smoking, with the addition of family history of CAD in males; obesity was not predictive in either gender. The most important predictors of CAC presence in males were dyslipidaemia and diabetes, while among females the most important predictors of CAC presence were diabetes followed by smoking. When analysed by age groups, in both males and females aged <70 years, diabetes, hypertension and dyslipidaemia were predictive, with diabetes being the strongest; in females aged <70 years, smoking was also predictive. Among those aged ≥70 years, the results are completely different, with only dyslipidaemia being predictive in males but smoking and diabetes were predictive in females. Paper 4: In the total cohort, age, male gender, diabetes, obesity, family history of CAD and number of risk factors predicted an increasing CAC score, with the most important being male gender and diabetes. In males, hypertension and dyslipidaemia were also predictive, although diabetes was the most important predictor. Diabetes was similarly the most important risk factor in females, followed by age and number of risk factors. Among patients with CAC, hypertension, dyslipidaemia and diabetes predicted CAC extent in both males and females, with diabetes being the strongest predictor in males followed by dyslipidaemia, while diabetes was also the strongest predictor in females, followed by hypertension. Quantile regression confirmed the consistent predictive ability of diabetes. Paper 5: In the systematic review, age was strongly predictive of both CAC presence and extent but not of CAC progression. The results for CAC presence were overwhelmed by data from one study of almost 10,000 patients, which found that white ethnicity, diabetes, hypertension and obesity were predictive of CAC presence but not male gender, dyslipidaemia, family history or smoking. With respect to CAC extent, only male gender and hypertension were clearly predictive, while in the one study of CAC progression, only diabetes and hypertension were predictive. In the meta-analysis, hypertension followed by male gender, diabetes and age were predictive of CAC presence, while for CAC extent mild-moderate CAC was predicted by hypertension alone, whereas severe CAC was predicted by hypertension followed by diabetes. ConclusionOur investigation of the Euro-CCAD cohort showed that the CAC score is far more predictive of significant stenosis than risk factors alone, followed by male gender and diabetes, and there was little benefit to risk factor assessment over and above the CAC score for >50% stenosis prediction. Regional variations made little difference to this result. Independent predictors of CAC presence were dyslipidaemia and diabetes in males and diabetes followed by smoking in females. The risk factor predictors alter at age 70. The most important risk factor predictors of CAC extent were male gender and diabetes; when analysed by gender, diabetes was the most important in both males and females. Our studies have consistently shown the strong predictive ability of male gender in the total cohort and diabetes in males and females and this is reflected in the meta-analysis, which also found hypertension to be independently predictive. Interestingly, dyslipidaemia does not appear to be a strong risk factor.
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| 9. |
- Engström, Gunnar, et al.
(författare)
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Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
- 2024
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Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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| 10. |
- Gonzalez Garcia, Manuel Cruz, 1969-
(författare)
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The role of leptin in endothelial dysfunction and cardiovascular disease
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objective: Obesity has become the leading cause of mortality worldwide; however, the fundamental pathophysiology underlying this association remains unclear. The discovery of adipokines, i.e., cytokines produced by adipose cells (adipocytes), revealed that adipose tissue is a highly endocrine organ, thus opening new lines of investigation. The prototypical adipokine leptin increases in obesity, and leptin receptors are found in vascular cells. However, results are contradictory regarding the role of leptin in vascular and endothelial functions. Leptin has been shown to elicit vasodilatation, but has also been linked with atherosclerotic and thrombotic disease. The main aim of the present thesis was to study the association of circulating levels of leptin with markers of endothelial function, and to analyze the effects of leptin infusion in vivo on vasomotor function and endogenous fibrinolysis.Material: Four associative studies and two interventional studies were conducted. The former included DISARM (studies 1 and 2), the PIVUS study (study 3), and the Scottish post-infarction study (study 4). The DISARM studies and study 4, respectively, recruited 20 men and 83 men and women with stable ischemic heart disease. Study 3 included a random sample of 1016 subjects (54% women, 70 years old) living in the community of Uppsala, Sweden. For the interventional studies (studies 5 and 6), 10 healthy men were recruited for each study.Methods: In all studies, endothelial function was estimated based on forearm blood flow (FBF) as measured by strain-gauge venous occlusion plethysmography, at rest or during infusion of vasodilators. In study 3, additional measurement techniques were used, such as brachial ultrasound flow-mediated dilation (FMD) and the aortic augmentation index (AoAIx) by tonometry in the radial artery. Fibrinolytic status was estimated based on basal and stimulated levels of tissue plasminogen activator antigen (t-PA), and by assessment of the endothelial release of t-PA (net t-PA release). Plasma leptin levels were measured by radioimmunoassay. In the associative studies, endothelial function and fibrinolytic status were related to circulating plasma leptin levels. In the experimental studies, exogenous leptin was administered in the brachial artery and endothelial function was assessed by strain-gauge plethysmographyResults: In elderly men and women, leptin was independently associated with decreased endothelial-dependent and -independent vasodilatation, reflecting disturbed endothelial function in resistance vessels. This association was attenuated after adjustment for BMI, and when analyzed among subjects with high plasma leptin levels. FMD (a measure of endothelial function in conduit vessels) was not associated with leptin. Exogenous leptin infusion did not alter vasomotor tone, but the endothelium-dependent and -independent vasodilatation was impaired during concomitant infusion of leptin and vasodilators. Infused leptin in the forearm did not affect blood pressure or pulse rate. Chronic hyperleptinemia, but not acutely induced hyperleptinemia, was associated with release of endothelial tissue plasminogen activator (net t-PA).Conclusions: In humans, leptin was associated with impaired vasodilatation. However, this relationship was blunted after adjustment for BMI, suggesting that leptin could be the mediator between obesity and impaired vascular function. Furthermore, the observed lack of association in hyperleptinemic subjects may reflect a state of leptin resistance. The experimental result showing attenuated vascular reactivity following leptin infusion is in accordance with the results of the associative studies. The augmented net t-PA release in patients with chronic hyperleptinemia may indicate a state of “vascular activation,” which was not observed in healthy endothelium during a short period of leptin infusion. This thesis addresses several controversial issues regarding the action of leptin on vascular tissue in humans. The final results indicate that the in vivo action of leptin on vascularity is complex and mediated by several mechanisms. Our findings suggest that leptin is an important mediator between obesity and endothelial dysfunction, and should stimulate further investigation of this matter.
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