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Sökning: WFRF:(Rosenqvist Mårten Professor)

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1.
  • Hendrikx, Tijn, 1975- (författare)
  • Catch Atrial Fibrillation, Prevent Stroke : Detection of atrial fibrillation and other arrhythmias with short intermittent ECG
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Atrial fibrillation (AF) is the most common arrhythmia in the adult population, affecting about 5% of the population over 65 years. Occurrence of AF is an independent risk factor for stroke, and together with other cardiovascular risk factors (CHADS2/CHA2DS2- VASc), the stroke risk increases. Since AF is often paroxysmal and asymptomatic (silent) it may remain undiagnosed for a long time and many AF patients are not discovered before suffering a stroke.Aims: To estimate the prevalence of previously undiagnosed AF in an out-of-hospital population with CHADS2 ≥1, in patients with an enlarged left atrium (LA) and of total AF prevalence in sleep apnea (SA) patients, conditions that have been associated with AF. To compare the efficacy of short intermittent ECG with continuous 24h Holter ECG in detecting arrhythmias.Methods: Patients without known AF recorded 10−30 second handheld ECG (Zenicor-EKG®) registrations during 14−28 days at home, both regular, asymptomatic registrations twice daily and when having cardiac symptoms. Recordings were transmitted through the in-built SIM card to an internet-based database. Patients with palpitations or dizziness/presyncope referred for 24h Holter ECG were asked to additionally record 30-second handheld ECG registrations during 28 days at home.Results: In the out-of-hospital population with increased stroke risk, previously unknown AF was diagnosed in 3.8% of 928 patients. Comparing AF detection in patients with an enlarged LA versus normal LA showed that eleven of 299 patients had AF. Five of these had an enlarged LA (volume/BSA). No statistical difference in AF prevalence was found between patients with enlarged and normal LA, 3.3% and 3.2% respectively, (p = 0.974). AF occurred in 7.6% of 170 patients with sleep apnea, in 15% of patients with sleep apnea ≥60 years, and in 35% of patients with central sleep apnea. AF prevalence was also associated with severity of sleep apnea, male gender and diabetes. Comparing the efficacy of arrhythmia detection in 95 patients with palpitations or dizziness/presyncope with continuous 24h Holter and short intermittent ECG, 24h Holter found AF in two and AV-block II in one patient, resulting in 3.2% relevant arrhythmias detected. Short intermittent ECG diagnosed nine patients with AF, three with PSVT and one with AV-block II, in total 13.7% relevant arrhythmias. (p = 0.0094).Conclusions: Screening in the out-of-hospital patient population (mean age 69.8 years) yielded almost 4% AF, making it seem worthwhile to screen older patients with increased stroke risk for AF with this method. Screening patients with LA enlargement (mean age 73.1 years) did not result in higher detection rates compared with the general out-of-hospital population. AF occurred in 7.6% of patients with sleep apnea, (mean age 57.6 years) and was associated with severity of sleep apnea, presence of central sleep apnea, male gender, age ≥60 years, and diabetes. Short intermittent ECG is more effective in detecting relevant arrhythmias than 24h Holter ECG in patients with palpitations or dizziness/presyncope.
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2.
  • Arvanitis, Panagiotis, 1973- (författare)
  • Clinical evaluation and implications of left atrial remodeling in atrial fibrillation : From silent cerebral lesions and atrial stunning to novel electrocardiographic tools for prediction of arrhythmia outcome
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Atrial fibrillation (AF) is the most common cardiac arrhythmia. Left atrial (LA) remodeling and reverse remodeling are associated with cerebral involvement and cognitive function (CF) changes. Risk stratification for AF related outcomes is essential in the management of patients with AF. This thesis aimed to 1) explore the effects of AF in a prospective cohort of anticoagulant-naïve patients, who underwent cardioversion (CV) within 48 hours after debut (Studies I and II) on i) occurrence of new silent thromboembolic events using brain magnetic resonance imaging, CF, cerebral biomarker ii) atrial remodeling and thrombogenicity using echocardiography, and hypercoagulability biomarkers; 2) identify novel electrocardiographic (ECG) predictors of 12-months AF recurrence, (Study III), in patients with non-permanent AF after CV or pulmonary vein isolation and study its effect on reverse atrial electrical remodeling (RAER) and 3) to evaluate traditional and novel ECG- and clinical predictors of new-onset AF (new-o-AF) on hospitalized Covid-19 patients (Study IV)  and explore the impact of AF on clinical outcomes.In Papers I and II, acute silent cerebral lesions could not be identified. A higher incidence of white matter hyperintensities was associated with higher CHA2DS2-VASc-score. A transient increase in cerebral damage biomarker was observed. Persistent AF patients had inferior CF test results. LA stunning resolved within ten days. The reverse functional remodeling was incomplete in patients with AF history. Higher levels of hypercoagulability-related biomarkers were observed prior to CV. In Paper III, the novel Peq-time>33ms, from P-wave onset to the peak positive deflection, independently predicted 12-months AF recurrence. The P-leftward-area, from peak positive deflection to the offset of P-wave, showed the largest change during follow-up, describing RAER. Machine-learning predictive model including variables from the novel P-wave partitioning showed the best predictive performance.In Paper IV, the novel Peq-time>33ms, PR-interval>190ms and P-wave-duration>115ms were independent predictors of n-o-AF. Admission to the intensive care unit (ICU), need for respiratory support, advanced age, males and increased body mass index (BMI) independently predicted new-o-AF. Logistic regression predictive models including age, sex, BMI, ICU admission and Peq-time or PR-interval had the best balanced accuracy.In conclusion, our findings in Studies I and II might suggest an enhanced thrombogenicity, even in patients with low stroke risk, supporting the concept of anticoagulation pericardioversion. We introduced the novel Peq-time, independently predicting AF recurrence in Study III and, along with PR-interval, new-o-AF in Study IV. Predictive models of arrhythmia outcome could be implemented in individually-tailored AF management and surveillance.
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3.
  • Bergman, Elin, 1983- (författare)
  • Trädgårdens textur : Rumsliga, materiella och sociala perspektiv på den privatägda trädgården i Sverige cirka 1900-1930
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The subject of this dissertation is privately owned gardens in Sweden circa 1900–1930 and aims to identify and make visible their meaning and impact on different societal levels. Sweden, like many other European countries, faced profound societal changes during the nineteenth and early twentieth centuries. This was in part due to a major increase in population, the development of new urban environments, a growing working class, and migration within and out of the country. The culmination of these circumstances had an impact on the development of society, more broadly, and on housing, in particular.Prior scholarly inquiries across multiple disciplines have studied the home as a locus for various social relations and expressions of aesthetic ideals. However, the outdoor space of the home has not been specifically included or emphasized in previous research. The focus of this dissertation is therefore to examine gardens within the private sphere – in physical form as well as in their conceptions –  concentrating on spatial organization and material constitution within the social context of the time. The aim is to make visible the ways in which the garden acted as an important part of the construction of the ideal home, in theory as well as in practice. In so doing, gardens and garden practices of the early twentieth century are historically, culturally, and socially situated.The theoretical framework is built upon the concept of texture which combines the theoretical fields of spatial theory and materiality. The approach and the use of texture emphasize the material elements that are essential in the constitution of the garden (but not always considered meaningful in their own right), as well as the relationship between humans and their surroundings, particularly with regard to home-making and relating practices. It includes analyses of individual materials’ physical conditions and the way they are experienced with the senses. Furthermore, it highlights the material and visual merging of materials as a perceived whole and the relation of the parts to that whole. Finally, it elucidates the socio-cultural relations between objects and environments which are then experienced, used, and changed by human subjects. The dissertation demonstrates the various meanings of the garden and garden practices, based on a vast set of empirical sources selected on principles of geographical and demographical diversity during the selected time period. The result is presented in case studies. These include analyses of garden literature, the work of county gardeners employed by the Agricultural Society, and educational institutions such as Lillie Landgren’s Torshäll (Dalarna County). Furthermore, particular sites are investigated, such as the mining town of Boliden (Västerbotten County), and the private gardens of Crown Princess Margareta at Sofiero (Skåne County) and Ellen Key at Strand (Östergötand County). The study reveals the multifaceted functions of the garden. The conception of the garden’s potential was made visible in publications and visual material, which provided exemplary gardens, cultivated by – and at the same time cultivating – the human actors. The study’s emphasis on the manual elaboration of materials with a certain aesthetic ideal or practical purpose as the objective confirms that the garden is a result of spatial, material, and social prerequisites, all coalescing as the texture of the garden.
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4.
  • Johansson, Cecilia, 1988- (författare)
  • Risk markers and incidence of atrial fibrillation in northern Sweden
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Atrial fibrillation (AF) is the most common clinically significant arrythmia with a prevalence of approximately 3% in the general population. Less is known about the incidence of AF. In order to reduce the incidence of AF, it is of essence to identify modifiable risk factors for the disease.Aims: The aims of this thesis were (1) to estimate the incidence of AF and to assess the prevalence of provoking factors and risk factors for stroke and systemic embolism at the time of AF diagnosis, (2) to study the association between alcohol consumption and risk of AF, (3) to study the association between weight, height, weight change, and risk of AF, and (4) to study the association between normal or high normal blood pressure (BP), compared to optimal BP, and risk of AF.Methods: To determine the incidence of AF and the prevalence of provoking factors and risk factors for stroke and systemic embolism at AF diagnosis, an observational study was performed between January 1, 2011, and December 31, 2012, in the municipalities of Skellefteå and Norsjö, Västerbotten, Sweden. Diagnosis registries were searched for cases of incident AF. All AF diagnoses were verified by electrocardiogram. Data regarding provoking factors, type of AF and presence of risk factors for stroke and systemic embolism (as assessed by the CHA2DS2-VASc score) was obtained from medical records. Incidence was calculated by dividing the number of incident AF cases by the time at risk for the population.The association between alcohol consumption, weight, height, weight change, normal BP, high normal BP, and risk of AF was investigated in a population-based cohort study of participants of the Västerbotten Intervention Programme (VIP). Residents of Västerbotten County aged 30, 40, 50 and 60 years who had participated in the VIP health examinations between January 1, 1988, and September 5, 2014, were included. Individuals who had been diagnosed with AF before participating in the VIP were excluded. Study participants were followed until a diagnosis of AF, death, migration from the study area, or the end of the study on September 5, 2014. Incident AF cases were identified using the Swedish National Patient Registry. The health examinations included measurements of height and weight, systolic BP, diastolic BP, fasting glucose, oral glucose tolerance, and cholesterol. Participants also answered a questionnaire addressing any history of diabetes and myocardial infarction, alcohol use, education level, smoking habits, medications, and physical activity. Optimal BP was defined as BP < 120/80 mm Hg. Normal BP was defined as BP 120–129/80–84 mm Hg. High normal BP was defined as BP 130–139/85–89 mm Hg. Hypertension was defined as BP ≥ 140/90 mm Hg. Cox proportional hazards regression analysis was used to assess the associations between alcohol consumption, weight, height, weight change, normal BP, high normal BP, and risk of AF. These were performed with crude, age-adjusted, and multivariable models adjusted for other cardiovascular risk factors (age, sex, body mass index, hypertension, cholesterol, previous myocardial infarction, diabetes, problem drinking, smoking, education level, and leisure-time physical activity).Results: The incidence of AF was 4.0 cases of AF per 1000 person-years. In approximately one fifth of participants, a provoking factor was present at the first episode of AF. The CHA2DS2-VASc score was 2 or higher in 81% of participants. Permanent AF was the most common type of AF and was seen in about one third of the participants.When studying the association between alcohol consumption and risk of AF, 109,230 health examination participants were included in the study cohort and were followed for 1,484,547 person-years. During the study period, 5230 participants developed incident AF. Men with alcohol consumption in the highest quartile (≥ 4.83 standard drinks weekly) had a hazard ratio (HR) of 1.21 (95% confidence interval [CI] 1.09-1.34) for AF in a multivariable model when compared to men with an alcohol consumption in the lowest quartile (< 0.90 standard drinks weekly). In men, problem drinking was also associated with an increased risk of AF (HR 1.24, 95% CI 1.10–1.39 in a multivariable model). Among women, no significant association between alcohol consumption, problem drinking, and risk of AF was identified.In a fully adjusted model, height, weight, body mass index, and body surface area were positively associated with risk of incident AF. Among participants who underwent two health examinations 10 years apart, 1142 persons developed AF. The mean weight change from baseline was a weight gain of 4.8%. There was no significant association between either weight gain or weight loss and risk of AF.In the study of the association between normal BP, high normal BP, and risk of AF, 109,697 persons with a total of 162,982 health examinations were included. Incident AF was diagnosed in 5260 participants. There was an increased risk of incident AF in persons with normal BP (HR 1.11, 95% CI 1.01–1.27) and in persons with high normal BP (HR 1.23, 95% CI 1.10–1.38) compared to optimal BP in a multivariable model. Systolic BP and diastolic BP were associated with risk of incident AF, with HRs of 1.11 (95% CI 1.10–1.13) and 1.13 (95% CI 1.09–1.16) per 10 mmHg, respectively, in multivariable models. A restricted cubic spline analysis indicated a gradually increasing risk of AF with increasing systolic BP and diastolic BP.Conclusions: AF has an incidence of 4.0 per 1000 person-years. Alcohol consumption and problem drinking were associated with higher risk of AF in men, but not in women. Weight, height, body mass index, and body surface area were associated with increased risk of incident AF. Normal BP and high normal BP, when compared to optimal BP, were associated with increased risk of incident AF.
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5.
  • Bagge, Louise (författare)
  • Surgical ablation for the treatment of atrial fibrillation in different patient populations : A study of clinical outcomes including rhythm, quality of life, atrial function and safety
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Patients with atrial fibrillation (AF) have markedly reduced quality of life (QoL) and catheter ablation has become a useful tool in the rhythm control therapy. However, because of the poor outcome for patients with persistent AF, new surgical ablation strategies for rhythm control are emerging.The aims of this thesis were to evaluate QoL, the main indication for rhythm control, after three different types of surgical ablation for AF, two stand-alone epicardial AF ablation procedures and one concomitant procedure during mitral valve surgery (MVS), and to perform a long-term follow-up of one of the techniques with regard to rhythm outcome, left atrial function, exercise capacity and safety.As the first center in the Nordic countries to adopt the video-assisted epicardial pulmonary vein isolation and ganglionated plexi ablation combined with left atrial appendage excision (LAA), the  freedom from AF at one year follow-up was found to be 71% and associated with improved exercise capacity, QoL and symptoms as well as preserved left atrial function and size. The most common complication was bleeding events (14%). After 10 years, the improved symptoms and QoL remained, reaching comparable levels of the general Swedish population, despite a marked decline in the rate of freedom from AF (36%). 4 strokes appeared during follow-up despite LAA excision in 3 of these patients.In order to improve the rhythm outcome for patients with longstanding persistent AF a box-lesion was added to the procedure. At one year follow-up, both symptoms and QoL improved and was indistinguishable from those in the Swedish general population.Finally, concomitant AF ablation during MVS did not improve QoL compared to MVS alone in a double blinded randomized controlled trial. Moreover, no difference was seen between patients in AF or sinus rhythm at one year follow-up, irrespective of the allocated therapy, indicating that their preoperative symptoms were mainly related to their valve disease.In conclusion, the stand-alone procedures using surgical ablation was found to be effective but at the expense of procedural complications. In contrast, the concomitant surgical AF ablation did not improve QoL, a finding that raises concerns regarding current recommendations for this procedure. 
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6.
  • Barmano, Neshro, 1980- (författare)
  • Structured management, Symptoms, Health-related Quality of Life and Alcohol in Patients with Atrial Fibrillation
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting at least 2.9 % of the Swedish population. Although AF is associated with increased risk of ischaemic stroke, there have been many reports on the underuse of oral anticoagulants (OAC) and non-adherence to guidelines in other areas as well. AF is also associated with disabling symptoms and decreased health-related quality of life (HRQoL), but some patients are asymptomatic. The reasons for the great variation of symptoms remain unclear. Furthermore, although research on AF has increased, studies have mainly focused on treatment, while studies on risk factors, such as alcohol consumption, have only recently gained attention.The aim of this thesis was to investigate whether structured care of patients with AF could improve guideline adherence and HRQoL compared to standard care, and to determine which factors affect symptoms and HRQoL prior to treatment with radiofrequency catheter ablation (RFA), as well as improvement after RFA. Furthermore, we aimed to examine the associations of alcohol consumption with cardiac biomarkers, the size of the left atrium (LA), and re-ablation.This thesis is based on two studies. In the ‘Structured Management and Coaching – Patients with Atrial Fibrillation’ (SMaC-PAF) study, 176 patients were recruited to the intervention group, receiving a structured follow-up programme, and 146 patients were recruited to the control group, receiving standard care. The two groups were compared in regard to adherence to guidelines and patient-reported outcome measures (PROMs) assessing symptoms and HRQoL.In the ‘Symptom burden, Metabolic profile, Ultrasound findings, Rhythm, neurohormonal activation, haemodynamics and health-related quality of life in patients with atrial Fibrillation’ (SMURF) study, 192 patients referred for their first RFA of AF were included. PROMs questionnaires were filled out, echocardiography was performed, and cardiac biomarkers were analysed. Alcohol consumption was assessed through interview and through analysis of ethyl glucuronide in hair (hEtG). AF recurrence and re-ablation within 12 months were examined.In the first study, after one year, 94% (n=112) and 74% (n=87) of patients with indication for OAC in the intervention and the control groups, respectively, actually received treatment with OAC (p <0.01). Both groups improved in anxiety and HRQoL scores over the year, but in the intervention group, arrhythmia-specific symptoms were less frequently experienced and the SF-36 scores were more similar to the norm population.In the second study, the most important predictors of arrhythmia-related symptoms and HRQoL prior to RFA were anxiety, depression and low-grade inflammation, while frequent AF attacks prior to RFA, freedom from AF recurrence after RFA, female gender, no enlarged LA, absence of diabetes, and the presence of heart failure were significant predictors of improvement in symptoms and HRQoL after RFA. Men with hEtG ≥7 pg/mg had higher levels of cardiac biomarkers, larger LA volumes and a higher re-ablation rate than men with hEtG <7 pg/mg, while no such findings were present in women.In conclusion, structured management was superior to standard care in patients with AF, emphasising the importance of structured care, adjusted to local requirements, in order to improve the care and well-being of patients with AF. Although the reasons for the great variety of symptoms in patients with AF still are not yet fully understood, it seems that psychological factors and inflammation play a role, and that improvement in symptoms and HRQoL after RFA is influenced by gender, diabetes, heart failure, LA size and the frequency of attacks before, as well as freedom from AF after, RFA. Finally, alcohol consumption corresponding to hEtG ≥7 pg/mg was associated with higher levels of cardiac biomarkers, larger LA size and a higher rate of re-ablation in men, implying that men with an hEtG-value ≥7 pg/mg have a higher risk for LA remodelling that could potentially lead to a deterioration of the AF situation.
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7.
  • Häggmark, Sören, 1949- (författare)
  • Detection of myocardial ischemia : clinical and experimental studies with focus on vectorcardiography, heart rate and perioperative conditions.
  • 2005
  • 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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8.
  • Wallby, Lars, 1955- (författare)
  • Signs of inflammation in different types of heart valve disease : The VOCIN study
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Heart valve dysfunction is a relatively common condition in the population, whereas significant heart valve disease is more unusual. The cause of different types of heart valve disease depends on which valve is concerned. Rheumatic heart valve disease, has for a long time been considered to constitute a post-inflammatory condition. During the 1990s it was also shown that the so-called non-rheumatic or degenerative tricuspid aortic stenosis, comprised signs of inflammation.In this study, 118 patients (the VOCIN study group) referred to the University Hospital for preoperative investigation due to significant heart valve disease, were examined regarding signs of inflammation.Twenty-nine aortic valves from patients with significant aortic stenosis were divided into tricuspid and bicuspid aortic valves. The bicuspid aortic stenotic valves revealed signs of inflammation to a similar extent as the tricuspid valves. However, the tricuspid and bicuspid valves differed regarding distribution of calcification. In contrast, inflammation was not a predominant feature in 15 aortic and mitral valves from patients with significant heart valve regurgitation.Gross valvular pathology consistent with rheumatic aortic stenosis was found in 10 patients. These valves revealed a somewhat lower degree of inflammatory cell infiltration, but on the whole, there were no substantial differences when compared to non-rheumatic aortic stenotic valves. They did, however, reveal a similar distribution of calcification as the bicuspid, non-rheumatic aortic valves.The VOCIN study group was compared to an age- and gender matched control group with regard to history and signs of rheumatic disease. There was not any increased prevalence of clinical manifestations of non-cardiac inflammatory disease in patients with significant heart valve disease, when compared to healthy control subjects. However, patients with heart valve disease had significantly increased serum levels of inflammatory markers compared to controls. The increase in inflammatory markers remained significant even in the subgroup of non-rheumatic aortic stenosis devoid of coronary artery disease. These results indicate that a systemic inflammatory component is associated with stenotic, non-rheumatic heart valve disease.The similarities between different forms of calcific aortic valve disease indicate a similar pathogenesis. The question is raised whether aortic stenosis is one disease, mainly caused by a general and non-specific response to dynamic tissue stress due to an underlying malformation of the valve.
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