Lipoprotein(a) (Lp(a)) consists of an LDL-like particle and the specific protein apo(a), which is very similar to plasminogen. Apo(a) contains repeated kringle structures and a serine protease domain, which cannot be activated by t-PA. Lp(a) is considered to be a predictor for atherosclerotic disease. It has been found incorporated in atherosclerotic plaques and inhibits in vitro fibrinolysis. Lp(a) was determined in 1527 randomly selected individuals participating in the Northern Sweden WHO-MONICA project. A weak but significant relation between Lp(a) and increasing age was found. Menopausal status was the strongest independent predictor of Lp(a) level in women. Fibrinogen was independently related to Lp(a) in both sexes. Only a minor fraction of Lp(a) variance could be explained for in a multiple regression model, which is in agreement with the contention that Lp(a) is highly genetically determined. Lp(a) was determined in 1571 patients investigated with coronary angiography because of suspected severe coronary artery disease (CAD). Patients with proven CAD at elective angiography had significantly higher Lp(a) than patients without significant CAD or healthy controls. Lp(a) was found to be an independent discriminator of CAD in both sexes. HLA-DR genotype 13 or 17 was found more frequently in 30 male patients with angiographic CAD at young age (&lt; 50 years) than in 30 age matched controls. These genotypes were common in patients with high Lp(a) levels, which indicates that Lp(a) may be related to immunological processes. The reaction of Lp(a) was investigated in 32 patients with acute myocardial infarction (AMI). Lp(a) increased during the first week, but the response was comparatively weak. Individual Lp(a) responses were heterogeneous and no correlations to infarct size or changes in the acute phase proteins were found. In a randomized cross-over study on 36 hypercholesterolaemic patients treated with simvastatin/placebo during 12+12 weeks Lp(a) did not change significantly, but patients with high Lp(a) levels at baseline tended to develop further increased Lp(a). To conclude, Lp(a) was found to be an independent predictor of angiographic CAD in both men and women. Lp(a) levels are primarily genetically determined and only a small fraction of Lp(a) variance could be explained by other factors in this study. Lp(a) may be related to HLA DR types and immunological processes involved in atherosclerotic disease. Lp(a) increased slightly during the first week of AMI, but was not related to changes in the acute-phase proteins. The effective LDL-lowering agent simvastatin did not influence Lp(a) significantly. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1993, härtill 5 uppsatser.</p> / digitalisering@umu

Congenital heart disease (CHD) is the most common birth defect in infants. Identifying factors that are critical to embryonic heart development or CHDs in general could further our understanding of the disease and may lead to new strategies of its prevention and treatment. Endothelial nitric oxide synthase (NOS3/eNOS) is known for many important biological functions including vasodilation, vascular homeostasis and angiogenesis. Previous studies have shown that deficiency in NOS3 results in congenital septal defects, cardiac hypertrophy and postnatal heart failure. In addition, NOS3 is pivotal to morphogenesis of aortic valve and myocardial capillary development. The aim of my thesis was to investigate the role of NOS3 in the embryonic and adult heart. I discovered that NOS3 deficiency resulted in coronary artery hypoplasia in fetal mice and spontaneous myocardial infarction in postnatal hearts. Coronary artery diameters, vessel density and volume were significantly decreased in NOS3-/- mice at postnatal day 0. Lack of NOS3 also down-regulated the expression of Gata4, Wilms tumor-1, vascular endothelial growth factor, basic fibroblast growth factor and erythropoietin in the embryonic heart at E12.5, and inhibited migration of epicardial cells into the myocardium. In addition, my data show that the overall size and length of mitral and tricuspid valves were decreased in NOS3-/- compared with WT mice. Echocardiographic assessment showed significant regurgitation of mitral and tricuspid valves during systole in NOS3-/- mice. Immunostaining of Snail1 was performed in the embryonic heart. Snail1 positive and total mesenchymal cells in the AV cushion were decreased in NOS3-/- compared with WT mice at E10.5 and E12.5. Finally, in the adult aortic valves, NOS3 is important in inhibition of thrombosis formation. Deficiency in NOS3 leads to aortic valve thrombosis and calcification. At 12 months old, 72% (13/18) of NOS3-/- mice showed severe spontaneous aortic valve thrombosis compared with WT mice (0/12). Ex vivo culture of aortic valves showed that platelet aggregation and adhesion were significantly increased in NOS3-/- aortic valves compared with WT aortic valves. There was also a significant regurgitation of the aortic valve during systole in the NOS3-/- compared with WT mice. In addition, NOS3 deficiency resulted in significant aortic valve stenosis, calcification and fibrosis. In summary, these data suggest NOS3 plays a critical role in embryonic heart development and morphogenesis of coronary arteries and inhibits thrombosis formation in the adult aortic valves.

Background: Pulmonary artery sarcoma is a rare tumor with a poor prognosis. Case Report: We report the case of a 64-year-old man with an intimal pulmonary artery sarcoma presenting with severe high oxygen flow-demanding dyspnea and weight loss of 12 kg in the last 6 months. On echocardiography, right heart insufficiency, markedly elevated right ventricular pressure, a pressure gradient along the right outflow tract, and a tumor mass adherent to the wall of the truncus pulmonalis were detected. The tentative diagnosis by echocardiographic findings was pulmonary artery sarcoma. Computed tomography of the thorax and 18-fluorodeoxyglucose positron emission tomography showed an advanced local tumor manifestation. Surgical resection of the tumor to improve hemodynamics confirmed the diagnosis. Conclusions: Pulmonary artery sarcoma should be considered as a rare differential diagnosis in patients with dyspnea due to right heart failure, particular in the case of additional weight loss, and echocardiographic examination is a useful first diagnostic approach in establishing the diagnosis. / Hintergrund: Das Pulmonalarteriensarkom ist eine seltene Erkrankung mit einer schlechten Prognose. Fallbericht: Wir berichten über einen 64-jährigen Mann mit einem intimalen Pulmonalarteriensarkom, der sich mit starker Luftnot trotz hoher Sauerstoffsubstitution und einem Gewichtsverlust von 12 kg in den letzten 6 Monaten vorstellte. Echokardiographisch fielen eine Rechtsherzinsuffizienz, ein deutlich erhöhter rechtsventrikulärer Druck, ein Druckgradient über dem rechten Ausflusstrakt und eine Tumormasse im Bereich des Trunkus pulmonalis mit Kontakt zur Gefäßwand auf. Die mittels Echokardiographie erhobene Verdachtsdiagnose lautete Pulmonalarteriensarkom. Die Computertomographie des Thorax und die 18-Flur-Desoxyglukose-Positron-Emissionstomographie erbrachten den Befund eines lokal fortgeschrittenen Tumors. Die chirurgische Resektion des Tumors, die zur Verbesserung der Hämodynamik durchgeführt wurde, bestätigte die Diagnose. Schlussfolgerungen: Das Pulmonalarteriensarkom sollte differenzialdiagnostisch als eine seltene Ursache der Luftnot im Rahmen einer Rechtsherzinsuffizienz, insbesondere bei zusätzlichem Gewichtsverlust, in Erwägung gezogen werden. Die Echokardiographie stellt eine wertvolle initiale Untersuchungsmethode bei der Diagnosestellung dar. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Coronary artery bypass surgery (CABS) is highly stressful for couples, since comorbid anxiety and depression are most commonly reported and hence most researched pre- and postoperative emotional states. Thus, patients' psychological well-being may contribute more to the level of disability than their physical impairment. Despite this extremely stressful process, psychological preparation is ironically often neglected in CABS couples. The primary aim of the study was to examine the feasibility of hypnotherapeutic ego strengthening (HES) to enhance the ability of CABS couples' to cope with psychological distress associated with hospitalisation and surgery. Secondary aims were to determine the contribution of HES in reducing anxiety and depression, as well as enhancing and maintaining ego strength, quality of life and dispositional optimism in CABS patients and spouses. An overview of coronary heart disease (CHD), risk factors involved, psychological aspects concomitant to CABS (specifically anxiety and depression) and a conceptualisation of HES according to the relevant literature, preceded the empirical study. The experimental design consisted of a two-group, pre-post-follow-up assessment design. A sample of fifty married, male patients admitted to Unitas Hospital in Pretoria with a first, uncomplicated CABS was randomly assigned, together with their spouses, to an experimental- (n = 25) and control group (n = 25). Informed consent was obtained for all project participants. Thus, both groups consisted of twenty-five patients and spouses. To test the hypotheses, experimental patients and spouses were required to participate in the HES intervention. Respondents completed the Beck Depression Inventory (BDI-II) (Beck, Steer, & Brown, 1995). Profile of Mood States (POMS) (McNair, Lorr & Doppleman, 1992), Epstein and O'Brien Ego Strength Scale (1982), Quality of Life Inventory (QOLI) (Frisch, 1994) as well as the Life Orientation Test (LOT) (Scheier & Carver, 1985). Test administration of couples occurred preoperatively, on the day of discharge, and at six-week follow-up. Before commencing the intervention, group comparability was confirmed by means of the t-test for independent groups. At programme completion the significance of differences within and between groups was determined by means of t-tests. Statistically significant p-values were subjected to Cohen's d statistic to determine the practical significance of the findings. A confidence interval of 99% determined the values of the differences between the postoperative and follow-up findings. Results confirmed that the HES intervention significantly reduced postoperative anxiety and depression levels in experimental CABS patients and spouses, which was maintained at follow-up. No change was observed among control group patients and spouses. Moreover, the HES intervention significantly improved and maintained postoperative ego strength, quality of life and dispositional optimism in experimental CABS couples. The overall outcome of the control patients and spouses revealed a decreasing trend with regard to dispositional optimism and quality of life. Qualitative responses largely confirmed quantitative indications of reduced comorbidity and enhanced psychological well-being among experimental participants. Despite design limitations, the results confirmed that HES enhanced CABS couples' inner resources and attenuated concomitant negative mood states. Thus, it was concluded that HES played a meaningful role in the preparation and care of CABS couples by reducing comorbidity and improving their psychological well-being. Finally, recommendations for further studies were made. / Thesis (Ph.D. (Psychology))--North-West University, Potchefstroom Campus, 2004.

The potential that telemedicine interventions may have in effectively delivering remote specialized cardiovascular care to large numbers of patients with heart diseases has recently come under question. In the first phase of this thesis, a systematic review and meta-analysis was conducted to compare the impact of a basic form of telemedicine that is regular patient follow-up by telephone, with usual care for individuals with coronary artery disease following their discharge. In the second phase of this thesis, a network meta-analysis, using Bayesian methods for multiple treatment comparisons, was conducted to compare the more complex forms of telemedicine for patients with heart failure. In the third and final phase of this thesis, a randomized controlled trial was designed to compare the impact of two forms of telemedicine, identified in the earlier two phases as being the most promising, on clinical outcomes, cardiac risk factors and patient reported outcomes.

Psichosocialiniai veiksniai turi įtakos išeminės širdies ligos (IŠL) vystymuisi ir komplikacijų atsiradimui. Depresijos ir nerimo patogenezėje dalyvauja pagumburio-hipofizės-antinksčių ašis. Skydliaukės hormonų pokyčiai taip pat dažnai randami sergantiesiems IŠL bei depresija. Nuovargis ir su sveikata susijusi gyvenimo kokybė priklauso ne tik nuo geros fizinės sveikatos, bet ir nuo psichoemocinės būklės, todėl svarbu kompleksiškai įvertinti hormoninių žymenų ir elgesio veiksnių (depresijos, nerimo ir nuovargio) sąveikos įtaką sergančiųjų IŠL gyvenimo kokybei, ligos eigai bei baigtims. Šio tyrimo tikslas buvo išnagrinėti kortizolio ir skydliaukės ašies hormonų koncentracijų ryšį sergantiesiems IŠL su N-galinio smegenų tipo natriuretinio propeptido (NT-proBNP) koncentracija bei subjektyviomis sveikatos būklėmis: depresijos, nerimo simptomais, nuovargiu ir su sveikata susijusia gyvenimo kokybe. Tyrimas parodė skydliaukės hormonų ir kortizolio koncentracijų reikšmingą ryšį su subjektyviu sveikatos vertinimu sergantiesiems IŠL. Mažesnė bendrojo T3, laisvojo T4 ir didesnė reversinio T3 koncentracija susijusi su didesne NT-proBNP koncentracija, depresijos simptomų pasireiškimu, didesniu nuovargiu ir blogesniu su sveikata susijusios gyvenimo kokybės vertinimu. Didesnė rytinio kortizolio koncentracija susijusi su depresijos simptomų pasireiškimu moterims. Gauti duomenys gali būti panaudoti sergančiųjų IŠL depresijos bei nerimo simptomams, ligos eigai, prognozei ir gyvenimo kokybei... [toliau žr. visą tekstą] / Psychosocial factors affect the occurrence of coronary artery disease (CAD) disease and development of complications. People with depression or anxiety symptoms have the activate hypothalamic-pituitary-adrenal axis. Thyroid hormone changes are also found in patients with CAD. Fatigue and health-related quality of life (HRQoL) depends not only on good physical health, but also on psychoemotional state, especially on the presence of depression and anxiety disorders. Therefore, it is important to evaluate complex of hormonal markers and behavioral factors (depression, anxiety and fatigue) interaction on patients with CAD for quality of life, disease course and outcome. The aim of this study was examine relationship of cortisol and thyroid axis hormones concentrations with NT-pro B type natriuretic peptide (NT-proBNP) concentrations and with patient oriented outcomes such as depressive symptoms, fatigue and HRQoL in CAD patients. Study demonstrates relationship between thyroid axis hormones and cortisol concentrations with depression, anxiety symptoms, fatigue and HRQoL in CAD patients. Low T3, free T4 and higher RT3 concentrations are associated with higher NT-proBNP levels, depression symptoms, higher fatigue and worse HRQoL. Higher morning cortisol concentrations are associated with depression symptoms in women. The data obtained can be used in patients with coronary artery disease and depressive anxiety disorder, disease progression, and prognosis and quality of life... [to full text]

Didėjant vyresnių žmonių populiacijai amžinė geltonosios dėmės degeneracija (AGDD) yra vis dažnesnė vyresnio nei 50 metų amžiaus žmonių negrįžtamo regos netekimo priežastis. AGDD prevencinės priemonės bei gydymo galimybės ribotos, nes ligos etiopatogenezė iki šiol nėra visiškai aiški. Disertacinio darbo metu įvertintos AGDD ir išeminės širdies ligos (IŠL) sąsajos, atsižvelgiant į vainikinių arterijų aterosklerozinius pažeidimus. Pirmą kartą analizuota SCARB1 rs5888 C/T genotipų įtaka AGDD ir IŠL pasireiškimui. Tyrimo rezultatai parodė, kad AGDD ir IŠL, kai vainikinėse arterijose yra aterosklerozinių pažeidimų (IŠLath+), sieja bendri, šių ligų pasireiškimo galimybę didinantys, klinikiniai veiksniai ir oksidacinis stresas. Nustatytas „apsauginis“ SCARB1 rs5888 T/T genotipas, mažinantis AGDD ir IŠLath+, bei „rizikingas“ SCARB1 rs5888 C/T genotipas, didinantis AGDD+IŠLath+ galimybę. Pritaikius matematinės morfologijos metodus, nustatyta, jog sergantiems vėlyvąja AGDD SCARB1 rs5888 „rizikingas“ genetinis variantas susijęs su didesniu centrinės tinklainės dalies pažeidimo plotu. Bendrų AGDD ir IŠL patogenezinių grandžių tyrimas suteikia naujos informacijos apie AGDD etiologiją, patogenezę ir galbūt pasitarnaus efektyvaus gydymo bei prevencijos krypčių kūrimui. Tyrimo metu taikyti morfometriniai geltonosios dėmės pažaidos ploto matavimai gali būti naudojami gydytojų-oftalmologų klinikinėje praktikoje, siekiant tiksliau įvertinti centrinės tinklainės dalies pokyčius dinamikoje... [toliau žr. visą tekstą] / Age-related macular degeneration (ARMD) is the commonest cause of blindness among persons over the age of 50 and its prevalence is likely to increase as a consequence of population ageing. ARMD is a disorder of unknown cause and pathogenesis, therefore current options for ARMD prevention and treatment are limited. In the recent study the associations between ARMD and CAD, according the angiographic findings of atherosclerosis in the coronary arteries, were analyzed. The oxidative stress impact and clinical factors determining susceptibility to ARMD and CADath+, separately and common susceptibility factors for both diseases prediction were ascertained. Analysis of novel genetic biomarker, the rs5888 variant of SCARB1 gene, identified the „protective“ SCARB1 rs5888 TT genotype, associated with the lower risk of ARMD and CADath+, and a „risk-determining“ CT genotype, determining higher ARMD+CADath+ risk. The evaluation of macular lesion area by using the methods of mathematical morphology revealed that in late stage ARMD subjects carriers of SCARB1 rs5888 CT genotype the area of macular lesion was larger than in TT genotype carriers. New information about ARMD and CAD discovered additional knowledge about ARMD etiopathogenesis and might be helpfull in search of new treatments or strategies for ARMD prevention. Evaluation of macular lesion area by mathematical morphology methods used in this study may be useful in ophthalmological practice to monitor the dynamics of ARMD.

Non invasive in vivo imaging will lead to better understanding of Angiotensin II Type 1 Receptor’s (AT1R) role in disease progression and may guide therapy in cardiovascular patients. Two models were used in this project: 5/6 nephrectomy and transient left anterior descending (LAD) ligation. Rats were scanned with [13N]ammonia and [11C]methyl-candesartan, both of which are Positron Emission Tomography (PET) tracers, at 8 weeks (nephrectomy) and 2 weeks (LAD ligation) after surgery. Western blot analysis was used to corroborate PET data. Nephrectomy: Renal AT1R image analysis displayed a 40% decrease in kidney AT1R in nephrectomized animals compared to sham (p<0.05) which was confirmed with Western blot and biodistribution. LAD ligation: Left Ventricle AT1R Western blot analysis exhibited a 60% increase in 20min ligation (p<0.05) with maintained myocardial blood flow. In conclusion, changes in renal AT1R were successfully imaged using [11C]methyl-candesartan in nephrectomized animals, and 20min LAD ligation/reperfusion is an appropriate model to image an increase in cardiac AT1R following ischemic injury.

Arteries respond to changes in global mechanical parameters (pressure, flow rate, and longitudinal stretching) by remodeling to restore local parameters (circumferential stress, shear stress, and axial strain) to baseline levels. Because a change in a single global parameter results in changes of multiple local parameters, the effects of individual local parameters on remodeling remain unknown. This study uses a novel approach to study remodeling in organ culture based on independent control of local mechanical parameters. The approach is illustrated by studying the effects of circumferential and shear stress on remodeling-related biological markers. Porcine carotid arteries were cultured for three days at a circumferential stress of 50 kPa or 150 kPa or, in separate experiments, a shear stress of 0.75 Pa or 2.25 Pa. At high circumferential stress, matrix synthesis, smooth muscle cell proliferation, and cell death are significantly greater, but matrix metalloproteinase-2 (MMP-2) and pro-MMP-2 activity are significantly less. In contrast, biological markers measured were unaffected by shear stress. Applications of the proposed approach for improved understanding of remodeling, optimizing mechanical conditioning of tissue engineered arteries, and selection of experimentally motivated growth laws are discussed.

Myocardial ischemia is a major cause of postoperative heart failure and adverse outcome in coronary artery bypass graft surgery (CABG). Conventional treatment of postoperative heart failure with inotropic drugs may aggravate underlying ischemic injury. Glutamate has been claimed to increase myocardial tolerance to ischemia and promote metabolic and hemodynamic recovery after ischemia. The aim of this work was to investigate if intravenous glutamate infusion given in association with CABG for acute coronary syndrome can reduce mortality and prevent or mitigate myocardial injury and postoperative heart failure. We also wanted to assess neurological safety issues, as a concern with the use of glutamate is that it may act as an excitotoxin under certain conditions.A metabolic strategy for perioperative care was assessed in an observational study on 104 consecutive patients with severe left ventricular dysfunction undergoing CABG. Based on encouraging clinical results, unsurpassed in the literature, the GLUTAMICS-trial was initiated. 861 patients undergoing CABG for acute coronary syndrome were randomly allocated to blinded intravenous infusion of L-glutamicacid solution or saline. The primary endpoint was a composite of postoperative mortality (≤30 days), perioperative myocardial infarction and left ventric ular heart failure in association with weaning from cardiopulmonary bypass. Secondary endpoints included neurological safety issues, degree of myocardial injury,postoperative hemodynamic state, use of circulatory support and cardiac mortality.The event rate was lower than anticipated and the primary endpoint did not differ significantly between the groups. Regarding secondary endpoints there were significant differences compatible with a beneficial effect of glutamate on post-ischemic myocardial recovery. The putative effect of glutamate infusion was seen in more ischemic patients (CCS class IV) and in patients with evident or anticipated LV-failure on weaning from CPB. No evidence for increased incidence of clinical or subclinical neurological injury was found. In conclusion, intravenous glutamate infusion is safe in the dosages employed and could provide a novel and important way of promoting myocardial recovery after ischemic injury.