Les patients coronariens stables ou stabilisés sont à haut risque d’évènements cardiovasculaires. Ils représentent une population hétérogène avec une présentation clinique, un terrain et un pronostic pouvant être extrêmement variables d’un patient à l’autre. Pourtant, d’après les recommandations internationales, tous doivent bénéficier d’une prise en charge relativement comparable basée sur des essais cliniques réalisés dans des sous-populations restreintes de patients stables et instables, pour la plupart anciens, et ne correspondant plus à la prise en charge actuelle des patients. Préciser les déterminants du pronostic de cette population, et notamment les stratégies thérapeutiques, est un enjeu majeur.Les antagonistes du système rénine-angiotensine (IEC/ARA2) font partie de l’arsenal médicamenteux de tout patient coronarien. Pourtant leur intérêt, en association aux antiagrégants plaquettaires et statines, est incertain chez les patients sans dysfonction ventriculaire gauche qui constituent un sous-groupe important parmi les patients stables.Le registre international REACH a évalué l’impact des IEC/ARA2 dans cette population avec 4 ans de suivi. La méthodologie statistique utilisée a été une analyse observationnelle avec ajustement ou avec appariement selon le score de propension. Il n’a pas été mis en évidence de bénéfice des IEC/ARA2 sur le critère de jugement principal composite associant décès cardiovasculaire – IDM – AVC, de même que sur le critère de jugement secondaire associant décès cardiovasculaire – IDM – AVC – Hospitalisation pour évènement athéro-thrombotique ou sur les critères tertiaires comprenant individuellement chacun des critères de jugement secondaire ainsi que sur la mortalité toute cause. Enfin il n’est pas ressorti non plus de bénéfice franc dans les sous-groupes d’analyse. Les résultats ont été concordants lorsque les analyses ont été réalisées pour les IEC seuls ou pour les ARA2 seuls, et ont été confortés par diverses analyses de sensibilité.Ces données méritent confirmation dans une cohorte indépendante. C’est l’un des objectifs du registre CLARIFY, registre de 32703 patients coronariens stables ou stabilisés, dont le suivi à 5 ans est terminé. Dans ce registre contemporain international, le taux global à 5 ans de mortalité toute cause a été de 7,9%, de mortalité non cardiovasculaire de 5% et de mortalité cardiovasculaire de 2,9%. Un évènement cardiovasculaire comprenant infarctus du myocarde (fatal ou non), angor instable, revascularisation coronaire par angioplastie ou pontage est survenu chez 15,9% des patients.Tout comme les IEC/ARA2, l’impact des bétabloquants dans la prise en charge du coronarien stable ou stabilisé, sans dysfonction ventriculaire est également controversé. Cette classe médicamenteuse est en cours d’évaluation dans CLARIFY. L’analyse tient compte du type de bétabloquant, de la dose prescrite, des éventuelles intolérances amenant à modifier leur utilisation, de la présence et de l’ancienneté d’un infarctus du myocarde et la fraction d’éjection ventriculaire gauche.CLARIFY a également pour objectif d’approfondir les déterminants du pronostic de la maladie coronarienne stable, avec une analyse spécifiquement focalisée sur la présence de symptômes angineux, d’ischémie myocardique et sur leur combinaison, en fonction de l’utilisation des méthodes de revascularisation myocardiques, pour mieux comprendre les mécanismes responsables des évènements cardiovasculaires et évoluer vers une prise en charge plus personnalisée. / Stable or stabilized coronary artery disease patients are at high risk for cardiovascular events. They represent a heterogeneous population. The clinical presentation, the context and the prognosis can be extremely variable from one patient to another. However, according to the international guidelines, those patients should be given a relatively comparable treatment based on clinical trials realized in restricted subpopulations of stable and unstable patients. Most of these trials are old, and no longer correspond to the current management. Specifying the determinants of the prognosis of this population, and in particular the therapeutic strategies, is a major challenge.The antagonist receptors of renin-angiotensin system (ACEI/ARB) are a part of the treatment of any coronary artery disease patient. Yet their interest in the prognosis of this population without left ventricular dysfunction in association with antiplatelet agents and statins is uncertain.The contemporary REACH registry has assessed the impact of ACEI/ARB in this population with a 4-year of follow-up. The statistical methodology used was based on the propensity score. After adjustment or matching with the propensity score, there was no benefit of ACEI/ARB on the primary endpoint of cardiovascular death - MI - stroke. No benefit was found on the secondary endpoint of cardiovascular death - MI - stroke - hospitalization for atherothrombotic events. No benefit was found on the tertiary criteria including individually each of the secondary endpoints and on any cause mortality. Finally,there was no clear benefit in the analyzes subgroups. These results were consistent when the analyzes were performed for ACEI alone or for ARB alone. They were also supported by sensitivity analyzes.These data should be confirmed or reversed in an independent cohort. This will be one of the many objectives of the CLARIFY registry, that enrolled 32,703 stable or stabilized coronary artery disease patients. The 5-year follow-up is complete. In this international contemporary registry, the overall 5-year rate of total mortality was 7.9%, non-cardiovascular mortality was 5% and cardiovascular mortality was 2.9%. A cardiovascular event including myocardial infarction (fatal or not), unstable angina, coronary revascularization by angioplasty or bypass surgery occured in 15.9% of patients.Like ACEI/ARB, the impact of betablockers on the management of stable or stabilized coronary artery disease without left ventricular dysfunction is also controversial. This drug class is being evaluated in CLARIFY. The analyzis takes into account the type of beta-blocker, the prescribed dose, any intolerance leading to changes in their use, the history of a myocardial infarction, and the left ventricular ejection fraction.CLARIFY will help to more define the determinants of the prognosis of stable coronary artery disease, with a more particular focus on symptomatic or not, ischemic or not, and revascularized or not, in order to better understand the mechanisms responsible for cardiovascular events, and evolve towards a more personalized and cost-effective care.

Sleep is a basic need, important to physical and psychological recovery. Insomnia implies sleep-related complaints, such as difficulty falling asleep, difficulty staying asleep, early awakening, or non-restorative sleep (NRS) in an individual who has adequate circumstances and opportunity to sleep.  Insomnia is also related to impairment of daytime functions. The prevalence of reported sleep disturbances varies between 15% and 60% in patients with coronary artery disease (CAD) up to five years after intervention. Disturbed sleep may have a negative impact on self-care capacity and behaviours. Little attention has been given to evaluation of sleep promotion through individualized non-pharmacological interventions among CAD patients. The overall aim of this thesis was to describe the impact of sleep quality and disrupted sleep on health-related quality of life (HRQoL) in patients with stable CAD, in comparison to a population-based group. The objective was also to evaluate an individualized non-pharmacological programme to promote self-care in sleep. Four studies were conducted during seven years, starting in 2001. Patients from six hospitals in the south of Sweden were invited to participate. In addition, an age and gender matched population-based group was randomly selected during the same period as the patients and was used for comparison with the CAD patients in two of the studies. Data was collected through interviews, self-reported questionnaires, a study specific sleep diary and actigraphy registrations. A pretest-posttest control design was used to evaluate whether an individualized non-pharmacological intervention programme could promote self-care in sleep-activity in CAD patients. The results showed a high prevalence of insomniac CAD patients out of whom a large proportion were non-rested insomniacs. This showed that NRS is one of the core symptoms of insomnia. On the other hand there were weak or non-significant gender differences with increasing insomnia severity. Severe insomniac CAD patients displayed a two or threefold higher presleep arousal or anxiety score and were more limited in taking physical exercise than the general population. Generally low sleep efficiency (SE%) was revealed in the studies, particularly among severe non-rested insomniac CAD patients. Among CAD patients, the individualized non-pharmacological programme to promote self-care in sleep-activity indicated improvements in sleep and HRQoL. This thesis elucidates the importance of focusing on the individual’s perception of their sleep-activity and health in their local context and supporting self-care management. Furthermore, it is of importance that nurses set individual goals together with the patient in order to increase self-efficacy to promote HRQoL.

Despite the currently recommended dual antiplatelet treatment (DAT) with aspirin and P2Y12 inhibition in patients with coronary artery disease (CAD) there is a risk of adverse clinical outcome. Pharmacodynamic (PD) poor response to clopidogrel occurs in ~ 30% of clopidogrel-treated patients and is associated with an increased risk of recurrent thrombotic events. The aims of this thesis were to compare the PD and pharmacokinetic effects of clopidogrel 600 mg loading dose (LD)/ 75 mg standard maintenance dose (MD) with the novel P2Y12 inhibitor prasugrel 60 mg LD/10 mg MD, in 110 patients with CAD. The mechanisms behind clopidogrel poor response were investigated by assessing the pharmacodynamics after adding clopidogrel active metabolite (AM) and genotyping for variation in CYP-genes involved in thienopyridine metabolism. In another study, we compared the on-clopidogrel platelet reactivity of patients with stent thrombosis (ST) (n=48) or myocardial infarction (MI) (n=30) while on DAT and their matched controls (n=50 + 28). Prasugrel achieved a faster and greater P2Y12-mediated platelet inhibition than clopidogrel measured with light transmission aggregometry, VASP and VerifyNow® P2Y12. Prasugrel’s greater platelet inhibition was associated with higher exposure of AM. The addition of clopidogrel AM led to maximal platelet inhibition in all subjects, suggesting that prasugrel’s greater antiplatelet effect was related to more efficient AM generation compared to that of clopidogrel. Lower levels of AM as well as less platelet inhibition were seen in clopidogrel-treated patients with reduced-metabolizer genotype CYP2C19 compared to those with normal genotype. Patients with ST while on DAT showed higher on-clopidogrel platelet reactivity compared to matched stented controls. Patients with spontaneous MI after stenting did not. In conclusion, these results showed a high rate PD poor response to a high bolus dose of clopidogrel because of a partly genetically caused lower generation of AM which could be overcome by prasugrel treatment. In patients after coronary stenting, clopidogrel poor response was related to ST but not to spontaneous MI, illustrating difficulties in optimizing treatment with clopidogrel based on platelet function or genetic testing in individual patients.

This study utilized data from the Hispanic Established Populations for Epidemiologic Studies of the Elderly (H-EPESE) at two different time points, seven years apart, to examine the relationship between physical illness and depressive symptoms in elderly Mexican Americans. The two physical illnesses studied are coronary artery disease and type II diabetes due to their high prevalence among Mexican Americans. The relationship between physical illness and depressive symptoms is examined longitudinally and prospectively, in both directions. In addition, the relationship between depressive symptoms and three behavioral health risk factors: alcohol use, cigarette smoking, and physical inactivity, at baseline is examined. The roles of gender, acculturation, nativity, and locus of control are examined as moderators of the key relationships studied. Additionally, self-rated health at baseline is examined as a predictor of physical illness and mortality at follow-up. / text

Η ασβέστωση των στεφανιαίων αρτηριών αποτελεί αξιόπιστο δείκτη της στεφανιαίας αθηρωμάτωσης. Η ψηφιακή ακτινοσκόπηση/ακτινογράφηση είναι μία ακριβής μη αιματηρή μέθοδος ανάδειξης της στεφανιαίας ασβέστωσης, εύκολα διαθέσιμη, χαμηλού κόστους, γρήγορη και με χαμηλή δόση ακτινοβολίας. Μέχρι τώρα δεν έχει ερευνηθεί πολύπλευρα η αξία της για την ανίχνευση της ασβέστωσης των στεφανιαίων αρτηριών. / Coronary artery calcification is a reliable indicator of coronary artery atherosclerosis. Digital subtraction cinefluoroscopy is an accurate, noninvasive, rapid, widely available method for coronary calcium detection, with low average skin penetration dose. Until now, digital cinefluoroscopy value for coronary calcium detection has not been fully elucidated.

Contents 1. Introduction 7 1.1. The aim of the study 8 1.2. Tasks of the study 9 1.3. The scientific novelty and originality of the study 9 1.4. Practical importance of the study 9 2. Material and methods 11 2.1. The contingent of studied patients 11 2.2. Methods 12 2.2.1.Coronary artery bypass grafting 12 2.2.2. The used equipment 12 2.2.3. The method of myocardial SPECT performance 12 2.2.4. Evaluation of myocardial SPECT 13 2.3. Statistical analysis of data 15 3. Results 16 3.1. The evaluation of influence of left ventricular ejection fraction on postoperative changes of perfusion of revascularized myocardium 16 3.2. The evaluation of influence of left ventricle ejection fraction on postoperative changes of contraction of revascularized myocardium 18 3.3. The evaluation of influence of collaterals on postoperative changes of perfusion of revasculized myocardium 19 3.4. The evaluation of influence of collaterals on postoperative changes of contraction of revasculized myocardium 21 3.5. The prediction of postoperative myocardial perfusion and contraction 23 3.6. The identification of period of the maximal recovery of myocardial perfusion and contraction after surgical revascularization 27 4. Conclusions 29 5. List of publications 30 6. Summary in Lithuanian 31 7. Autobiography 34 1. Introduction Heart and blood vessels diseases, the most common of which is coronary artery disease (CAD), are the leading causes of death and disability of middle-aged and elderly... [to full text]

Širdies ir kraujagyslių sistemos ligos sudaro didžiąją dalį tarp sergamumo, mirtingumo ir neįgalumo priežasčių. Mirtingumo rodiklių vertinimas - tradicinis pirminis išeičių matavimas, tačiau ir pacientai, ir medikai vis labiau domisi ne vien tuo, kaip sumažinti mirtingumą, bet ir kaip sumažinti simptomus, padidinti funkcines galimybes, kitaip tariant, pagerinti su sveikata susijusią gyvenimo kokybę. Darbo tikslas – išnagrinėti sergančiųjų IŠL su sveikata susijusią gyvenimo kokybę bei jos pokyčius ilgalaikio stebėjimo metu. Uždaviniai: 1. Išnagrinėti sergančiųjų IŠL su sveikata susijusią gyvenimo kokybę priklausomai nuo sociodemografinių rodiklių (amžiaus, lyties, išsilavinimo, darbinės padėties). 2. Išnagrinėti sergančiųjų IŠL su sveikata susijusią gyvenimo kokybę priklausomai nuo pradinės funkcinės būklės (kardiovaskulinės, psichoemocinės, miego kokybės). 3. Įvertinti kardiovaskulinės, psichoemocinės būklės bei miego kokybės įtaką sergančiųjų IŠL su sveikata susijusiai gyvenimo kokybei. 4. Įvertinti sergančiųjų IŠL (po ūminio miokardo infarkto, perkutaninės transliuminalinės vainikinių arterijų angioplastikos ir aorto-vainikinių arterijų jungčių operacijos) su sveikata susijusios gyvenimo kokybės pokyčius ilgalaikio stebėjimo metu. Tyrimo kontingentas ir metodai. Tiriamąjį kontingentą sudarė KMU Psichofiziologijos ir reabilitacijos instituto kardiovaskulinės reabilitacijos klinikos pacientai, atvykę reabilitaciniam gydymui po ūmaus miokardo infarkto, perkutaninės... [toliau žr. visą tekstą] / Cardiovascular diseases including coronary artery disease (CAD) are very prevalent in Lithuania. The primary outcome interest has traditionally been mortality, but patients and researchers are increasingly interest in identifying interventions that not only improve mortality, but also reduce symptoms, increase functional ability; in other words, improve patients health-related quality of life. Health-related quality of life represents the effect of an illness and its treatment as perceived by the patient, that it is modified by impairments, functional stress, perceptions and social opportunities, and is influenced by disease, injury, treatment or policy. The aim of the study was to analyze health-related quality of life in CAD patients and to assess its changes during long-term period. The objectives of the study: 1. To evaluate health-related quality of life in CAD patients according to sociodemographic factors (gander, age, education level and employment status). 2. To evaluate health-related quality of life in CAD patients according to functional status ���� angina pectoris, heart failure, NYHA functional class, anxiety, depression and sleep quality. 3. To assess the impact of demographic factors, cardiovascular status, psycho-emotional status and sleep quality on health-related quality of life in CAD patients. 4. To assess the health-related quality of life changes during long-term period in CAD patients (after acute myocardial infarction (MI), percutaneous transluminal... [to full text]

Advances in coronary Computed Tomography Angiography (CTA) have resulted in a boost in the use of this new technique in recent years, creating a challenge for radiologists due to the increasing number of exams and the large amount of data for each patient. The main goal of this study was to develop a computer tool to facilitate coronary CTA analysis by combining knowledge of medicine and image processing, and to evaluate the performance in clinical settings. Firstly, a competing fuzzy connectedness tree algorithm was developed to segment the coronary arteries and extract centerlines for each branch. The new algorithm, which is an extension of the “virtual contrast injection” (VC) method, preserves the low-density soft tissue around the artery, and thus reduces the possibility of introducing false positive stenoses during segmentation. Visually reasonable results were obtained in clinical cases. Secondly, this algorithm was implemented in open source software in which multiple visualization techniques were integrated into an intuitive user interface to facilitate user interaction and provide good over­views of the processing results. An automatic seeding method was introduced into the interactive segmentation workflow to eliminate the requirement of user initialization during post-processing. In 42 clinical cases, all main arteries and more than 85% of visible branches were identified, and testing the centerline extraction in a reference database gave results in good agreement with the gold standard. Thirdly, the diagnostic accuracy of coronary CTA using the segmented 3D data from the VC method was evaluated on 30 clinical coronary CTA datasets and compared with the conventional reading method and a different 3D reading method, region growing (RG), from a commercial software. As a reference method, catheter angiography was used. The percentage of evaluable arteries, accuracy and negative predictive value (NPV) for detecting stenosis were, respectively, 86%, 74% and 93% for the conventional method, 83%, 71% and 92% for VC, and 64%, 56% and 93% for RG. Accuracy was significantly lower for the RG method than for the other two methods (p<0.01), whereas there was no significant difference in accuracy between the VC method and the conventional method (p = 0.22). Furthermore, we developed a fast, level set-based algorithm for vessel segmentation, which is 10-20 times faster than the conventional methods without losing segmentation accuracy. It enables quantitative stenosis analysis at interactive speed. In conclusion, the presented software provides fast and automatic coron­ary artery segmentation and visualization. The NPV of using only segmented 3D data is as good as using conventional 2D viewing techniques, which suggests a potential of using them as an initial step, with access to 2D reviewing techniques for suspected lesions and cases with heavy calcification. Combining the 3D visualization of segmentation data with the clinical workflow could shorten reading time.

This study determined whether a pre-operative cardiac “pre-habilitation” (Prehab) program improves the health of elective coronary artery bypass graft (CABG) surgery patients to a greater extent than standard care (StanC). Seventeen elective CABG patients were randomized to StanC (n= 9) or Prehab (n= 8) at Baseline and were followed at 1-2 weeks pre-operatively (Preop) and Three months post-operatively. Functional walking ability was assessed using the 6-Minute Walk Test (6MWT) and 5-meter Gait Speed Test. Baseline data was not different between groups. Patients in StanC did not improve 6MWT scores; whereas Prehab patients improved 6MWT distance by 35% and 39% at Preop and Three months post-operatively, respectively (p<0.05). Gait speed scores were 25% and 27% lower in Prehab patients at Preop and Three months post-operatively, respectively, as compared to StanC (p<0.05). These data suggest that Prehab is an attractive intervention for enhancing functional walking ability before and after elective CABG surgery.

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