Background: Sleep disorders have been considered risk factors for cardiovascular disease, including coronary artery disease (CAD). Therefore, poor sleep quality should be frequent complaint in patients with coronary disease. However, in patients with CAD, the prevalence of poor sleepers and factors associated were not properly investigated. Objectives: To evaluate the frequency and the factors associated with poor sleepers in patients with chronic CAD. Method: We used validated questionnaires to examine sleep quality (Pittsburgh Sleep Quality Index; PSQI), high risk of obstructive sleep apnea (Berlin Questionnaire; BQ), excessive sleepiness (Epworth Sleepiness Scale; ESS), angina-related health status (Seattle Angina Questionnaire; SAQ) and quality of life (Medical Outcomes Study 36-item Short Form; SF-36) in 257 volunteers with stable CAD, mean age 62.5 ± 10.5 years. We categorized and compared good and poor sleepers, according to PSQI global score. Subsequently, adjusted analysis was performed to investigate the factors associated with poor sleepers and demographics, clinical characteristics, risk for obstructive sleep apnea, excessive sleepiness, angina-related health status and quality of life. Results: The majority of CAD patients (75.1%) were poor sleepers. The adjusted analysis indicated that older patients (OR 1.05, 95% CI 1.02 to 1.09; p = 0.004), women gender (OR 3.09, 95% CI 1.48 to 6.45; p = 0.003), lower ejection fraction (OR 1.04, 95% CI 1.01 to 1.06; p = 0.015), lower physical limitation (OR 1.03, 95% CI 1.00 to 1.05; p = 0.020), lower angina stability (OR 1.02, 95% CI 1.00 to 1.04; p = 0.027), worse angina-related quality of life (OR 1.03, 95% CI 1.01 to 1.05; p = 0.002) and lower vitality (OR 1.02, 95% CI 1.00 to 01.03; p = 0.042) were associated with poor sleepers. Conclusion: Poor sleepers were highly frequency in chronic CAD patients. Patients with chronic CAD and poor sleepers present higher age, women gender, lower ejection fraction, higher physical limitation, lower angina stability, lower angina-related quality of life and lower vitality. / Introdução: Distúrbios do sono têm sido considerados fatores de risco para doença cardiovascular, inclusive para doença arterial coronariana (DAC). Portanto, qualidade do sono ruim deve ser queixa frequente em portadores de doença coronariana. Entretanto, em portadores de DAC, a prevalência de qualidade do sono ruim e os fatores associados não foram devidamente investigados. Objetivos: Avaliar a prevalência e investigar os fatores associados à qualidade do sono ruim em pacientes portadores de DAC crônica. Métodos: Foram utilizados questionários validados para examinar a qualidade do sono (Índice de Qualidade de Sono de Pittsburgh; PSQI), o alto risco para apneia obstrutiva do sono (Questionário de Berlim; QB), a sonolência excessiva (Escala de Sonolência de Epworth; ESE), o status funcional relacionado à angina (Questionário de Seattle sobre Crise de Angina; QSA) e a qualidade de vida relacionada à saúde (Questionário de Qualidade de Vida SF-36; SF-36), em 257 voluntários com DAC crônica, com idade média de 62,5 ± 10,5 anos. Os pacientes foram categorizados em dois grupos, boa qualidade do sono e qualidade do sono ruim, de acordo com a pontuação global do PSQI. Posteriormente, foi realizada a análise multivariada para investigar a associação entre qualidade do sono ruim e fatores demográficos, características clínicas gerais, risco para apneia obstrutiva do sono, sonolência excessiva, status funcional relacionado à angina e qualidade de vida relacionada à saúde. Resultados: A maioria dos pacientes com DAC crônica (75,1%) apresentaram qualidade do sono ruim. A Análise multivariada indicou que pacientes com idade avançada (OR 1.05, IC 95% 1.02 - 1.09; p = 0,004), gênero feminino (OR 3.09, IC 95% 1.48 - 6.45; p = 0,003), menor fração de ejeção (OR 1.04, IC 95% 1.01 - 1.06; p = 0,015), maior limitação física (OR 1.03, IC 95% 1.00 - 1.05; p = 0,020), menor estabilidade da angina (OR 1.02, IC 95% 1.00 - 1.04; p = 0,027), pior qualidade de vida relacionada à angina (OR 1.03, IC 95% 1.01 - 1.05; p = 0,002) e menor vitalidade (OR 1.02, IC 95% 1.00 - 1.03; p = 0,042), foram associados à qualidade do sono ruim. Conclusão: Qualidade do sono ruim foi altamente frequente em pacientes com DAC crônica. Pacientes portadores de DAC crônica e pior qualidade do sono apresentam maior probabilidade de serem mais idosos, do gênero feminino, apresentarem menor fração de ejeção, maior limitação funcional, menor estabilidade da angina, pior qualidade de vida relacionada à angina e menor vitalidade.

Introduction: Jusqu’à la moitié des patients souffrant d’angine de poitrine vont continuer à être symptomatiques malgré une revascularisation coronarienne pour leur angine. Par ailleurs, l’évaluation de l’angine souffre du biais d’adaptation au seuil ischémique, phénomène par lequel les patients réduisent leur niveau d’activité physique pour limiter leurs symptômes. L’étude NOVA-SKIN (NCT02591758) utilise une veste intelligente (Hexoskin™) afin de (i) valider l’électrocardiogramme (ECG) de cette veste avec le Holter et l’épreuve d’effort (ii) dériver un “indice de vitalité” à partir des mesures biométriques de la veste, afin d’ajuster les mesures conventionnelles d’angine pour le biais d’adaptation au seuil ischémique et dériver des mesures d’angine digitale et (iii) évaluer si la réadaptation cardiaque à domicile peut être surveillée à distance avec le Hexoskin. Méthodes: Trente patients référés pour angiographie coronarienne pour leur angine réfractaire au traitement médical ont complété une épreuve d’effort et ont porté la veste Hexoskin (avec enregistrement simultané d’Holter) pendant 48 heures, 2 semaines avant leur examen. Les patients furent revus 2 semaines après la revascularisation coronarienne percutanée ou 6 semaines après la chirurgie cardiaque s’ils ont eu des pontages, où ils ont porté la veste Hexoskin avec Holter pendant 48 heures et fait une épreuve d’effort. Nous avons dérivé un indice de vitalité digital (Indice de vitalité = fréquence cardiaque * activité) chez chaque patient pour les deux enregistrements de la veste. Nous avons dérivé des mesures d’angine digitale en divisant ou multipliant (selon la direction de l’effet post coronarographie attendu) les mesures d’angine conventionnelle (classe SCC, pointage de qualité de vie, décompte de nitroglycérine et décompte d’angine) par l’indice de vitalité propre au patient. Nous avons comparé les différences (pré- et post-coronarographie) de mesures d’angine ajustées pour l’indice de vitalité dérivé à partir d’une veste intelligente (« angine digitale ») avec les mesures d’angine conventionnelles non ajustées. Les participants devaient ensuite compléter 6 sessions de réadaptation cardiaque à domicile sur une période de 1 mois. Une corrélation de Pearson fut obtenue entre la fréquence cardiaque de l’ECG de l’Hexoskin et celle du Holter et du tapis roulant. L’indice de vitalité pré et post-angiographie fut comparé en utilisant un test t et nous avons mesuré la taille de l’effet du traitement de l’angine dans le même patient, pour les mesures ajustées et non ajustées d’angine. Résultats: Trente patients, âgés de 68.0±7.0 ans, majoritairement des hommes (n=28; 93.3%) ont subi une angiographie coronarienne et ont été traités, pour leur angine, de façon percutanée (n=20; 66.7%), avec pontages (n=6; 20.0%) ou avec traitement médical (n= 4; 13.3%). Tous les patients étaient en rythme sinusal au départ. La fréquence cardiaque obtenue avec l’ECG de l’Hexoskin avait une corrélation très forte avec celle obtenue avec l’ECG du tapis roulant (r=0.95) et forte avec l’Holter (r=0.85). L’indice de vitalité a augmenté de manière significative (2.30±1.38 pré vs 2.70±1.12 post-traitement de l’angine; p=0.05). Les mesures d’angine digitale ayant montré une différence plus importante que les mesures conventionnelles sont le décompte hebdomadaire de nitroglycérine, l’échelle de santé globale du SF-36, la durée d’effort sur le tapis roulant et le nombre de METS maximal. Par ailleurs, chez les patients classifiés comme non-répondants au traitement de l’angine par mesures conventionnelles, les mesures d’angine digitale suivantes se sont améliorées de façon significative: classe SCC, décompte hebdomadaire d’angine, questionnaire d’angine de Seattle et la durée d’effort pendant l’épreuve d’effort. Aucun évènement cardiovasculaire ne s’est produit durant la réadaptation cardiaque à domicile et 93.3% des patients ont complété les 6 sessions. Conclusion : Dans notre étude pilote, l’ECG de Hexoskin a obtenu des mesures de fréquence cardiaque valides lorsque comparées au Holter et au tapis d’effort. L’incorporation d’un indice de vitalité obtenu à partir d’une veste intelligente a permis d’ajuster des mesures d’angine pour celui-ci et obtenir une angine digitale. La mesure d’angine digitale a une plus grande taille de l’effet post traitement de l’angine par revascularisation et peut détecter davantage de changements, au-delà des mesures d’angine conventionnelles. Cela est plus marqué chez les patients initialement classifiés comme “non-répondants” au traitement de l’angine. La réadaptation cardiaque à domicile fut sécuritaire et complétée par la majorité des patients. / Introduction : Up to half of coronary artery disease patients will remain symptomatic of angina, despite coronary revascularization. Moreover, the assessment of angina suffers from the ischemic threshold adaptation bias where patients will restrict their physical activity level in order to minimize their angina symptoms. The NOVA-SKIN study (NCT02591758) was designed to use a novel “smart clothing” (Hexoskin™) to (i) validate the electrocardiogram (ECG) signal of against traditional Holter and Treadmill stress tests (ii) to derive a ‘vitality index’ using the biometric measures obtained from the Hexoskin in order to adjust conventional angina assessment metrics to account for the ischemic threshold adaptation bias and derive a digital measure of angina and to (iii) assess if home cardiac rehabilitation can be remotely monitored using the Hexoskin system. Methods: Thirty stable angina patients referred for coronary angiography for refractory angina underwent a treadmill stress test and then simultaneously wore the Hexoskin vest and a traditional Holter monitor for 48 hours, 2 weeks before their exam. The patients were followed up 2 weeks after the percutaneous coronary intervention and 6 weeks after their cardiac surgery if they had coronary artery bypass graft. During the follow-up visit, they wore the vest with a Holter monitor for 48 hours and underwent another treadmill stress test. We obtained an average vitality index pre- and post-angiogram (Vitality index=heart rate * activity) using recordings from the vest. We also obtained health related questionnaires during the same timeframe. We compared differences in conventional angina metrics adjusted for the vitality index (“digital angina”) with the conventional metrics unadjusted for the vitality index, pre- and post-coronary angiography. Patients then had to complete 6 home cardiac rehabilitation sessions during a 1-month period. Pearson correlation was obtained between the heart rate (HR) derived from the ECG of the vest and the HR of the Holter and treadmill stress test. The vitality index pre and post-angiography was compared using a t-test. We derived digital angina metrics by dividing or multiplying (according to the direction of the effect expected post-coronarography) the conventional angina metrics. Then we measured the effect size of the angina treatment and compared it between adjusted and unadjusted metrics within the same patient. Results: Thirty patients aged 68.0±7.0 years (93.3% men; n=28) were enrolled in the study. Patients were treated with percutaneous coronary intervention (n=20; 66.7%), coronary artery bypass grafting (n=6; 20.0%) or medical therapy (n=4; 13.3%). The heart rate from ECG signal of the Hexoskin demonstrated a very strong correlation with that of the treadmill stress test ECG (r=0.95) and a strong correlation with the Holter (r=0.85). The vitality index increased significantly from 2.30±1.38 to 2.70±1.12 (p=0.05). The digital angina metrics (adjusted for the vitality index) that were found to be more responsive to the treatment of the angina than conventional were: the weekly nitroglycerin count, the global health sub-scale of the SF-36, the treadmill stress test length and the peak METs. Furthermore, in patients classified as non-responders to the treatment of angina by conventional metrics, the digital angina measures improved significantly, when looking at the CCS class, the weekly angina count, the Seattle Angina Questionnaire metrics and the duration of exercise on the treadmill stress test. No adverse events occurred during home cardiac rehabilitation and 28 patients completed all 6 sessions wearing the Hexoskin. Conclusion : In our pilot study, the Hexoskin ECG was well correlated with standard HR measurement using a treadmill ECG or a Holter. Adjusting conventional metrics for the vitality index allows for greater sensitivity in gauging the effect of revascularization on angina than conventional metrics alone, particularly for patients who would be considered non-responders to their treatment based on conventional metrics. Home cardiac rehabilitation was safe and was completed by most patients.

Hjärt-kärl sjukdom är den vanligaste dödsorsaken i västvärlden. Samtidigt som antalet patienter med hjärtinfarkt har minskat, har antalet patienter med instabil kranskärlsjukdom d.v.s. svår kärlkramp ökat påtagligt. Diagnosen är nu den vanligaste orsaken till vård på hjärtinfarktavdelningar i Sverige. Modern behandling av instabil kranskärlssjukdom består av en kombination av läkemedel för att minska blodproppsbildning och avlasta hjärtarbetet samt, i de flesta fall, s.k. ballongvidning eller operation av hjärtats kranskärl. Trots stora behandlingsframsteg är risken för hjärtinfarkt och död hög, såväl på kort som lång sikt. Det finns därför ett stort behov av ytterligare förbättrad behandling utan att samtidigt erhålla oacceptabelt hög risk för allvarliga biverkningar. För att erbjuda en effektiv behandling till patienter med hög risk och samtidigt undvika dyr och potentiellt riskfylld behandling till patienter med låg risk behövs också bättre instrument för tidig riskbedömning. Syftet med avhandlingen var att undersöka en stor grupp patienter med instabil kranskärlssjukdom avseende säkerhet och effektivitet av en behandlingskombination av två moderna blodproppshämmande läkemedel, dalteparin och abciximab (ca 1000 patienter). Syftet var också att studera hur denna behandling påverkar system för inflammation och koagulation (ca 400 patienter). Dessutom ville vi värdera hur blodnivåer av markörer för inflammation, hjärtmuskelskada och nedsatt hjärtfunktion kan förutsäga risken för framtida komplikationer (ca 7000 patienter). Tillägg av abciximab till dalteparin minskade inte risken för dödsfall eller hjärtinfarkt inom trettio dagar. Däremot ökade antalet blödningskomplikationer. Totala antalet blödningar var emellertid relativt lågt och behandlingen syntes vara lika säker som kombinationen av abciximab och det internationellt mycket använda blodproppshämmande medlet heparin. Trots den kraftfulla behandlingskombinationen skedde en samtidig aktivering av system för såväl inflammation som koagulation. Detta kan vara en orsak till den observerade avsaknaden av behandlingseffekt av abciximab. Att hindra denna aktivering skulle samtidigt kunna innebära möjligheter för nya behandlingsstrategier. Förhöjda nivåer av markörer för hjärtmuskelskada (troponin T), inflammation (CRP), nedsatt hjärtfunktion (proBNP) eller nedsatt njurfunktion (kreatininclearance) ökade risken för dödlig utgång både på kort och lång sikt, oberoende av andra riskfaktorer. En kombination av två av dessa markörer gav den högsta risken för dödlig utgång. Således dog endast 0.3 % av patienter med låga nivåer av proBNP och normal njurfunktion inom ett år, jämfört med 25.7 % av patienter med höga nivåer av proBNP och nedsatt njurfunktion. Förhöjda nivåer av troponin T eller nedsatt kreatininclearance (men inte av CRP eller proBNP) ökade dessutom risken för hjärtinfarkt. Resultaten i avhandlingsarbetet har givit kliniskt tillämpbar kunskap om hur kärlkrampspatienter med hög respektive låg risk kan selekteras tidigt efter inkomst till sjukhus och ny kunskap om behandlingseffekt av abciximab och dalteparin. Resultaten har redovisats på internationella kongresser och i högt rankade medicinska tidskrifter och har citerats i europeiska och amerikanska ”guidelines” för behandling av instabil kranskärlssjukdom. / Patients with unstable coronary artery disease (CAD) have an increased risk of subsequent myocardial infarction and death. This study evaluated the safety and efficacy of treatment with glycoprotein IIb/IIIa inhibition in addition to aspirin, low molecular-weight heparin and its influence on coagulation and inflammation. Also, early and differentiated risk assessment utilising markers of inflammation, myocardial damage and dysfunction were evaluated. The Global Utilisation of Strategies To open Occluded arteries- IV (GUSTO-IV) trial randomised 7800 patients with unstable CAD to 24 or 48 hours infusion of abciximab or placebo in addition to routine treatment with aspirin and unfactionated heparin or dalteparin. Baseline levels of creatinine, C-reactive protein (CRP), Troponin-T (TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were analysed. At selected sites, all patients received subcutaneous dalteparin (n=974), in stead of unfractionated heparin infusion (n=6826). In a sub-population of dalteparin treated patients (n=404), serial measurements of markers of inflammation , coagulation and fibrinolysis were also performed. Addition of abciximab to dalteparin as the primary treatment of unstable CAD was not associated with any significant reduction in cardiac events but a doubled risk of bleedings. The combination of abciximab and dalteparin seemed to be as safe as when used with unfractionated heparin. Despite full dose dalteparin and aspirin there was a simultaneous activation of the inflammation, coagulation and fibrinolysis systems without any influence of the abciximab treatment. Elevated levels of CRP, TnT, and NT-proBNP and reduced creatinine clearance were independently related to short and long-term mortality. The best prediction of high and low risk was provided by a combination of NT-proBNP and creatinine clearance. Any detectable elevation of TnT and reduced creatinine clearance, but neither elevation of CRP nor NT-proBNP, were also independently associated to a raised risk of subsequent myocardial infarction.

D.Litt. et Phil. / This research investigated the effectiveness of the treatment programme used by the South African Recurrent Coronary Prevention Project (SARCPP) in reducing the risk of not only recurrent heart disease, but also of original occurrence of heart disease. Heart disease can often be attributed to lifestyle factors such as obesity, high fat content diets and smoking (Friedman & Ulmer, 1995 and Richards & Baker, 1988). Another lifestyle risk factor of heart disease is Type A behaviour, as first discovered by Rosenman and Friedman (1959). Type A behaviour is made up of various components, such as hostility, time urgency and insecurity. The SARCPP has effectively reduced Type A behaviour in past studies (Venter, 1993; Viljoen, 1993; MacLennan, 1994 and Webster, 1994) and it has been found that reducing Type A behaviour through this programme increases high density lipoproteins and decreases total triglycerides, thus decreasing physiological risk factors of heart disease (Wolff, Thoresen, Viljoen, & Venter, 1994). The SARCPP thus far had only been used with Type A persons who had already suffered a form of heart disease, such as myocardial infarction and angina pectoris (here called "unhealthy" Type As). Other interventions have been used to decrease Type A behaviour in subjects who had not yet suffered heart disease (or "healthy" Type As). A leading researcher in this field is Ethel Roskies (1979-1990). Due to ineffective measurement and ineffective treatment programmes, her attempts were not successful, though. This research study applied the treatment used in the SARCPP to both "healthy" and "unhealthy" Type As and it was found that it was as successful in reducing Type A behaviour in both the "healthy" subjects as in the "unhealthy" subjects. Not only was global Type A behaviour as measured by the Videotaped Structured Interview decreased in the treatment groups, but so were the components of Hostility, Time Urgency and Insecurity (although Insecurity was not decreased in the "unhealthy" subjects). The tendency by the subjects to repress angry feelings was reduced in both "unhealthy" and "healthy" subjects, as was cynical hostility in the "healthy" subjects. It was found that the "unhealthy" subjects had significantly more State and Trait anxiety before the treatment took place than the "healthy" subjects and that the treatment reduced that anxiety in the "unhealthy" subjects significantly. Depression was decreased in both "healthy" and "unhealthy" subjects. Thus, the treatment programme of the SARCPP was effective in reducing coronary-prone behavioural factors and can be used as both prevention in recurrence and prevention in original occurrence of heart disease.

La maladie coronaire stable est une maladie chronique pour laquelle de nombreuses stratégies thérapeutiques sont disponibles, dont le traitement par médicaments seuls et les traitements invasifs par angioplastie avec stent ou par pontage aortocoronaire. Face aux résultats de plusieurs méta-analyses mettant en évidence un taux de mortalité comparable entre ces traitements, nous avons décidé d’effectuer un travail de recherche comparant leurs coûts. Dans la première partie de mon travail, nous avons comparé, après une période de un an et une autre de 3 ans de suivi des patients, les données cliniques et économiques publiées pour 5 traitements de l’angor stable : les médicaments seuls, le pontage aortocoronaire, l’angioplastie sans stent, l’angioplastie avec stent nu et l’angioplastie avec stent actif. La mortalité et le taux d’IDM étaient nos critères de jugement clinique. Les coûts directs, liés au traitement effectué et liés à la prise en charge des éventuelles complications, ont été uniformisés via la parité de pouvoir d’achat et exprimés en US $ 2008. Il s’agissait de notre critère de jugement économique. Un total de 19 études cliniques a été retenu dans notre méta-analyse en réseau. Nos résultats mettent en évidence une absence de différence significative sur le critère clinique. En revanche, nous avons observé une différence concernant le coût moyen de chaque traitement après un an et 3 ans de suivi. Le traitement le moins onéreux était le traitement par médicaments seuls, après un an et 3 ans de suivi, avec respectivement un coût moyen par patient de 3 069 US $ et 13 854 US $. Le coût moyen le plus élevé a toujours été obtenu avec le traitement par pontage aortocoronaire : 27 003 US $ après un an et 28 670 US $ après 3 ans de suivi. Cependant, nos conclusions sont limitées d’une part, par la variabilité des méthodes économiques utilisées dans les études sélectionnées dans notre méta-analyse et, d’autre part, par l’évolution des traitements dans le temps. Dans la seconde partie de mon travail de recherche, nous avons calculé le coût de prise en charge d’un patient angoreux stable traité par l’une des 4 stratégies thérapeutiques suivantes : médicaments seuls, pontage aortocoronaire, angioplastie avec stent nu et angioplastie avec stent actif. Pour se faire, nous avons défini d’une part 6 situations cliniques correspondant aux possibles états cliniques du patient un an après l’instauration du traitement étudié et, d’autre part, déterminé les quantités de soins consommés pour chacune de ces situations cliniques. La perspective retenue était celle de l’Assurance Maladie. Les coûts calculés étaient liés aux hospitalisations, aux soins ambulatoires et aux moyens de transport utilisés pour accéder à l’hôpital. La stratégie médicamenteuse était la moins onéreuse avec un coût moyen annuel de 1 518 € ; ce coût prenant en compte les probabilités de survenue des 6 états cliniques. Le traitement par pontage aortocoronaire était le plus onéreux des 4 traitements étudiés, avec un coût moyen annuel de 15 237 €. La perspective de mes travaux est de modéliser la prise en charge d’un patient angoreux stable en envisageant un second traitement si le premier traitement effectué conduit à une situation d’échec thérapeutique. Les arbres que nous avons construits nous permettront ensuite d’effectuer une analyse coût-efficacité de deux stratégies thérapeutiques avec une durée totale de suivi des patients de 2 ans. Enfin, si nos travaux mettent en avant l’intérêt économique du traitement par médicaments, nous soulignons que ces résultats sont obtenus après avoir suivi les patients sur une courte durée (études à un an et à 3 ans), alors que l’angor stable est une maladie chronique où les stratégies thérapeutiques peuvent se succéder en cas d’échec à l’un des traitements... / Stable coronary artery disease is a chronic disease for which many treatment strategies are available, treatment with drugs alone and invasive treatment by stenting or coronary artery bypass graft. With the results of several meta-analyzes showing a mortality rate comparable between treatments, we decided to conduct a research comparing costs. In the first part of my work, we compared, after a period of one year and of 3 years of patient follow-up, clinical and economic data for five treatment of stable angina: medication alone, coronary artery bypass graft, angioplasty without stent, angioplasty with bare metal stent and angioplasty with drug-eluting stent. Mortality and MI rates were our clinical end point. Direct costs related to the treatment performed and related to the management of complications, have been standardized using the purchasing power parity and expressed in U.S. $ 2008. It was our criterion for economic analysis. A total of 19 clinical studies have been selected in our network meta-analysis. Our results show there is no significant difference in clinical end point. In contrast, we observed a difference in the average cost of each treatment after one year and three year follow-up. The least expensive treatment was the only treatment with drugs, after a year and 3 years of follow-up, each with an average cost per patient of U.S. $ 3,069 and U.S. $ 13,854. The highest average cost has been obtained with the treatment coronary artery bypass graft: U.S. $ 27,003 after one year and U.S. $ 28,670 after 3 years of follow-up. However, our conclusions are limited due to the high variability of the economic methods used in the selected studies and because of the evolution of revascularization techniques. In the second part of my research work, we calculated the cost of management of stable angina pectoris patients treated with one of the following four treatment strategies: medication alone, coronary artery bypass graft, angioplasty with bare metal stent and angioplasty with stent active. We defined a part 6 clinical situations corresponding to the possible clinical conditions of the patient one year after the treatment. We have defined the quantities of care consumed for each of these clinical situations. The perspective selected was the statutory health insurance in 2011. The calculated costs were related to hospitalization, ambulatory care and medical transport used to reach the hospital. The drug strategy was the least expensive with an average annual cost of € 1,518, the cost taking into account the probability of occurrence of 6 clinical conditions. Treatment with coronary artery bypass graft was the most expensive of the four treatments studied, with an average annual cost of € 15,237. The prospect of my work is to model the management of stable angina pectoris patient considering a second treatment if the first treatment led to a situation of treatment failure. The trees we built then allow us to perform a cost-effectiveness analysis of two strategies with a total duration of patient follow-up of 2 years. Finally, if our work highlights the economic benefits of drug treatment, we emphasize that these results are obtained after following patients over a short period (1 year and 3 years), while stable angina is a chronic disease where therapeutic strategies may succeed in case of failure to one of the treatments. In addition, we keep in mind that the choice of treatment, whether conservative or by drugs, by invasive myocardial revascularization should be done individually, i.e. taking into account the individual characteristics of each patient.

Enligt Socialstyrelsen år 2019 var hjärt-och kärlsjukdomar den vanligaste dödsanledningen i Sverige och svarade för 31 % av alla dödsfall i landet. Akut kranskärlssjukdom tillhör hjärt- och kärlsjukdomar och är en folksjukdom som drabbar både kvinnor och män i hela västvärlden med högst mortalitet till följd. Kliniska studier har visat att den västerländska kosten med för högt animaliskt proteinintag, för högt intag av raffinerat socker och fett är den primära bakomliggande orsaken till dödsfall i hjärt-kärlsjukdom. Största riskfaktorn för kranskärl-och andra hjärtsjukdomar är arterioskleros (åderförkalkning). En växtbaserad 10 % lågfetthaltig Whole Food Plant Based-diet (WFPB) har visat sig ha en positiv effekt på arteriosklerosprocessen och vidare på hjärt-kärlsjukdomars utveckling. Syftet med detta projekt var att genom en systematisk litteraturstudie undersöka om hjärtsjukdomar, framförallt kranskärlsjukdomar (CAD) kan stagneras och/eller reverseras med hjälp av en lågfetthaltig WFPB-diet. Studien är baserad på 10 vetenskapliga artiklar framtagna ur databaserna CINAHL, PubMed, Google Scholar samt från referenslistan på två av de redan utvalda artiklarna. Samtliga tio artiklar som inkluderats i litteraturstudien valdes genom datainsamling, relevansbedömning och kvalitetsgranskning. För att säkerställa artiklarnas kvalité kvalitetsgranskades de relevanta artiklarna utifrån frågor skapade från en mall från Statens beredning för medicinsk och social utvärdering, SBU. De analyserade mätparametrarna i artiklarna var bl. a. angiografiparametrar, lipidbiomarkörer, anginasymtom, Flödesmedierat vasodilatationstest (FMD) samt Positronemissions tomografi (PET). De flesta granskade studierna visade reversering av CAD, två artiklar visade både reversering och stagnering och en artikel kunde inte bedömas. Stagnering eller reversering av kranskärlsjukdomar kan åstadkommas antingen genom en kombination av dietintervention och andra livstilförändringar som komplement till lipidsänkande medicinsk behandling eller genom endast diet-och andra livstilförändringar. / According to the National Board of Health and Welfare in 2019, cardiovascular disease was the most common cause of death in Sweden and accounted for 31% of all deaths in the country. Acute coronary heart disease belongs to cardiovascular disease and is a common disease that affects both women and men throughout the Western world with the highest mortality as a result. Clinical studies have shown that the Western diet with too high animal protein intake, too high intake of refined sugar and fat is the primary underlying cause of death in cardiovascular disease. The biggest risk factor for coronary heart disease and other heart diseases is arteriosclerosis (atherosclerosis). A plant-based 10% low-fat Whole Food Plant Based Diet (WFPB) has been shown to have a positive effect on the arteriosclerosis process and further on the development of cardiovascular disease. The purpose of this project was to investigate through a systematic literature study whether heart disease, especially coronary heart disease (CAD) can be stagnated and / or reversed with the help of a low-fat WFPB diet. The study is based on 10 scientific articles produced from the databases CINAHL, PubMed, Google Scholar and from the reference list of two of the already selected articles. All ten articles included in the literature study were selected through data collection, relevance assessment and quality review. To ensure the quality of the articles, the relevant articles were quality examined on the basis of questions created from a template from the Swedish Agency for Medical and Social Evaluation, SBU. The analyzed measurement parameters in the articles were for example angiography parameters, lipid biomarkers, angina symptoms, Flow-mediated vasodilation test (FMD) and Positron emission tomography (PET). Most of the studies examined showed reversal of CAD, two articles showed both reversal and stagnation and one article could not be assessed. Stagnation or reversal of coronary heart disease can be achieved either through a combination of dietary intervention and other lifestyle changes in addition to lipid-lowering medical treatment or through dietary and other lifestyle changes only.

The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.

The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.

The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.