Introduction: The association between daily air pollution exposure and risk of mortality is well established. Few studies have investigated in detail the associations beyond a seven day lag. The aim of this thesis was to investigate the change in risk across longer (30 day) periods post exposure for three specific causes of death: pneumonia, chronic obstructive pulmonary disease (COPD), and ischaemic heart disease (IHD). Methods: Daily Scottish mortality data (1980-2011) was matched to measurements from local fixed site pollution (Black smoke, PM10, PM2.5, SO2, & NO2) and temperature monitors. Exposure on subjects' 'day of death' was compared with control days in a time-stratified case-crossover analysis. Exposure effects on 30 days prior to day of death were modelled using distributed lag non-linear, lag stratified, and cubic distributed lag models. Matching hospital admissions data inferred subject location during exposure, further analyses investigated extreme outliers and missing data using multiple imputation techniques. The analysis accounted for several confounders including accurately modelling temperature relationships unique for each cause of death. Results: Of the 919,301 deaths, 20% were classified as being caused by pneumonia, 9.5% as COPD, and 30% as IHD in the 'any' cause of death field. Non-linear effects for temperature and linear effects for the pollutants were present across all 30 days. Temperature-mortality was observed to be U-shaped at shorter lags. Consistently increased risk occurred for longer in cold temperatures with 1oC increase (30 days lag) = %RR -0.35% Pneumonia, -0.62% COPD, and -0.26% IHD. PM2.5 on all three outcomes, and all pollutants on COPD showed the greatest effect sizes. In general, COPD risk only occurred after a delay, peaking between 12-18 days. COPD risk due to PM2.5 was immediate (%RR (95% C.I.) = 1.05% (0.14%,2.01%)) and lasted the full 30 days. Pneumonia risk often reported the shortest lag of 10-15 days, whereas IHD risk occurred 2 days after exposure but lasted the remaining 30 days. There was some evidence especially for pneumonia of a smaller association between air pollution on mortality when subjects included were present in hospital. A simulation study indicated slight improvement in accuracy when 'multiple imputation' was performed compared to 'complete cases' analysis; though both techniques reported similarly underestimated effect estimates. Extreme outliers in the main analysis of pollution exposure did not appear to have a strong influence on the risk. However, large variability between monitor measurements of pollution exposure was present and appeared to be influencing the results. Conclusion: This study provides additional evidence on the link between air pollution, and temperature, and acute mortality. Particular focus was on three causes of death (pneumonia, COPD, and IHD) that are shown to be influenced by air pollution in subtly different ways. Results also indicated that the 'true' effect of air pollution on mortality might be greater than shown by mortality studies which do not use hospital admission location during exposure into account.

Background:  The right ventricle (RV) is multi-compartmental in orientation with a complex structural geometry. However, assessment of this part of the heart has remained an elusive clinical challenge. As a matter of fact, its importance has been underestimated in the past, especially its role as a determinant of cardiac symptoms, exercise capacity in chronic heart failure and survival in patients with valvular disease of the left heart. Evidence also exists that pulmonary hypertension (PH) affects primarily the right ventricular function. On the other hand, previous literature suggested that severe aortic stenosis (AS) affects left ventricular (LV) structure and function which partially recover after aortic valve replacement (AVR). However, the impact of that on RV global and segmental function remains undetermined.  Objectives: We sought to gain more insight into the RV physiology using 3D technology, Speckle tracking as well as already applicable echocardiographic measures. Our first aim was to assess the normal differential function of the RV inflow tract (IT), apical and outflow tract (OT) compartments, also their interrelations and the response to pulmonary hypertension. We also investigated the extent of RV dysfunction in severe AS and its response to AVR. Lastly, we studied the extent of global and regional right ventricular dysfunction in patients with pulmonary hypertension of different aetiologies and normal LV function. Methods: The studies were performed on three different groups; (1) left sided heart failure with (Group 1) and without (Group 2) secondary pulmonary hypertension, (2) severe aortic stenosis and six months post AVR and (3) pulmonary hypertension of different aetiologies and normal left ventricular function. We used 3D, speckle tracking echocardiography and conventionally available Doppler echocardiographic transthoracic techniques including M-mode, 2D and myocardial tissue Doppler. All patients’ measurements were compared with healthy subjects (controls). Statistics were performed using a commercially available SPSS software. Results: 1-  Our RV 3D tripartite model was validated with 2D measures and eventually showed strong correlations between RV inflow diameter (2D) and end diastolic volume (3D) (r=0.69, p<0.001) and between tricuspid annular systolic excursion (TAPSE) and RV ejection fraction (3D) (r=0.71, p<0.001). In patients (group 1 & 2) we found that the apical ejection fraction (EF) was less than the inflow and outflow (controls:  p<0.01 & p<0.01, Group 1:  p<0.05 & p<0.01 and Group 2: p<0.05 & p<0.01, respectively). Ejection fraction (EF) was reduced in both patient groups (p<0.05 for all compartments). Whilst in controls, the inflow compartment reached the minimum volume 20 ms before the outflow and apex, in Group 2 it was virtually simultaneous. Both patient groups showed prolonged isovolumic contraction (IVC) and relaxation (IVR) times (p<0.05 for all). Also, in controls, the outflow tract was the only compartment where the rate of volume fall correlated with the time to peak RV ejection (r = 0.62, p = 0.03). In Group 1, this relationship was lost and became with the inflow compartment (r = 0.61, p = 0.01). In Group 2, the highest correlation was with the apex (r=0.60, p<0.05), but not with the outflow tract. 2- In patients with severe aortic stenosis, time to peak RV ejection correlated with the basal cavity segment (r = 0.72, p<0.001) but not with the RVOT. The same pattern of disturbance remained after 6 months of AVR (r = 0.71, p<0.001). In contrast to the pre-operative and post-operative patients, time to RV peak ejection correlated with the time to peak outflow tract strain rate (r = 0.7, p<0.001), but not with basal cavity function. Finally in patients, RVOT strain rate (SR) did not change after AVR but basal cavity SR fell  (p=0.04). 3- In patients with pulmonary hypertension of different aetiologies and normal LV function, RV inflow and outflow tracts were dilated (p<0.001 for both). Furthermore, TAPSE (p<0.001), inflow velocities (p<0.001), basal and mid-cavity strain rate (SR) and longitudinal displacement (p<0.001 for all) were all reduced. The time to peak systolic SR at basal, mid-cavity (p<0.001 for both) and RVOT (p=0.007) was short as was that to peak displacement (p<0.001 for all). The time to peak pulmonary ejection correlated with time to peak SR at RVOT (r=0.7, p<0.001) in controls, but with that of the mid cavity in patients (r=0.71, p<0.001). Finally, pulmonary ejection acceleration (PAc) was faster (p=0.001) and RV filling time shorter in patients (p=0.03) with respect to controls. Conclusion: RV has distinct features for the inflow, apical and outflow tract compartments, with different extent of contribution to the overall systolic function. In PH, RV becomes one dyssynchronous compartment which itself may have perpetual effect on overall cardiac dysfunction. In addition, critical aortic stenosis results in RV configuration changes with the inflow tract, rather than outflow tract, determining peak ejection. This pattern of disturbance remains six month after valve replacement, which confirms that once RV physiology is disturbed it does not fully recover. The findings of this study suggest an organised RV remodelling which might explain the known limited exercise capacity in such patients. Furthermore, in patients with PH of different aetiologies and normal LV function, there is a similar pattern of RV disturbance. Therefore, we can conclude that early identification of such changes might help in identifying patients who need more aggressive therapy early on in the disease process.

Background: Ischaemic heart disease is a diagnostic and therapeutic challenge to most general practitioners. We sought to identify diagnostic characteristics and prognoses of patients in primary care that received exercise electrocardiography (ECG). We compared the ECG test results with respect to probability of subsequent cardiologist referrals. We also aimed to identify determinants for pre-hospital delays and lack of statin treatment before a first-time myocardial infarction (MI). Methods: Setting: Region of Jämtland Härjedalen, Sweden (adult population, approximately 99 000); study period 2010-2014. Patients and study designs: studies I and II: 865 patients referred to exercise ECG. Primary outcome: Incidence of cardiovascular events (I) and cardiologist referrals within six months after exercise ECG (II). Observed outcomes were compared to predictions from multivariable logistic models. Study III: 265 patients with first-time MI. Characteristics were analysed for determinants of pre-hospital delay ≥ 2 hours. Study IV: Survey of 931 patients with first-time MI. Analyses of characteristics associated with rates of statin treatment in patients with previously diagnosed cardiovascular diseases (CVD). Results: Study I: Exercise test results were associated with exertional chest pain, a pathologic ST-T segment on resting ECG, angina diagnosis according to the patient's opinion, and medication for dyslipidaemia. Cardiovascular events occurred in 52.7%, 18.3%, and 2.0% of patients with positive (ST-segment depression >1mm and chest pain indicative of angina), inconclusive (ST depression or chest pain), or negative tests, respectively. Study II: Positive or inconclusive exercise tests were associated with cardiologist referrals. Among patients with positive exercise tests, referral rates decreased with age, after adjusting for co-morbidity. Self-employed women were referred to cardiologic evaluations more often than other employed women. Study III: The first medical contact was a primary care facility for 52.3% of patients. The pre-hospital delay time was ≥ 2 h for 67.0% of patients in primary care and 44.7% of patients that called emergency medical services or were self-referred to hospital. Study IV: Among patients with prior CVD, 34.5% received current statin treatment before for the first MI. Statin treatment rates decreased with age, after adjusting for CVD and diabetes; women ≥70 years old were treated half as often as men of the same age. Conclusions: Clinical characteristics can be used to identify patients at low risk of cardiac events. The prognosis in patients with a negative exercise ECG was benign for six months after the exercise ECG. Exercise tests are important for selecting patients that require cardiologic evaluations. Age, gender, and employment status interacted with rates of referrals for cardiac evaluation. The pre-hospital delay time was considerably prolonged, particularly when primary care was the first medical contact. Only one third of patients with a prior CVD received statin treatment. Pre-MI statin treatment decreased with age, particularly among women ≥70 years old. In making medical decisions, it is necessary to be aware of biases regarding age, gender, and socioeconomic status. Methodologies for case finding and follow-up need to be improved and implemented in clinical practice. Keywords: Exercise ECG, Ischaemic heart disease, Myocardial infarction, Pre-hospital delay, Primary care, Prognosis, Referral, Statins, Secondary prevention / Sammanfattning på svenska: Bakgrund och syfte: Patienter med ischemisk hjärtsjukdom (IHD) utgör en diagnostisk och terapeutisk utmaning för läkare inom primärvården. Arbets-EKG är en vanlig metod vid utredning av patienter som söker till primärvården för besvär som kan vara förorsakade av IHD. Vi undersökte primärvårdspatienter remitterade till arbets-EKG, med avseende på de kliniska karakteristika (egenskaper och symtom) som kunde associeras med resultatet av arbets-EKG och med prognosen inom sex månader efter undersökningen. Vi jämförde arbets-EKG-svaren med avseende på efterföljande remittering för utredning vid hjärtklinik. Vi kartlade även faktorer av betydelse för tidsfördröjningen före sjukhusvård och för sekundärpreventiv behandling med kolesterolsänkande läkemedel (statiner), före insjuknande i hjärtinfarkt. Metod: De studier som ingår i avhandlingsarbetet (studier I-IV) genomfördes i Region Jämtland och Härjedalen, befolkningsunderlag cirka 99 000 personer i åldrar från 20 år och äldre, under åren 2010-2014. Undersökta patienter och studiedesign: Studier I och II: Prospektiv studie av 865 patienter undersökta med arbets-EKG, klassificerade som: positivt arbets-EKG (dynamisk ST-sänkning >1mm under arbetsprov och bröstsmärta typisk för kärlkramp), inkonklusivt (ST-sänkning eller bröstsmärta) eller negativt arbets-EKG. Utfallsvariabler: hjärt-kärlhändelser (instabil kärlkrampssjukdom, hjärtinfarkt, öppen kranskärlsoperation, ballongvidgning av kranskärl och kardiovaskulära dödsfall) (I) och remittering för utredning vid hjärtklinik inom sex månader efter arbets-EKG (II). Observerade hjärt-kärlhändelser jämfördes med förväntat utfall, enligt multivariabla statistiska modeller. Studie III: Retrospektiv studie av 265 patienter med förstagångs hjärtinfarkt, analyserade med avseende på faktorer av betydelse för tid från symtomdebut och till sjukhusvård, med brytpunkten två timmar eller längre tid för vård på sjukhus. Studie IV: Tvärsnittsstudie av 931 patienter med förstagångs hjärtinfarkt. Patienter med tidigare hjärt-kärlsjukdom analyserades med avseende på statinbehandling före hjärtinfarkten. Resultat: Studie I: Faktorer associerade med arbets-EKG-resultatet (positivt eller inkonklusivt svar mot negativt svar) var: ansträngningskorrelerad bröstsmärta före arbetsprovet, ST-T-segmentsförändringar på vilo-EKG, kärlkrampsdiagnos enligt patientens egen bedömning, samt medicinering för förhöjda kolesterolvärden i blodet. Hjärt-kärlhändelser inträffade i 52.7%, 18.3%, och 2.0% bland patienter med positivt, inkonklusivt respektive negativt arbets-EKG. Studie II: Resultatet från arbets-EKG styrde remitteringen av patienter till hjärtklinik, med högre sannolikhet för remiss efter positivt test. Bland patienter med positivt arbets-EKG remitterades färre patienter vid stigande ålder, justerat för tidigare känd hjärt-kärlsjukdom. Egenföretagande kvinnor blev oftare remitterade än andra kvinnor, justerat för ålder, bröstsmärtesymtom och arbets-EKG-svar. Studie III: I 52.3% av samtliga fall var primärvården (personligt besök eller via telefonrådgivning) den första vårdkontakten för patienter med förstagångs hjärtinfarkt. Tidsfördröjningen före sjukhusvård var 2 timmar eller mer bland 67.0% av alla patienter från primärvården och 44.7% bland de patienter som först ringde larmcentralen (112) eller sökte direkt till sjukhusets akutmottagning. Studie IV: Patienter med tidigare konstaterad hjärt-kärlsjukdom hade en pågående statinbehandling i 34.5% av fallen, före insjuknandet i förstagångs hjärtinfarkt. Andelen patienter med pågående statinbehandling avtog med stigande ålder, justerat för diabetes och tidigare hjärt-kärlsjukdom. Kvinnor från 70 år och äldre erhöll statinbehandling hälften så ofta som jämförbara män. Slutsats: Patienter med låg risk för hjärt-kärlhändelser kan identifieras före remittering till arbets-EKG, med hjälp av kliniska karakteristika. Patienter med negativt svar på arbets-EKG har en god prognos, med få hjärt-kärlhändelser inom sex månader efter arbetsprovet. Urvalet av patienter som remitteras för fortsatt hjärtutredning styrs av resultatet från arbets-EKG, men interaktioner mellan ålder, kön och anställningsförhållanden påverkar sannolikheten för remittering. Tiden från symtomdebut och till sjukhusvård var avsevärt fördröjd, särskilt för de patienter som primärt kontaktade primärvården. Endast en tredjedel av alla patienter med tidigare konstaterad hjärt-kärlsjukdom hade en pågående statinbehandling vid hjärtinfarktinsjuknandet. Andelen patienter med pågående statinbehandling avtog med högre ålder, särskilt bland kvinnor från 70 års ålder och äldre. En ökad medvetenhet om hur ålder, kön och social ställning påverkar den medicinska beslutsprocessen är angelägen. Metoder för bättre identifiering och uppföljning av riskpersoner behöver utvecklas och införas i den medicinska verksamheten. Nyckelord och förklaringar: Arbets-EKG (kliniskt arbetsprov på ergometercykel med samtidig EKG-registrering), positivt arbets-EKG (talar för kärlkrampssjukdom), negativt arbets-EKG (talar för frånvaro av sjukdom). EKG (elektrokardiografi), hjärtinfarkt, ischemisk hjärtsjukdom (sjukdomstillstånd med otillräcklig blodtillförsel till hjärtat), sekundärprevention (förhindra återinsjuknande i tidigare genomliden sjukdom).

Ischaemic heart disease (IHD) is the leading cause of death worldwide. Currently, even optimal medical therapies do not attenuate deterioration of the left ventricular (LV) function completely. Stem cell therapies, and recently cardiac stem cell therapies, have emerged as potential novel treatments for IHD. However, clinical evidence from randomised controlled studies has shown mixed results. Thus understanding what patient-related factors may affect the therapeutic performance of the cells may help improving treatment outcomes. The studies described in this thesis aim to understand how cardiac progenitor cells (CPCs) can re-vascularise ischaemic myocardium and promote functional repair of the heart. Resident CPCs were isolated and expanded from the right atrial appendage of 68 patients following the ‘cardiosphere’ method (cardiosphere-derived cells or CDCs). They resemble mesenchymal progenitors as they lack the expression of endothelial and haematopoietic cell surface markers but express mesenchymal progenitor cell markers (e.g. CD105, CD90). Cell function was evaluated by support of angiogenesis, mesenchymal lineage differentiation potential in vitro, and improvement in heart function in vivo. Notably in vitro, CDC from different patients differed in their angiogenic supportive and differentiation potentials. In a rodent model of myocardial infarction (MI), transplantation of CDC reduced infarct size significantly (p<0.05). However, only those CDCs with a robust pro-angiogenic ability in vitro improved vessel density and heart systolic function (p<0.05) in vivo. A multiple regression model, which accounted for 51% of the variability observed, identified New York Heart Association (NYHA) class, smoking, hypertension, type of ischaemic disease and diseased vessel as independent predictors of angiogenesis. In addition, gene expression analyses revealed that differential gene expression of several extracellular matrix components (e.g. CUX1, COL1A2, BMP1 genes and microRNA-29b) could explain the differences observed in CDC’s vascular supportive function. In summary, this is the first description of variability in the pro-angiogenic and differentiation potential of CDCs and its correlation with their therapeutic potential. This study indicates that patient stratification may need to be included in the design of future trials to improve the efficacy of cell-based therapies.

<p>Biochemical and epidemiological aspects of pre-eclampsia were investigated, with the main focus on possible pathophysiological differences between early-onset and late-onset disease.</p><p>In pre-eclamptic women poor correlation was found between albumin-creatinine ratio (ACR) in a random urine sample and total amount of albumin in a 24-hour urine collection. <i>(Paper I)</i><b> </b></p><p>In a cohort of women giving birth in Sweden in 1973-82 we estimated the adjusted incidence rate ratio (IRR) for ischaemic heart disease (IHD) during the years 1987–2001. The adjusted IRR for development of IHD was 1.6-2.8 in woman exposed to gestational hypertensive disease during her pregnancy compared with unexposed women. The higher risk represents more severe or recurrent hypertensive disease. <i>(Paper II)</i></p><p>Before delivery, in early-onset pre-eclampsia (24-32 weeks) there were pronounced alterations in plasma concentrations of soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF), and also a higher placental 8-iso-PGF_2α concentration and an elevated serum ratio of plasminogen-activator inhibitor (PAI)-1 to PAI-2 compared with early controls. In late-onset pre-eclampsia (35-42 weeks) there were only moderate alterations in sFlt1 and PlGF concentrations, and the placental 8-iso-PGF_2α concentration and PAI-1/ PAI-2 ratio were similar to those in late controls. <i>(Papers III, V)</i> There was a rapid postpartum decrease in sFlt1 concentration in all groups. One week postpartum the sFlt1 concentration was persistently higher, however, in women with early-onset pre-eclampsia compared with early controls. <i>(Paper IV)</i></p><p>In conclusion: random ACR cannot replace 24-hour urine collections for quantification of albuminuria in pre-eclamptic women; gestational hypertensive disease, especially severe or recurrent, increases the risk for later IHD; early-onset, but not late-onset pre-eclampsia is associated with pronounced alterations of angiogenesis-related markers and only early-onset pre-eclampsia is associated with placental oxidative stress and an increased PAI-1/ PAI-2 ratio, all suggesting a stronger link between early-onset than late-onset pre-eclampsia and a dysfunctional placenta.</p>

Biochemical and epidemiological aspects of pre-eclampsia were investigated, with the main focus on possible pathophysiological differences between early-onset and late-onset disease. In pre-eclamptic women poor correlation was found between albumin-creatinine ratio (ACR) in a random urine sample and total amount of albumin in a 24-hour urine collection. (Paper I)<b> </b> In a cohort of women giving birth in Sweden in 1973-82 we estimated the adjusted incidence rate ratio (IRR) for ischaemic heart disease (IHD) during the years 1987–2001. The adjusted IRR for development of IHD was 1.6-2.8 in woman exposed to gestational hypertensive disease during her pregnancy compared with unexposed women. The higher risk represents more severe or recurrent hypertensive disease. (Paper II) Before delivery, in early-onset pre-eclampsia (24-32 weeks) there were pronounced alterations in plasma concentrations of soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF), and also a higher placental 8-iso-PGF2α concentration and an elevated serum ratio of plasminogen-activator inhibitor (PAI)-1 to PAI-2 compared with early controls. In late-onset pre-eclampsia (35-42 weeks) there were only moderate alterations in sFlt1 and PlGF concentrations, and the placental 8-iso-PGF2α concentration and PAI-1/ PAI-2 ratio were similar to those in late controls. (Papers III, V) There was a rapid postpartum decrease in sFlt1 concentration in all groups. One week postpartum the sFlt1 concentration was persistently higher, however, in women with early-onset pre-eclampsia compared with early controls. (Paper IV) In conclusion: random ACR cannot replace 24-hour urine collections for quantification of albuminuria in pre-eclamptic women; gestational hypertensive disease, especially severe or recurrent, increases the risk for later IHD; early-onset, but not late-onset pre-eclampsia is associated with pronounced alterations of angiogenesis-related markers and only early-onset pre-eclampsia is associated with placental oxidative stress and an increased PAI-1/ PAI-2 ratio, all suggesting a stronger link between early-onset than late-onset pre-eclampsia and a dysfunctional placenta.

To aid diagnosis, treatment planning, and patient education, clinicians require tools to anal- yse and explore the increasingly large three-dimensional (3-D) datasets generated by modern medical scanners. Direct volume rendering is one such tool finding favour with radiologists and surgeons for its photorealistic representation. More recently, volume illustration — or non-photorealistic rendering (NPR) — has begun to move beyond the mere depiction of data, borrowing concepts from illustrators to visually enhance desired information and suppress un- wanted clutter. Direct volume rendering generates images by accumulating pixel values along rays cast into a 3-D image. Transfer functions allow users to interactively assign material properties such as colour and opacity (a process known as classification). To achieve real-time framerates, the rendering must be accelerated using a technique such as 3-D texture mapping on commod- ity graphics processing units (GPUs). Unfortunately, current methods do not allow users to intuitively enhance regions of interest or suppress occluding structures. Furthermore, addi- tional scalar images describing clinically relevant measures have not been integrated into the direct rendering method. These tasks are essential for the effective exploration, analysis, and presentation of 3-D images. This body of work seeks to address the aforementioned limitations. First, to facilitate the research program, a flexible architecture for prototyping volume illustration methods is pro- posed. This program unifies a number of existing techniques into a single framework based on 3-D texture mapping, while also providing for the rapid experimentation of novel methods. Next, the prototyping environment is employed to improve an existing method—called tagged volume rendering — which restricts transfer functions to given spatial regions using a number of binary segmentations (tags). An efficient method for implementing binary tagged volume rendering is presented, along with various technical considerations for improving the classifi- cation. Finally, the concept of greyscale tags is proposed, leading to a number of novel volume visualisation techniques including position modulated classification and dynamic exploration. The novel methods proposed in this work are generic and can be employed to solve a wide range of problems. However, to demonstrate their usefulness, they are applied to a specific case study. Ischaemic heart disease, caused by narrowed coronary arteries, is a leading healthconcern in many countries including Australia. Computed tomography angiography (CTA) is an imaging modality which has the potential to allow clinicians to visualise diseased coronary arteries in their natural 3-D environment. To apply tagged volume rendering for this case study, an active contour method and minimal path extraction technique are proposed to segment the heart and arteries respectively. The resultant images provide new insight and possibilities for diagnosing and treating ischaemic heart disease.

This thesis discusses the design and the utilization of the artificial neural networks as ECG classifiers and the detectors of heart diseases in ECG signal especially myocardial ischaemia. The changes of ST-T complexes are the important indicator of ischaemia in ECG signal. Different types of ischaemia are expressed particularly by depression or elevation of ST segments and changes of T wave. The first part of this thesis is orientated towards the theoretical knowledges and describes changes in the ECG signal rising close to different types of ischaemia. The second part deals with to the ECG signal pre-processing for the classification by neural network, filtration, QRS detection, ST-T detection, principal component analysis. In the last part there is described design of detector of myocardial ischaemia based on artificial neural networks with utilisation of two types of neural networks back – propagation and self-organizing map and the results of used algorithms. The appendix contains detailed description of each neural networks, description of the programme for classification of ECG signals by ANN and description of functions of programme. The programme was developed in Matlab R2007b.

Acute myocardial infarction (AMI), caused by ischaemic heart disease (IHD), is a leading cause of death in both men and women in the western society. Hypertension, diabetes, and smoking are examples of well-known risk factors of IHD, but also there are psychosocial factors, such as stress, vital exhaustion (unusual fatigue, irritability, and demoralization) and depression that have been associated with an increased risk in both genders. After an AMI, however, women are more likely than men to be psychosocially impaired resulting in suffering and a presumed increase in the risk of recurrent cardiac events. Psychosocial factors may be targeted in secondary prevention, complementary to drug treatment and conventional lifestyle advice. There is some evidence of beneficial effects on both psychosocial well-being and cardiac outcomes by psychosocial interventions in men. Far fewer women have been studied and the results have been inconsistent. It is not clear how psychosocial factors convey the increased risk of cardiac events, but many possible psychopathological mechanisms, including biochemical and physiological links, have been suggested. In the Women’s Hearts study we have, in a randomised controlled trial, evaluated a one-year cognitive-behavioural stress management programme designed specifically for women with IHD. We included 198 women with IHD, with a mean age of 61 years and from the county of Västerbotten in Northern Sweden, who were randomised to either conventional treatment and follow-up, or to stress management in addition to conventional care. Extensive questionnaires, blood samplings, and biomedical and physiologic data were obtained before randomisation, as well as at follow-ups approximately one and two years after randomisation. Two groups of healthy controls were included for comparisons with women with IHD. Compared to women without IHD, women with IHD reported more stress behaviour and vital exhaustion. Women with IHD also had a lower heart rate variability (HRV) than the healthy controls, possibly reflecting a dysfunctional autonomic nervous regulation of the heart. Reduced HRV has been shown to increase the risk of cardiac arrhythmias and sudden death. At the first follow-up, performed at the end of the one-year stress management programme, women who had participated in the programme had reduced the stress behaviour and vital exhaustion, compared to the women in the conventional care group. We could not find any evidence of a direct cause-effect relationship between stress management and biological cardiovascular risk indicators, or HRV; the intervention and control groups did not differ in insulin resistance, inflammatory, haemostatic and fibrinolytic factors, or HRV. At second follow-up one year later, several additional psychosocial domains were studied. The stress management programme had accelerated psychosocial recovery at the first follow-up over and above that observed in the control group. At the second follow-up, there was further marked improvement in the control group, so the differences in psychosocial variables between the intervention and control groups were no longer significant. In conclusion, a cognitive-behavioural stress management programme could accelerate psychosocial improvement in women with IHD, and thus reduce the amount of psychological and psychosocial suffering. We could not find any evidence that the stress management programme was associated with a concomitant improvement in biological cardiovascular risk indicators, or HRV. Our results suggest that the women with the greatest psychosocial burden should be identified and targeted in new clinical trials of cognitive-behavioural interventions in women with IHD. Future studies within the Women’s Hearts project will evaluate the psychosocial effects at a five-year follow-up, as well as investigations of other possible pathways by which psychosocial interventions might mediate beneficial effects on cardiac events.