Stroke is a leading cause of death and the most common cause of disability in adults in the United Kingdom. Several treatments are effective in preventing stroke in the long term after TIA and minor ischaemic stroke, including aspirin, other antiplatelet agents, and blood pressure lowering drugs, statins and anticoagulation in atrial fibrillation. However, failure of secondary prevention to prevent recurrent vascular events is still a major clinical problem, as is the risk of bleeding associated with antiplatelet agents and anticoagulants. This thesis determines the risks associated with urgent secondary prevention in the acute phase after TIA and minor stroke, particularly the reduction in risk of early recurrent stroke, the risk of bleeding with combination of aspirin and clopidogrel in the acute phase and whether or not there is a rebound increase risk of ischaemic stroke or recurrent TIA after withdrawal of a short course of clopidogrel. I have shown that urgent and early treatment of ischaemic stroke with secondary prevention leads to an 80% reduction in recurrent stroke. I have also shown that an increased bleeding risk exists among aspirin naïve patients treated with combination antiplatelet medications compared to those already treated with aspirin. My work has also shown that discontinuation of clopidogrel following treatment for 30 days or more does not lead to a rebound increase in ischaemic stroke. Bleeding events are a frequent complication of antiplatelet treatment in TIA and ischaemic stroke. I have shown that the long term risk of bleeding in a population study treated with antiplatelets is 6% per 100 person years. Using this information I identified risk factors for bleeding to develop a clinical baseline bleeding model to identify those at higher risk of bleeding. Age was identified as a significnant risk factor for both bleeding and recurrent ischaemic risk. In addition, bleeding events are associated with higher rates of fatality and disability in the older population. Finally, I have shown that the time trends in stroke recurrence differ depending on the presenting event i.e TIA or stroke. Stroke recurrence risk after minor stroke is delayed compared with TIA, and remains high during the late phase despite current best medical treatment. Blood pressure control and atrial fibrillation are risk factors for late stroke recurrence identifying the unmet need for better detection and treatment potentials to reduce late recurrent stroke.

Stroke is a significant contributor to the global burden of disease in adults. With the risk of recurrent stroke high, preventative medicines aimed at risk factor reduction are the method of choice for addressing the challenge of increased morbidity and mortality and improving patient outcomes. Research in stroke has shown that adherence to medication is problematic and survivors face considerable practical and physical barriers to taking prescribed medicines. Understanding these challenges can inform the development of strategies to improve medication taking behaviour through delivery of interventions in the primary care setting. This thesis aims to identify potential strategies to inform interventions to improve medication taking in stroke. The research: identified key barriers and facilitators of medication adherence for the secondary prevention of stroke - firstly from within the primary care setting and then from the perspective of an online stroke forum; explored the appropriateness of the online forum as a method of data collection for conducting qualitative research compared with a traditional qualitative interview approach; investigated medication taking among community stroke survivors to characterise patients who receive help with medicines and estimate the proportion who have unmet needs and miss medicines; and examined attitudes from across the stroke spectrum towards a novel approach to medication taking for secondary prevention (i.e. fixed-dose combination polypill). Findings showed that survivors face considerable barriers to medicine taking, but that facilitators, particularly the caregiver role, can encourage good medication taking practice. The online forum has potential as a source of data to understand stroke survivors' behaviour, and a novel strategy to taking stroke medicines has promise. These findings enhance current thinking around medicine taking behaviour in stroke and can inform the development of effective interventions to improve medication taking practices and address nonadherence among stroke survivors. Implications for clinical practice are discussed, and recommendations are provided for future research.

Purpose: The purpose of this study was to determine the influence of out-of-pocket prescription and healthcare costs on adherence to guideline recommended statins, angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARB), and beta-blockers (BB) used for secondary prevention of coronary heart disease and the associations of adherence with cardiovascular mortality in community-dwelling Medicare beneficiaries ≥ 65 years. Methods: Data from the 2004, 2005, and 2006 Medicare Current Beneficiary Survey (MCBS) was utilized to conduct a retrospective, cross-sectional (i.e., multiple cohort) study. Dependent variables of interest included adherence to statins, ACE/ARBs or BBs, and all-cause mortality, with out-of-pocket (OOP) costs, and adherence to these medications the primary independent variables of interest in these models. Adherence was analyzed as a binary variable with ≥ 80 percent annual adherence the threshold utilized in primary analyses. Total OOP prescription costs for all medications and total OOP healthcare costs borne by the beneficiary were reported. Complex survey design-specified logistic regression with sampling weights was the main statistical analysis used. Sensitivity analyses on adherence thresholds and subgroups were additionally conducted. Results: A significant positive relationship between total OOP prescription costs and statin adherence was identified across observation years in the primary models. Similar relationships were noted for ACE/ARBs and BB in 2004, and ACE/ARBs in 2005. No significant association between adherence and total OOP healthcare costs was indicated in the primary models. Mortality could not be used as a clinical outcome of interest due to limitations with the data. Thus, acute coronary syndrome (ACS) events were used as the clinical outcome. At the ≥ 80 percent threshold, no significant reductions in ACS events were reported. However, various sensitivity analyses did suggest significant reductions in ACS events with ACE/ARBs. Additionally, significantly higher risk of ACS was noted when BB adherence thresholds were reduced to ≥ 60 percent. Conclusions: OOP prescription costs are a significant factor influencing adherence to these medications used for secondary prevention of CAD/MI in Medicare beneficiaries. Continuing to monitor how these costs impact adherence and ultimately outcomes will be critical, particularly given policy changes such as Medicare Part-D.

Anxiety sensitivity, defined as the fear of anxiety-related sensations and their consequences (Reiss & McNally, 1985), has been consistently shown to be associated with risk for anxiety psychopathology as well as other mental health problems. The primary objective of the present secondary prevention trial sought to examine strategies to reduce anxiety sensitivity among persons with elevated anxiety sensitivity by testing the singular and combined efficacy of two commonly used strategies in multi-component interventions for reducing anxiety sensitivity: (a) anxiety psychoeducation emphasizing the benign nature of stress and (b) interoceptive exposure (i.e. repeated inhalations of 35% CO₂ gas mixture). To provide a stringent control for non-specific effects associated with anxiety psychoeducation and interoceptive exposure with CO₂, two control strategies were included in the study design: general health and nutrition education and repeated inhalations of regular room air. Utilizing a 2X2 design, participants were randomly assigned to receive an education component and intervention sessions consisting of one of two gas mixtures. The current study did not support the relative efficacy of hypothesized active intervention strategies. Rather, all conditions led to significant reductions in anxiety sensitivity. In addition, within-condition effect sizes for conditions in the present study were comparable to effect sizes of active interventions that were efficacious in previous research. Findings from the present study support that anxiety sensitivity is malleable following brief, cost-efficient interventions and these reductions are maintained over a one-month follow-up period. Data from the present study suggest that in the presence of stringent control conditions, hypothesized active intervention strategies provided little additional benefit. The present study has implications for methodological considerations for future secondary prevention trials for the reduction of anxiety sensitivity. The absence of stringent control groups might lead to premature conclusions that reductions in anxiety sensitivity are due to the specific effects of active interventions. Further research is needed to elucidate specific effects of intervention strategies for the reduction of anxiety sensitivity in at risk populations in order to refine secondary prevention interventions aimed to reduce risk for psychopathology. / text

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Background Stroke is a serious condition that can have significant impact on an individual’s health and is a significant burden on public health and public finances. Secondary preventive drug treatment after stroke is important for decreasing the risk of recurrent strokes. Non-adherence to drug treatment hampers the treatment effect, especially in long-term preventive treatments. The aim of this thesis was to study the use of secondary preventive drugs after stroke among Swedish stroke patients in terms of inequalities in implementation in clinical practice and patient adherence to treatment over time. Methods Riks-Stroke, the Swedish stroke register, was used to sample stroke patients and as a source of information on background characteristics and medical and health care-related information including information on prescribed preventive drugs. The patients that were included had a stroke between 2004 and 2012. Individual patient data on prescriptions filled in Swedish pharmacies were retrieved from the Swedish Prescribed Drug Register and used to estimate patient adherence to drug treatment. Data on education, income, and country of birth were included from the LISA database at Statistics Sweden. A questionnaire survey was used to collect information about patients’ perceptions about stroke, beliefs about medicines, and self-reported adherence. Results Results showed that a larger proportion of men than women were prescribed statins and warfarin after stroke. There was also a social stratification in the prescribing of statins. Patients with higher income and a higher level of education were more likely to be prescribed a statin compared to patients with low income and low level of education. Statins were also more often prescribed to patients born in Nordic countries, Europe, or outside of Europe compared to patients born in Sweden. Primary non-adherence (not continuing treatment at all within 4 months of discharge from hospital) was low for preventive drug treatment after stroke. Data on filled prescriptions, however, indicated that the proportion of patients who continued to use the drugs declined during the first 2 years after stroke. For most drugs, refill adherence in drug treatment was associated with female sex, good self-rated health, and living in institutions and (for antihypertensive drugs and statins) having used the drug before the stroke. For statins and warfarin, a first-ever stroke was also associated with continuous drug use. Self-reported adherence 3 months after stroke also showed associations with patients’ personal beliefs about medicines; non-adherent patients scored higher on negative beliefs and lower on positive beliefs about medicines. Conclusion Inequalities between men and women and between different socioeconomic groups were found in the prescribing of secondary preventive drugs after stroke. Only a small proportion of Swedish stroke patients did not continue treatment after discharge from hospital, but the proportion of non-adherent patients increased over time. Poor adherence to preventive drug treatment after stroke is a public health problem, and improving adherence to drug treatment requires consideration of patients’ personal beliefs and perceptions about drugs.

Background: Atrial fibrillation (AF) is the most common arrhythmia in the adult population, affecting about 5% of the population over 65 years. Occurrence of AF is an independent risk factor for stroke, and together with other cardiovascular risk factors (CHADS2/CHA2DS2- VASc), the stroke risk increases. Since AF is often paroxysmal and asymptomatic (silent) it may remain undiagnosed for a long time and many AF patients are not discovered before suffering a stroke. Aims: To estimate the prevalence of previously undiagnosed AF in an out-of-hospital population with CHADS2 ≥1, in patients with an enlarged left atrium (LA) and of total AF prevalence in sleep apnea (SA) patients, conditions that have been associated with AF. To compare the efficacy of short intermittent ECG with continuous 24h Holter ECG in detecting arrhythmias. Methods: Patients without known AF recorded 10−30 second handheld ECG (Zenicor-EKG®) registrations during 14−28 days at home, both regular, asymptomatic registrations twice daily and when having cardiac symptoms. Recordings were transmitted through the in-built SIM card to an internet-based database. Patients with palpitations or dizziness/presyncope referred for 24h Holter ECG were asked to additionally record 30-second handheld ECG registrations during 28 days at home. Results: In the out-of-hospital population with increased stroke risk, previously unknown AF was diagnosed in 3.8% of 928 patients. Comparing AF detection in patients with an enlarged LA versus normal LA showed that eleven of 299 patients had AF. Five of these had an enlarged LA (volume/BSA). No statistical difference in AF prevalence was found between patients with enlarged and normal LA, 3.3% and 3.2% respectively, (p = 0.974). AF occurred in 7.6% of 170 patients with sleep apnea, in 15% of patients with sleep apnea ≥60 years, and in 35% of patients with central sleep apnea. AF prevalence was also associated with severity of sleep apnea, male gender and diabetes. Comparing the efficacy of arrhythmia detection in 95 patients with palpitations or dizziness/presyncope with continuous 24h Holter and short intermittent ECG, 24h Holter found AF in two and AV-block II in one patient, resulting in 3.2% relevant arrhythmias detected. Short intermittent ECG diagnosed nine patients with AF, three with PSVT and one with AV-block II, in total 13.7% relevant arrhythmias. (p = 0.0094). Conclusions: Screening in the out-of-hospital patient population (mean age 69.8 years) yielded almost 4% AF, making it seem worthwhile to screen older patients with increased stroke risk for AF with this method. Screening patients with LA enlargement (mean age 73.1 years) did not result in higher detection rates compared with the general out-of-hospital population. AF occurred in 7.6% of patients with sleep apnea, (mean age 57.6 years) and was associated with severity of sleep apnea, presence of central sleep apnea, male gender, age ≥60 years, and diabetes. Short intermittent ECG is more effective in detecting relevant arrhythmias than 24h Holter ECG in patients with palpitations or dizziness/presyncope.

Bakgrund: Efter akut kranskärlssjukdom är det viktigt att förändra sin livsstil då det har stor betydelse för framtidsutsikten för dessa patienter. Trots detta så förändrar inte alla patienter sina livsstilsvanor, eller klarar av att bibehålla de nyligen förändrade vanorna.   Syfte: Syftet var att studera vad som påverkar genomförandet av livsstilsförändringar hos personer i efterförloppet av akut kranskärlssjukdom.   Metod: Litteraturstudie med ett systematiskt tillvägagångssätt. Datainsamling genomfördes i databaserna CINAHL, PsycINFO, PubMed, Swemed+ och UniSearch. Efter datainsamling och kvalitetsgranskning inkluderades 15 artiklar varav nio kvalitativa artiklar och sex kvantitativa artiklar. För bearbetning av data utfördes en analys där fyra huvudkategorier identifierades.   Resultat: De fyra huvudkategorierna som identifierades var: Den enskilde individen, Kunskap, Inre faktorer och Yttre faktorer. Dessa områden kunde både främja och/eller hämma genomförandet av livsstilsförändring i efterförloppet av akut kranskärlssjukdom.    Konklusion: Sjuksköterskan bör vara medveten om den multifaktoriella process som livsstilsförändring innebär för patienten. Patientens behov kan tillgodoses genom tydlig information om sjukdomen men även andra aspekter såsom livsstilsförändring och hantering av förändring. Patienten behöver stöd från sjukvården, likasinnade och närstående för att kunna förändra sin livsstil.

Le pronostic à long-terme actuel après un accident ischémique transitoire (AIT) ou un infarctus cérébral reste mal connu. Ainsi, j’ai déterminé les risques absolus à long-terme de récidive d’infarctus cérébral et d’évènement coronarien aigu après un AIT ou un infarctus cérébral et identifié les individus qui restent à haut risque absolu de récidive ischémique malgré la prévention secondaire actuelle.Dans une cohorte populationnelle contemporaine de patients ayant eu un AIT ou un infarctus cérébral (OXVASC study, 2002-2014), les risques absolus de récidive d’infarctus cérébral et d’infarctus du myocarde après un AIT/infarctus cérébral ont significativement diminué au cours de la période d’étude, très probablement du fait de l’amélioration de la prévention secondaire avec le temps. Cependant, malgré la prévention secondaire actuelle les sous-groupes de patients avec un antécédent de pathologie coronarienne et ceux sans antécédent coronaire mais avec un score Essen 4 sont exposés à un risque absolu de récidive d’évènement ischémique suffisamment élevé pour justifier d’une intensification du traitement. Néanmoins, les thérapeutiques de prévention secondaire futures nécessitent de permettre d’obtenir une réduction absolue du risque de récidive d’évènement ischémique importante pour compenser un risque augmenté d’effets indésirables ou de surcoût par rapport aux thérapeutiques actuelles. En effet, chez ces sous-groupes de patients à haut risque de récidive ischémique, une réduction plus intensive du taux de cholestérol avec les inhibiteurs des PCSK-9 parait tout à fait justifiée, cependant nous avons montré que le coût de ces traitements excède la limite du rapport coût-efficacité généralement accepté tandis que le bénéfice d’une majoration du traitement antithrombotique semble contrebalancé par l’augmentation du risque hémorragique extracrânien. / The current long-term prognosis after transient ischaemic attack (TIA) or ischaemic stroke is not well known. I aimed to determine the long-term absolute residual risks of recurrent stroke and coronary events after TIA or ischaemic stroke and identify individuals who remain at high absolute risk of recurrent ischaemic events despite current secondary prevention management.In a population-based cohort of consecutive TIA or ischaemic stroke patients (OXVASC study, 2002-2014), the overall absolute risks of recurrent ischaemic stroke and coronary events after TIA/ischaemic stroke have decreased over the study period, and are likely to be explained by the improvement of secondary prevention over time. However, despite current secondary prevention, the subgroups of patients with prior coronary artery disease and those without prior coronary artery disease but with an Essen score of 4 remain at sufficiently high absolute risk of recurrent ischaemic events to justify more intensive treatment. Nevertheless, future secondary prevention therapies would need to achieve a substantial absolute risk reduction to outweigh increased side effects or cost compared to current therapies. Indeed, in these high-risk subgroups, more intensive lipid-lowering therapies might be justified, but we showed that the total cost of PCSK-9 inhibitors seems to exceed the generally accepted cost-effectiveness threshold while benefit from increased antithrombotic treatment might be offset by the higher risk of extracranial bleeding.

Purpose: The purposes of this study were to translate current knowledge regarding cardiovascular risk factors, screening, and prevention to a disparate population of women and to ascertain the cardiovascular health status and risk factors in a sample of minority and underserved Appalachian women.Data sources: Demographic data were collected from a voluntary sample of women from a disparate population living in Appalachian Tennessee. A coronary risk profile recorded family health history, personal health history, and lifestyle habits affecting risk for cardiovascular disease. Physiologic measurements included body mass index, blood pressure, fasting glucose, cholesterol levels, ankle brachial index, and carotid artery stenosis.Conclusions: Women in Appalachia Tennessee from a disparate population have high risks for heart disease and stroke. This is a critical time to address any modifiable risk factors and aggressively treat underlying cardiovascular diseases such as hypertension and hypercholesterolemia.Implications for practice: Nurse practitioners (NPs) often provide primary care to women who may not be aware of their cardiovascular risks or actual disease. NPs can ensure that their practice incorporates primary and secondary cardiovascular prevention through screening, individual health education, and aggressive evidence-based treatment plans for women.