| 1. |
- Johansson, Karna, 1982-
(författare)
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Altered body composition in adults with complex congenital heart disease
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Thanks to achievements in paediatric heart surgery and medicine, the population of adults with surgically repaired or palliated congenital heart defects is growing. Many of these adults have reduced exercise capacity, weaker muscular strength and shorter height, all of which suggest an altered body composition.The overall aim of this thesis was to evaluate the body composition, in terms of bone, muscle and fat mass, in adults with complex congenital heart disease (CHD). Changes as such may be of prognostic importance and thus suggest future therapeutic targets outside the traditional hunting grounds of the cardiologist.Material and methods: The overall material consisted of two cohorts. The first cohort, recruited in a Swedish multicentre study, comprised 73 adult patients with complex CHD and 73 controls, matched for age and sex. Participants were examined with full body dual-energy x-ray absorptiometry (DXA), providing muscle, bone and fat mass for arms, legs and trunk respectively (papers I and II).The second cohort, recruited within a single centre study, comprised 49 adult patients with complex CHD and 49 age and sex matched controls. Participants were examined with peripheral quantitative computed tomography (pQCT), providing slices of forearm and calf, describing muscle, bone and fat area and corresponding density (papers III and IV). Muscular strength in selected muscle groups was also evaluated in both cohorts.Results: More than half of the adults with complex CHD had a pathologically low skeletal muscle mass and strength compared to controls, a trait referred to as sarcopenia. There was a strong association between forearm muscle mass and grip strength.Bone mass was lower in adults with complex CHD, according to both DXA and pQCT analyses, also when adjusting for shorter height. Patients also had lower full body bone mineral density (BMD) as measured with DXA. However, analysis of BMD in limbs with pQCT showed no such reduction. Despite this latter finding, the strength-strain index (a surrogate marker for bone strength provided by pQCT in the lower limbs) was still lower in patients compared to controls.Female patients had a higher amount of fat, both in terms of fat mass and proportion of fat, in comparison to controls. The fat mass was predominantly distributed around the internal organs, known as visceral adipose tissue. Male patients showed no such difference regarding fat mass compared to controls.Conclusion: Consequences of living with complex CHD go far beyond the heart; this young population presents a reduced skeletal muscle mass as well as reduced bone strength – both premature traits of frailty, prone to increase with further ageing. Also, women with complex CHD have an increased amount of visceral adipose tissue, which may elevate the risk of acquired heart disease.The extent of future complications remains to be seen. However, the standard treatments for both sarcopenia and osteoporosis include optimal nutritional intake and increased physical exercise. These measures should start sooner rather than later, preferably evaluated through existing quality registers and interventional trials.
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| 2. |
- Henriksson, Robin, 1986-
(författare)
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Secondary prevention after acute coronary syndrome : antiplatelet therapy and risk factor control
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: One of the leading causes of death and disability worldwide is cardiovascular disease (CVD), including acute myocardial infarction (AMI). Despite improvements in medical treatment, management, and care over the years and the halving of mortality in recent decades, there is considerable room for improvement. Following myocardial infarction (MI), a patient is at great risk for subsequent infarctions or other related complications. In addition, the risk of ischemic stroke is increased following MI. Secondary prevention after MI is paramount for reducing further complications and consists of lifestyle changes, optimised medical treatment, and risk factor control of blood pressure (BP) and blood lipid levels. Although secondary preventive measures are effective, the proportion of patients reaching set treatment target levels is disappointingly low.Most patients are prescribed dual antiplatelet therapy (DAPT) following MI as part of their secondary preventive treatment. Several articles have been published on treatment efficacy based on comparisons with different kinds of antiplatelet drugs and in different combinations. However, little data specifically address the incidence of ischemic stroke after MI in real-world populations. In addition to antiplatelet treatment, secondary prevention comprises risk factor control of hypertension and hyperlipidaemia. Given the low proportion of patients reaching set target levels for BP and blood lipids, new strategies are needed.Aims: The aim of this dissertation is partly to elucidate if the rapid change in preferred DAPT in Sweden, from clopidogrel to ticagrelor in addition to aspirin, affected the incidence of ischemic stroke in patients suffering AMI (paper I) and in patients suffering AMI who have a history of ischemic stroke (paper II).The second part of the dissertation aims to investigate the feasibility and implementation of a randomised controlled trial of a nurse-led telephone-based secondary preventive program, and to assess the proportion of patients who can be included in an unselected acute coronary syndrome (ACS) population (paper III). Furthermore, the aim of the trial was to assess the long term results regarding systolic BP (SBP), diastolic BP (DBP), and low-density lipoprotein cholesterol (LDL-C) after 36 months of intervention and follow-up compared to a control group receiving usual care (paper IV).Methods: Papers I and II examined the impact of a change in the antiplatelet regimen following MI in regard to ischemic stroke occurrence. Data were obtained from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (i.e., RIKS-HIA). The register was combined with the National Patient Register (NPR) and the Cause of Death Register (CDR) in order to obtain data on stroke occurrence. Patients with AMI and treated with either clopidogrel or ticagrelor were assigned to one of two cohorts, each covering a 2- year time period, with the initial prescription of ticagrelor (20 Dec 2011) used as a cutoff point. Patients in the early cohort (n=23,447) were treated exclusively with clopidogrel, whereas those in the later cohort (n=24,227) were treated with either clopidogrel (47.9%) or ticagrelor (52.1%). In paper II, the same methodology was used, but with a study sample restricted to AMI patients with a history of ischemic stroke. In paper II, there were 1633 patients in the early cohort and 1642 in the late cohort. In the late cohort, 66.3% patients were treated with clopidogrel and 33.7% with ticagrelor. Kaplan–Meier analysis was used to assess the risk of ischemic stroke over time, with multivariable Cox regression analysis used to identify predictors of ischemic stroke. Nurse-based Age independent Intervention to Limit Evolution of Disease (Papers III and IV were based on the NAILED)-ACS trial. The NAILED-ACS trial was an open randomised controlled trial of whether a nurse-led telephone-based follow-up and medical titration after MI or unstable angina achieved lower levels of BP and LDL-C than usual care. In paper III, patients admitted for ACS during January 2010 and December 2013 were evaluated for participation. Factors predicting participation and non- participation were assessed using logistic regression. Mortality rates after one year among included and excluded patients and patients declining participation were assessed using Kaplan–Meier analysis. For paper IV, all patients admitted with ACS at Östersund Hospital between January 2010 and December 2014 were screened for inclusion based on their ability to participate in a telephone- based follow-up. Participants were randomised into two parallel groups, an intervention group and a control group receiving usual care. BP and LDL-C were measured at 1, 12, 24, and 36 months. The baseline consisted of randomised patients who completed the one-month follow-up. The intervention group received counselling and medical titration to attain treatment targets (BP <140/<90 mmHg and LDL-C <2.5/<1.8 mmol/L). Adjusted means stratified by sex and type of ACS were calculated for SBP and DBP and LDL-C. The proportion of patients who achieved treatment target levels at the end of the study was also assessed.Results: Among the general AMI population treated with either clopidogrel or ticagrelor, the incidence of ischemic stroke after one year was 2.8% in the early cohort vs. 2.4% in the late cohort (p=0.001) (paper I). The study population in paper II, in which all patients had a history of previous ischemic stroke, was overall older and had a higher prevalence of comorbidities than the population in paper I. In paper II, incidence of ischemic stroke in the early cohort was 12.1% vs. 8.6% in the late cohort (p<0.01). Corresponding incidence of intracranial bleeding for the population in paper II was a non-significant 1.2% vs 1.5%.In the feasibility study of the NAILED-ACS trial (paper III), 907 patients were assessed for inclusion. Among these, 72.9% could be included (n=661), 146 patients (16.1%) were excluded, and 100 patients declined participation (11 %). Reasons for exclusion were mainly participation in another trial, dementia, inability to use a telephone, and advanced disease. Examples of predictors of both exclusion and declining participation were older age, lower functional status, and lower education. Non-participating patients had significantly higher mortality rates at one year compared to participating patients.Paper IV presents the final results of the NAILED-ACS risk factor trial in which a total of 962 patients were randomised and completed the one-month follow- up. Of this group, 797 were available for analysis after 36 months. Compared to the control group, in the intervention group, mean SBP was 4.1 mmHg lower, mean DBP was 2.9 mmHg lower, and mean LDL-C was 0.28 mmol/L lower (p<0.001 for all). The proportions of patients reaching treatment target goals for SBP, DBP, and LDL-C were significantly higher in the intervention group. In regard to SBP, 77.6% of intervention patients achieved treatment target levels, compared to 62.9% in the control group. Corresponding numbers for DBP were 90.9% vs. 80.8% and for LDL-C, they were 65.6% vs. 53.1%Conclusion: The incidence of ischemic stroke was significantly lower in a cohort of AMI patients following a change in preferred treatment from clopidogrel to ticagrelor (paper I). In AMI patients with a history of ischemic stroke (paper II), the incidence rate of ischemic stroke was significantly lower in the late cohort compared to the early cohort, and overall incidence rates were markedly higher than in paper I.The NAILED-ACS trial was shown to be both feasible (paper III) and successful, with a higher proportion of patients reaching treatment target levels in the intervention group, and significantly lower mean values for SBP, DBP, and LDL- C (paper IV).
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| 3. |
- Huber, Daniel, 1980-
(författare)
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On secondary prevention after acute coronary syndrome : -what, when, and who
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundCardiovascular disease, of which coronary heart disease constitutes the lion’s share, is the leading cause of premature morbidity and mortality worldwide. Management of the condition has evolved rapidly in recent decades, and mortality has more than halved in the western world. Because of intense research, solid evidence supports effective and inexpensive means of preventing disease progression. However, secondary prevention still yields disappointingly low success in meeting guideline-recommended risk factor targets. It is therefore vital to develop more effective risk factor management.AimsWe aimed to assess the feasibility of a nurse-led, telephone-based, secondary preventive intervention in an unselected population with acute coronary syndrome (ACS). Furthermore, we sought to evaluate the flexibility of the intervention to adapt to a change in guidelines. We also aimed to evaluate whether the intervention was more effective than usual care at improving risk factor levels for blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) 12 months after discharge. Finally, we aimed to measure whether the intervention improved long-term adherence to statins.MethodsAll papers are based on the Nurse-based Age-independent Intervention to Limit Evolution of Disease after ACS (NAILED-ACS) trial. The NAILED trail has two arms, one after stroke/transient ischemic attack (NAILED-Stroke) and one after ACS (NAILED-ACS). All studies are based on NAILED-ACS aside from study II which includes both arms. The trial was an open, 1:1 randomized, controlled, parallel group trial that compared nurse-led telephone follow-up with medical titration (intervention) to a control group with follow-up by a general practitioner (control). All patients admitted to Östersund Hospital for ACS during 2010–2014 were eligible if available for preventive management by telephone. A baseline assessment was made at 1 month after discharge and thereafter every 12 months for at least 3 years. Feasibility was assessed among patients admitted until 31 January 2013, and predictors of exclusion and non-participation were identified. The performance of the intervention in implementing a guideline change was evaluated in patients with diabetes with both ACS and stroke as inclusion events after a change in LDLC target from <2.5 mmol/L to <1.8 mmol/L. LDL-C levels were compared between intervention and control patients before and after the guideline changed. Reasons for not reaching the target level were recorded. The outcomes of the intervention on BP and LDL-C were studied in patients admitted until 31 December 2013. We measured proportions reaching targets and levels of LDL-C and BP during the first 12 months of follow-up, with comparisons between the intervention and control groups. Adherence to statin treatment was measured in the entire study cohort, with at least 36 months of follow-up, with classification of reasons and analysis of predictors for both a first and a permanent discontinuation.ResultsOf 907 screened patients with ACS in the first study, 72.9% were included, and 11% declined participation. Among the 16.1% who were excluded, the predominant reasons were participation in other trial, dementia, and advanced disease. Non-included patients were significantly older, with more comorbidities, decreased functional capability, and lower level of education compared to included. Excluded and declining patients also had a reduced oneyear survival in comparison with included.Before the guideline changed, 96% of the 101 patients in the intervention group reached LDL-C <2.5 mmol/L compared to 70% of the 100 control patients (p<0.001). One year after target reduction to <1.8 mmol/L, the same proportions were 65% and 36%, respectively (p<0.001). The predominant reason for nonattainment of target in the intervention group was full-dose treatment; for the control group, it was that no medication adjustment was made. After medical titration, at 1 month (baseline), 94.1% in the intervention group achieved target for LDL-C (<2.5 mmol/L) compared to 68.4% in the control group. Mean LDL-C was 0.38 mmol/L lower in the intervention group (p<0.05 for both). At the 12-month assessment, 77.7% of the intervention group attained the LDL-C target compared to 63.2% of the control group, and mean LDL-C was 0.3 mmol/L lower among intervention patients (p<0.05 for both). In the intervention group, 91.9% achieved targets for systolic BP and 96.2% for diastolic BP after baseline titration compared to 65.6% and 82.0%, respectively, in the control group (p<0.05 for both). At 12 months, 68.9% in the intervention group reached the target for systolic BP and 88.1% for diastolic BP, compared to 63.7% and 82.8%, respectively, in the control group (p=0.125 and <0.05). Mean systolic BP was 7 mmHg lower and mean diastolic BP 4 mmHg lower in the intervention group after 1-month titration compared to controls. At 12 months, the mean systolic BP was 1.5 mmHg lower and mean diastolic BP 2.1 mmHg lower in the intervention group.In our assessment of adherence to statin treatment, 89.3% in the intervention group and 81.7% in the control group were adherent to treatment during a mean follow-up of 3.9 years (p<0.001). In the intervention group, 27.8% discontinued at least once during the period, compared to 20.8% in the control group (p<0.05). The main reason for a first discontinuation was avoidable in both groups: sideeffects without a compelling association with treatment. The main reason for permanent discontinuation was predominantly non-avoidable in the intervention group (advanced disease and dementia) but avoidable in the control group (sideeffects without a compelling association with treatment). Predictors for increased risk for discontinuation were female sex, and for a first event, inclusion in the intervention group. Predictors for reduced risk of non-adherence were ST elevation myocardial infarction as an including event, and for permanent discontinuation, inclusion in the intervention group.ConclusionA nurse-led telephone-based method for secondary prevention can encompass a large proportion of an ordinary ACS cohort. Compared to usual care, it is more adaptable to changes in treatment guidelines and leads to better achievement of major risk factor targets as well as improved medication adherence.
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| 4. |
- Ulvenstam, Anders, 1975-
(författare)
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Cardiovascular events after acute coronary syndrome with special reference to ischemic stroke
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Acute coronary syndrome (ACS) encompasses acute myocardial infarction (AMI) and unstable angina (UA). It is a global major cause of morbidity and mortality in both the short and long terms. The risk for recurrent ischemic cardiovascular (CV) events and death after ACS depends on patient factors at presentation, revascularization and secondary prevention measures. Of these, ischemic stroke (IS) is a feared and potentially devastating complication that confers suffering for the individual patient and an economic burden on society. ACS and secondary prevention treatment have gone through dramatic improvements during recent decades. These improvements, together with an improved risk factor profile in the general population, have led to lower morbidity and halved mortality. ACS and IS share many risk factors. Most of our knowledge about prognosis and risk of recurrent ischemic events after ACS is based on clinical trials and it is uncertain whether these findings can be translated to the general population. Aims: The study aims were as follows: to estimate the rate, time trends, risk factors and effects on mortality of IS after an AMI during the decades that ACS and secondary prevention treatment improved; to study wether the switch from the antiplatelet agent clopidogrel to ticagrelor influenced post-AMI IS risk in patients treated with PCI, based on data from the SWEDEHEART register; and to estimate the long-term rate of subsequent CV events after ACS in an unselected cohort of ACS patients, based on the ACS-population in the Nurse-based Age- independent Intervention to Limit Evolution of Disease After Acute Coronary Syndrome (NAILED-ACS) study. Methods: In papers I–IV, data from the SWEDEHEART register were merged with the Swedish National Patient Register (NPR) to identify patients with AMI and subsequent ischemic stroke. In paper V, data were obtained from the NAILED-ACS study. Survival analysis with Kaplan–Meier estimates and hazard ratios for risk factors with Cox proportional hazards regression models were calculated in all five studies. When appropriate, propensity scores and competing risk analyses were used to adjust for baseline differences and a high overall mortality rate, respectively. Results: The overall IS rates at 30 days and 1 year after AMI were 2.1 and 4.1% respectively, during the study period (1998–2008). The rate of IS after AMI decreased over time, both at 30 days and at 1 year, with relative risk reductions (RRRs) of 11% at 30 days and 20% at 1 iii year respectively, when comparing the beginning and end of the study period. AMI complicated by IS within 1 year had a higher mortality rate than AMI without IS (36.5 vs. 18.3%). The mortality rates decreased during 1998– 2008, by 9.4% in patients with IS and 7.5% in those without IS.The introduction of dual antiplatelet therapy (DAPT) with ticagrelor instead of clopidogrel was associated with a 21% relative risk reduction of IS within 1 year after AMI in patients treated with PCI. The rate of recurrent CV events (CV death, AMI and IS) after ACS during the first year was 10.3% and remained high during a median follow-up time of 4.7 years, at 28.6%.Predictors of increased risk of recurrent ischemic events were older age, female sex, previously established CV and cerebrovascular disease, hypertension, atrial fibrillation, diabetes mellitus, heart failure and renal disease. Reperfusion and revascularization procedures in the acute phase as well as evidence-based secondary prevention treatment were associated with a protective effect against recurrent ischemic events. Conclusion: The results reported in this thesis indicate an overall high rate of recurrent CV events after ACS based on a contemporary, unselected population of ACS patients. IS a relatively rare, but serious complication after AMI that confers a substantially increased mortality risk. The rate and mortality risk of IS after AMI have decreased over time. Improved, evidence-based treatment, both in the acute phase and in the long term, has most likely reduced the post-ACS risk of recurrent ischemic events in general and more specifically of IS. The switch from clopidogrel to ticagrelor was associated with a small, but statistically significant reduction in IS risk in PCI-treated AMI patients.
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| 5. |
- Björklund, Fredrik, 1968-
(författare)
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Platelet reactivity and comorbidities in acute coronary syndrome
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background In the event of an acute coronary syndrome (ACS), the risk of death and complications such as stroke and re-infarction is high during the first month. Diabetes, impaired kidney function, elevated markers of systemic inflammation and high level of platelet reactivity have all been associated with worsened prognosis in ACS patients. Impaired kidney function is a condition with high cardiovascular morbidity and there is an established association between level of kidney function and outcome in the event of an ACS. Aims We sought to investigate the level of platelet reactivity during the first days of an ACS and specifically the level of platelet reactivity in patients with different conditions associated with worsened prognosis in the event of an ACS. We also wanted to investigate the prognostic impact of baseline levels of cystatin C as well as the importance of decreasing kidney function during the first days of an ACS. Methods We included 1028 unselected patients with ACS or suspected ACS during the years 2002 and 2003, of which 534 were diagnosed with an acute myocardial infarction (AMI). Blood samples for measuring platelet aggregation, cystatin C levels and other clinically important biomarkers were collected day 1, 2, 3 and 5 following admission. Platelet reactivity was measured using 2 different methods. Platelet aggregation was measured using Pa-200, a particle count method, based on scattering of laser light. PFA 100 is a method of measuring primary hemostasis in whole blood. Results Platelet aggregation and comorbidities. We found an increase in platelet aggregation when an ACS was complicated by an infection and there was an increased frequency of aspirin non-responsiveness in patients suffering from pneumonia during the first days of an ACS. Furthermore, we found an independent association between levels of C-reactive protein and platelet aggregation. During the first 3 days following an acute myocardial infarction, platelet aggregation increased despite treatment with anti-platelet agents. Platelet aggregation was found to be more pronounced in patients with diabetes. Patients with impaired kidney function, showed increased platelet aggregation compared to patients with normal renal function, however, this difference was explained by older age, higher prevalence of DM and levels of inflammatory biomarkers. We found no independent association between chronic kidney disease (CKD) and levels of platelet aggregation. Kidney function and outcome Serum levels of cystatin C on admission had an independent association with outcome following an acute myocardial infarction. With a mean follow-up time of 2.9 years, the adjusted HR for death was 1.62 (95% CI 1.28-2.03; p<0.001) for each unit of increase in cystatin C on admission. The level of dynamic changes in cystatin C during admission for an acute myocardial infarction was independently associated with prognosis in patients with normal or mild impairment of renal function. The adjusted HR for death was 10.1 (95% CI 3.4-29.9; p<0.001). Conclusion In patients suffering from an AMI platelet aggregation increases during the first days, despite anti-platelet treatment. Diabetes, age and biomarkers of inflammation are independently associated with platelet aggregation. Admission levels of cystatin C as well as changes in cystatin C levels during hospitalisation are independently associated with outcome.
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| 6. |
- Graipe, Anna, 1973-
(författare)
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Bleeding complications after acute coronary syndrome with special reference to intracranial hemorrhage
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Bleeding complications following acute coronary syndrome (ACS) have attracted considerable attention in recent years. The gradual implementation of new evidence-based treatments in patients with ACS, with a focus on anti-ischemic therapy, has reduced the risk of ischemic events (new myocardial infarction or ischemic stroke) but at the expense of increased bleeding risk. Bleeding is associated with both increased morbidity and mortality and, with major bleeding, the risk of death is comparable to that seen in myocardial infarction. Avoidance of bleeding is one possible way to further improve post-ACS outcomes. During the 1990s reperfusion approaches shifted from thrombolysis, with its increased risk of bleeding and intracranial hemorrhage (ICH), to percutaneous coronary intervention (PCI), with an expected lower risk. Treatment recommendations are derived from randomized controlled trials in which high-risk patients are excluded, and observational studies are needed to assess outcomes. Antithrombotic treatment is associated with increased risk of serious bleeding and even more so with the new potent P2Y12 inhibitors. However, their association with ICH is not well studied, and knowledge is limited regarding temporal trends in ICH after ACS. Furthermore, few studies have long-term follow-up for serious bleedings and associated risk factors.Aims: The aims of this thesis were to assess the incidence, temporal trends and factors associated with ICH after acute myocardial infarction (AMI); investigate the impact on ICH risk of changing the treatment regimen from clopidogrel to ticagrelor; estimate the risk of serious bleeding (bleeding requiring hospitalization) after ACS and characterize the type of bleeding; identify factors associated with increased bleeding risk; and assess if serious bleeding is associated with increased mortality. Method: In studies I–III, patients with AMI were identified using the Register of Information and Knowledge About Swedish Heart Intensive Care Admission (RIKS-HIA), and the data were combined with information from the Swedish National Patient Register, 1998–2013 to identify ICH. In study II, we included a matched reference group from Statistics Sweden. Study IV included all patients who were identified with an ACS during the inclusion period of the Nurse-Based Age-Independent Intervention to Limit Evolution of Disease After Acute Coronary Syndrome risk factor trial (2010–2014), and patients were followed until December 2017. Serious bleedings were identified in the local diagnosis registry, and scrutinizing of the medical records validated all diagnoses. Baseline characteristics in all studies were evaluated using the student t-test, Mann–Whitney U test, or the chi-square test as appropriate. In studies I and II, the observational time was divided into periods and in study I the chi-square test for trend was used to evaluate the trend over time. Temporal trends in study II were assessed by Kaplan–Meier analysis and evaluated using log-rank test. To reduce selection bias related to the choice of antiplatelet treatment in study III, the date of the first prescription of ticagrelor was identified in the RIKS-HIA registry and used as a cutoff point, and the study period was divided into two periods of similar length to create two cohorts. The risk in the first with respect to the second cohort was assessed by Kaplan–Meier analysis, and cohorts were compared with the log-rank test. Kaplan–Meier analysis was also used in study IV to assess serious bleeds. Predictors were assessed by Cox regression analyses. Results: The 30-day risk of hemorrhagic stroke decreased from 0.2% in 1998 to 0.1% in 2008. The decrease can be explained by the shift in reperfusion method from thrombolysis to PCI in patients with a ST-elevation myocardial infarction. Age, hypertension and previous hemorrhagic stroke were associated with increased risk. The cumulative incidence of ICH within one year of AMI was 0.35%, which did not change during the 13-year follow-up (1998–2010) despite a considerable increase in the use of dual antiplatelet therapy. The incidence of ICH in the AMI cohort was twice that of a matched reference group. Age, decreased kidney function and previous ischemic and hemorrhagic stroke were associated with increased ICH risk. None of the medications included in the analysis were associated with a significant change in ICH risk. For antiplatelets, ticagrelor is a more potent P2Y12 inhibitor compared to clopidogrel and has previously been associated with increased bleeding risk; however, in this work ticagrelor was not associated with increased risk of ICH compared to clopidogrel. In study IV, during a median follow-up of 4.6 years, 8.6% of patients had a serious bleed after their ACS. This rate was 13.4% in patients aged ≥75 years. The most common location was gastrointestinal, followed by ICH. Risk factors associated with serious bleeding were age ≥75 years, hypertension, and previous heart failure. Bleeding per se was not associated with increased mortality.Conclusion: The shift in reperfusion method from thrombolysis to PCI likely explained the decrease in ICH in the acute phase after an AMI. The incidence of ICH post-discharge was stable over the study period despite increased use of antithrombotic therapy, and the use of more potent P2Y12 inhibitor did not increase the ICH risk. Serious bleeding was relatively frequent in the long term after ACS, and bleeding recurrence was common. Important risk factors for bleeding were age, hypertension, previous ischemic or hemorrhagic stroke, decreased renal function and previous heart failure. Individualized assessment of risk factors and comorbidity and individualized intensity and duration of antithrombotic treatment may further improve outcome in ACS patients. Continuous re-evaluation of bleeding risk is needed.
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| 7. |
- Irewall, Anna-Lotta, 1987-
(författare)
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Recurrent events and secondary prevention after acute cerebrovascular disease
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Patients who experience a stroke or transient ischemic attack (TIA) are at high risk of recurrent stroke, but little is known about temporal trends in unselected populations. Reports of low adherence to recommended treatments indicate a need for enhanced secondary preventive follow-up to achieve the full potential of evidence-based treatments. In addition, socioeconomic factors have been associated with poor health outcomes in a variety of contexts. Therefore, it is important to assess the implementation and results of secondary prevention in different socioeconomic groups.Aims The aims of this thesis were to assess temporal trends in ischemic stroke recurrence and evaluate the implementation and results of a nurse-led, telephone-based follow-up program to improve blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels after stroke/TIA.Methods In study I, we collected baseline data for unique patients with an ischemic stroke event between 1998 and 2009 (n=196 765) from the Swedish Stroke Register (Riksstroke). Recurrent ischemic stroke events within 1 year were collected from the Swedish National Inpatient Register (IPR) and the cumulative incidence was compared between four time periods using the Kaplan-Meier survival analysis and the logrank test. Implementation (study II) and 1-year results (study III-IV) for the secondary preventive follow-up were studied in the NAILED (Nurse-based Age-independent Intervention to Limit Evolution of Disease) study. Between 1 Jan 2010 and 31 Dec 2013, the baseline characteristics of consecutive patients admitted to Östersund Hospital for acute stroke or TIA were collected prospectively (n=1776). Consenting patients in a condition permitting telephone-based follow-up were randomized to nurse-led, telephone-based follow-up or follow-up according to usual care. Follow-up was cunducted at 1 and 12 months after discharge and the intervention included BP and LDL-C measurements, titration of medication, and lifestyle counseling. In study II, we analyzed factors associated with non-participation in the randomized phase of the NAILED study, including association with education level. In addition, we compared the 1-year prognosis in terms of cumulative survival between participants and non-participants. In study III, we compared differences in BP and LDL-C levels between the intervention and control groups during the first year of follow-up and, in study IV, in relation to level of education (low, ≤10 years; high, >10 years).Results The cumulative 1-year incidence of recurrent ischemic stroke decreased from 15.0% to 12.0%. Among surviving stroke and TIA patients, 53.1% were included for randomization, 35.7% were excluded mainly due to physical or cognitive disability, and 11.2% declined participation in the randomized phase. A low level of education was independently associated with exclusion, as well as the patient’s decision to abstain from randomization. Excluded patients had a more than 12-times higher risk of death within 1 year than patients who were randomized. After 1 year of follow-up, the mean systolic BP, diastolic BP, and LDL-C levels were 3.3 mmHg (95% CI 0.3 to 6.3), 2.3 mmHg (95% CI 0.5 to 4.2), and 0.3 mmol/L (95% CI 0.1 to 0.4) lower in the intervention group than among controls. Among participants with values above the treatment goal at baseline, the differences in systolic BP and LDL-C levels were more pronounced (8.0 mmHg, 95% CI 4.0 to 12.1; 0.6 mmol/L, 95% CI 0.4 to 0.9). In the intervention group, participants with a low level of education achieved similar or larger improvements in BP and LDL-C than participants with a high level of education. In the control group, BP remained unaltered and the LDL-C levels increased among participants with a low level of education.Conclusion The 1-year risk of ischemic stroke recurrence decreased in Sweden between 1998 and 2010. Nurse-led, telephone-based secondary preventive follow-up is feasible in just over half of the survivors of acute stroke and TIA and achieve better than usual care in terms of BP and LDL-C levels, and equality in BP improvements across groups defined by education level. However, a large proportion of stroke survivors are in a general condition precluding this form of follow-up, and their prognosis in terms of 1-year survival is poor. Patients with a low education level are over-represented within this group and among patients declining randomization for secondary preventive follow-up.
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| 8. |
- Jakobsson, Stina, 1987-
(författare)
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Cardiovascular disease and diabetes or renal insufficiency : the risk of ischemic stroke and risk factor intervention
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundIn patients with diabetes mellitus (DM) or chronic kidney disease (CKD), established cardiovascular disease (CVD) is associated with an increased risk of recurrent events and poor outcome. Ischemic stroke after an acute myocardial infarction (AMI) is a devastating event that carries high risks of decreased patient independence and death. Among patients with DM or CKD, the risk of an ischemic stroke within a year following an AMI is not known. Improved risk factor control is required to reduce the likelihood of CVD recurrence. Guidelines recommend target lipid profile and blood pressure values; however, data show that these targets are often not met. Therefore, there remains an urgent need for improved cardiovascular secondary preventive follow- up.AimsThe aims of the present studies were to define trends in the incidence and predictors of ischemic stroke after an AMI in patients with DM or CKD. Furthermore to assess whether secondary preventive follow-up with nurse-based telephone follow-up including medication titration after CVD improves risk factor values in patients with DM or CKD and to investigate if this method performs better than usual care to implement a new treatment guideline in diabetic patients.MethodsTo assess the risk of post-AMI ischemic stroke, patient data were obtained from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA). In separate studies, we compared a total of 173 233 AMI patients with and without DM, and 118 434 AMI patients with and without CKD.Within the nurse-based age-independent intervention to limit evolution of disease (NAILED) trial, we investigated a nurse-based cardiovascular secondary preventive follow-up protocol. Patients with acute coronary syndrome, stroke, or transient ischemic attack were randomized to receive either nurse-based telephone follow-up (intervention) or usual care (control). Low-density lipoprotein (LDL-C) levels and blood pressure (BP) were measured at 1 month (baseline) and 12 months post- discharge. Intervention patients with above-target baseline values received medication titration to achieve treatment goals, while the measurements for control patients were forwarded to their general practitioners for assessment. We calculated the changes in LDL-C level and BP between baseline and 12 months post-discharge, and compared these changes between 225 intervention patients and 215 control patients with concurrent DM or CKD. During the course of the NAILED trial, new secondary preventive guidelines for DM patients were released, including a new LDL-C target value. To assess adherence to the new guidelines within the NAILED trial, we compared LDL-C levels in the 101 intervention patients and 100 control patients with DM.ResultsIschemic stroke after AMIThe rates of ischemic stroke within one-year after admission for an AMI decreased over time, from 7.1% in 1998–2000 to 4.7% in 2007–2008 among DM patients, and from 4.2% to 3.7% during the same time periods for non-diabetic patients. Lower stroke risk was associated with percutaneous coronary intervention (PCI) and initiation of secondary preventive treatments in-hospital.In-hospital ischemic stroke occurred in 2.3% of CKD patients and 1.2% of non-CKD patients, with no change in these incidences over time. The rates of one-year post- discharge ischemic stroke decreased between 2003–2004 and 2009–2010 from 4.1% to 2.5% among CKD patients, and from 2.0% to 1.3% among non-CKD patients. Lower rates of post-discharge stroke were associated with PCI and statins.Cardiovascular secondary preventive follow-upAmong DM and CKD patients with above-target baseline values in the NAILED trial, the median LDL-C value at 12 months was 2.2 versus 3.0 mmol/L (p<0.001) and median systolic BP was 140 versus 145 mmHg (p=0.26) for intervention and control patients, respectively.Before the guideline change, 96% of the intervention and 70% of the control patients reached the target LDL-C value (p<0.001). After the guideline change, the corresponding respective proportions were 65% and 36% (p<0.001).ConclusionIschemic stroke is a fairly common post-AMI complication among patients with DM and CKD. This risk of stroke has decreased during recent years, possibly due to the increased use of evidence-based therapies. Compared with usual care, cardiovascular secondary prevention including nurse-based telephone follow-up improved LDL-C values at 12 months after discharge in patients with DM or CVD, and led to more efficient implementation of new secondary preventive guidelines.
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| 9. |
- Nilsson, Gunnar, 1957-
(författare)
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Ischaemic heart disease - risk assessment, diagnosis, and secondary preventive treatment in primary care : with special reference to the relevance of exercise ECG
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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
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| 10. |
- Ögren, Joachim, 1981-
(författare)
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Serious hemorrhage and secondary prevention after stroke and TIA
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The number of stroke survivors is growing worldwide, and these patients have an increased risk of new vascular events and death. This risk decreases with secondary treatment medications recommended in guidelines. However, the characteristics of unselected stroke patients differ from patients included in randomized controlled trials (RCTs). Thus, the efficacy of these treatments based on RCT results may not be directly transferable to the patients treated in clinical practice. A treatment may be associated with a higher risk of serious side-effects or less benefit than expected:1) Antithrombotic treatment increases the risk of a serious hemorrhage, a risk that is not well studied in an unselected population with older age and more comorbidities; 2) Treatment of modifiable risk factors after a stroke can be improved. Many patients do not reach treatment targets, which indicates a need for strategies to improve secondary prevention and increase treatment benefit.It is therefore essential to evaluate recommended treatments through studies in a real-world setting.Aims: The aims of this thesis were to assessincidence, temporal trends, effect on mortality, and factors associated with an increased risk of a serious hemorrhage after ischemic stroke (IS) or transient ischemic attack (TIA); andif a nurse-led, telephone-based intervention including medical titration could improve modifiable risk factors in patients after stroke or TIA.Methods: In paper I, all patients registered with an IS in the national stroke register Riksstroke during 1998–2009 were studied. The register was combined with the In-Patient Register and a diagnosis of intracranial haemorrhage (ICrH) within 1 year after IS was identified. In paper II, any diagnosis of serious hemorrhage was identified during follow-up up to 2015 in all patients with an IS or TIA diagnosis, 2010–2013, at Östersund hospital. The incidences of ICrH (papers I and II) and all serious hemorrhages (paper II) were calculated. Kaplan–Meier analysis was used to assess any temporal trend in paper I and if a serious hemorrhage affected survival in study II. Cox regression analysis was used in both studies I and II to assess any factor associated with hemorrhage.In the randomized controlled NAILED stroke trial, all patients with acute stroke or TIA treated at Östersund hospital during 2010–2013 were screened for participation. Patients whose condition permitted a telephone-based follow-up were randomized to either a control group with follow-up according to usual care or to an intervention group with a nurse-led, telephone-based follow-up including titration of medication. Blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) were assessed at 1, 12, 24, and 36 months. We assessed the effect of the intervention on mean levels of BP and LDL-C and on the proportion of patients reaching treatment targets at 12 months (Study III) and at 36 months (Study IV). Study III also assessed for interactions between group allocation and measurement levels at baseline with BP and LDL-C at the 12-month follow-up. Study IV also explored temporal trends.Results: The risk of an ICrH was 1.97% per year at risk, within the first year after IS, and 0.85% excluding the first 30 days. Between 1998 and 2009, the risk of an ICrH increased during the first 30 days after an IS but decreased during days 31–365. The risk of a serious hemorrhage was 2.48% per year at risk in paper II. It was more common in elderly. The incidence rate was higher in patients discharged with AP compared with RCTs. A hemorrhage increased the risk of death in patients with good functional status but did not affect the already high mortality in patients with impaired functional status. Male sex and previous ICrH were associated with an increased risk of ICrH during the first year after IS, thrombolytic treatment, atrial fibrillation and warfarin were associated with an increased risk in the acute phase. A previous diagnosis of hypertension was associated with an increased risk of all serious hemorrhages. The NAILED trial intervention group had a significantly lower mean systolic BP (SBP), diastolic BP (DBP), and LDL-C at 12 and 36 months. The mean SBP at 36 months was 128.1 mmHg (95% confidence interval (CI): 125.8–130.5) in the intervention group, 6.1 mmHg (95% CI: 3.6–8.6; p<0.001) lower than the control group. The interaction analysis at 12 months showed that the effect of the intervention was confined to patients whose values were above the respective targets at baseline and therefore had their medication adjusted. At 36 months, a significantly higher proportion of patients in the intervention group reached treatment targets for SBP, DBP, and LDL-C. The mean differences and differences in proportions reaching treatment target for BP increased during the 36 months of follow-up.Conclusion: A serious hemorrhage after an IS or TIA is fairly common. It is more common in elderly and patients with impaired functional status. The incidence is higher in patients discharged with AP compared with RCTs. A serious hemorrhage could affect survival in patients with good functional status. The nurse-led, telephone-based intervention including medical titration used in the NAILED stroke trial improved risk factor levels after stroke and TIA, and more patients reached treatment targets. The effect increased over time.
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