| 1. |
- Grip, Lars, 1952, et al.
(author)
-
From European to National guidelines on heart disease
- 2011
-
In: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 45:1, s. 3-13
-
Research review (peer-reviewed)abstract
- Background/aims. Guidelines from the European Society of Cardiology are important tools for defining and establishing current standards of care for various heart diseases. The aim of the present paper is to describe the process of how these international guidelines may be transformed and implemented at a national level in Sweden. Methods/results. The structure and process behind the national guidelines for heart diseases in Sweden and their relationship to the underlying European guidelines are described and differences between the national and European levels highlighted. We also give examples of how the scientific values of health care measures are weighted against health economic perspectives and integrated in a prioritization process. Compared to the European guidelines, the Swedish national guidelines have a broader economic perspective and aim to ensure that health care is cost effective and provided to all Swedish citizens on equal terms. Discussion. When certain health care measures are implemented, the national process can result in other priorities than could be expected from the European guidelines alone. On the other hand, a forceful implementation may be facilitated by the societal context in which these national guidelines are produced.
|
|
| 2. |
- Folkersen, Lasse, et al.
(author)
-
Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
-
In: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
-
Journal article (peer-reviewed)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
|
|
| 3. |
- Klaric, Lucija, et al.
(author)
-
Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
- 2021
-
In: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
-
Other publication (other academic/artistic)abstract
- Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
|
|
| 4. |
- Simonsson, Moa, et al.
(author)
-
Temporal trends in bleeding events in acute myocardial infarction : insights from the SWEDEHEART registry
- 2020
-
In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 41:7, s. 833-843
-
Journal article (peer-reviewed)abstract
- AIMS: To describe the time trends of in-hospital and out-of-hospital bleeding parallel to the development of new treatments and ischaemic outcomes over the last 20 years in a nationwide myocardial infarction (MI) population.METHODS AND RESULTS: Patients with acute MI (n = 371 431) enrolled in the SWEDEHEART registry from 1995 until May 2018 were selected and evaluated for in-hospital bleeding and out-of-hospital bleeding events at 1 year. In-hospital bleeding increased from 0.5% to a peak at 2% 2005/2006 and thereafter slightly decreased to a new plateau around 1.3% by the end of the study period. Out-of-hospital bleeding increased in a stepwise fashion from 2.5% to 3.5 % in the middle of the study period and to 4.8% at the end of the study period. The increase in both in-hospital and out-of-hospital bleeding was parallel to increasing use of invasive strategy and adjunctive antithrombotic treatment, dual antiplatelet therapy (DAPT), and potent DAPT, while the decrease in in-hospital bleeding from 2007 to 2010 was parallel to implementation of bleeding avoidance strategies. In-hospital re-infarction decreased from 2.8% to 0.6% and out-of-hospital MI decreased from 12.6% to 7.1%. The composite out-of-hospital MI, cardiovascular death, and stroke decreased in a similar fashion from 18.4% to 9.1%.CONCLUSION: During the last 20 years, the introduction of invasive and more intense antithrombotic treatment has been associated with an increase in bleeding events but concomitant there has been a substantial greater reduction of ischaemic events including improved survival.
|
|
| 5. |
- Alexander, John H., et al.
(author)
-
Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome : results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) trial
- 2009
-
In: Circulation. - 0009-7322 .- 1524-4539. ; 119:22, s. 2877-2885
-
Journal article (peer-reviewed)abstract
- BACKGROUND: After an acute coronary syndrome, patients remain at risk of recurrent events. Apixaban, an oral direct factor Xa inhibitor, is a novel anticoagulant that may reduce these events but also poses a risk of bleeding. METHODS AND RESULTS: Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) was a phase 2, double-blind, placebo-controlled, dose-ranging study. Patients (n=1715) with recent ST-elevation or non-ST-elevation acute coronary syndrome were randomized to 6 months of placebo (n=611) or 1 of 4 doses of apixaban: 2.5 mg twice daily (n=317), 10 mg once daily (n=318), 10 mg twice daily (n=248), or 20 mg once daily (n=221). Nearly all patients received aspirin; 76% received clopidogrel. The primary outcome was International Society of Thrombosis and Hemostasis major or clinically relevant nonmajor bleeding. A secondary outcome was cardiovascular death, myocardial infarction, severe recurrent ischemia, or ischemic stroke. At the recommendation of the Data Monitoring Committee, the 2 higher-dose apixaban arms were discontinued because of excess total bleeding. Compared with placebo, apixaban 2.5 mg twice daily (hazard ratio, 1.78; 95% confidence interval, 0.91 to 3.48; P=0.09) and 10 mg once daily (hazard ratio, 2.45; 95% confidence interval, 1.31 to 4.61; P=0.005) resulted in a dose-dependent increase in major or clinically relevant nonmajor bleeding. Apixaban 2.5 mg twice daily (hazard ratio, 0.73; 95% confidence interval, 0.44 to 1.19; P=0.21) and 10 mg once daily (hazard ratio, 0.61; 95% confidence interval, 0.35 to 1.04; P=0.07) resulted in lower rates of ischemic events compared with placebo. The increase in bleeding was more pronounced and the reduction in ischemic events was less evident in patients taking aspirin plus clopidogrel than in those taking aspirin alone. CONCLUSIONS: We observed a dose-related increase in bleeding and a trend toward a reduction in ischemic events with the addition of apixaban to antiplatelet therapy in patients with recent acute coronary syndrome. The safety and efficacy of apixaban may vary depending on background antiplatelet therapy. Further testing of apixaban in patients at risk of recurrent ischemic events is warranted.
|
|
| 6. |
- Björck, Lena, 1959, et al.
(author)
-
Smoking in relation to ST-segment elevation acute myocardial infarction: findings from the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions.
- 2009
-
In: Heart (British Cardiac Society). - : BMJ. - 1468-201X .- 1355-6037. ; 95:12, s. 1006-11
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: In the past few decades, clinical presentation in AMI has been reported to be changing, with milder cases and less ST-elevation myocardial infarction, the most serious form of AMI. The better outcome may be due to improved medical and interventional management, as well as more sensitive methods for detecting AMI. However, changes in risk factors have also been documented, especially lower tobacco-smoking rates. Therefore, the relation between smoking and ST-elevation AMI in a large observational cohort was analysed. METHODS: Data were derived from 93 416 consecutive patients aged 25 to 84 years and admitted to hospital between 1996 and 2004 with a first AMI. RESULTS: Tobacco smoking was more prevalent in younger patients (ie, <65 years). More than 50% of younger patients presenting with STEMI were smokers at the time of hospitalisation. After multiple adjustments, smoking was found to be an independent determinant for presenting with STEMI compared with non-STEMI. The adjusted odds ratio (OR) associated with smoking was 2.01 (99% CI 1.75 to 2.30) in younger women and 1.33 (99% CI 1.22 to 1.43) in younger men, with a significant interaction between smoking and gender. In older women and men (> or =65 years), the corresponding ORs were 1.33 (99% CI 1.20 to 1.48) and 1.14 (99% CI 1.04 to 1.25), respectively. CONCLUSION: Tobacco smoking is a major determinant for presenting with STEMI compared with non-STEMI, particularly among younger patients and among women. These results indicate that smoking is one of the major risk factors for presenting with more severe AMIs.
|
|
| 7. |
- Björklund, Erik, et al.
(author)
-
Admission N-terminal pro-brain natriuretic peptide and its interaction with admission troponin T and ST segment resolution for early risk stratification in ST elevation myocardial infarction
- 2006
-
In: Heart. - : BMJ Publishing Group. - 1468-201X .- 1355-6037. ; 92:6, s. 735-40
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To assess the long term prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) on admission and its prognostic interaction with both admission troponin T (TnT) concentrations and resolution of ST segment elevation in fibrinolytic treated ST elevation myocardial infarction (STEMI). DESIGN AND SETTING: Substudy of the ASSENT (assessment of the safety and efficacy of a new thrombolytic) -2 and ASSENT-PLUS trials. PATIENTS: NT-proBNP and TnT concentrations were determined on admission in 782 patients. According to NT-proBNP concentrations, patients were divided into three groups: normal concentration (for patients < or = 65 years, < or = 184 ng/l and < or = 268 ng/l and for those > 65 years, < or = 269 ng/l and < or = 391 ng/l in men and women, respectively); higher than normal but less than the median concentration (742 ng/l); and above the median concentration. For TnT, a cut off of 0.1 microg/l was used. Of the 782 patients, 456 had ST segment resolution (< 50% or > or = 50%) at 60 minutes calculated from ST monitoring. MAIN OUTCOME MEASURES: All cause one year mortality. RESULTS: One year mortality increased stepwise according to increasing concentrations of NT-proBNP (3.4%, 6.5%, and 23.5%, respectively, p < 0.001). In receiver operating characteristic analysis, NT-proBNP strongly trended to be associated more with mortality than TnT and time to 50% ST resolution (area under the curve 0.81, 95% confidence interval (CI) 0.72 to 0.9, 0.67, 95% CI 0.56 to 0.79, and 0.66, 95% CI 0.56 to 0.77, respectively). In a multivariable analysis adjusted for baseline risk factors and TnT, both raised NT-proBNP and ST resolution < 50% were independently associated with higher one year mortality, whereas raised TnT contributed independently only before information on ST resolution was added to the model. CONCLUSION: Admission NT-proBNP is a strong independent predictor of mortality and gives, together with 50% ST resolution at 60 minutes, important prognostic information even after adjustment for TnT and baseline characteristics in STEMI.
|
|
| 8. |
- Bäck, Maria, 1978, et al.
(author)
-
The SWEDEHEART secondary prevention and cardiac rehabilitation registry (SWEDEHEART CR registry)
- 2021
-
In: European Heart Journal-Quality of Care and Clinical Outcomes. - : Oxford University Press (OUP). - 2058-5225 .- 2058-1742. ; 7:5, s. 431-437
-
Journal article (peer-reviewed)abstract
- Aims The quality registry SWEDEHEART covers data across the patient pathway after an acute myocardial infarction (MI), from hospital care to secondary prevention. Although cardiac rehabilitation (CR) is strongly recommended after an MI, there is still heterogeneity regarding standards, uptake, and adherence rates. The aim of the SWEDEHEART-CR registry is to provide continuous information on secondary prevention and CR performance to support the audit and development of evidence-based practice. To facilitate quality improvement and research initiatives, a description of the characteristics and development of the SWEDEHEART-CR registry is needed. Methods and results The SWEDEHEART-CR registry starts with data obtained during hospital care and then collects data at out-patient visits 2 months and 1-year after discharge, and at start and end of an exercise-based CR programme. The registry data covers comorbidities, biochemistry, blood pressure, anthropometric variables, medication, psychosocial- and lifestyle variables, readmissions, patient-reported outcome measures, attendance in CR-related programmes, and physical fitness variables. Over 100 000 patients with MI have been included in the SWEDEHEART-CR registry since its start in 2005. From initially covering 35 centres (47%) and 2200 patients annually (27%), SWEDEHEART-CR has developed to a nation-wide registry with 75 centres (100%) and 8800 patients annually (80%) in 2020. Conclusion The SWEDEHEART-CR registry includes a high proportion of the national MI population entering a CR programme and is a powerful tool for quality audit, improvement, and research. The registry provides insights into the characteristics, treatment, and outcomes of evidence-based secondary preventive practice, ultimately leading to better cardiovascular health.
|
|
| 9. |
- Johanson, Per, 1963, et al.
(author)
-
ST resolution 1 hour after fibrinolysis for prediction of myocardial infarct size: insights from ASSENT 3.
- 2009
-
In: The American journal of cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 103:2, s. 154-8
-
Journal article (peer-reviewed)abstract
- Acute ST-segment elevation myocardial infarction requires prompt restoration of myocardial perfusion to salvage myocardium at risk of ischemic necrosis and improve clinical outcome. Early resolution of ST-segment elevation during the time after reperfusion has been associated with both these end points. From the ASsessment of the Safety and Efficacy of a New Thrombolytic regimen (ASSENT) 3 trial, 3,425 patients were analyzed to investigate whether the amount of ST-segment resolution, divided into 3 groups (complete, >70%; partial, 30% to 70%; and no resolution, <30%), in the first hour after initiation of therapy was a predictor of final infarct size, estimated by peak creatine kinase and Selvester QRS score on the discharge electrocardiogram. Complete compared with partial and no ST resolution resulted in significantly (p<0.001) smaller infarct sizes of 10.5%, 13.2%, and 15.0% of the left ventricle and significantly (p=0.001) fewer patients with peak creatine >5 times the upper reference level at 50.3%, 71.8%, and 76.3%, respectively. In conclusion, our findings supported previous smaller studies suggesting that early resolution of ST elevation, as a sign of early myocardial reperfusion, resulted in less myocardial damage and preservation of left ventricular function.
|
|
| 10. |
- Rosengren, Annika, 1951, et al.
(author)
-
Age, clinical presentation, and outcome of acute coronary syndromes in the Euroheart acute coronary syndrome survey
- 2006
-
In: Eur Heart J. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 27:7, s. 789-95
-
Journal article (peer-reviewed)abstract
- AIMS: Age is one of the most powerful determinants of prognosis in myocardial infarction, but there is comparatively little recent data across the whole spectrum of acute coronary syndromes (ACS). We examined the impact of increasing age on clinical presentation and hospital outcome in a large sample of patients with ACS. METHODS AND RESULTS: Patients (n = 10 253) from the Euroheart ACS survey in 103 hospitals in 25 countries were investigated. There was a significant inverse association between the age and the likelihood of presenting with ST-elevation. For each decade of life, the odds of presenting with ST-elevation decreased by 0.82 [95% confidence interval (CI) 0.79-0.84]; P < 0.0001. Elderly patients were considerably less often treated by cardiologists, less extensively investigated, and, when presenting with ST-elevation ACS, less likely to be treated with reperfusion. Compared with patients <55 years, the odds ratios of hospital mortality were 1.87 (1.21-2.88) at age 55-64, 3.70 (2.51-5.44) at age 65-74, 6.23 (4.25-9.14) at age 75-84, and 14.5 (9.47-22.1) among patients > or =85 years, with no major differences across different types of admission or discharge diagnoses. CONCLUSION: Elderly ACS patients were less likely to present with ST-elevation but had substantial in-hospital mortality, yet they were markedly less intensively treated and investigated.
|
|
