Publications by authors named "Bertil Lindahl"

294 Publications

Sex-differences in circulating biomarkers during acute myocardial infarction: An analysis from the SWEDEHEART registry.

PLoS One 2021 8;16(4):e0249830. Epub 2021 Apr 8.

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Background: Sex-differences in the pathobiology of myocardial infarction are well established but incompletely understood. Improved knowledge on this topic may help clinicians to improve management of men and women with myocardial infarction.

Methods: In this registry-based cohort study (SWEDEHEART), we analyzed 175 circulating biomarkers reflecting various pathobiological axes in 856 men and 243 women admitted to Swedish coronary care units because of myocardial infarction. Two multimarker panels were applied (Proximity Extension Assay [Olink Bioscience], Multiple Reaction Monitoring mass spectrometry). Lasso analysis (penalized logistic regression), multiple testing-corrected Mann-Whitney tests and Cox regressions were used to assess sex-differences in the concentrations of these biomarkers and their implications on all-cause mortality and major adverse events (median follow-up up to 6.6 years).

Results: Biomarkers provided a very high discrimination between both sexes, when considered simultaneously (c-statistics 0.972). Compared to women, men had higher concentrations of six biomarkers with the most pronounced differences seen for those reflecting atherogenesis, myocardial necrosis and metabolism. Women had higher concentrations of 14 biomarkers with the most pronounced differences seen for those reflecting activation of the renin-angiotensin-aldosterone axis, inflammation and for adipokines. There were no major variations between sexes in the associations of these biomarkers with outcome.

Conclusions: Severable sex-differences exist in the expression of biomarkers in patients with myocardial infarction. While these differences had no impact on outcome, our data suggest the presence of various sex-related pathways involved in the development of coronary atherosclerosis, the progression to plaque rupture and acute myocardial damage, with a greater heterogeneity in women.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249830PLOS
April 2021

Routine Oxygen Therapy Does Not Improve Health-Related Quality of Life in Patients With Acute Myocardial Infarction-Insights From the Randomized DETO2X-AMI Trial.

Front Cardiovasc Med 2021 15;8:638829. Epub 2021 Mar 15.

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

After decades of ubiquitous oxygen therapy in all patients with acute myocardial infarction (MI), recent guidelines are more restrictive based on lack of efficacy in contemporary trials evaluating hard clinical outcomes in patients without hypoxemia at baseline. However, no evidence regarding treatment effects on health-related quality of life (HRQoL) exists. In this study, we investigated the impact of routine oxygen supplementation on HRQoL 6-8 weeks after hospitalization with acute MI. Secondary objectives included analyses of MI subtypes, further adjustment for infarct size, and oxygen saturation at baseline and 1-year follow-up. In the DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial, 6,629 normoxemic patients with suspected MI were randomized to oxygen at 6 L/min for 6-12 h or ambient air. In this prespecified analysis, patients younger than 75 years of age with confirmed MI who had available HRQoL data by European Quality of Life Five Dimensions questionnaire (EQ-5D) in the national registry were included. Primary endpoint was the EQ-5D index assessed by multivariate linear regression at 6-10 weeks after MI occurrence. A total of 3,086 patients (median age 64, 22% female) were eligible, 1,518 allocated to oxygen and 1,568 to ambient air. We found no statistically significant effect of oxygen therapy on EQ-5D index (-0.01; 95% CI: -0.03-0.01; = 0.23) or EQ-VAS score (-0.57; 95% CI: -1.88-0.75; = 0.40) compared to ambient air after 6-10 weeks. Furthermore, no significant difference was observed between the treatment groups in EQ-5D dimensions. Results remained consistent across MI subtypes and at 1-year follow-up, including further adjustment for infarct size or oxygen saturation at baseline. Routine oxygen therapy provided to normoxemic patients with acute MI did not improve HRQoL up to 1 year after MI occurrence. ClinicalTrials.gov number, NCT01787110.
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http://dx.doi.org/10.3389/fcvm.2021.638829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006541PMC
March 2021

Prasugrel versus ticagrelor in patients with myocardial infarction undergoing percutaneous coronary intervention.

Heart 2021 Mar 12. Epub 2021 Mar 12.

Department of Cardiology and Department of Health, Medicine and Caring Sciences, Unit of Cardiovascular Sciences, Linköping University Linköping, Linkopings Universitet, Linkoping, Sweden.

Objective: The comparative efficacy and safety of prasugrel and ticagrelor in patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) remain unclear. We aimed to investigate the association of treatment with clinical outcomes.

Methods: In the SWEDEHEART (Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies) registry, all patients with MI treated with PCI and discharged on prasugrel or ticagrelor from 2010 to 2016 were included. Outcomes were 1-year major adverse cardiac and cerebrovascular events (MACCE, death, MI or stroke), individual components and bleeding. Multivariable adjustment, inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were used to adjust for confounders.

Results: We included 37 990 patients, 2073 in the prasugrel group and 35 917 in the ticagrelor group. Patients in the prasugrel group were younger, more often admitted with ST elevation MI and more likely to have diabetes. Six to twelve months after discharge, 20% of patients in each group discontinued the P2Y12 receptor inhibitor they received at discharge. The risk for MACCE did not significantly differ between prasugrel-treated and ticagrelor-treated patients (adjusted HR 1.03, 95% CI 0.86 to 1.24). We found no significant difference in the adjusted risk for death, recurrent MI or stroke alone between the two treatments. There was no significant difference in the risk for bleeding with prasugrel versus ticagrelor (2.5% vs 3.2%, adjusted HR 0.92, 95% CI 0.69 to 1.22). IPTW and PSM analyses confirmed the results.

Conclusion: In patients with MI treated with PCI, prasugrel and ticagrelor were associated with similar efficacy and safety during 1-year follow-up.
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http://dx.doi.org/10.1136/heartjnl-2020-318694DOI Listing
March 2021

Randomized comparison of early supplemental oxygen versus ambient air in patients with confirmed myocardial infarction: Sex related outcomes from DETO2X-AMI.

Am Heart J 2021 Mar 6. Epub 2021 Mar 6.

Department of Clinical Science and Education, Division of Cardiology, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden. Electronic address:

Aims: To study the impact of oxygen therapy on cardiovascular outcomes in relation to sex in patients with confirmed myocardial infarction (MI).

Methods: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial randomized 6,629 patients to oxygen at 6 L/min for 6-12 hours or ambient air. In the present subgroup analysis in 5,010 patients (1,388 women and 3,622 men) with confirmed MI, we report the effect of supplemental oxygen on the composite of all-cause death, rehospitalization with MI, or heart failure (HF) at long-term follow-up, stratified according to sex.

Results: Event rate for the composite endpoint was 18.1% in women allocated to oxygen, compared to 21.4% in women allocated to ambient air (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.65-1.05). In men, the incidence was 13.6% in patients allocated to oxygen compared to 13.3% in patients allocated to ambient air (HR 1.03, 95% CI 0.86-1.23). No significant interaction in relation to sex was found (p=0.16). Irrespective of allocated treatment, the composite endpoint occurred more often in women compared to men (19.7 vs. 13.4%, HR 1.51; 95% CI, 1.30-1.75). After adjustment for age alone there was no difference between the sexes (HR 1.06, 95% CI 0.91-1.24), which remained consistent after multivariate adjustment.

Conclusion: Oxygen therapy in normoxemic MI patients did not significantly affect all-cause mortality or rehospitalization for MI or HF in women or men. The observed worse outcome in women was explained by differences in baseline characteristics, especially age.
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http://dx.doi.org/10.1016/j.ahj.2021.03.001DOI Listing
March 2021

Cardiovascular biomarkers in patients with COVID-19.

Eur Heart J Acute Cardiovasc Care 2021 Feb 28. Epub 2021 Feb 28.

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

The coronavirus disease 2019 (COVID-19) pandemic has increased awareness that severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) may have profound effects on the cardiovascular system. COVID-19 often affects patients with pre-existing cardiac disease, and may trigger acute respiratory distress syndrome (ARDS), venous thromboembolism (VTE), acute myocardial infarction (AMI), and acute heart failure (AHF). However, as COVID-19 is primarily a respiratory infectious disease, there remain substantial uncertainty and controversy whether and how cardiovascular biomarkers should be used in patients with suspected COVID-19. To help clinicians understand the possible value as well as the most appropriate interpretation of cardiovascular biomarkers in COVID-19, it is important to highlight that recent findings regarding the prognostic role of cardiovascular biomarkers in patients hospitalized with COVID-19 are similar to those obtained in studies for pneumonia and ARDS in general. Cardiovascular biomarkers reflecting pathophysiological processes involved in COVID-19/pneumonia and its complications have a role evaluating disease severity, cardiac involvement, and risk of death in COVID-19 as well as in pneumonias caused by other pathogens. First, cardiomyocyte injury, as quantified by cardiac troponin concentrations, and haemodynamic cardiac stress, as quantified by natriuretic peptide concentrations, may occur in COVID-19 as in other pneumonias. The level of those biomarkers correlates with disease severity and mortality. Interpretation of cardiac troponin and natriuretic peptide concentrations as quantitative variables may aid in risk stratification in COVID-19/pneumonia and also will ensure that these biomarkers maintain high diagnostic accuracy for AMI and AHF. Second, activated coagulation as quantified by D-dimers seems more prominent in COVID-19 as in other pneumonias. Due to the central role of endothelitis and VTE in COVID-19, serial measurements of D-dimers may help physicians in the selection of patients for VTE imaging and the intensification of the level of anticoagulation from prophylactic to slightly higher or even therapeutic doses.
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http://dx.doi.org/10.1093/ehjacc/zuab009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989520PMC
February 2021

Biomarkers of coagulation and fibrinolysis in acute myocardial infarction: a joint position paper of the Association for Acute CardioVascular Care and the European Society of Cardiology Working Group on Thrombosis.

Eur Heart J Acute Cardiovasc Care 2020 Nov 7. Epub 2020 Nov 7.

Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Blvd. 161, 8200 Aarhus N, Denmark.

The formation of a thrombus in an epicardial artery may result in an acute myocardial infarction (AMI). Despite major advances in acute treatment using network approaches to allocate patients to timely reperfusion and optimal antithrombotic treatment, patients remain at high risk for thrombotic complications. Ongoing activation of the coagulation system as well as thrombin-mediated platelet activation may both play a crucial role in this context. Whether measurement of circulating biomarkers of coagulation and fibrinolysis could be useful for risk stratification in secondary prevention is currently not fully understood. In addition, measurement of such biomarkers could be helpful to identify thrombus formation as the leading mechanism for AMI. The introduction of biomarkers of myocardial injury such as high-sensitivity cardiac troponins made rule-out of AMI even more precise. However, elevated markers of myocardial injury cannot provide proof of a type 1 AMI, let alone thrombus formation. The combined measurement of markers of myocardial injury with biomarkers reflecting ongoing thrombus formation might be helpful for the fast and correct diagnosis of an atherothrombotic type 1 AMI. This position paper gives an overview of the current knowledge and possible role of biomarkers of coagulation and fibrinolysis for the diagnosis of AMI, risk stratification, and individualized treatment strategies in patients with AMI.
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http://dx.doi.org/10.1093/ehjacc/zuaa025DOI Listing
November 2020

Clinical risk scores identify more patients at risk for cardiovascular events within 30 days as compared to standard ACS risk criteria: the WESTCOR study.

Eur Heart J Acute Cardiovasc Care 2020 Oct 2. Epub 2020 Oct 2.

Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Aims: Troponin-based algorithms are made to identify myocardial infarctions (MIs) but adding either standard acute coronary syndrome (ACS) risk criteria or a clinical risk score may identify more patients eligible for early discharge and patients in need of urgent revascularization.

Methods And Results: Post-hoc analysis of the WESTCOR study including 932 patients (mean 63 years, 61% male) with suspected NSTE-ACS. Serum samples were collected at 0, 3, and 8-12 h and high-sensitivity cTnT (Roche Diagnostics) and cTnI (Abbott Diagnostics) were analysed. The primary endpoint was MI, all-cause mortality, and unplanned revascularizations within 30 days. Secondary endpoint was non-ST-elevation myocardial infarction (NSTEMI) during index hospitalization. Two combinations were compared: troponin-based algorithms (ESC 0/3 h and the High-STEACS algorithm) and either ACS risk criteria recommended in the ESC guidelines, or one of eleven clinical risk scores, HEART, mHEART, CARE, GRACE, T-MACS, sT-MACS, TIMI, EDACS, sEDACS, Goldman, and Geleijnse-Sanchis. The prevalence of primary events was 21%. Patients ruled out for NSTEMI and regarded low risk of ACS according to ESC guidelines had 3.8-4.9% risk of an event, primarily unplanned revascularizations. Using HEART score instead of ACS risk criteria reduced the number of events to 2.2-2.7%, with maintained efficacy. The secondary endpoint was met by 13%. The troponin-based algorithms without evaluation of ACS risk missed three-index NSTEMIs with a negative predictive value (NPV) of 99.5% and 99.6%.

Conclusion: Combining ESC 0/3 h or the High-STEACS algorithm with standardized clinical risk scores instead of ACS risk criteria halved the prevalence of rule-out patients in need of revascularization, with maintained efficacy.
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http://dx.doi.org/10.1093/ehjacc/zuaa016DOI Listing
October 2020

Treatment and Prognosis of Myocardial Infarction Outside Cardiology Departments.

J Clin Med 2020 Dec 30;10(1). Epub 2020 Dec 30.

Department of Medical Sciences, Cardiology, Uppsala University, 751 85 Uppsala, Sweden.

Aim: Our aim was to investigate the characteristics, treatment and prognosis of patients with myocardial infarction (MI) treated outside a cardiology department (CD), compared with MI patients treated at a CD.

Methods: A cohort of 1310 patients diagnosed with MI at eight Swedish hospitals in 2011 were included in this observational study. Patients were followed regarding all-cause mortality until 2018.

Results: A total of 235 patients, exclusively treated outside CDs, were identified. These patients had more non-cardiac comorbidities, were older (mean age 83.7 vs. 73.1 years) and had less often type 1 MIs (33.2% vs. 74.2%), in comparison with the CD patients. Advanced age and an absence of chest pain were the strongest predictors of non-CD care. Only 3.8% of non-CD patients were investigated with coronary angiography and they were also prescribed secondary preventive pharmacological treatments to a lesser degree, with only 32.3% having statin therapy at discharge. The all-cause mortality was higher in non-CD patients, also after adjustment for baseline parameters, both at 30 days (hazard ratio (HR) 2.28; 95% confidence interval (CI) 1.62-3.22), one year (HR 1.82; 95% CI 1.39-2.36) and five years (HR 1.62; 95% CI 1.32-1.98).

Conclusions: MI treatment outside CDs is associated with an adverse short- and long-term prognosis. An improved use of percutaneous coronary intervention (PCI) and secondary preventive pharmacological treatment might improve the long-term prognosis in these patients.
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http://dx.doi.org/10.3390/jcm10010106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795967PMC
December 2020

Low-density lipoprotein cholesterol reduction and statin intensity in myocardial infarction patients and major adverse outcomes: a Swedish nationwide cohort study.

Eur Heart J 2021 Jan;42(3):243-252

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Aims : Clinical trials have demonstrated that a reduction in low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular (CV) events. This has, however, not yet been shown in a real-world setting. We aimed to investigate the association between LDL-C changes and statin intensity with prognosis after a myocardial infarction (MI).

Methods And Results : Patients admitted with MI were followed for mortality and major CV events. Changes in LDL-C between the MI and a 6- to 10-week follow-up visit were analysed. The associations between quartiles of LDL-C change and statin intensity with outcomes were assessed using adjusted Cox regression analyses. A total of 40 607 patients were followed for a median of 3.78 years. The median change in LDL-C was a 1.20 mmol/L reduction. Patients with larger LDL-C reduction (1.85 mmol/L, 75th percentile) compared with a smaller reduction (0.36 mmol/L, 25th percentile) had lower hazard ratios (HR) for all outcomes (95% confidence interval): composite of CV mortality, MI, and ischaemic stroke 0.77 (0.70-0.84); all-cause mortality 0.71 (0.63-0.80); CV mortality 0.68 (0.57-0.81); MI 0.81 (0.73-0.91); ischaemic stroke 0.76 (0.62-0.93); heart failure hospitalization 0.73 (0.63-0.85), and coronary artery revascularization 0.86 (0.79-0.94). Patients with ≥50% LDL-C reduction using high-intensity statins at discharge had a lower incidence of all outcomes compared with those using a lower intensity statin.

Conclusions : Larger early LDL-C reduction and more intensive statin therapy after MI were associated with a reduced hazard of all CV outcomes and all-cause mortality. This supports clinical trial data suggesting that earlier lowering of LDL-C after an MI confers the greatest benefit.
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http://dx.doi.org/10.1093/eurheartj/ehaa1011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954251PMC
January 2021

Randomized evaluation of beta blocker and ACE-inhibitor/angiotensin receptor blocker treatment in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA-BAT): Rationale and design.

Am Heart J 2021 01 24;231:96-104. Epub 2020 Oct 24.

Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is common and occurs in 6-8% of all patients fulfilling the diagnostic criteria for acute myocardial infarction (AMI). This paper describes the rationale behind the trial 'Randomized Evaluation of Beta Blocker and ACE-Inhibitor/Angiotensin Receptor Blocker Treatment (ACEI/ARB) of MINOCA patients' (MINOCA-BAT) and the need to improve the secondary preventive treatment of MINOCA patients. METHODS: MINOCA-BAT is a registry-based, randomized, parallel, open-label, multicenter trial with 2:2 factorial design. The primary aim is to determine whether oral beta blockade compared with no oral beta blockade, and ACEI/ARB compared with no ACEI/ARB, reduce the composite endpoint of death of any cause, readmission because of AMI, ischemic stroke or heart failure in patients discharged after MINOCA without clinical signs of heart failure and with left ventricular ejection fraction ≥40%. A total of 3500 patients will be randomized into four groups; e.g. ACEI/ARB and beta blocker, beta blocker only, ACEI/ARB only and neither ACEI/ARB nor beta blocker, and followed for a mean of 4 years. SUMMARY: While patients with MINOCA have an increased risk of serious cardiovascular events and death, whether conventional secondary preventive therapies are beneficial has not been assessed in randomized trials. There is a limited basis for guideline recommendations in MINOCA. Furthermore, studies of routine clinical practice suggest that use of secondary prevention therapies in MINOCA varies considerably. Thus results from this trial may influence future treatment strategies and guidelines specific to MINOCA patients.
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http://dx.doi.org/10.1016/j.ahj.2020.10.059DOI Listing
January 2021

Novel clearance of muscle proteins by muscle cells.

Eur J Cell Biol 2020 Nov 4;99(8):151127. Epub 2020 Nov 4.

Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address:

Blood levels of cardiac troponins (cTn) and myoglobin are analysed when myocardial infarction (MI) is suspected. Here we describe a novel clearance mechanism for muscle proteins by muscle cells. The complete plasma clearance profile of cTn and myoglobin was followed in rats after intravenous or intermuscular injections and analysed by PET and fluorescence microscopy of muscle biopsies and muscle cells. Compared with intravenous injections, only 5 % of cTnT, 0.6 % of cTnI and 8 % of myoglobin were recovered in the circulation following intramuscular injection. In contrast, 47 % of the renal filtration marker FITC-sinistrin and 81 % of cTn fragments from MI-patients were recovered after intramuscular injection. In addition, PET and biopsy analysis revealed that cTn was taken up by the quadriceps muscle and both cTn and myoglobin were endocytosed by cultured muscle cells. This local clearance mechanism could possibly be the dominant clearance mechanism for cTn, myoglobin and other muscle damage biomarkers released by muscle cells.
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http://dx.doi.org/10.1016/j.ejcb.2020.151127DOI Listing
November 2020

Use of Warfarin or Direct Oral Anticoagulants and Risk of Prostate Cancer in PCBaSe: A Nationwide Case-Control Study.

Front Oncol 2020 8;10:571838. Epub 2020 Oct 8.

Translational Oncology and Urology Research Group, School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.

Existing literature examining warfarin's association with prostate cancer (PCa) risk provides conflicting results, while the association with direct oral anticoagulants (DOACs) has not yet been studied. We investigated the association of warfarin and DOAC use on PCa risk among men within the population-based Prostate Cancer database Sweden (PCBaSe), using a case-control design. The study population included PCa cases diagnosed 2014-2016 and five age-matched PCa-free controls. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CI) for PCa associated with warfarin and DOAC use, adjusted for marital status, education level, other drug use, and comorbidities. Among 31,591 cases and 156,802 controls, there were 18,522 (9.8%) warfarin and 4,455 (2.4%) DOAC users. Warfarin ever-use was associated with reduced risk of PCa overall (OR 0.92 95% CI 0.88-0.96) as were both past and current use. DOAC use was not associated with PCa risk. For some warfarin exposures, decreased risk was observed for unfavorable PCa (high risk/locally advanced/distant metastatic) but not with favorable PCa (low/intermediate risk). Increased risk of favorable PCa was observed for men whose initial warfarin exposure occurred in the 12 month period before diagnosis (OR 1.39; 95% CI 1.13-1.70). Our findings are consistent with previous publications reporting decreased PCa risk with warfarin exposure. Increased risk of favorable PCa suggests detection bias due to increased prostate specific antigen testing when starting on warfarin. Decreased overall PCa risk could reflect bias due to reduced biopsy rates among long-term warfarin users.
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http://dx.doi.org/10.3389/fonc.2020.571838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578339PMC
October 2020

Incidence and outcome of myocardial infarction treated with percutaneous coronary intervention during COVID-19 pandemic.

Heart 2020 12 6;106(23):1812-1818. Epub 2020 Oct 6.

Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden

Objective: Most reports on the declining incidence of myocardial infarction (MI) during the COVID-19 have either been anecdotal, survey results or geographically limited to areas with lockdowns. We examined the incidence of MI during the COVID-19 pandemic in Sweden, which has remained an open society with a different public health approach fighting COVID-19.

Methods: We assessed the incidence rate (IR) as well as the incidence rate ratios (IRRs) of all MI referred for coronary angiography in Sweden using the nationwide Swedish Coronary Angiography and Angioplasty Registry (SCAAR), during the COVID-19 pandemic in Sweden (1 March 2020-7 May 2020) in relation to the same days 2015-2019.

Results: A total of 2443 MIs were referred for coronary angiography during the COVID-19 pandemic resulting in an IR 36 MIs/day (204 MIs/100 000 per year) compared with 15 213 MIs during the reference period with an IR of 45 MIs/day (254 MIs/100 000 per year) resulting in IRR of 0.80, 95% CI (0.74 to 0.86), p<0.001. Results were consistent in all investigated patient subgroups, indicating no change in patient category seeking cardiac care. Kaplan-Meier event rates for 7-day case fatality were 439 (2.3%) compared with 37 (2.9%) (HR: 0.81, 95% CI (0.58 to 1.13), p=0.21). Time to percutaneous coronary intervention (PCI) was shorter during the pandemic and PCI was equally performed, indicating no change in quality of care during the pandemic.

Conclusion: The COVID-19 pandemic has significantly reduced the incidence of MI referred for invasive treatment strategy. No differences in overall short-term case fatality or quality of care indicators were observed.
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http://dx.doi.org/10.1136/heartjnl-2020-317685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677488PMC
December 2020

Sex-specific effects of implementing a high-sensitivity troponin I assay in patients with suspected acute coronary syndrome: results from SWEDEHEART registry.

Sci Rep 2020 09 17;10(1):15227. Epub 2020 Sep 17.

Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.

Using high-sensitivity cardiac troponin (hs-cTn) assays with sex-specific 99th percentiles may improve management of patients with suspected acute myocardial infarction (AMI). We investigated the impact of transitioning from a conventional troponin I assay to a high-sensitivity assay with sex-specific thresholds, in patients with suspected acute coronary syndrome admitted to Swedish coronary care units. Based on data from SWEDEHEART registry (females, n = 4,819/males, n = 7,670), we compared periods before and after implementation of hs-cTnI assay (Abbott) using sex-specific 99th percentiles. We investigated differences on discharge diagnosis, in-hospital examinations, treatments, and clinical outcome. Upon implementation of the hs-cTnI assay, proportion of patients with troponin levels above diagnostic AMI threshold increased in women and men by 24.3% versus 14.8%, respectively. Similarly, incidence of AMI increased by 11.5% and 9.8%. Diagnostic interventions and treatments increased regardless of sex. However, these associations did not persist following multivariable adjustment, probably due to the effect of temporal management trends during the observation period. Overall, no risk reduction on major adverse cardiovascular events was observed (HR: 0.91 [95% CI 0.80-1.03], P = 0.126). The implementation of hs-cTnI assay together with sex-specific 99th percentiles was associated with an increase in incidence of AMI regardless of sex, but had no major impact on clinical management and prognosis.
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http://dx.doi.org/10.1038/s41598-020-72204-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499170PMC
September 2020

Comparison Between Ticagrelor and Clopidogrel in Elderly Patients With an Acute Coronary Syndrome: Insights From the SWEDEHEART Registry.

Circulation 2020 Nov 1;142(18):1700-1708. Epub 2020 Sep 1.

Department of Clinical Sciences, Danderyd University Hospital (T.J.), Karolinska Institutet, Stockholm, Sweden.

Background: The comparative efficacy and safety of ticagrelor versus clopidogrel in older patients with myocardial infarction (MI) has received limited study.

Methods: We performed an observational analysis of all patients ≥80 years (n=14 005) who were discharged alive with aspirin combined with either clopidogrel (60.2%) or ticagrelor (39.8%) after a MI between 2010 and 2017 registered in the national registry SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies). Inverse probability treatment weighting was used in Cox regression models to adjust for differences in demographics, in-hospital therapies, and medications. The primary ischemic outcome (death, MI, or stroke), and bleeding were obtained from national registries at 1 year. A sensitivity analysis in <80-year-old patients was performed.

Results: In patients ≥80 years, the incidence of the primary ischemic outcome (hazard ratio [HR], 0.97 [95% CI, 0.88-1.06]) was similar for ticagrelor- and clopidogrel-treated patients. Ticagrelor was associated with a 17% and 48% higher risk of death (HR, 1.17 [95% CI, 1.03-1.32]) and bleeding (HR, 1.48 [95% CI, 1.25-1.76]), but a lower risk of MI (HR, 0.80 [95% CI, 0.70-0.92]) and stroke (HR, 0.72 [95% CI, 0.56-0.93]). In <80-year-old patients, the incidence of the primary ischemic outcome was 17% (HR, 0.83 [95% CI, 0.77-0.89]) lower with ticagrelor. Ticagrelor was associated with 15% (HR, 0.85 [95% CI, 0.76-0.96]) lower risk of death, 32% higher risk of bleeding (HR, 1.32 [95% CI, 1.18-1.47]), but lower risk of MI (HR, 0.82 [95% CI, 0.75-0.91]) and stroke (HR, 0.82 [95% CI, 0.69-0.98]).

Conclusions: Ticagrelor use among elderly patients with MI was associated with higher risk of bleeding and death compared with clopidogrel. A randomized study of ticagrelor versus clopidogrel in the elderly is needed.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050645DOI Listing
November 2020

Effectiveness and Safety of the European Society of Cardiology 0-/1-h Troponin Rule-Out Protocol: The Design of the ESC-TROP Multicenter Implementation Study.

Cardiology 2020 20;145(11):685-692. Epub 2020 Aug 20.

Department of Emergency Medicine, Skåne University Hospital, Lund University, Lund, Sweden.

Chest pain is one of the most common complaints at the emergency department (ED), and it is commonly the perceived likelihood of acute coronary syndrome (ACS) that drives management. Guidelines from the European Society of Cardiology (ESC) recommend the use of a 0-/1-h high-sensitivity cardiac troponin T (hs-cTnT) protocol to rule out or in ACS, but this is mostly based on observational studies. The aim of the ESC-TROP trial is to determine the safety and effectiveness of the ESC 0-/1-h hs-cTnT protocol when implemented in routine care. Adult chest pain patients at 5 EDs in the Skåne Region, Sweden, are included in the trial. The 0-/1-h hs-cTnT ESC protocol supplemented with clinical assessment and electrocardiography (ECG) is implemented at 3 EDs, and the other 2 EDs act as concurrent controls. Outcomes will be evaluated during the 10 months after the implementation and the corresponding 10 months of the previous year. The 2 co-primary outcomes are (a) acute myocardial infarction (AMI) and all-cause death within 30 days in patients discharged from the ED, and (b) ED length of stay of the same patients. Secondary outcomes include the proportion of chest pain patients discharged from the ED and the number of ruled-out patients undergoing objective testing within 30 days. The ESC-TROP trial will determine the performance and applicability of the 0-/1-h hs-cTnT ESC protocol supplemented with clinical assessment and ECG when implemented in routine ED care. It will provide evidence whether 0-/1-h hs-cTnT testing is safe, effective, and feasible, and whether widespread implementation as recommended by ESC guidelines should be supported.
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http://dx.doi.org/10.1159/000509390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677994PMC
August 2020

Application of the fourth universal definition of myocardial infarction in clinical practice.

Biomarkers 2020 Jun 14;25(4):322-330. Epub 2020 May 14.

Department of Medical Sciences, Uppsala University and Uppsala Clinical Research Center, Uppsala University, Sweden.

The Fourth Universal Definition of Myocardial Infarction (MI) has highlighted the different pathophysiological mechanisms that may lead to ischaemic and non-ischaemic myocardial injury and has emphasised that the diagnosis of myocardial infarction requires the presence of acute myocardial ischaemia in the setting of acute myocardial injury. This case based review intends to illustrate basic principles on how to apply this new, revised definition in clinical practice. The distinction between different types of MIs (type 1 or type 2) and the delineation of MI from acute non-ischaemic myocardial injury may be challenging in individual patients, which is illustrated by presenting and discussing real-life routine cases. Type 1 MI is a consequence of coronary plaque rupture or erosion with intracoronary thrombus formation that is usually apparent on coronary angiography. Plausible triggering mechanisms causing myocardial oxygen supply/demand mismatch must be identified for the diagnosis of type 2 MI and its treatment should focus initially on management of the underlying disease attributable to acute myocardial ischaemia.
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http://dx.doi.org/10.1080/1354750X.2020.1764108DOI Listing
June 2020

The Liver and Kidneys mediate clearance of cardiac troponin in the rat.

Sci Rep 2020 04 22;10(1):6791. Epub 2020 Apr 22.

Institute of Biomedicine, Department of Laboratory Medicine, Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.

Cardiac-specific troponins (cTn), troponin T (cTnT) and troponin I (cTnI) are diagnostic biomarkers when myocardial infarction is suspected. Despite its clinical importance it is still not known how cTn is cleared once it is released from damaged cardiac cells. The aim of this study was to examine the clearance of cTn in the rat. A cTn preparation from pig heart was labeled with fluorescent dye or fluorine 18 ( F). The accumulation of the fluorescence signal using organ extracts, or the 18 F signal using positron emission tomography (PET) was examined after a tail vein injection. The endocytosis of fluorescently labeled cTn was studied using a mouse hepatoma cell line. Close to 99% of the cTnT and cTnI measured with clinical immunoassays were cleared from the circulation two hours after a tail vein injection. The fluorescence signal from the fluorescently labeled cTn preparation and the radioactivity from the 18F-labeled cTn preparation mainly accumulated in the liver and kidneys. The fluorescently labeled cTn preparation was efficiently endocytosed by mouse hepatoma cells. In conclusion, we find that the liver and the kidneys are responsible for the clearance of cTn from plasma in the rat.
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http://dx.doi.org/10.1038/s41598-020-63744-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176693PMC
April 2020

Spironolactone use is associated with lower prostate cancer risk: a population-wide case-control study.

Prostate Cancer Prostatic Dis 2020 09 2;23(3):527-533. Epub 2020 Mar 2.

Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Studies, King's College London, London, UK.

Background: Spironolactone, a cheap effective diuretic used to manage hypertension and heart failure, also has anti-androgenic effects through its non-selective binding to steroid receptors, and hence may affect prostate cancer (PCa) risk. This study investigated the association between spironolactone use and PCa risk. For comparison, we also examined associations with thiazide diuretics which do not have anti-androgenic properties.

Methods: A matched case-control study was undertaken using population-wide data from the Prostate Cancer Data Base Sweden (PCBaSe). All PCa cases diagnosed from 2014 to 2016 were matched by birth year and county with PCa-free controls selected from the general population (1:5). Multivariable conditional logistic regression was used to examine associations between spironolactone use (dose and duration) and PCa risk, and similarly for thiazides.

Results: Three percent of the 31,591 cases and 4% of the 156,802 controls had been prescribed spironolactone. Multivariable analyses indicated reduced risk of PCa among those ever exposed to spironolactone (odds ratio [OR] 0.83; 95% confidence interval [CI]: 0.76-0.89), with a stronger association for current users (OR: 0.77, 95% CI: 0.69-0.86) than past users (OR: 0.88; 95% CI: 0.79-0.97) and decreasing risk with increasing dose (p-trend < 0.001). No association was observed for thiazide exposure and PCa risk. Biases due to differences in prescribing patterns or frequency of PSA testing may have influenced these findings.

Conclusion: PCa risk was reduced among men exposed to the diuretic spironolactone. Further investigation of spironolactone's potential chemopreventive effects is warranted.
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http://dx.doi.org/10.1038/s41391-020-0220-8DOI Listing
September 2020

Effectiveness by gender and age of renin-angiotensin system blockade in heart failure-A national register-based cohort study.

Pharmacoepidemiol Drug Saf 2020 05 17;29(5):518-529. Epub 2020 Feb 17.

Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.

Purpose: Investigate effectiveness by gender and age and equity implications of treatment with renin-angiotensin system blockade (RASb) in heart failure (HF) patients.

Methods: In this population-based register study, we used inpatient data from 2006 to 2010 for patients age 20 years or older with no HF hospitalisation for minimum of 1 year before an index hospitalisation. A wash-out period for RASb of 6 months preceding admission was used. Hospital data were linked with drug dispensation data and cause of death data. The associations between time-dependent RASb exposure and all-cause death and HF death, respectively, were examined by Cox regression models. Interactions by gender and age were also investigated on the multiplicative and additive scales.

Results: Thirty thousand seven hundred twenty-one patients were analysed. Fifty-one percent were women. Median age was 83. Fifty-three percent of women and 64% of men received RASb after the index hospitalisation. Younger patients were more likely to receive RASb than older ones. One-year mortality was 28%. RASb was associated with an overall hazard ratio (HR) for all-cause death of 0.72 (95% confidence interval 0.69-0.75), and an HR of 0.85 (0.77-0.93) for HF death. Interaction analyses showed HRs for all-cause death associated with RASb between 0.12 (0.10-0.13) in the youngest, and 0.80 (0.76-0.84) in the oldest patients.

Conclusions: RASb appeared effective for women and men and for patients of all ages in this hospitalised HF cohort. No gender difference in effectiveness was found. RASb exposure was low overall, indicating a need for improved adherence to treatment guidelines. Treatment with RASb may be inequitable for women and older patients.
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http://dx.doi.org/10.1002/pds.4958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318275PMC
May 2020

A Possible Mechanism behind Faster Clearance and Higher Peak Concentrations of Cardiac Troponin I Compared with Troponin T in Acute Myocardial Infarction.

Clin Chem 2020 02;66(2):333-341

Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.

Background: Although cardiac troponin I (cTnI) and troponin T (cTnT) form a complex in the human myocardium and bind to thin filaments in the sarcomere, cTnI often reaches higher concentrations and returns to normal concentrations faster than cTnT in patients with acute myocardial infarction (MI).

Methods: We compared the overall clearance of cTnT and cTnI in rats and in patients with heart failure and examined the release of cTnT and cTnI from damaged human cardiac tissue in vitro.

Results: Ground rat heart tissue was injected into the quadriceps muscle in rats to simulate myocardial damage with a defined onset. cTnT and cTnI peaked at the same time after injection. cTnI returned to baseline concentrations after 54 h, compared with 168 h for cTnT. There was no difference in the rate of clearance of solubilized cTnT or cTnI after intravenous or intramuscular injection. Renal clearance of cTnT and cTnI was similar in 7 heart failure patients. cTnI was degraded and released faster and reached higher concentrations than cTnT when human cardiac tissue was incubated in 37°C plasma.

Conclusion: Once cTnI and cTnT are released to the circulation, there seems to be no difference in clearance. However, cTnI is degraded and released faster than cTnT from necrotic cardiac tissue. Faster degradation and release may be the main reason why cTnI reaches higher peak concentrations and returns to normal concentrations faster in patients with MI.
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http://dx.doi.org/10.1093/clinchem/hvz003DOI Listing
February 2020

Do self-reported pregnancy complications add to risk evaluation in older women with established cardiovascular disease?

BMC Womens Health 2019 12 16;19(1):160. Epub 2019 Dec 16.

Department of Medical Sciences, Cardiology, Uppsala University, S-751 85, Uppsala, Sweden.

Background: In postmenopausal women with established cardiovascular disease (CVD), it is unknown whether a history of pregnancy complications are related to multisite artery disease (MSAD), defined as atherosclerotic lesions in at least two major vascular beds. Pregnancy complications are an established risk factor for CVD. This study aimed to investigate the frequency of pregnancy complications and their association to specific atherosclerotic manifestations and prediction of MSAD in older women with and without CVD.

Methods: In total, 556 women were invited to participate in the study. Of these women 307 reported former pregnancy from a cohort of women with (n = 233) and without CVD (n = 74). The self-reported frequency of pregnancy complications were surveyed retrospectively by a questionnaire that included miscarriage, subfertility, gestational hypertension (GHT) and/or preeclampsia (PE), low birth weight, preterm birth, bleeding in late pregnancy, gestational diabetes mellitus and high birth weight. Three vascular beds were examined, the peripheral, carotid and coronary arteries.

Results: The mean age was 67.5 (SD 9.5) years. GHT and/or PE tended to be more common, but not significant, in women with CVD than in women without (20.3% vs 10.8%, p = 0.066). Among women with GHT and/or PE, hypertension later in life were more frequent than in women without (66.7% vs 47.4%, p = 0.010). GHT and/or PE were not associated with specific atherosclerotic manifestations or prediction of MSAD.

Conclusions: In older women with established CVD, pregnancy complications was not associated to specific atherosclerotic manifestations and may not provide additional value to the risk evaluation for MSAD.
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http://dx.doi.org/10.1186/s12905-019-0851-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916002PMC
December 2019

Effect of Oxygen Therapy on Cardiovascular Outcomes in Relation to Baseline Oxygen Saturation.

JACC Cardiovasc Interv 2020 02 11;13(4):502-513. Epub 2019 Dec 11.

Department of Clinical Science and Education, Division of Cardiology, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden. Electronic address:

Objectives: The aim of this study was to determine the effect of supplemental oxygen in patients with myocardial infarction (MI) on the composite of all-cause death, rehospitalization with MI, or heart failure related to baseline oxygen saturation. A secondary objective was to investigate outcomes in patients developing hypoxemia.

Background: In the DETO2X-AMI (Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction) trial, 6,629 normoxemic patients with suspected MI were randomized to oxygen at 6 l/min for 6 to 12 h or ambient air.

Methods: The study population of 5,010 patients with confirmed MI was divided by baseline oxygen saturation into a low-normal (90% to 94%) and a high-normal (95% to 100%) cohort. Outcomes are reported within 1 year. To increase power, all follow-up time (between 1 and 4 years) was included post hoc, and interaction analyses were performed with oxygen saturation as a continuous covariate.

Results: The composite endpoint of all-cause death, rehospitalization with MI, or heart failure occurred significantly more often in patients in the low-normal cohort (17.3%) compared with those in the high-normal cohort (9.5%) (p < 0.001), and most often in patients developing hypoxemia (23.6%). Oxygen therapy compared with ambient air was not associated with improved outcomes regardless of baseline oxygen saturation (interaction p values: composite endpoint, p = 0.79; all-cause death, p = 0.33; rehospitalization with MI, p = 0.86; hospitalization for heart failure, p = 0.35).

Conclusions: Irrespective of oxygen saturation at baseline, we found no clinically relevant beneficial effect of routine oxygen therapy in normoxemic patients with MI regarding cardiovascular outcomes. Low-normal baseline oxygen saturation or development of hypoxemia was identified as an independent marker of poor prognosis. (An Efficacy and Outcome Study of Supplemental Oxygen Treatment in Patients With Suspected Myocardial Infarction; NCT01787110).
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http://dx.doi.org/10.1016/j.jcin.2019.09.016DOI Listing
February 2020

Sex differences in sickness absence and the morbidity-mortality paradox: a longitudinal study using Swedish administrative registers.

BMJ Open 2019 09 3;9(8):e024098. Epub 2019 Sep 3.

Statistics, Uppsala Universitet Humanistisk-samhallsvetenskapliga vetenskapsomradet, Uppsala, Sweden

Objective: To analyse whether gender-specific health behaviour can be an explanation for why women outlive men, while having worse morbidity outcomes, known as the morbidity-mortality or gender paradox.

Setting: The working population in Sweden.

Participants: Thirty per cent random sample of Swedish women and men aged 40-59 with a hospital admission in the 1993-2004 period were included. The sample for analysis consists of 233 274 individuals (115 430 men and 117 844 women) and in total 1 867 013 observations on sickness absence.

Intervention: Hospital admission across 18 disease categories.

Main Outcome Measures: The main outcome measures were sickness absence (morbidity) and mortality. Longitudinal data at the individual level allow us to study how sickness absence changed after a hospital admission in men and women using a difference-in-differences regression analysis. Cox regression models are used to study differences in mortality after the admission.

Results: Women increased their sickness absence after a hospital admission by around five more days per year than men (95% CI 5.25 to 6.22). At the same time, men had higher mortality in the 18 diagnosis categories analysed. The pattern of more sickness absence in women was the same across 17 different diagnosis categories. For neoplasm, with a 57% higher risk of death for men (54.18%-59.89%), the results depended on the imputation method of sickness for those deceased. By using the premortality means of sickness absence, men had an additional 14.47 (-16.30- -12.64) days of absence, but with zero imputation women had an additional 1.6 days of absence (0.05-3.20). Analyses with or without covariates revealed a coherent picture.

Conclusions: The pattern of increased sickness absence (morbidity) and lower mortality in women provides evidence on the more proactive and preventive behaviour of women than of men, which could thus explain the morbidity-mortality paradox.
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http://dx.doi.org/10.1136/bmjopen-2018-024098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731828PMC
September 2019

Oxygen Therapy in Myocardial Infarction Patients With or Without Diabetes: A Predefined Subgroup Analysis From the DETO2X-AMI Trial.

Diabetes Care 2019 11 31;42(11):2032-2041. Epub 2019 Aug 31.

Cardiology, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.

Objective: To determine the effects of oxygen therapy in myocardial infarction (MI) patients with and without diabetes.

Research Design And Methods: In the Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction (DETO2X-AMI) trial, 6,629 normoxemic patients with suspected MI were randomized to oxygen at 6 L/min for 6-12 h or ambient air. In this prespecified analysis involving 5,010 patients with confirmed MI, 934 had known diabetes. Oxidative stress may be of particular importance in diabetes, and the primary objective was to study the effect of supplemental oxygen on the composite of all-cause death and rehospitalization with MI or heart failure (HF) at 1 year in patients with and without diabetes.

Results: As expected, event rates were significantly higher in patients with diabetes compared with patients without diabetes (main composite end point: hazard ratio [HR] 1.60 [95% CI 1.32-1.93], < 0.01). In patients with diabetes, the main composite end point occurred in 16.2% (72 of 445) allocated to oxygen as compared with 16.6% (81 of 489) allocated to ambient air (HR 0.93 [95% CI 0.67-1.27], = 0.81). There was no statistically significant difference for the individual components of the composite end point or the rate of cardiovascular death up to 1 year. Likewise, corresponding end points in patients without diabetes were similar between the treatment groups.

Conclusions: Despite markedly higher event rates in patients with MI and diabetes, oxygen therapy did not significantly affect 1-year all-cause death, cardiovascular death, or rehospitalization with MI or HF, irrespective of underlying diabetes, in line with the results of the entire study.
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http://dx.doi.org/10.2337/dc19-0590DOI Listing
November 2019

Statistics on mortality following acute myocardial infarction in 842 897 Europeans.

Cardiovasc Res 2020 01;116(1):149-157

Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.

Aims: To compare ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) mortality between Sweden and the UK, adjusting for background population rates of expected death, case mix, and treatments.

Methods And Results: National data were collected from hospitals in Sweden [n = 73 hospitals, 180 368 patients, Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART)] and the UK [n = 247, 662 529 patients, Myocardial Ischaemia National Audit Project (MINAP)] between 2003 and 2013. There were lower rates of revascularization [STEMI (43.8% vs. 74.9%); NSTEMI (27.5% vs. 43.6%)] and pharmacotherapies at time of hospital discharge including [aspirin (82.9% vs. 90.2%) and (79.9% vs. 88.0%), β-blockers (73.4% vs. 86.4%) and (65.3% vs. 85.1%)] in the UK compared with Sweden, respectively. Standardized net probability of death (NPD) between admission and 1 month was higher in the UK for STEMI [8.0 (95% confidence interval 7.4-8.5) vs. 6.7 (6.5-6.9)] and NSTEMI [6.8 (6.4-7.2) vs. 4.9 (4.7-5.0)]. Between 6 months and 1 year and more than 1 year, NPD remained higher in the UK for NSTEMI [2.9 (2.5-3.3) vs. 2.3 (2.2-2.5)] and [21.4 (20.0-22.8) vs. 18.3 (17.6-19.0)], but was similar for STEMI [0.7 (0.4-1.0) vs. 0.9 (0.7-1.0)] and [8.4 (6.7-10.1) vs. 8.3 (7.5-9.1)].

Conclusion: Short-term mortality following STEMI and NSTEMI was higher in the UK compared with Sweden. Mid- and longer-term mortality remained higher in the UK for NSTEMI but was similar for STEMI. Differences in mortality may be due to differential use of guideline-indicated treatments.
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http://dx.doi.org/10.1093/cvr/cvz197DOI Listing
January 2020

Diagnosing type 2 myocardial infarction in clinical routine. A validation study.

Scand Cardiovasc J 2019 Oct 13;53(5):259-265. Epub 2019 Jul 13.

Department of Medical Sciences, Cardiology, Uppsala University , Uppsala , Sweden.

Since 2010, myocardial infarction (MI) patients reported to the Swedish registry for MI (SWEDEHEART) are routinely classified into MI subtypes. The registry has been used to study the type 2 MI population but the MI-classification in the registry has not previously been validated. The aim of this study was to validate the type 2 MI classification in the registry. A total of 772 patients diagnosed with MI in 2011 and reported to the SWEDEHEART registry were included in the study. All patients were retrospectively classified into MI type 1-5 or myocardial injury by independent reviewers strictly adhering to This gold standard classification was compared with the classification in the registry. Forty-eight (6.2%) patients were classified as type 2 MI in the registry compared with 93 (12.0%) according to the gold standard classification. A type 2 MI diagnosis was confirmed in 30 out of the 48 type 2 MI patients in the registry (PPV: 62.5%). There was a moderate rate of agreement (κ: 0.43) between the gold standard classification and the classification in SWEDEHEART in deciding a type 2 MI diagnosis. The SWEDEHEART registry agreed moderately with the gold standard in classifying patients with type 2 MI diagnosis. Thus, studies on patients with type 2 MI in the registry should be interpreted with caution. Since the prevalence of type 2 MI is substantially underestimated in SWEDEHEART, the registry should not be used to study the prevalence of type 2 MI.
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http://dx.doi.org/10.1080/14017431.2019.1638961DOI Listing
October 2019

Application of High-Sensitivity Troponin in Suspected Myocardial Infarction.

N Engl J Med 2019 06;380(26):2529-2540

From the University Heart Center Hamburg (J.T.N., R.T., F.O., N.A.S., T.Z., D.W., S.B.), German Center for Cardiovascular Research (DZHK) Partner Site Hamburg-Kiel-Lübeck (J.T.N., N.A.S., T.Z., D.W., S.B.), and the Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf (T.R.), Hamburg, the Department of Cardiology, Heidelberg University Hospital (M.M.-H., H.A.K., E.G.), and DZHK Partner Site Heidelberg-Mannheim (M.M.-H., H.A.K., E.G.), Heidelberg, Cardiology I (T.G., T.M.) and Preventive Cardiology and Preventive Medicine (P.W.), Center for Cardiology, and the Center for Thrombosis and Hemostasis (P.W.), University Medical Center of Johannes Gutenberg University Mainz, and the Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz (K.J.L.), Mainz, DZHK Partner Site Rhine-Main and the Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim (C.L., C.H., T.K.), the Department of Cardiology, Justus Liebig University of Giessen and Marburg, Giessen (C.L., C.H.), the Department of Cardiology, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin Institute of Health, and DZHK Partner Site Berlin, Berlin (U.L.), and the Institute of Epidemiology, Helmholtz Zentrum, German Research Center for Environmental Health (B.T., A.P.), and DZHK Partner Site Munich Heart Alliance (A.P.), Munich - all in Germany; the Cardiovascular Research Institute Basel and the Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland (R.T., J.B., T.N., P.B., C.M.); the British Heart Foundation Centre for Cardiovascular Science (A.R.C., A.S.V.S., A.A., N.L.M.) and the Usher Institute of Population Health Sciences and Informatics (A.S.V.S., N.L.M.), University of Edinburgh, Edinburgh, the University of Manchester and Manchester University Foundation Trust, Manchester (N.M., R. Body), U.K. Clinical Research Collaboration for Public Health, Queens University of Belfast, Belfast (F.K.), and the Cardiovascular Epidemiology Unit, Institute of Cardiovascular Research, University of Dundee, Dundee (H.T.-P.) - all in the United Kingdom; the Department of Internal and Emergency Medicine, Lund University, Skåne University Hospital, Lund (A.M., U.E.), the Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm (T. Jernberg), the Department of Public Health and Clinical Medicine, and Heart Center, Cardiology, Umeå University, Umeå (S. Söderberg), and the Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala (B.L.) - all in Sweden; the Department of Medicine, University of Otago Christchurch, and Emergency Department, Christchurch Hospital, Christchurch, New Zealand (J.W.P., R.W.T., M.T.); the Departments of Emergency Medicine (J.G., L.A.C.) and Cardiology (W.P.), Royal Brisbane and Women's Hospital, Herston, QLD, and the Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove (J.G., W.P., L.A.C.) - all in Australia; the National Institute for Health and Welfare, Helsinki, Finland (V.S., K.K.); the Department of Epidemiology and Prevention, Istituto di Ricovero e Cura a Carattere Scientifico Neuromed, Pozzilli (L.I.), the Department of Medicine and Surgery, Research Center in Epidemiology and Preventive Medicine, University of Insubria, Varese (L.I., M.M.F., R. Borchini), and the Department of Cardiovascular, Dysmetabolic, and Aging-Associated Diseases, National Institutes of Health, Rome (S.G.) - all in Italy; the Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (T. Jørgensen), the Research Center for Prevention and Health, Capital Region of Denmark, Glostrup (T. Jørgensen), and the Medical Faculty, Aalborg University, Aalborg (T. Jørgensen) - all in Denmark; the Catalan Department of Health, Barcelona (S. Sans); and the Division of Emergency Medicine (A.W.) and the Department of Pathology and Molecular Medicine (P.A.K.), McMaster University, Hamilton, ON, Canada.

Background: Data regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes.

Methods: In 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days.

Results: Among 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set.

Conclusions: A risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes. (Funded by the German Center for Cardiovascular Research [DZHK]; ClinicalTrials.gov numbers, NCT00470587, NCT02355457, NCT01852123, NCT01994577, and NCT03227159; and Australian New Zealand Clinical Trials Registry numbers, ACTRN12611001069943, ACTRN12610000766011, ACTRN12613000745741, and ACTRN12611000206921.).
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http://dx.doi.org/10.1056/NEJMoa1803377DOI Listing
June 2019

Aiming toWards Evidence baSed inTerpretation of Cardiac biOmarkers in patients pResenting with chest pain-the WESTCOR study: study design.

Scand Cardiovasc J 2019 Oct 1;53(5):280-285. Epub 2019 Jul 1.

Department of Clinical Science, University of Bergen , Bergen , Norway.

The main aim of the Aiming toWards Evidence baSed inTerpretation of Cardiac biOmarkers in patients pResenting with chest pain (WESTCOR-study) (Clinical Trials number NCT02620202) is to improve diagnostic pathways for patients presenting to the Emergency department (ED) with acute chest pain. The WESTCOR-study is a two center, cross-sectional and prospective observational study recruiting unselected patients presenting to the ED with suspected non-ST elevation acute coronary syndrome (NSTE-ACS). Patient inclusion started September 2015 and we plan to include 2250 patients, finishing in 2019. The final diagnosis will be adjudicated by two independent cardiologists based on all available information including serial high sensitivity cardiac troponin measurements, coronary angiography, coronary CT angiography and echocardiography. The study includes one derivation cohort ( = 985) that will be used to develop rule out/rule in algorithms for NSTEMI and NSTE-ACS (if possible) using novel troponin assays, and to validate established NSTEMI algorithms, with and without clinical scoring systems. The study further includes one subcohort ( = 500) where all patients are examined with coronary CT angiography independent of biomarker status, aiming to assess the associations between biomarkers and the extent and severity of coronary atherosclerosis. Finally, an external validation cohort ( = 750) will be included at Stavanger University Hospital. Prospective studies will be based on the merged cohorts. The WESTCOR study will provide new diagnostic algorithms for early inclusion and exclusion of NSTE-ACS and insights in the associations between cardiovascular biomarkers, CT-angiographic findings and short and long-term clinical outcomes.
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http://dx.doi.org/10.1080/14017431.2019.1634280DOI Listing
October 2019