Cardiovascular medications, high-sensitivity cardiac troponin T concentrations, and long-term outcome in non-ST segment elevation acute coronary syndrome.

AIMS: Cardiac troponin plays an essential role in the management of non-ST segment elevation acute coronary syndrome (NSTE-ACS). However, it is not clear whether troponin concentrations provide guidance regarding the initiation of prognostically beneficial cardiovascular medications [i.e. betablockers, renin-angiotensin-aldosterone system (RAAS) inhibitors, and statins] in NSTE-ACS. METHODS AND RESULTS: Registry-based study investigating three NSTE-ACS cohorts (n = 43 075, 40 162, and 46 698) with elevated high-sensitivity cardiac troponin concentrations >14 ng/L. Cox proportional regression models with the addition of interaction terms were used to analyse the interrelations of high-sensitivity cardiac troponin T (hs-cTnT) concentrations, new initiated medications with the respective three drug classes, and long-term risk of all-cause mortality and major adverse events (MAE). Betablockers were associated with risk reductions of 8 and 5% regarding all-cause mortality and MAE, respectively. There was no evidence of an interaction with hs-cTnT concentrations. RAAS inhibitors were associated with 13 and 8% risk reductions, respectively, with a weak interaction between hs-cTnT and MAE (Pinteraction = 0.016). However, no increasing prognostic benefit was noted at hs-cTnT concentrations >100 ng/L. Statins were associated with 38 and 32% risk reductions, respectively, with prognostic benefit across the entire range of hs-cTnT concentrations, and with a weak interaction regarding MAE (Pinteraction = 0.011). CONCLUSION: Cardiovascular medications provide different prognostic benefit in patients with NSTE-ACS with elevated hs-cTnT, and there was some evidence of greater treatment effects regarding MAE along with higher hs-cTnT concentrations. However, hs-cTnT appears only to have limited value overall for customizing such treatments.

Medical treatment of heart failure with renin-angiotensin-aldosterone system inhibitors and beta-blockers in aortic stenosis: association with long-term outcome after aortic valve replacement.

Aims: There is a lack of robust data on the optimal medical treatment of heart failure in patients with severe aortic stenosis, with no randomized controlled trials guiding treatment. The study aimed to study the association between exposure to renin-angiotensin-aldosterone system (RAS) inhibitors or beta-blockers and outcome after aortic valve replacement in patients with aortic stenosis and heart failure. Methods and results: The study included all patients with heart failure undergoing aortic valve replacement for aortic stenosis in Sweden between 2008 and 2016 (n = 4668 patients). Exposure to treatment was assessed by a continuous tracking of drug dispensations, and outcome events were all-cause mortality and hospitalization for heart failure collected from national patient registries. After adjustment for age, sex, atrial fibrillation, hypertension, diabetes mellitus, and prior myocardial infarction, Cox regression analysis showed that RAS inhibition was associated with a lower risk of all-cause mortality in patients with reduced left ventricular ejection fraction (LV-EF) [hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.51-0.65] and preserved LV-EF (HR 0.69, 95% CI 0.56-0.85). Beta-blockade was associated with a lower risk of all-cause mortality in patients with reduced LV-EF (HR 0.81, 95% CI 0.71-0.92), but not in preserved LV-EF (HR 0.87, 95% CI 0.69-1.10). There was no association between RAS inhibition or beta-blockade and the risk of hospitalization for heart failure. Conclusion: The RAS inhibition was associated with a lower all-cause mortality after valve replacement in patients with both reduced and preserved LV-EF. Beta-blockade was associated with lower all-cause mortality only in patients with reduced LV-EF.

Comparison of the patient-derived modified Japanese Orthopaedic Association scale and the European myelopathy score.

PURPOSE: To compare the patient-derived modified Japanese Orthopaedic Association (P-mJOA) scale with the European myelopathy score (EMS) for the assessment of patients with degenerative cervical myelopathy (DCM). METHODS: In this register-based cohort study with prospectively collected data, included patients were surgically treated for DCM and had reported both P-mJOA and EMS scores at baseline, 1-year follow-up, and/or 2-year follow-up to the Swedish Spine Register. P-mJOA and EMS scores were defined as severe (P-mJOA 0-11 and EMS 5-8), moderate (P-mJOA 12-14 and EMS 9-12), or mild (P-mJOA 15-18 and EMS 13-18). P-mJOA and EMS mean scores were compared, and agreement was evaluated with Spearman's rank correlation coefficient (ρ), the intraclass correlation coefficient (ICC), and kappa (κ) statistics. RESULTS: Included patients (n = 714, mean age 63.2 years, 42.2% female) completed 937 pairs of the P-mJOA and the EMS. The mean P-mJOA and EMS scores were 13.9 ± 3.0 and 14.5 ± 2.7, respectively (mean difference -0.61 [95% CI -0.72 to -0.51; p < 0.001]). Spearman's ρ was 0.84 (p < 0.001), and intra-rater agreement measured with ICC was 0.83 (p < 0.001). Agreement of severity level measured with unweighted and weighted κ was fair (κ = 0.22 [p < 0.001]; κ = 0.34 [p < 0.001], respectively). Severity levels were significantly higher using the P-mJOA (p < 0.001). CONCLUSION: The P-mJOA and the EMS had similar mean scores, and intra-rater agreement was high, whereas severity levels only demonstrated fair agreement. The EMS has a lower sensitivity for detecting severe myelopathy but shows an increasing agreement with the P-mJOA for milder disease severity. A larger interval to define severe myelopathy with the EMS is recommended.

MRI-based measurements of spondylolisthesis and kyphosis in degenerative cervical myelopathy.

BACKGROUND: To provide normative data and to determine accuracy and reliability of preoperative measurements of spondylolisthesis and kyphosis on supine static magnetic resonance imaging (MRI) of patients with degenerative cervical myelopathy. METHODS: T2-weighted midsagittal images of the cervical spine were in 100 cases reviewed twice by one junior observer, with an interval of 3 months, and once by a senior observer. The spondylolisthesis slip (SSlip, mm) and the modified K-line interval (mK-line INT, mm) were assessed for accuracy with the standard error of measurement (SEm) and the minimum detectable change (MDC). Intraobserver and interobserver reliability levels were determined using the intraclass correlation coefficient (ICC). RESULTS: The SEm was 0.5 mm (95% CI 0.4-0.6) for spondylolisthesis and 0.6 mm (95% CI 0.5-0.7) for kyphosis. The MDC, i.e., the smallest difference between two examinations that can be detected with statistical certainty, was 1.5 mm (95% CI 1.2-1.8) for spondylolisthesis and 1.6 mm (95% CI 1.3-1.8) for kyphosis. The highest reliability levels were seen between the second observation of the junior examiner and the senior observer (ICC = 0.80 [95% CI 0.70-0.87] and ICC = 0.96 [95% CI 0.94-0.98] for SSlip and mK-line INT, respectively). CONCLUSIONS: This study provides normative values of alignment measurements of spondylolisthesis and kyphosis in DCM patients. It further shows the importance of taking measurement errors into account when defining cut-off values for cervical deformity parameters and their potential clinical application in surgical decision-making.

Association of beta-blockers beyond 1 year after myocardial infarction and cardiovascular outcomes.

OBJECTIVE: Beta-blockers (BB) are an established treatment following myocardial infarction (MI). However, there is uncertainty as to whether BB beyond the first year of MI have a role in patients without heart failure or left ventricular systolic dysfunction (LVSD). METHODS: A nationwide cohort study was conducted including 43 618 patients with MI between 2005 and 2016 in the Swedish register for coronary heart disease. Follow-up started 1 year after hospitalisation (index date). Patients with heart failure or LVSD up until the index date were excluded. Patients were allocated into two groups according to BB treatment. Primary outcome was a composite of all-cause mortality, MI, unscheduled revascularisation and hospitalisation for heart failure. Outcomes were analysed using Cox and Fine-Grey regression models after inverse propensity score weighting. RESULTS: Overall, 34 253 (78.5%) patients received BB and 9365 (21.5%) did not at the index date 1 year following MI. The median age was 64 years and 25.5% were female. In the intention-to-treat analysis, the unadjusted rate of primary outcome was lower among patients who received versus not received BB (3.8 vs 4.9 events/100 person-years) (HR 0.76; 95% CI 0.73 to 1.04). Following inverse propensity score weighting and multivariable adjustment, the risk of the primary outcome was not different according to BB treatment (HR 0.99; 95% CI 0.93 to 1.04). Similar findings were observed when censoring for BB discontinuation or treatment switch during follow-up. CONCLUSION: Evidence from this nationwide cohort study suggests that BB treatment beyond 1 year of MI for patients without heart failure or LVSD was not associated with improved cardiovascular outcomes.

Screening for Biomarkers Associated with Left Ventricular Function During Follow-up After Acute Coronary Syndrome.

A proportion of patients with the acute coronary syndrome (ACS) will suffer progressive remodeling of the left ventricular (LV). The aim was to screen for important biomarkers from a large-scale protein profiling in 420 ACS patients and define biomarkers associated with reduced LV function early and 1 year after the ACS. Transferrin receptor protein 1 and NT-proBNP were associated with LV function early and after 1 year, whereas osteopontin and soluble ST2 were associated with LV function in the early phase and, tissue-type plasminogen activator after 1 year. Fatty-acid-binding protein and galectin 3 were related to worse GLS but not to LVEF 1 year after the ACS. Proteins involved in remodeling and iron transport in cardiomyocytes were related to worse LV function after ACS. Biomarkers for energy metabolism and fibrosis were exclusively related to worse LV function by GLS. Studies on the functions of these proteins might add knowledge to the biological processes involved in heart failure in long term after ACS.

Improvement rates, adverse events and predictors of clinical outcome following surgery for degenerative cervical myelopathy.

PURPOSE: To investigate improvement rates, adverse events and predictors of clinical outcome after laminectomy alone (LAM) or laminectomy with instrumented fusion (LAM + F) for degenerative cervical myelopathy (DCM). METHODS: This is a post hoc analysis of a previously published DCM cohort. Improvement rates for European myelopathy score (EMS) and Neck Disability Index (NDI) at 2- and 5-year follow-ups and adverse events are presented descriptively for available cases. Predictor endpoints were EMS and NDI scores at follow-ups, surgeon- and patient-reported complications, and reoperation-free interval. For predictors, univariate and multivariable models were fitted to imputed data. RESULTS: Mean age of patients (LAM n = 412; LAM + F n = 305) was 68 years, and 37.4% were women. LAM + F patients had more severe spondylolisthesis and less severe kyphosis at baseline, more surgeon-reported complications, more patient-reported complications, and more reoperations (p ≤ 0.05). After imputation, the overall EMS improvement rate was 43.8% at 2 years and 36.3% at 5 years. At follow-ups, worse EMS scores were independent predictors of worse EMS outcomes and older age and worse NDI scores were independent predictors of worse NDI outcomes. LAM + F was associated with more surgeon-reported complications (ratio 1.81; 95% CI 1.17-2.80; p = 0.008). More operated levels were associated with more patient-reported complications (ratio 1.12; 95% CI 1.02-1.22; p = 0.012) and a shorter reoperation-free interval (hazard ratio 1.30; 95% CI 1.08-1.58; p = 0.046). CONCLUSIONS: These findings suggest that surgical intervention at an earlier myelopathy stage might be beneficial and that less invasive procedures are preferable in this patient population.

Real-World Effectiveness of Anti-Resorptive Treatment in Patients With Incident Fragility Fractures-The STORM Cohort-A Swedish Retrospective Observational Study.

Results from real-world evidence (RWE) from the largest healthcare region in Sweden show low uptake of antiresorptive (AR) treatment, but beneficial effect in those receiving treatment, especially for the composite outcome of hip fracture or death. For RWE studies, Sweden is unique, with virtually complete coverage of electronic medical records (EMRs) and both regional and national registries, in a universal publicly funded healthcare system. To our knowledge, there is no previous RWE study evaluating the efficacy of AR treatment compared to no AR treatment after fragility fracture, including data on parenteral treatments administered in hospital settings. The Stockholm Real World Management (STORM) study cohort was established in the healthcare region of Stockholm to retrospectively assess the effectiveness of AR treatment after first fragility fracture using the regional EMR system for both hospital and primary care. Between 2012 and 2018, we identified 69,577 fragility fracture episodes among 59,078 patients, men and women, 50 years and older. Of those, 21,141 patients met inclusion and exclusion criteria (eligible cohort). From these, the final matched study cohort comprised 9840 fragility fractures (cases receiving AR treatment [n = 1640] and controls not receiving AR treatment [n = 8200]). Propensity scores were estimated using logistic regression models with AR treatment as outcome and confounders as independent variables followed by analysis using Cox proportional hazard models. Real world evidence from Sweden's largest healthcare region, comprising a quarter of the Swedish population, show that only 10% of patients receive AR treatment within 1 year after a fragility fracture. Factors associated with not receiving treatment include having a diagnosis of cardiovascular disease. In those treated, AR have positive effects particularly on the composite of fracture and death (any fracture/death and hip fracture/death) in individuals matched for all major confounders. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Pre-operative heart failure worsens outcome after aortic valve replacement irrespective of left ventricular ejection fraction.

AIMS: Left ventricular ejection fraction (LVEF) affects the outcome of aortic valve replacement (AVR) in aortic stenosis (AS). The study aim was to investigate the prognostic importance of concomitant cardiovascular disease in relation to pre-operative LVEF. METHODS AND RESULTS: All adult patients undergoing AVR due to AS 2008-14 in a national register for heart diseases were included. All-cause mortality and hospitalization for heart failure during follow-up after AVR, stratified by preserved or reduced LVEF (≤50%), were derived from national patient registers and analysed by Cox regression. During the study period, 10 406 patients, median age 73 years, a median follow-up of 35 months were identified. Preserved LVEF was present in 7512 (72.2%). Among them, 647 (8.6%) had a history of heart failure (HF) and 1099 (14.6%) atrial fibrillation (AF) before the intervention. Pre-operative HF was associated with higher mortality irrespective of preserved or reduced LVEF: hazard ratio (HR) 1.64 [95% confidence interval (CI) 1.35-1.99] and 1.58 (95% CI 1.30-1.92). Prior AF was associated with a higher risk of mortality in patients with preserved but not in those with reduced LVEF: HR 1.62 (95% CI 1.36-1.92) and 1.05 (95% CI 0.86-1.28). Irrespective of LVEF, pre-operative HF and AF were associated with an increased risk of post-operative heart failure hospitalization. CONCLUSION: In patients planned for AVR, a history of HF or AF, irrespective of LVEF, worsens the post-operative prognosis. Heart failure and AF can be seen as markers of myocardial fibrosis not necessarily discovered by LVEF and the merely use of it, besides symptoms, for the timing of AVR seems suboptimal.

Laminectomy alone versus laminectomy with fusion for degenerative cervical myelopathy: a long-term study of a national cohort.

PURPOSE: To compare patient-reported 5-year clinical outcomes between laminectomy alone versus laminectomy with instrumented fusion in patients with degenerative cervical myelopathy in a population-based cohort. METHODS: All patients in the national Swedish Spine Register (Swespine) from January 2006 until March 2019, with degenerative cervical myelopathy, were assessed. Multiple imputation and propensity score matching based on clinicodemographic and radiographic parameters were used to compare patients treated with laminectomy alone with patients treated with laminectomy plus posterior-lateral instrumented fusion. The primary outcome measure was the European Myelopathy Score, a validated patient-reported outcome measure. The scale ranges from 5 to 18, with lower scores reflecting more severe myelopathy. RESULTS: Among 967 eligible patients, 717 (74%) patients were included. Laminectomy alone was performed on 412 patients (mean age 68 years; 149 women [36%]), whereas instrumented fusion was added for 305 patients (mean age 68 years; 119 women [39%]). After imputation, the propensity for smoking, worse myelopathy scores, spondylolisthesis, and kyphosis was slightly higher in the fusion group. After imputation and propensity score matching, there were on average 212 pairs patients with a 5-year follow-up in each group. There were no important differences in patient-reported clinical outcomes between the methods after 5 years. Due to longer hospitalization times and implant-related costs, the mean cost increase per instrumented patient was approximately $4700 US. CONCLUSIONS: Instrumented fusions generated higher costs and were not associated with superior long-term clinical outcomes. These findings are based on a national cohort and can thus be regarded as generalizable.

No Benefit with Preservation of Midline Structures in Decompression for Lumbar Spinal Stenosis: Results From the National Swedish Spine Registry 2-Year Post-Op.

STUDY DESIGN: Observational cohort study. OBJECTIVE: The aim of this study was to investigate whether preservation of the midline structures is associated with a better clinical outcome compared to classic central decompression for lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: The classic surgical procedure for LSS is a central, facet joint sparing decompressive laminectomy (LE). Alternative approaches have been developed to preserve the midline structures. The effect of the alternative techniques compared to LE remains unclear. METHODS: All patients >50 years of age who underwent decompression surgery for LSS without concomitant fusion in the National Swedish Spine Registry (Swespine) from December 31, 2015 until October 6, 2017 were included in this study based on surgeon-reported data and patient questionnaires before and 2 years postoperatively. Propensity score matching was used to compare decompression with preservation of midline structures with patients who underwent LE. The primary outcome was the Oswestry Disability Index (ODI) and secondary outcomes were the Numeric Rating Scale (NRS) for leg and back pain, EuroQol-5 Dimensions (EQ-5D), Global Assessment (GA), patient satisfaction and rate of subsequent surgery. RESULTS: Some 3339 patients completed a 2-year follow-up. Of these, 2974 (89%) had decompression with LE and 365 underwent midline preserving surgery. Baseline scores were comparable between the groups. Mean ODI improvement at follow-up was 16.6 (SD = 20.0) in the LE group and 16.9 (SD = 20.2) in the midline preserving surgery group. In the propensity score-matched analysis the difference in improved ODI was 0.53 (95% confidence interval, CI -1.71 to 2.76; P = 0.64). The proportion of patients who showed a decreased ODI score of at least our defined minimal clinically important difference (=8) was 68.3% after LE and 67.0% after preserving the midline structures (P = 0.73). No significant differences were found in the improvement of NRS for leg and back pain, EQ-5D, GA or patient satisfaction. The rate of subsequent surgery was 5.5% after LE and 4.9% after midline preserving surgery without a significant difference in the propensity score-matched analysis (hazard ratio, HR 0.87; 95% CI 0.49-1.54; P = 0.64). CONCLUSION: In this study on decompression techniques for LSS, there was no benefit in preserving the midline structures compared to LE 2 years after decompression. The conclusion is that the surgeon is free to choose the surgical method that is thought most suitable for the patient and the condition with which the patient presents.Level of Evidence: 3.

Androgen deprivation therapy, comorbidity, cancer stage and mortality from COVID-19 in men with prostate cancer.

BACKGROUND: Androgens facilitate entrance of the severe acute respiratory syndrome coronavirus 2 into respiratory epithelial cells, and male sex is associated with a higher risk of death from corona virus disease (COVID-19). Androgen deprivation therapy (ADT) could possibly improve COVID-19 outcomes. METHODS: In a case-control study nested in the Prostate Cancer data Base Sweden (PCBaSe) RAPID 2019, we evaluated the association between ADT and COVID-19 as registered cause of death in men with prostate cancer. Each case was matched to 50 controls by region. We used conditional logistic regression to adjust for confounders and also evaluated potential impact of residual confounding. RESULTS: We identified 474 men who died from COVID-19 in March-December 2020. In crude analyses, ADT exposure was associated with an increased risk of COVID-19 death (odds ratio [OR] 5.05, 95% CI: 4.18-6.10); however, the OR was substantially attenuated after adjustment for age, comorbidity, prostate cancer characteristics at diagnosis, recent healthcare use, and indicators of advanced cancer (adjusted OR 1.25, 95% CI: 0.95-1.65). If adjustment has accounted for at least 85% of confounding, then the true effect could be no more than a 5% reduction of the odds for COVID-19 death. CONCLUSIONS: The increased mortality from COVID-19 in men with prostate cancer treated with ADT was mainly related to high age, comorbidity, and more advanced prostate cancer. There was no evidence to support the hypothesis that ADT is associated with improved COVID-19 outcomes.

Differences in biomarker concentrations and predictions of long-term outcome in patients with ST-elevation and non-ST-elevation myocardial infarction.

BACKGROUND: Differences in biomarkers reflective of pathobiology and prognosis between ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) are incompletely understood and may offer insights for tailoring of treatment. METHODS: This registry-based study included 538 STEMI and 544 NSTEMI patients admitted 2008-2014. Blood samples were collected day 1-3 after admission and 175 biomarkers were analyzed using Proximity Extension Assay and Multiple Reaction Monitoring mass spectrometry. Adjusted Lasso analysis (penalized logistic regression model) was used to select biomarkers that discriminated STEMI from NSTEMI patients. Biomarkers identified by the Lasso analysis were then evaluated in adjusted Cox regressions for associations with death or major adverse cardiovascular events. RESULTS: Biomarkers strongly discriminated STEMI and NSTEMI when considered simultaneously in adjusted Lasso analysis (c-statistic 0.764). Eleven biomarkers independently discriminated STEMI and NSTEMI; seven showing higher concentrations in STEMI: myoglobin, N-terminal pro-B-type natriuretic peptide, serum amyloid A-1 and A-2 protein, ST2 protein, interleukin-6 and chitinase-3-like protein 1; and four showing higher concentrations in NSTEMI: fibroblast growth factor 23, membrane-bound aminopeptidase P, tumor necrosis factor-related activation-induced cytokine and apolipoprotein C-I. During up to 6.6 years of prognostic follow-up, none of these biomarkers exhibited different associations with adverse outcome between STEMI and NSTEMI. CONCLUSIONS: In the acute setting, biomarkers indicated greater myocardial dysfunction and inflammation in STEMI, whereas they displayed a more diverse pathophysiologic pattern in NSTEMI patients. These biomarkers were similarly prognostic in STEMI and NSTEMI patients. The results do not support treating STEMI and NSTEMI patients differently based on the concentrations of these biomarkers.

Screening of biomarkers for prediction of multisite artery disease in patients with recent myocardial infarction.

A few studies have examined biomarkers in patients with myocardial infarction (MI) and peripheral artery disease (PAD), i.e. multisite artery disease (MSAD). The aim of the study was firstly, to associate biomarkers with the occurrence of PAD/MSAD and secondly, if those can, in addition to clinical characteristics, identify MI patients with MSAD.In two prospectively observational studies including unselected patients with recent MI, PAD was defined as an abnormal ankle-brachial index (ABI) score (<0.9 or >1.4). The proximity extension assay (PEA) technique was used, simultaneously analyzing 92 biomarkers with association to cardiovascular disease. Biomarkers were tested for univariate associations with PAD. Random forest was used to identify biomarkers with a higher association to PAD. The additional discriminatory accuracy of adding biomarkers to clinical characteristics was analyzed by the c-statistics. Nine biomarkers were identified as significantly associated with MSAD/PAD in the primary patient cohort, analyzed early after the MI. In the prediction analysis, six biomarkers were identified associated with PAD. Three of these; Tumor necrosis factor receptor (TNFR-1), Tumor necrosis factor receptor 2 (TNFR-2) and Growth Differentiation Factor 15 (GDF-15) improved c-statistics when added to clinical characteristics from 0.683 (95% CI 0.610-0.756) to 0.715 (95% CI 0.645-0.784) in the primary patient cohort with a similar result, 0.729 (95% CI 0.687-0.770) to 0.752 (95% CI 0.771-0.792) in the secondary patient cohort. Biomarkers associated with inflammatory pathways are associated with MSAD in MI patients. Three biomarkers of 92; TNFR-1, TNFR-2 and GDF-15, in this exploratory added information in the prediction of MSAD and emphasis the importance of further studies.

Predicting outcome in acute myocardial infarction: an analysis investigating 175 circulating biomarkers.

AIMS: There is a paucity of studies comprehensively comparing the prognostic value of larger arrays of biomarkers indicative of different pathobiological axes in acute myocardial infarction (MI). METHODS AND RESULTS: In this explorative investigation, we simultaneously analysed 175 circulating biomarkers reflecting different inflammatory traits, coagulation activity, endothelial dysfunction, atherogenesis, myocardial dysfunction and damage, apoptosis, kidney function, glucose-, and lipid metabolism. Measurements were performed in samples from 1099 MI patients (SWEDEHEART registry) applying two newer multimarker panels [Proximity Extension Assay (Olink Bioscience), Multiple Reaction Monitoring mass spectrometry]. The prognostic value of biomarkers regarding all-cause mortality, recurrent MI, and heart failure hospitalizations (median follow-up ≤6.6 years) was studied using Lasso analysis, a penalized logistic regression model that considers all biomarkers simultaneously while minimizing the risk for spurious findings. Tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), ovarian cancer-related tumour marker CA 125 (CA-125), and fibroblast growth factor 23 (FGF-23) consistently predicted all-cause mortality in crude and age/sex-adjusted analyses. Growth-differentiation factor 15 (GDF-15) was strongly predictive in the crude model. TRAIL-R2 and B-type natriuretic peptide (BNP) consistently predicted heart failure hospitalizations. No biomarker predicted recurrent MI. The prognostic value of all biomarkers was abrogated following additional adjustment for clinical variables owing to our rigorous statistical approach. CONCLUSION: Apart from biomarkers with established prognostic value (i.e. BNP and to some extent GDF-15), several 'novel' biomarkers (i.e. TRAIL-R2, CA-125, FGF-23) emerged as risk predictors in patients with MI. Our data warrant further investigation regarding the utility of these biomarkers for clinical decision-making in acute MI.

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

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.

Haemorrhagic stroke and major bleeding after intervention with biological aortic valve prosthesis: risk factors and antithrombotic treatment.

The majority of patients with severe aortic stenosis are recommended intervention with a surgical biological prosthesis (bioSAVR) or a transcatheter aortic valve intervention (TAVI). The antithrombotic strategies after aortic valve intervention vary and include drugs targeting both platelets and the coagulation cascade. Long-term exposure and changes of antithrombotic treatment influence the risk of both bleeding and thromboembolic events.The aim was to describe an unselected sample of patients who have experienced haemorrhagic stroke and other major bleeding events after biological aortic prosthesis, their antithrombotic treatment and changes of treatments in relation to the bleeding event.All patients performing an bioSAVR or a TAVI 2008-2014 were identified in the SWEDEHEART registry and included in the study (n = 10 711). The outcome events were haemorrhagic stroke and other major bleeding event. Information of drug exposure was collected from the dispensed drug registry.The incidence rate of any bleeding event was 2.85/100 patient-years the first year after aortic valve intervention. Heart failure and atrial fibrillation were present more often in patients with a first haemorrhagic stroke or other major bleeding event compared to without. The proportion of exposure to warfarin was 28.7% vs. 21.3% in patients with and without a haemorrhagic stroke. Comparable figures were 31.2% vs. 19.0% in patients with and without other major bleeding event. During 1 month prior a haemorrhagic stroke or other major bleeding event 39.4% and 38.0%, respectively, of the patients not previously exposed to antithrombotic treatment started warfarin or single antiplatelet therapy.Major bleeding events are not uncommon after aortic valve intervention with a biological prosthesis. Evaluation of comorbidities and previous bleeding might improve risk stratification for bleeding in these elderly patients. The pattern of change of antithrombotic treatment was similar in the groups with and without a bleeding event and in most patients the antithrombotic regime was unchanged the month before an event.

A la mayoría de los pacientes con estenosis de la válvula aórtica grave se les recomienda someterse a una valvuloplastia con prótesis biológica (bioSAVR) o a una valvuloplastia aórtica transcateteral (TAVI). Las estrategias antitrombóticas tras una valvuloplastia aórtica son distintas y, entre ellas, se incluyen fármacos dirigidos tanto a las plaquetas como a la cascada de la coagulación. La exposición prolongada y los cambios en el tratamiento antitrombótico influyen en el riesgo de sufrir complicaciones hemorrágicas y tromboembólicas.El objetivo es describir una muestra de pacientes sin seleccionar que han padecido ictus hemorrágicos u otros episodios hemorrágicos importantes tras una valvuloplastia aórtica con prótesis biológica, así como el tratamiento antitrombótico y los cambios de tratamientos en relación con la hemorragia.Todos los pacientes sometidos a bioSAVR o TAVI en 2008-2014 se encontraban en el registro SWEDEHEART y se incluyeron en el estudio (n = 10 711). Los criterios de valoración fueron ictus hemorrágico y otras hemorragias importantes. La información de la exposición al fármaco se recogió del registro de dispensación de fármacos.En el primer año tras la valvuloplastia aórtica, la tasa de incidencia de cualquier episodio hemorrágico fue de 2,85 por 100 pacientes. La insuficiencia cardíaca y la fibrilación auricular fueron más frecuentes en pacientes con presencia de un primer ictus hemorrágico u otras hemorragias importantes en comparación con el grupo de control. La proporción de exposición a warfarina fue del 28,7% frente al 21,3% en pacientes con presencia y ausencia de un ictus hemorrágico, respectivamente. Cifras comparables fueron el 31,2% frente al 19,0% en pacientes con presencia y ausencia de otros episodios hemorrágicos importantes, respectivamente. Un mes antes de que se produjera el ictus hemorrágico u otras hemorragias importantes, el 39,4% y el 38,0%, respectivamente, de los pacientes que no estaban previamente expuestos a un tratamiento antitrombótico comenzaron un tratamiento con warfarina o antiagregante plaquetario simple.La presencia de episodios hemorrágicos importantes es frecuente tras una valvuloplastia aórtica con prótesis biológica. La evaluación de comorbilidades y hemorragias anteriores puede mejorar la estratificación de riesgos de sufrir hemorragias en pacientes de avanzada edad. El tipo de cambio del tratamiento antitrombótico fue similar en el grupo de control y en el grupo con presencia de un episodio hemorrágico y, en la mayoría de los pacientes, no se modificó la pauta de administración del antitrombótico en el mes previo al episodio hemorrágico.

Temporal trends in bleeding events in acute myocardial infarction: insights from the SWEDEHEART registry.

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.

Comparison of warfarin versus antiplatelet therapy after surgical bioprosthetic aortic valve replacement.

OBJECTIVES: To compare effectiveness of warfarin and antiplatelet exposure regarding both thrombotic and bleeding events, following surgical aortic valve replacement with a biological prosthesis(bioSAVR). METHODS: The study included all patients in Sweden undergoing a bioSAVR during 2008-2014 who were alive at discharge from the index hospital stay. Exposure was analysed and defined as postdischarge dispension of any antithrombotic pharmaceutical, updated at each following dispensions and categorised as single antiplatelet (SAPT), warfarin, warfarin combined with SAPT, dual antiplatelet (DAPT) or no antithrombotic treatment. Exposure to SAPT was used as comparator. Outcome events were all-cause mortality, ischaemic stroke, haemorrhagic stroke, any thromboembolism and major bleedings. We continuously updated adjustments for comorbidities with any indication for antithrombotic treatment by Cox regression analysis. RESULTS: We identified 9539 patients with bioSAVR (36.8% women) at median age of 73 years with a mean follow-up of 3.13 years. As compared with SAPT, warfarin alone was associated with a lower incidence of ischaemic stroke (HR 0.49, 95% CI 0.35 to 0.70) and any thromboembolism (HR 0.75, 95% CI 0.60 to 0.94) but with no difference in mortality (HR 0.94, 95% CI 0.78 to 1.13). The incidence of haemorrhagic stroke (HR 1.94, 95% CI 1.07 to 3.51) and major bleeding (HR 1.67, 95% CI 1.30 to 2.15) was higher during warfarin exposure. As compared with SAPT, DAPT was not associated with any difference in ischaemic stroke or any thromboembolism. Risk-benefit analyses demonstrated that 2.7 (95% CI 1.0 to 11.9) of the ischaemic stroke cases could potentially be avoided per every haemorrhagic stroke caused by warfarin exposure instead of SAPT during the first year. CONCLUSION: In patients discharged after bioSAVR, warfarin exposure as compared with SAPT exposure was associated with lower long-term risk of ischaemic stroke and thromboembolic events, and with a higher incidence of bleeding events but with similar mortality.