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Pressure-overload-induced cardiac hypertrophy represents one cause of the development of heart failure. The aim of this study is to characterize the influence of the TIR-domain-containing adapter-inducing interferon-β (TRIF) during afterload-induced myocardial remodeling. After trans-aortic constriction (TAC), cardiac pressure overload leads to an early increase in MyD88- (Myeloid differentiation primary response gene 88) and TRIF-dependent cytokines. The maximum cytokine expression appeared within the first week and decreased to its control level within five weeks. While cardiomyocyte hypertrophy was comparable, the myocardial accumulation of the inflammatory cells was lower in TRIF−/−mice. At d7, TRIF deficiency reduced transcription factors and TRIF-dependent cytokines. Through the modulation of the TGF-β-signaling pathway and anti-fibrotic microRNAs, TRIF was involved in the development of interstitial fibrosis. The absence of TRIF was associated with a decreased expression of proapoptotic proteins. In echocardiography and working heart analyses, TRIF deficiency slowed left-ventricular wall thickening, myocardial hypertrophy, and reduces the ejection fraction. In summary, TRIF is an important adapter protein for the release of inflammatory cytokines and the accumulation of inflammatory cells in the early stage of maladaptive cardiac remodeling. TRIF is involved in the development of cardiac fibrosis by modulating inflammatory and fibrotic signal transduction pathways.

Inflammation and fibrosis play an important pathophysiological role in chronic kidney disease (CKD), with pro-inflammatory mediators and leukocytes promoting organ damage with subsequent fibrosis. Since chemokines are the main regulators of leukocyte chemotaxis and tissue inflammation, we performed systemic chemokine profiling in early CKD in mice. This revealed (C-C motif) ligands 6 and 9 (CCL6 and CCL9) as the most upregulated chemokines, with significantly higher levels of both chemokines in blood (CCL6: 3–4 fold; CCL9: 3–5 fold) as well as kidney as confirmed by Enzyme-linked Immunosorbent Assay (ELISA) in two additional CKD models. Chemokine treatment in a mouse model of early adenine-induced CKD almost completely abolished the CKD-induced infiltration of macrophages and myeloid cells in the kidney without impact on circulating leukocyte numbers. The other way around, especially CCL9-blockade aggravated monocyte and macrophage accumulation in kidney during CKD development, without impact on the ratio of M1-to-M2 macrophages. In parallel, CCL9-blockade raised serum creatinine and urea levels as readouts of kidney dysfunction. It also exacerbated CKD-induced expression of collagen (3.2-fold) and the pro-inflammatory chemokines CCL2 (1.8-fold) and CCL3 (2.1-fold) in kidney. Altogether, this study reveals for the first time that chemokines CCL6 and CCL9 are upregulated early in experimental CKD, with CCL9-blockade during CKD initiation enhancing kidney inflammation and fibrosis.

Coronary collateral arteries function as natural bypasses in the event of coronary obstruction. The degree of collateral network development significantly impacts the outcome of patients after an acute myocardial infarction (AMI). MicroRNAs (miRNAs, miRs) have arisen as biomarkers to identify heterogeneous patients, as well as new therapeutic targets in cardiovascular disease. We sought to identify miRNAs that are differentially expressed in chronic total occlusion (CTO) patients with well or poorly developed collateral arteries.Forty-one CTO patients undergoing coronary angiography and invasive assessment of their coronary collateralization were dichotomized based on their collateral flow index (CFI). After miRNA profiling was conducted on aortic plasma, four miRNAs were selected for validation by real-time quantitative reverse transcription polymerase chain reaction in patients with low (CFI0.39) collateral artery capacity. We confirmed significantly elevated levels of miR423-5p (p

Collateral artery growth is a potent natural defence mechanism to prevent death and myocardial infarction in occlusive artery disease. Given the high prevalence of arterial obstructive disease, a therapeutic compound stimulating collateral vessel growth could have a major impact on morbidity and mortality world wide. Although experimental studies on the stimulation of arteriogenesis have been promising, not a single drug has been proved to be applicable in clinical practice, either because of lack of efficacy or because of undesired side effects. This review summarises current knowledge on the mechanisms of collateral artery growth and examines problems that arise from the clinical implementation of pro-arteriogenic treatments to date. Future directions in the translation from bench to bedside and potential new approaches to the stimulation of vascular growth are discussed. [ABSTRACT FROM AUTHOR]

Spousal bereavement is associated with health declines and increased mortality risk, but its specific impact on physical and cognitive capabilities is less studied. A historical cohort study design was applied including married Tromsø study participants (N=5739) aged 50-70 years with baseline self-reported overall health and health-related factors and measured capability (grip strength, finger tapping, digit symbol coding, and short-term recall) at follow-up. Participants had data from Tromsø4 (1994-1995) and Tromsø5 (2001), or Tromsø6 (2007-2008) and Tromsø7 (2015-2016). Propensity score matching, adjusted for baseline confounders (and baseline capability in a subset), was used to investigate whether spousal bereavement was associated with poorer subsequent capability. Spousal bereavement occurred for 6.2% on average 3.7 years (SD 2.0) before the capability assessment. There were no significant bereavement effects on subsequent grip strength, immediate recall, or finger-tapping speed. Without adjustment for baseline digit symbol coding test performance, there was a negative significant effect on the digit symbol coding test (ATT -1.33; 95% confidence interval -2.57, -0.10), but when baseline digit symbol coding test performance was taken into account in a smaller subsample, using the same set of matching confounders, there was no longer any association (in the subsample ATT changed from -1.29 (95% CI -3.38, 0.80) to -0.04 (95% CI -1.83, 1.75). The results in our study suggest that spousal bereavement does not have long-term effects on the intrinsic capacity components physical or cognition capability to a notable degree., (© 2024. The Author(s).)

Background: Noninvasive assessment of elevated filling pressure in the left ventricle (LV) remains an unresolved problem. Of the many echocardiographic parameters used to evaluate diastolic pressure, the left atrial strain and strain rate (LA S/SR) have shown promise in clinical settings. However, only a few previous studies have evaluated LA S/SR in larger populations., Methods: A total of 2033 participants from Norwegian (Tromsø 7) and Russian (Know Your Heart) population studies, equally distributed by age and sex, underwent echocardiography, including atrial and ventricular S/SR and NT-proBNP measurements. Of these, 1069 were identified as healthy (without hypertension (HT), atrial fibrillation (AF), or structural cardiac disease) and were used to define the age- and sex-adjusted normal ranges of LA S/SR. Furthermore, the total study population was divided into groups according to ejection fraction (EF) ≥50%, EF <50%, and AF. In each group, uni- and multiple regression and receiver operating characteristic curve analyses were performed to test LA and LV functional parameters as potential indicators of NT-proBNP levels above 250 ng/ml., Results: The mean LA S/SR values in this study were higher than those in previous large studies, whereas the lower references were comparable. In normal hearts, atrial total strain (ATS) and mitral valve E deceleration time (MV DT) were independent factors indicating elevated NT-proBNP levels, whereas in hearts with reduced EFs, the independent indicators were peak atrial contraction strain (PACS) and LV stroke volume. The areas under the curve for these significant indicators to discriminate elevated NT-proBNP levels were 0.639 (95% confidence interval (CI): 0.577-0.701) for normal EF and 0.805 (CI: 0.675-0.935) for reduced EF., Conclusion: The results confirm good intrastudy reproducibility, with mean values in the upper range of previous meta-analyses. In the future, automated border-detection algorithms may be able to generate highly reproducible normal values. Furthermore, the study showed atrial S/SR as an additional indicator of elevated NT-proBNP levels in the general population, demonstrating the incremental value of both ATS and PACS in addition to conventional and ventricular strain echocardiography. Thus, the LA S/SR may be regarded as an important addition to the multiparametric approach used for evaluating LV filling., Competing Interests: HS has received lecture fees from Amgen and Novartis. Other authors declare that they have no conflicts of interest., (Copyright © 2024 Assami Rösner et al.)

We aimed to develop and validate a Loop-mediated Isothermal Amplification (LAMP) assay to Sporothrix brasiliensis. LAMP reaction was developed using six primers designed based on calmodulin gene. In the LAMP reaction, we tested twenty isolates of S. brasiliensis from animals and humans, along with ten tissue samples extracted from the left footpad of mice that had been experimentally infected with S. brasiliensis. In addition, it included DNA samples from various other fungal species for specificity evaluation. All S. brasiliensis isolates yielded positive results in the LAMP, and the limit of DNA detection was 1 ng/μL. All murine samples were positive in the test while DNA from other fungal species were all negative, resulting in 100% of sensitivity and specificity of primers. LAMP diagnosis technique is a promising alternative to sporotrichosis diagnosis, in a simple and cost-effective way. Further studies are warranted to validate this technique using animal model samples obtained from both humans and animals., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: Previous studies have suggested that experimental pain sensitivity is associated with cognitive function. The aim of this study is to assess this relationship in a large population-based sample., Methods: We included 5,753 participants (aged 40-84 years) from the seventh wave of the population-based Tromsø Study who had been examined with cognitive tests and experimental pain assessments, and for whom information on covariates were available. Cox regression models were fitted using standardized scores on cognitive tests (12-word immediate recall test, digit symbol coding test, and Mini-Mental State Examination [MMS-E]) as the independent variable and cold pressor or cuff pressure pain tolerance as the dependent variables. Statistical adjustment was made for putative confounders, namely, age, sex, education, smoking, exercise, systolic blood pressure, body mass index, symptoms indicating anxiety or depression, analgesic use, and chronic pain., Results: In multivariate analysis, cold pressor tolerance time was significantly associated with test scores on the 12-word immediate recall test (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.90-0.97, p < 0.001), the digit symbol coding test (HR 0.94, 95% CI 0.89-0.98, p = 0.004), and the MMS-E (HR 0.93, 95% CI 0.90-0.96 p < 0.001). Tolerance to cuff pressure algometry was significantly associated with 12-word immediate recall (HR 0.94-0.97, p < 0.001) and Digit Symbol Coding test scores (HR 0.93, 95% CI 0.89-0.96, p < 0.001) while there was no significant association with Mini Mental State Examination test score (HR 0.98, 95% CI 0.95-1.00, p = 0.082)., Conclusion: Lower pain tolerance was associated with poorer performance on cognitive tests., (© 2024 the author(s), published by De Gruyter.)

Objectives: In this cross-sectional study from Botswana, we investigated knowledge of myocardial infarction (MI) symptoms and risk factors among the general public and outpatients with MI risk factors based on age and lifestyle behaviors, in addition to assessing associations with sociodemographic and MI risk factors., Method: Open-ended questionnaires about 8 MI symptoms and 10 risk factors, were administered by research assistants to a representative selection of outpatients (n = 525) and the public (n = 2248). Weight and height were measured in all participants and BMI was calculated. Knowledge scores were compared between the two groups. We examined whether sociodemographic and MI risk factors had impact on the scores. Analyses were further adjusted for lifestyle behavior (smoking status, dietary status and physical activities)., Results: The valid response rate was 97.9% comprising 97.8% for the public (n = 2199) and 98.1% for outpatients (n = 515). Public respondents (35.2 ± 12.3 years) were younger than outpatients (38.5 ± 12.6 years). The public comprised 56.9% females while outpatients 54.6%. In general, outpatients had higher knowledge of MI symptoms than the public, with mean scores ± SD of 3.49 ± 2.84 vs 2.80 ± 2.54. Outpatients also had higher knowledge score of MI risk factors than the public, with mean scores, 5.33 ± 3.22 vs 3.82 ± 3.07. For MI symptoms, outpatients were more aware than the public for chest pains among all ages, for arm pain/ numbness, neck/ jaw pain radiating to/ from chest, and feeling sick or looking pallor on the skin among those aged 35-49 years. Among both the public and outpatients, lower knowledge of both MI symptoms and risk factors was associated with primary education, not residing/working together, history of hypertension, no history of heart disease/stroke, and obesity. There were similarities and disparities on MI knowledge among respondents with various numbers of healthy lifestyle behaviours., Conclusion: Results call for urgent educational campaigns on awareness and knowledge of MI and using strategies based on age and lifestyle behavior., (© 2024. The Author(s).)

A better understanding of patients' adherence to treatment is a prerequisite to maximize the benefit of healthcare provision for patients, reduce treatment costs, and is a key factor in a variety of subsequent health outcomes. We aim to understand the state of the art of scientific evidence about which factors influence patients' adherence to treatment. A systematic literature review was conducted using PRISMA guidelines in five separate electronic databases of scientific publications: PubMed, PsycINFO (ProQuest), Cochrane library (Ovid), Google Scholar, and Web of Science. The search focused on literature reporting the significance of factors in adherence to treatment between 2011 and 2021, including only experimental studies (e.g., randomized controlled trials [RCT], clinical trials, etc.). We included 47 experimental studies. The results of the systematic review (SR) are grouped according to predetermined categories of the World Health Organization (WHO): socioeconomic, treatment, condition, personal, and healthcare-related factors. This review gives an actual overview of evidence-based studies on adherence and analyzed the significance of factors defined by the WHO classification. By showing the strength of certain factors in several independent studies and concomitantly uncovering gaps in research, these insights could serve as a basis for the design of future adherence studies and models., (© 2024 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Objective: This study aims to assess the ability of state-of-the-art machine learning algorithms to detect valvular heart disease (VHD) from digital heart sound recordings in a general population that includes asymptomatic cases and intermediate stages of disease progression., Methods: We trained a recurrent neural network to predict murmurs from heart sound audio using annotated recordings collected with digital stethoscopes from four auscultation positions in 2,124 participants from the Tromsø7 study. The predicted murmurs were used to predict VHD as determined by echocardiography., Results: The presence of aortic stenosis (AS) was detected with a sensitivity of 90.9%, a specificity of 94.5%, and an area under the curve (AUC) of 0.979 (CI: 0.963-0.995). At least moderate AS was detected with an AUC of 0.993 (CI: 0.989-0.997). Moderate or greater aortic and mitral regurgitation (AR and MR) were predicted with AUC values of 0.634 (CI: 0.565-703) and 0.549 (CI: 0.506-0.593), respectively, which increased to 0.766 and 0.677 when clinical variables were added as predictors. The AUC for predicting symptomatic cases was higher for AR and MR, 0.756 and 0.711, respectively. Screening jointly for symptomatic regurgitation or presence of stenosis resulted in an AUC of 0.86, with 97.7% of AS cases ( n  = 44) and all 12 MS cases detected., Conclusions: The algorithm demonstrated excellent performance in detecting AS in a general cohort, surpassing observations from similar studies on selected cohorts. The detection of AR and MR based on HS audio was poor, but accuracy was considerably higher for symptomatic cases, and the inclusion of clinical variables improved the performance of the model significantly., Competing Interests: Medsensio AS is a company that provides products for automatic detection of abnormal lung sounds. JR and MJ are employed by Medsensio. HM was working for Medsensio during this research project, and PW was employed for some time by Medsensio after the research project was mostly completed. JR, MJ, and LB owns shares in Medsensio. PW, HM, HS, MJ, TD, JR, SA, AD, JS, and LB have filed two patents for the algorithms outlined in this paper., (© 2024 Waaler, Malbye, Schirmer, Johnsen, Donnem, Ravn, Andersen, Davidsen, Aviles Solis, Stylidis and Bongo.)

Introduction: Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD)., Methods: We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8-11.5] years)., Results: General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes., Discussion: These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Myocardial infarction is likely to be experienced as a life-threatening and potentially traumatic event. Approximately one-third of patients with myocardial infarction experience clinically significant symptoms of anxiety/depression. However, it is unclear how many of these patients experience these symptoms because of post-traumatic stress disorder (PTSD). We conducted a clinical screening of individuals with a confirmed myocardial infarction diagnosis. Our goal was to examine the prevalence of PTSD in myocardial infarction patients and study how PTSD symptoms were associated with exposure to potentially traumatic events., Method: This is epidemiological research with a cross-sectional design following up participants from the Tromsø Study with a confirmed diagnosis of myocardial infarction. We sent invitations to participants in the Tromsø Study with clinically significant self-reported anxiety or depression symptoms following myocardial infarction. A cross-sectional sample of N = 79 participants (61 men and 18 women) was collected. During an interview, participants completed the Stressful Life Events Screening Questionnaire and the PTSD checklist PCL-5., Results: We found nine participants (11.6%) with probable PTSD. This was significantly higher than the postulated population prevalence in Norway (p < 0.015). We found no direct association between myocardial infarction as illness trauma and symptom levels (p = 0.123). However, we found a significant linear trend (p = 0.002), indicating that symptom severity increased proportionately as the number of post-traumatic events increased., Conclusion: PTSD prevalence in myocardial infarction patients was related to lifetime exposure to traumatic events, not the myocardial infarction event alone. More research is required to examine the interaction between myocardial infarction and PTSD. Clinicians should be aware that anxiety or depression symptoms after MI could be secondary symptoms of PTSD., (© 2023. The Author(s).)

Introduction: Low socioeconomic status (SES) is associated with poor mental health and cognitive function. Individual-level SES and area-level SES (ASES) may affect mental health and cognitive function through lifestyle. We aimed to quantify the associations of ASES with mental health and cognitive function and examine the mediating role of lifestyle behaviours independent of individual-level SES in a Norwegian population., Methods: In this cross-sectional study, we included 7211 participants (54% women) from the seventh survey of the Tromsø Study (2015-2016) (Tromsø7). The exposure variable ASES was created by aggregating individual-level SES variables (education, income, housing ownership) from Statistics Norway at the geographical subdivision level. Tromsø7 data were used as mediators (smoking, snuff, alcohol, physical activity, diet) and outcomes (cognitive function, anxiety, depression, insomnia). Mediation and mediated moderation analysis were performed with age as a moderator, stratified by sex., Results: Higher ASES was associated with better cognitive function and fewer depression and insomnia symptoms, independent of individual-level SES. These associations were mediated by smoking and physical activity. Alcohol was a mediator for depression and cognitive function in women. Age was a significant moderator of the association between ASES and global cognitive function in women. The largest total indirect effect of ASES was found for depression, with the joint effect of the mediators accounting for 36% of the total effect., Conclusions: People living in areas with lower ASES are at higher risk of poor mental health, such as depression and insomnia, and have lower cognitive function possibly due to unhealthy lifestyle (smoking, alcohol and physical inactivity)., Competing Interests: Competing interests: M-LL has received lecture fees from Sanofi, BMS/Pfizer and Bayer not related to this study., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: In Norway, the prevalence of dementia is higher than in demographically comparable, high income countries, but reliable incidence studies are lacking. This study calculated the incidence of age-specific dementia from 2000 to 2019., Methods: Participants from The Tromsø Study ( n  = 44,214) were included. Participants with a dementia diagnosis ( n  = 2049 cases) were identified. Poisson regression was used to calculate age-specific yearly and 5-year incidence rates from 2000 to 2019., Results: The incidence of dementia has decreased from 2000 to 2019. The trend was highly significant for ages of 60-99 years, and was similar for both sexes., Discussion: The incidence of dementia in North Norway has decreased over the past two decades similar to that in Western countries, indicating that the total prevalence is increasing due to an aging population. This decrease of incidence could introduce a reduction in future estimation of dementia prevalence., Competing Interests: The authors declare no conflicts of interest. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background and Purpose: A heart age biomarker has been developed using deep neural networks applied to electrocardiograms. Whether this biomarker is associated with cognitive function was investigated., Methods: Using 12-lead electrocardiograms, heart age was estimated for a population-based sample (N = 7779, age 40-85 years, 45.3% men). Associations between heart delta age (HDA) and cognitive test scores were studied adjusted for cardiovascular risk factors. In addition, the relationship between HDA, brain delta age (BDA) and cognitive test scores was investigated in mediation analysis., Results: Significant associations between HDA and the Word test, Digit Symbol Coding Test and tapping test scores were found. HDA was correlated with BDA (Pearson's r = 0.12, p = 0.0001). Moreover, 13% (95% confidence interval 3-36) of the HDA effect on the tapping test score was mediated through BDA., Discussion: Heart delta age, representing the cumulative effects of life-long exposures, was associated with brain age. HDA was associated with cognitive function that was minimally explained through BDA., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Left ventricular (LV) systolic and diastolic functions are important cardiovascular risk predictors in patients with hypertension. However, data on segmental, layer-specific strain, and diastolic strain rates in these patients are limited. The aim of this study was to investigate segmental two-dimensional strain rate imaging (SRI)-derived parameters to characterize LV systolic and diastolic function in hypertensive individuals compared with that in normotensive individuals., Methods: The study sample comprised 1194 participants from the population-based Know Your Heart study in Arkhangelsk and Novosibirsk, Russia, and 1013 individuals from the Seventh Tromsø Study in Norway. The study population was divided into four subgroups: (A) healthy individuals with normal blood pressure (BP), (B) individuals on antihypertensive medication with normal BP, (C) individuals with systolic BP 140-159 mmHg and/or diastolic BP > 90 mm HG, and (D) individuals with systolic BP ≥160 mmHg. In addition to conventional echocardiographic parameters, global and segmental layer-specific strains and strain rates in early diastole and atrial contraction (SR E, SR A) were extracted. The strain and SR (S/SR) analysis included only segments without strain curve artifacts., Results: With increasing BP, the systolic and diastolic global and segmental S/SR gradually decreased. SR E, a marker of impaired relaxation, showed the most distinctive differences between the groups. In normotensive controls and the three hypertension groups, all segmental parameters displayed apico-basal gradients, with the lowest S/SR in the basal septal and highest in apical segments. Only SR A did not differ between the segmental groups but increased gradually with increasing BP. End-systolic strain showed incremental epi-towards endocardial gradients, irrespective of the study group., Conclusion: Arterial hypertension reduces global and segmental systolic and diastolic left ventricular S/SR parameters. Impaired relaxation determined by SR E is the dominant factor of diastolic dysfunction, whereas end-diastolic compliance (by SR A) does not seem to be influenced by different degrees of hypertension. Segmental strain, SR E and SR A provide new insights into the LV cardio mechanics in hypertensive hearts., (© 2023 The Authors. Echocardiography published by Wiley Periodicals LLC.)

Aims: To establish a set of quality indicators (QIs) for the cardiovascular (CV) assessment and management of patients undergoing non-cardiac surgery (NCS)., Methods and Results: The Quality Indicator Committee of the European Society of Cardiology (ESC) and European Society of Anaesthesiology and Intensive Care (ESAIC) in collaboration with Task Force members of the 2022 ESC Guidelines on CV assessment and management of patients undergoing NCS followed the ESC methodology for QI development. This included (1) identification, by constructing a conceptual framework of care, of domains of the CV assessment, and management of patients with risk factors or established cardiovascular disease (CVD) who are considered for or undergoing NCS, (2) development of candidate QIs following a systematic literature review, (3) selection of the final set of QIs using a modified Delphi method, and (4) evaluation of the feasibility of the developed QIs. In total, eight main and nine secondary QIs were selected across six domains: (1) structural framework (written policy), (2) patient education and quality of life (CV risk discussion), (3) peri-operative risk assessment (indication for diagnostic tests), (4) peri-operative risk mitigation (use of hospital therapies), (5) follow-up (post-discharge assessment), and (6) outcomes (major CV events)., Conclusion: We present the 2022 ESC/ESAIC QIs for the CV assessment and management of patients with risk factors or established CVD who are considered for or are undergoing NCS y. These indicators are supported by evidence from the literature, underpinned by expert consensus, and align with the 2022 ESC Guidelines on CV assessment and management of patients undergoing NCS., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: The objective of this study was to determine the diagnostic accuracy in detecting valvular heart disease (VHD) by heart auscultation, performed by medical doctors., Design/methods: A systematic literature search for diagnostic studies comparing heart auscultation to echocardiography or angiography, to evaluate VHD in adults, was performed in MEDLINE (1947-November 2021) and EMBASE (1947-November 2021). Two reviewers screened all references by title and abstract, to select studies to be included. Disagreements were resolved by consensus meetings. Reference lists of included studies were also screened. The results are presented as a narrative synthesis, and risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2., Main Outcome Measures: Sensitivity, specificity and likelihood ratios (LRs)., Results: We found 23 articles meeting the inclusion criteria. Auscultation was compared with full echocardiography in 15 of the articles; pulsed Doppler was used as reference standard in 2 articles, while aortography and ventriculography was used in 5 articles. One article used point-of-care ultrasound. The articles were published from year 1967 to 2021. Sensitivity of auscultation ranged from 30% to 100%, and specificity ranged from 28% to 100%. LRs ranged from 1.35 to 26. Most of the included studies used cardiologists or internal medicine residents or specialists as auscultators, whereas two used general practitioners and two studied several different auscultators., Conclusion: Sensitivity, specificity and LRs of auscultation varied considerably across the different studies. There is a sparsity of data from general practice, where auscultation of the heart is usually one of the main methods for detecting VHD. Based on this review, the diagnostic utility of auscultation is unclear and medical doctors should not rely too much on auscultation alone. More research is needed on how auscultation, together with other clinical findings and history, can be used to distinguish patients with VHD., Prospero Registration Number: CRD42018091675., Competing Interests: Competing interests: AHD, SA, HS and HM take part in a patency application for an algorithm detecting heart disease from heart-sound recordings (United Kingdom Patent Application No. 2212073.7). HS: Grant from NOVARTIS, joint project with institution. HS: Consulting fees from NOVARTIS and AstraZeneca. HS: Lecture fee from Amgen and Pfizer. HS: Leadership / board member of Norwegian Council on Cardiovascular diseases and Norwegian Council on Dementia (both unpaid)., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To explore sex-specific time trends in atrial fibrillation (AF) incidence and to estimate the impact of changes in risk factor levels using individual participant-level data from the population-based Tromsø Study 1994-2016., Methods and Results: A total of 14 818 women and 13 225 men aged 25 years or older without AF were enrolled in the Tromsø Study between 1994 and 2008 and followed up for incident AF throughout 2016. Poisson regression was used for statistical analyses. During follow-up, age-adjusted AF incidence rates in women decreased from 1.19 to 0.71 per 1000 person-years. In men, AF incidence increased from 1.18 to 2.82 per 1000 person-years in 2004, and then declined to 1.94 per 1000 person-years in 2016. Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), body mass index (BMI), physical activity, smoking and alcohol consumption together accounted for 10.9% [95% confidence interval (CI): -2.4 to 28.6] of the AF incidence decline in women and for 44.7% (95% CI: 19.2; 100.0) of the AF incidence increase in men. Reduction in SBP and DBP had the largest contribution to the decrease in AF incidence in women. Increase in BMI had the largest contribution to the increase in AF incidence in men., Conclusion: In the population-based Tromsø Study 1994-2016, AF incidence decreased in women and increased following a reverse U-shape in men. Individual changes in SBP and DBP in women and individual changes in BMI in men were the most important risk factors contributing to the AF incidence trends., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives . Urinary albumin excretion is a risk marker for cardiovascular disease (CVD). Studies suggest that urinary orosomucoid may be a more sensitive marker of general endothelial dysfunction than albuminuria. The aim of this population-based cross-sectional study was to examine the associations between urinary orosomucoid to creatinine ratio (UOCR), urinary albumin to creatinine ratio (UACR) and subclinical CVD. Design . From the Tromsø Study (2007/2008), we included all men and women who had measurements of urinary orosomucoid ( n  = 7181). Among these, 6963 were examined with ultrasound of the right carotid artery and 2245 with echocardiography. We assessed the associations between urinary markers and subclinical CVD measured as intima media thickness of the carotid artery, presence and area of carotid plaque and diastolic dysfunction (DD). UOCR and UACR were dichotomized as upper quartile versus the three lowest. Results . High UOCR, adjusted for UACR, age, cardiovascular risk factors and kidney function, was associated with presence of DD in men (OR: 3.18, 95% CI [1.27, 7.95], p  = .013), and presence of plaque (OR: 1.20, 95% CI [1.01, 1.44], p  = .038) and intima media thickness in women (OR: 1.34, 95% CI [1.09, 1.65], p  = .005). Analyses showed no significant interaction between sex and UOCR for any endpoints. UACR was not significantly associated with DD, but the associations with intima media thickness and plaque were of magnitudes comparable to those observed for UOCR. Conclusions . UOCR was positively associated with subclinical CVD. We need prospective studies to confirm whether UOCR is a clinically useful biomarker and to study possible sex differences.

Aims: Strain artefacts are known to hamper the correct interpretation of segmental strain and strain-rate (S/SR). Defining the normal ranges of myocardial segmental deformation is important in clinical studies and routine echocardiographic practice. In order to define artefact-free normal ranges for segmental longitudinal S/SR parameters, we investigated the extent to which different types of artefacts and their segmental localisation in the three different myocardial layers created a bias in the results of echocardiographic strain measurements., Methods: The study included echocardiograms from men and women aged 40-69 years from two population-based studies, namely the Know Your Heart study (Russia) and the Tromsø Study (Norway). Of the 2207 individuals from these studies, 840 had normal results, defined as the absence of hypertension or indicators of any cardiovascular disease. Two-dimensional (2D) global and segmental S/SR of the three myocardial layers were analysed using speckle tracking echocardiography. Artefacts were assessed with two different methods: visual identification of image-artefacts and a novel conceptual approach of 'curve-artefacts' or unphysiological strain-curve formation., Results: Segmental strain values were found to have significantly reduced in the presence of strain-curve artefacts (14.9%±5.8% towards -20.7%±4.9%), and increased with the foreshortening of the 2D image. However, the individual global strain values were not substantially altered by discarding segmental artefacts. Reduction due to artefacts was observed in all segments, layers, systolic and diastolic strain, and SR. Thus, we presented normal ranges for basal-septal, basal, medial and apical segment groups after excluding artefacts., Conclusion: Strain-curve artefacts introduce systematic errors, resulting in reduced segmental S/SR values. In terms of artefact-robust global longitudinal strain, the detection of curve-artefacts is crucial for the correct interpretation of segmental S/SR patterns. Intersegmental S/SR gradients and artefacts need to be considered for the correct definition of normalcy and pathology., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate interrater and intrarater agreement between physicians and medical students on heart sound classification from audio recordings, and factors predicting agreement with a reference classification., Design: Intra- and interrater agreement study., Subjects: Seventeen GPs and eight cardiologists from Norway and the Netherlands, eight medical students from Norway., Main Outcome Measures: Proportion of agreement and kappa coefficients for intrarater agreement and agreement with a reference classification., Results: The proportion of intrarater agreement on the presence of any murmur was 83% on average, with a median kappa of 0.64 (range k  = 0.09-0.86) for all raters, and 0.65, 0.69, and 0.61 for GPs, cardiologist, and medical students, respectively.The proportion of agreement with the reference on any murmur was 81% on average, with a median kappa of 0.67 (range 0.29-0.90) for all raters, and 0.65, 0.69, and 0.51 for GPs, cardiologists, and medical students, respectively.Distinct murmur, more than five years of clinical practice, and cardiology specialty were most strongly associated with the agreement, with ORs of 2.41 (95% CI 1.63-3.58), 2.19 (1.58-3.04), and 2.53 (1.46-4.41), respectively., Conclusion: We observed fair but variable agreement with a reference on heart murmurs, and physician experience and specialty, as well as murmur intensity, were the factors most strongly associated with agreement.Key points:Heart auscultation is the main physical examination of the heart, but we lack knowledge of inter- and intrarater agreement on heart sounds.• Physicians identified heart murmurs from heart sound recordings fairly reliably compared with a reference classification, and with fair intrarater agreement.• Both intrarater agreement and agreement with the reference showed considerable variation between doctors• Murmur intensity, more than five years in clinical practice, and cardiology specialty were most strongly linked to agreement with the reference.

This study determined the association between respiratory symptoms and death from cardiovascular (CV) diseases during 45 years in a pooled sample of four cohorts of random samples of the Norwegian population with 95,704 participants. Respiratory symptoms were assessed using a modification of the MRC questionnaire on chronic bronchitis. We analyzed the association between respiratory symptoms and specific cardiovascular deaths by using Cox regression analysis with age as the time variable, accounting for cluster-specific random effects using shared frailty for study cohort. Hazard ratios (HR) for death were adjusted for sex, highest attained education, smoking habits, occupational air pollution, and birth cohort. Overall, 12,491 (13%) of participants died from CV diseases: 4,123 (33%) acute myocardial infarction, 2,326 (18%) other ischemic heart disease, 2,246 (18%) other heart diseases, 2,553 (20%) cerebrovascular diseases, and 1,120 (9%) other vascular diseases. The adjusted HR (95% confidence interval) for CV deaths was 1.9 (1.7-2.1) in men and 1.5 (1.2-1.9) in women for "yes" to the question "Are you breathless when you walk on level ground at an ordinary pace?". The same item response showed an adjusted HR for death from acute myocardial infarction of 1.8 (1.5-2.1), other ischemic heart disease 2.2 (1.8-2.7), other heart diseases 1.5 (1.1-1.9), cerebrovascular disease 1.8 (1.5-2.3), and other circulatory diseases 1.7 (1.2-2.4). The adjusted HR for CV death was 1.3 (1.2-1.4) when answering positive to the question" Are you more breathless than people of your own age when walking uphill?". However, positive answers to questions on cough, phlegm, wheezing and attacks of breathlessness were after adjustments not associated with early CV deaths. The associations between CV deaths and breathlessness were also present in never smokers. Self-reported breathlessness was associated with CV deaths and could be an early marker of CV deaths., Competing Interests: The authors have declared that no competing interests exist.