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Aim: This Norwegian case study examines groups at risk of drug overdose deaths, evidence-based harm reduction interventions, low-threshold services and treatment implemented, as well as trends in drug overdose deaths between 2010 and 2021. We aimed to explore the relevance of interventions for at-risk groups and discuss their potential impact on drug overdose trends. Method/data: Using an ecological approach, we analysed the following: (1) groups identified through latent profile analysis (LPA) among a sample of 413 high-risk drug users collected in 2010–2012, supplemented with other relevant studies up to 2021; (2) published information on harm-reduction interventions, low-threshold services and treatment in Norway; and (3) nationwide drug overdose mortality figures supplemented with published articles on the topic. Results: High-risk drug users in 2010–2012 commonly engaged in frequent illegal drug use, injecting and poly-drug use (including pharmaceutical opioids), which continued into following decade. The interventions implemented between 2010 and 2021 were relevant for at-risk groups identified in the surveys. However, there was no decrease in the trend of drug overdose deaths up to 2021. While relevant interventions may have mitigated a theoretical increase in mortality, new at-risk groups may have contributed to fatal outcomes associated with pharmaceutical opioids. Conclusion: The interventions were relevant to the risk groups identified among high-risk drug users and potentially effective in preventing an increase in drug overdose trends. However, tailored interventions are needed for individuals at risk of death from prescribed opioids. Comprehensive studies encompassing all at-risk populations, including both legal and non-medical users of prescription opioids, are needed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: To assess whether stroke diagnoses in national health registers are sufficiently correct and complete to replace manual collection of endpoint data for the Tromsø Study, a population-based epidemiological study. Method: Using the Tromsø Study Cardiovascular Disease Register for 2013–2014 as the gold standard, we calculated correctness (defined as positive predictive value, PPV) and completeness (defined as sensitivity) of stroke cases in four different data subsets derived from the Norwegian Patient Register and the Norwegian Stroke Register. We calculated the sensitivity and PPV with 95% confidence intervals (CIs) assuming a normal approximation of the binomial distribution. Results: In the Norwegian Stroke Register we found a sensitivity of 79.8% (95% CI 74.2–85.4) and a PPV of 97.5% (95% CI 95.1–99.9). In the Norwegian Patient Register the sensitivity was 86.4% (95% CI 81.6–91.1) and the PPV was 84.2% (95% CI 79.2–89.2). The overall highest levels were found in a subset based on a linkage between the Norwegian Stroke Register and the Norwegian Patient Register, with a sensitivity of 88.9% (95% CI 84.5–93.3), and a PPV of 89.3% (95% CI 85.0–93.6). Conclusions: Data from the Norwegian Patient Register and from the linked data set between the Norwegian Patient Register and the Norwegian Stroke Register had acceptable levels of correctness and completeness to be considered as endpoint sources for the Tromsø Study Cardiovascular Disease Register. The benefits of using data from national registers as endpoints in epidemiological studies must be weighed against the impact of potentially decreased data quality. [ABSTRACT FROM AUTHOR]

Background: Physical activity (PA) is associated with reduced mortality. However, whether there is an added benefit of long‐term endurance training is unclear. Thus, we aimed to examine 10‐year mortality in older male endurance athletes compared with an older male general population. Method: Male athletes (n = 503) participating in an annual long‐distance ski race (median years of participation: 14, range: 1–53) from the Norwegian Birkebeiner Aging study (BiAS), and non‐athletic men (n = 1867) attending the sixth Tromsø Study (Tromsø6) aged ≥65 years were included. Associations with endurance sport practice and joint exposures of endurance sport practice and self‐reported leisure‐time PA with all‐cause mortality were examined. We analyzed the data with Cox proportional hazard models and regression standardization. Results: After 10 years (median: 10.4, range: 0.5–11.1) the mortality rate was lower in athletes (hazard ratio (HR) 0.34, 95% confidence interval (CI): 0.24–0.49) compared with non‐athletes, corresponding to a 15% (95% CI: 12–19%) absolute risk reduction associated with endurance sport practice. In joint analyses categorized according to PA and endurance sport practice, we observed an inverse dose–response relationship with mortality (p < 0.001). Compared to inactive non‐athletes, PA was associated with lower mortality in both active non‐athletes and athletes. However, the observed benefit among participants reporting moderate‐to‐vigorous PA was larger in athletes (HR: 0.21, 95% CI: 0.14–0.32) than non‐athletes (HR: 0.43, 95% CI: 0.31–0.59) (p < 0.01). Conclusion: Endurance sport practice was associated with reduced 10‐year mortality, beyond the effect of PA in older men. This study suggests that long‐term endurance sport practice maintained into older adulthood promotes longevity. [ABSTRACT FROM AUTHOR]

Simple Summary: Cervical cancer is the fourth most common cancer in women worldwide. Persistent high-risk human papillomavirus (HPV) can cause invasive cervical cancer through a series of precancerous lesions. Screening women with either cytology examinations or a test detecting HPV infection can prevent cervical cancer. HPV tests are substituting cytology examinations in cervical cancer screening, but more knowledge is needed about the screening performance of HPV tests, especially among younger women. We aimed to determine the long-term performance of a five-type HPV mRNA test to predict CIN3+. These results contribute to the knowledge of the reliability of HPV mRNA testing in cervical cancer screening. Our findings suggest that women with a negative result may extend the screening interval up to 10 years. Background: The study's purpose was to evaluate the performance of a five-type HPV mRNA test to predict cervical intraepithelial neoplasia grade 3 or worse (CIN3+) during up to 12 years of follow-up. Methods: Overall, 19,153 women were recruited by gynecologists and general practitioners in different parts of Norway between 2003 and 2004. The study population comprised 9582 women of these women, aged 25–69 years with normal cytology and a valid five-type HPV mRNA test at baseline. Follow-up for CIN3+ through 2015 was conducted in the Norwegian Cervical Cancer Screening Programme. Results: The cumulative incidence of CIN3+ by baseline status for HPV mRNA-positive and mRNA-negative women were 20.8% and 1.1%, respectively (p < 0.001). Age did not affect the long-term ability of the HPV mRNA test to predict CIN3+ during follow-up. Conclusion: The low long-term risk of CIN3+ among HPV mRNA-negative women and the high long-term risk among HPV mRNA-positive women strengthen the evidence that the five-type HPV mRNA test is an appropriate screening test for women of all ages. Our findings suggest that women with a negative result may extend the screening interval up to 10 years. [ABSTRACT FROM AUTHOR]

Aims: Atrial fibrillation (AF) is becoming increasingly common. Traditional cardiovascular risk factors (CVRF) do not explain all AF cases. Blood‐based biomarkers reflecting cardiac injury such as high‐sensitivity troponin I (hsTnI) may help close this gap. Methods: We investigated the predictive ability of hsTnI for incident AF in 45,298 participants (median age 51.4 years, 45.0% men) across European community cohorts in comparison to CVRF and established biomarkers (C‐reactive protein, N‐terminal pro B‐type natriuretic peptide). Results: During a median follow‐up of 7.7 years, 1734 (3.8%) participants developed AF. Those in the highest hsTnI quarter (≥4.2 ng/L) had a 3.91‐fold (95% confidence interval (CI) 3.30, 4.63; p <.01) risk for developing AF compared to the lowest quarter (<1.4 ng/L). In multivariable‐adjusted Cox proportional hazards models a statistically significant association was seen between hsTnI and AF (hazard ratio (HR) per 1 standard deviation (SD) increase in log10(hsTnI) 1.08; 95% CI 1.01, 1.16; p =.03). Inclusion of hsTnI did improve model discrimination (C‐index CVRF 0.811 vs. C‐index CVRF and hsTnI 0.813; p <.01). Higher hsTnI concentrations were associated with heart failure (HR per SD 1.37; 95% CI 1.12, 1.68; p <.01) and overall mortality (HR per SD 1.24; 95% CI 1.09, 1.41; p <.01). Conclusion: hsTnI as a biomarker of myocardial injury does not improve prediction of AF incidence beyond classical CVRF and NT‐proBNP. However, it is associated with the AF‐related disease heart failure and mortality likely reflecting underlying subclinical cardiovascular impairment. [ABSTRACT FROM AUTHOR]

Machine Learning (ML) methods have become important for enhancing the performance of decision-support predictive models. However, class imbalance is one of the main challenges for developing ML models, because it may bias the learning process and the model generalization ability. In this paper, we consider oversampling methods for generating synthetic categorical clinical data aiming to improve the predictive performance in ML models, and the identification of risk factors for cardiovascular diseases (CVDs). We performed a comparative study of several categorical synthetic data generation methods, including Synthetic Minority Oversampling Technique Nominal (SMOTEN), Tabular Variational Autoencoder (TVAE) and Conditional Tabular Generative Adversarial Networks (CTGANs). Then, we assessed the impact of combining oversampling strategies and linear and nonlinear supervised ML methods. Lastly, we conducted a post-hoc model interpretability based on the importance of the risk factors. Experimental results show the potential of GAN-based models for generating high-quality categorical synthetic data, yielding probability mass functions that are very close to those provided by real data, maintaining relevant insights, and contributing to increasing the predictive performance. The GAN-based model and a linear classifier outperform other oversampling techniques, improving the area under the curve by 2%. These results demonstrate the capability of synthetic data to help with both determining risk factors and building models for CVD prediction. [ABSTRACT FROM AUTHOR]

Aims To identify robust circulating predictors for incident atrial fibrillation (AF) using classical regressions and machine learning (ML) techniques within a broad spectrum of candidate variables. Methods and results In pooled European community cohorts (n = 42 280 individuals), 14 routinely available biomarkers mirroring distinct pathophysiological pathways including lipids, inflammation, renal, and myocardium-specific markers (N-terminal pro B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin I [hsTnI]) were examined in relation to incident AF using Cox regressions and distinct ML methods. Of 42 280 individuals (21 843 women [51.7%]; median [interquartile range, IQR] age, 52.2 [42.7, 62.0] years), 1496 (3.5%) developed AF during a median follow-up time of 5.7 years. In multivariable-adjusted Cox-regression analysis, NT-proBNP was the strongest circulating predictor of incident AF [hazard ratio (HR) per standard deviation (SD), 1.93 (95% CI, 1.82–2.04); P < 0.001]. Further, hsTnI [HR per SD, 1.18 (95% CI, 1.13–1.22); P < 0.001], cystatin C [HR per SD, 1.16 (95% CI, 1.10–1.23); P < 0.001], and C-reactive protein [HR per SD, 1.08 (95% CI, 1.02–1.14); P = 0.012] correlated positively with incident AF. Applying various ML techniques, a high inter-method consistency of selected candidate variables was observed. NT-proBNP was identified as the blood-based marker with the highest predictive value for incident AF. Relevant clinical predictors were age, the use of antihypertensive medication, and body mass index. Conclusion Using different variable selection procedures including ML methods, NT-proBNP consistently remained the strongest blood-based predictor of incident AF and ranked before classical cardiovascular risk factors. The clinical benefit of these findings for identifying at-risk individuals for targeted AF screening needs to be elucidated and tested prospectively. [ABSTRACT FROM AUTHOR]

There is strong evidence that sex chromosomes and sex hormones influence blood pressure (BP) regulation, distribution of cardiovascular (CV) risk factors and co-morbidities differentially in females and males with essential arterial hypertension. The risk for CV disease increases at a lower BP level in females than in males, suggesting that sex-specific thresholds for diagnosis of hypertension may be reasonable. However, due to paucity of data, in particularly from specifically designed clinical trials, it is not yet known whether hypertension should be differently managed in females and males, including treatment goals and choice and dosages of antihypertensive drugs. Accordingly, this consensus document was conceived to provide a comprehensive overview of current knowledge on sex differences in essential hypertension including BP development over the life course, development of hypertension, pathophysiologic mechanisms regulating BP, interaction of BP with CV risk factors and co-morbidities, hypertension-mediated organ damage in the heart and the arteries, impact on incident CV disease, and differences in the effect of antihypertensive treatment. The consensus document also highlights areas where focused research is needed to advance sex-specific prevention and management of hypertension. [ABSTRACT FROM AUTHOR]

INTRODUCTION We examined if we could identify predictors for smoking cessation at six months post cessation, among smokers enrolled in a large Norwegian populationbased intervention study. METHODS We followed 4333 (72.1% women) smokers who enrolled in an internetbased smoking cessation intervention during 2010-2012. The baseline questionnaire collected information on sociodemographic and lifestyle factors, including current snus use. The cessation outcome was self-reported no smoking past seven days, at six months. We used logistic regression to estimate odds ratios (ORs) with 95% confidence intervals, to identify predictors of smoking cessation, adjusting for potential confounders. RESULTS Women (OR=1.30; 95% CI: 1.01-1.69) compared with men, and those with medium (OR=1.31; 95% CI: 1.02-1.68) and longer (OR=1.42; 95% CI: 1.06-1.90) education compared with those with shorter education, were more likely to be successful quitters. Overall, being a student (OR=0.56; 95% CI: 0.37-0.85) compared with having fulltime work, and a moderate to high Fagerström test for nicotine dependence (FTND) score (OR=0.69; 95% CI: 0.55-0.87) compared with a low score, were predictors for unsuccessful cessation. Current snus use was a predictor for unsuccessful cessation compared to no snus use for both men (OR=0.49; 95% CI: 0.28-0.88) and women (OR=0.49; 95% CI: 0.32-0.75). CONCLUSIONS Our study identifies female sex and longer education as predictors for successful smoking cessation, while a medium or high FTND score, being a student, and current snus use, were predictors for unsuccessful smoking cessation. Only current snus use was a predictor for unsuccessful cessation for both sexes. Our results indicate that smokers should be warned that snus use may prevent successful smoking cessation. [ABSTRACT FROM AUTHOR]

Aims: To (i) define the characteristics of snus users compared with non‐users and smokers and (ii) define the relationship between snus use and self‐reported anxiety and depression and compare it with the relation between smoking and anxiety and depression. Design, setting and participants: A cross‐sectional study based on data from the Norwegian population‐based survey, the Tromsø Study (2015–16). A total of 32 591 people aged 40 years and older in the municipality of Tromsø were invited to attend. There were 21 083 respondents, giving a 65% attendance rate. Measurements: Tobacco use was assessed by current and previous use of snus or cigarettes. Symptoms of anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). Findings Snus users were more often male, were younger and had higher income and higher alcohol consumption than smokers and non‐users of snus. In a linear regression analysis, we found no significant association between current snus use and anxiety and depression after adjusting for background variables. However, there was a positive association between previous snus use and anxiety among males [adjusted beta = 0.258; 99% confidence interval (CI) = 0.023–0.492]. Regarding anxiety, the adjusted beta‐coefficients for current smoking were 0.425 (99% CI = 0.184–0.666) for females and 0.303 (99% CI = 0.084–0.522) for males. Concerning depression, the adjusted beta coefficients for current smoking were 0.569 (99% CI = 0.358–0.780) for females and 0.281 (99% CI = 0.060–0.503) for males. Conclusions: In Norway, current snus users differ from current smokers by having a higher socio‐economic status and no detectable association with anxiety and depression. This suggests that the relationship between tobacco use and anxiety and depression is associated with the administration method. [ABSTRACT FROM AUTHOR]

Aims To study change over 8 years in cardiovascular risk, achievement of national guideline-based treatment targets of lipids, blood pressure (BP) and smoking in primary prevention of cardiovascular disease (CVD), medication use, and characteristics associated with target achievement among individuals with high CVD risk in a general population. Methods and results We followed 2524 women and men aged 40-79 years with high risk of CVD attending the population-based Troms0 study in 2007-08 (Troms06) to their participation in the next survey in 2015-16 (Troms07). We used descriptive statistics and regression models to study change in CVD risk and medication use, and characteristics associated with treatment target achievement. In total, 71.4% reported use of BP- and/or lipid-lowering medication at second screening. Overall, CVD risk decreased during follow-up, with a larger decrease among medication users compared with non-users. Treatment target achievement was 31.0% for total cholesterol <5 mmol/L, 27.3% for LDL cholesterol <3 mmol/L, 43.4% for BP <140/90 (<135/85 if diabetes) mmHg, and 85.4% for non-smoking. A total of 9.8% reached all treatment targets combined. Baseline risk factor levels and current medication use had the strongest associations with treatment target achievement. Conclusion We found an overall improvement in CVD risk factors among high-risk individuals over 8 years. However, guideline-based treatment target achievement was relatively low for all risk factors except smoking. Medication use was the strongest characteristic associated with achieving treatment targets. This study has demonstrated that primary prevention of CVD continues to remain a major challenge. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether acute myocardial infarction (MI) diagnoses in national health registers are sufficiently correct and complete to replace manual collection of endpoint data for a population-based, epidemiological study. Patients and Methods: Using the Tromsø Study Cardiovascular Disease Register for 2013– 2014 as gold standard, we calculated correctness (defined as positive predictive value (PPV)) and completeness (defined as sensitivity) of MI cases in the Norwegian Myocardial Infarction Register and the Norwegian Patient Register separately and in combination. We calculated the sensitivity and PPV with 95% confidence intervals using the Clopper-Pearson Exact test. Results: We identified 153 MI cases in the gold standard. In the Norwegian Myocardial Infarction Register, we found a PPV of 97.1% (95% confidence interval (CI) 92.8– 99.2) and a sensitivity of 88.2% (95% CI 82.0– 92.9). In the Norwegian Patient Register, the PPV was 96.3% (95% CI 91.6– 98.8) and the sensitivity was 85.6% (95% CI 79.0– 90.8). The combined dataset of the Norwegian Myocardial Infarction Register and the Norwegian Patient Register had a PPV of 96.6% (95% CI 92.1– 98.9) and a sensitivity of 91.5% (95% CI 85.9– 95.4). Conclusion: MI diagnoses in both the Norwegian Myocardial Infarction Register and the Norwegian Patient Register were highly correct and complete, and each of the registers could be considered as endpoint sources for the Tromsø Study. A combination of the two national registers seemed, however, to represent the most comprehensive data source overall. The benefits of using data from national registers as endpoints in epidemiological studies include faster, less resource-intensive access to nationwide data and considerably lower loss to follow-up, compared to manual data collection in a limited geographical area. [ABSTRACT FROM AUTHOR]

Aims  There is inconsistent evidence on the relation of alcohol intake with incident atrial fibrillation (AF), in particular at lower doses. We assessed the association between alcohol consumption, biomarkers, and incident AF across the spectrum of alcohol intake in European cohorts. Methods and results  In a community-based pooled cohort, we followed 107 845 individuals for the association between alcohol consumption, including types of alcohol and drinking patterns, and incident AF. We collected information on classical cardiovascular risk factors and incident heart failure (HF) and measured the biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I. The median age of individuals was 47.8 years, 48.3% were men. The median alcohol consumption was 3 g/day. N = 5854 individuals developed AF (median follow-up time: 13.9 years). In a sex- and cohort-stratified Cox regression analysis alcohol consumption was non-linearly and positively associated with incident AF. The hazard ratio for one drink (12 g) per day was 1.16, 95% CI 1.11–1.22, P < 0.001. Associations were similar across types of alcohol. In contrast, alcohol consumption at lower doses was associated with reduced risk of incident HF. The association between alcohol consumption and incident AF was neither fully explained by cardiac biomarker concentrations nor by the occurrence of HF. Conclusions  In contrast to other cardiovascular diseases such as HF, even modest habitual alcohol intake of 1.2 drinks/day was associated with an increased risk of AF, which needs to be considered in AF prevention. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to use the parametric g-formula to estimate the 19-year risk of myocardial infarction (MI) under hypothetical interventions on six cardiovascular risk factors. Design and setting A populations-based cohort study with repeated measurements, the Tromsø Study. Primary outcome measure Myocardial infarction. Participants We estimated the relative and absolute risk reduction under feasible and intensive risk reduction strategies for smoking, physical activity, alcohol drinking, body mass index, total serum cholesterol and systolic blood pressure in 14 965 men and women with 19 years of follow-up (1994–2013). Results The estimated 19-year risk of MI under no intervention was 7.5% in individuals with baseline mean age 49.3 years (range 25–69). This risk was reduced by 30% (95% CI 19% to 39%) under joint feasible interventions on all risk factors, and 70% (60%, 78%) under a set of more intensive interventions. The most effective interventions were lowering of total cholesterol to 5.18 mmol/L and lowering of systolic blood pressure to 120 mm Hg (33% and 37% lower MI risk, respectively). The absolute risk reductions were significantly larger in men, in older participants, in smokers and in those with low education. Conclusion Modification of population levels of cardiovascular risk factors could have prevented close to one-third of the cases of MI in the municipality of Tromsø during 19 years of follow-up. [ABSTRACT FROM AUTHOR]

Aims To explore sex-specific associations between long-term individual blood pressure (BP) patterns and risk of incident atrial fibrillation (AF) in the general population. Methods and results Blood pressure was measured in 8376 women and 7670 men who attended at least two of the three population-based Tromsø Study surveys conducted in 1986–87, 1994–95, and 2001. Participants were followed for incident AF throughout 2013. Latent mixed modelling was used to identify long-term trajectories of systolic BP and hypertension. Cox regression was used to estimate associations between the identified trajectories and incident AF. Elevated systolic BP throughout the exposure period (1986–2001) independently and differentially increased risk of AF in women and men. In women, having elevated systolic BP trajectories doubled AF risk compared to having persistently low levels, irrespective of whether systolic BP increased, decreased, or was persistently high over time, with hazard ratios of 1.88 (95% confidence interval 1.37–2.58), 2.32 (1.61–3.35), and 1.94 (1.28–2.94), respectively. In men, those with elevated systolic BP that continued to increase over time had a 50% increased AF risk: 1.51 (1.09–2.10). When compared to those persistently normotensive, women developing hypertension during the exposure period, and women and men with hypertension throughout the exposure period had 1.40 (1.06–1.86), 2.75 (1.99–3.80), and 1.36 (1.10–1.68) times increased risk of AF, respectively. Conclusion Long-term BP and hypertension trajectories were associated with increased incidence of AF in both women and men, but the associations were stronger in women. Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Aims: Limited evidence is available on the temporal relationship between atrial fibrillation (AF) and ischaemic stroke and their impact on mortality in the community. We sought to understand the temporal relationship of AF and ischaemic stroke and to determine the sequence of disease onset in relation to mortality.Methods and Results: Across five prospective community cohorts of the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project we assessed baseline cardiovascular risk factors in 100 132 individuals, median age 46.1 (25th-75th percentile 35.8-57.5) years, 48.4% men. We followed them for incident ischaemic stroke and AF and determined the relation of subsequent disease diagnosis with overall mortality. Over a median follow-up of 16.1 years, N = 4555 individuals were diagnosed solely with AF, N = 2269 had an ischaemic stroke but no AF diagnosed, and N = 898 developed both, ischaemic stroke and AF. Temporal relationships showed a clustering of diagnosis of both diseases within the years around the diagnosis of the other disease. In multivariable-adjusted Cox regression analyses with time-dependent covariates subsequent diagnosis of AF after ischaemic stroke was associated with increased mortality [hazard ratio (HR) 4.05, 95% confidence interval (CI) 2.17-7.54; P < 0.001] which was also apparent when ischaemic stroke followed after the diagnosis of AF (HR 3.08, 95% CI 1.90-5.00; P < 0.001).Conclusion: The temporal relations of ischaemic stroke and AF appear to be bidirectional. Ischaemic stroke may precede detection of AF by years. The subsequent diagnosis of both diseases significantly increases mortality risk. Future research needs to investigate the common underlying systemic disease processes. [ABSTRACT FROM AUTHOR]

Aims: To examine the associations between diastolic dysfunction indices and long‐term risk of all‐cause mortality in adults over 23‐year follow‐up. Methods and results: Participants (n = 2734) of the population‐based Tromsø Study of Norway had echocardiography in 1994–1995. Of these 67% were repeated in 2001 and/or 2007–2008. Mortality between 1994 and 2016 was determined by linkage to the national death registry. Cox regression was used to model the hazard of all‐cause mortality in relation to left atrial parameters (treated as time‐dependent using repeated measurements) adjusted for traditional risk factors and cardiovascular disease. During the follow‐up, 1399 participants died. Indexed left atrial diameter, mitral peak E deceleration time, and mitral peak E to peak A ratio showed an U‐shaped association with all‐cause mortality. Combining left atrial diameter with mitral peak E deceleration time increased the prognostic accuracy for all‐cause mortality whereas adding mitral peak E to peak A ratio did not increase prognostic value. We estimated new optimal cutoff values of left atrial diameter, mitral peak E deceleration time, and mitral peak E to peak A ratio for all‐cause mortality outcome. E/e′ had a cubic relation to mortality. Conclusion: Both enlarged and small left atrial diameters were associated with increased all‐cause mortality risk. A combination of Doppler‐based left ventricle filling parameters had an incremental effect on all‐cause mortality risk. The cutoff values of diastolic dysfunction indices we determined had similar all‐cause mortality prediction ability as those recommended by American Association of Echocardiography and European Association of Cardiovascular Imaging. [ABSTRACT FROM AUTHOR]