Joint effect of ischemic stroke and obesity on the risk of venous thromboembolism: the Tromsø Study.

Background: Patients with ischemic stroke have increased risk of venous thromboembolism (VTE). Obesity is prevalent in stroke patients and a well-established risk factor for VTE. Whether obesity further increases the VTE risk in patients with stroke remains unclear. Objectives: We investigated the joint effect of ischemic stroke and obesity on the risk of incident VTE in a population-based cohort. Methods: Participants (n = 29,920) were recruited from the fourth to sixth surveys of the Tromsø Study (1994-1995, 2001, and 2007-2008) and followed through 2014. Incident events of ischemic stroke and VTE during follow-up were recorded. Hazard ratios (HRs) of VTE with 95% CIs were estimated according to combined categories of ischemic stroke and obesity (body mass index ≥ 30 kg/m2), with exposure to neither risk factors as reference. Results: During a median follow-up of 19.6 years, 1388 participants experienced ischemic stroke and 807 participants developed VTE. Among those with stroke, 51 developed VTE, yielding an incidence rate of VTE after stroke of 7.2 per 1000 person-years (95% CI, 5.5-9.5). In subjects without stroke, obesity was associated with a 1.8-fold higher VTE risk (HR, 1.76; 95% CI, 1.47-2.11). In nonobese subjects, stroke was associated with a 1.8-fold higher VTE risk (HR, 1.77; 95% CI, 1.27-2.46). Obese subjects with stroke had a 2-fold increased VTE risk (HR, 2.44; 95% CI, 1.37-4.36). Conclusion: The combination of obesity and ischemic stroke did not yield an excess risk of VTE. Our findings suggest that obese subjects with ischemic stroke do not have a more than additive risk of VTE.

Associations between cognitive test scores and pain tolerance: The Tromsø study.

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.

Thrombolytic Treatment in Wake-Up Stroke: A Propensity Score-Matched Analysis of Treatment Effectiveness in the Norwegian Stroke Registry.

BACKGROUND: Previous clinical trials found improved outcome of thrombolytic treatment in patients with ischemic wake-up stroke (WUS) selected by advanced imaging techniques. The authors assessed the effectiveness of thrombolytic treatment in patients with WUS in a nationwide stroke registry. METHODS AND RESULTS: Using propensity score matching, the authors assessed the effectiveness and safety of thrombolytic treatment versus no thrombolytic treatment in 726 patients (363 matched pairs) with WUS in the Norwegian Stroke Registry in 2014 to 2019. Thrombolytic treatment in WUS versus known-onset stroke was compared in 730 patients (365 matched pairs). Functional outcomes were assessed by the modified Rankin Scale (mRS) at 3 months. A significant benefit of thrombolytic treatment in WUS was seen in ordinal analysis (odds ratio [OR], 1.48 [95% CI, 1.15-1.91]; P=0.003) and for mRS 0 to 2 (OR, 1.81 [95% CI, 1.29-2.52]; P=0.001) but not for mRS 0 or 1 (OR, 1.32 [95% CI, 1.00-1.74]; P=0.050). The proportion of patients with mRS 0 or 1 was lower in patients with WUS who underwent thrombolysis versus those with known-onset stroke (50.4% versus 59.5%; OR, 0.69 [95% CI, 0.52-0.93]; P=0.013), while outcomes were similar between groups for mRS 0 to 2 and ordinal analysis. Symptomatic intracranial hemorrhage after thrombolytic treatment occurred in 4.4% of patients with WUS and 3.9% of patients with known-onset stroke (OR, 1.14 [95% CI, 0.54-2.41]; P=0.726). CONCLUSIONS: Thrombolytic treatment in patients with WUS was associated with improved functional outcome compared with patients with no thrombolytic treatment and was not associated with increased rates of symptomatic intracranial hemorrhage compared with known-onset stroke. The results indicate that thrombolytic treatment is effective and safe in WUS in a real-life setting.

Females Display Lower Risk of Myocardial Infarction From Higher Estimated Cardiorespiratory Fitness Than Males: The Tromsø Study 1994-2014.

Objective: To examine the dose-response association between estimated cardiorespiratory fitness (eCRF) and risk of myocardial infarction (MI). Patients and Methods: Adults who attended Tromsø Study surveys 4-6 (Janurary 1,1994-December 20, 2008) with no previous cardiovascular disease were followed up through December 31, 2014 for incident MI. Associations were examined using restricted cubic splines Fine and Gray regressions, adjusted for education, smoking, alcohol, diet, sex, adiposity, physical activity, study survey, and age (timescale) in the total cohort and subsamples with hyperlipidemia (n=2956), hypertension (n=8290), obesity (n=5784), metabolic syndrome (n=1410), smokers (n=3823), and poor diet (n=3463) and in those who were physically inactive (n=6255). Results: Of 14,285 participants (mean age ± SD, 53.7±11.4 years), 979 (6.9%) experienced MI during follow-up (median, 7.2 years; 25th-75th, 5.3-14.6 years). Females with median eCRF (32 mL/kg/min) had 43% lower MI risk (subdistributed hazard ratio [SHR], 0.57; 95% CI, 0.48-0.68) than those at the 10th percentile (25 mL/kg/min) as reference. The lowest MI risk was observed at 47 mL/kg/min (SHR, 0.02; 95% CI, 0.01-0.11). Males had 26% lower MI risk at median eCRF (40 mL/kg/min; SHR, 0.74; 95% CI, 0.63-0.86) than those at the 10th percentile (32 mL/kg/min), and the lowest risk was 69% (SHR, 0.31; 95% CI, 0.14-0.71) at 60 mL/kg/min. The associations were similar in subsamples with cardiovascular disease risk factors. Conclusion: Higher eCRF associated with lower MI risk in females and males, but associations were more pronounced among females than those in males. This suggest eCRF as a vital estimate to implement in medical care to identify individuals at high risk of future MI, especially for females.

Prevalence of intracranial artery stenosis in a general population using 3D-time of flight magnetic resonance angiography.

BACKGROUND: Data on prevalence of intracranial artery stenosis (ICAS) in Western populations is sparse. The aim of the study was to assess the prevalence and risk factors for ICAS in a mainly Caucasian general population. METHODS: We assessed the prevalence of ICAS in 1847 men and women aged 40 to 84 years who participated in a cross-sectional population-based study, using 3-dimensional time-of-flight 3 Tesla magnetic resonance angiography. ICAS was defined as a focal luminal flow diameter reduction of ≥50 %. The association between cardiovascular risk factor levels and ICAS was assessed by multivariable regression analysis. RESULTS: The overall prevalence of ICAS was 6.0 % (95 % confidence interval (CI) 5.0-7.2), 4.3 % (95 % CI 3.1-5.7) in women and 8.0 % (95 % CI 6.3-10.0) in men. The prevalence increased by age from 0.8 % in 40-54 years age group to 15.2 % in the 75-84 years age group. The majority of stenoses was located to the internal carotid artery (52.2 %), followed by the posterior circulation (33.1 %), the middle cerebral artery (10.8 %) and the anterior cerebral artery (3.8 %). The risk of ICAS was independently associated with higher age, male sex, hypertension, hyperlipidemia, diabetes mellitus, current smoking and higher BMI. CONCLUSIONS: The prevalence of ICAS in a general population of Caucasians was relatively high and similar to the prevalence of extracranial internal carotid artery stenosis in previous population-based studies.

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking. METHODS: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality. RESULTS: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6). CONCLUSIONS: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.).

Anatomical variations in the circle of Willis are associated with increased odds of intracranial aneurysms: The Tromsø study.

PURPOSE: Studies on patients suggest an association between anatomical variations in the Circle of Willis (CoW) and intracranial aneurysms (IA), but it is unclear whether this association is present in the general population. In this cross-sectional population study, we investigated the associations between CoW anatomical variations and IA. METHODS: We included 1667 participants from a population sample with 3 T MRI time-of-flight angiography (40-84 years, 46.5% men). Saccular IAs were defined as protrusions in the intracranial arteries ≥2 mm, while variants of the CoW were classified according to whether segments were missing or hypoplastic (< 1 mm). We used logistic regression, adjusting for age and IA risk factors, to assess whether participants with incomplete CoW variants had a greater prevalence of IA and whether participants with specific incomplete variants had a greater prevalence of IA. RESULTS: Participants with an incomplete CoW had an increased prevalence of IA (OR, 2.3 [95% CI 1.05-5.04]). This was mainly driven by the variant missing all three communicating arteries (OR, 4.2 [95% CI 1.7-1 0.3]) and the variant missing the P1 segment of the posterior cerebral artery (OR, 3.6 [95% CI 1.2-10.1]). The combined prevalence of the two variants was 15.4% but accounted for 28% of the IAs. CONCLUSION: The findings suggest that an incomplete CoW is associated with an increased risk of IA for adults in the general population.

Pain tolerance after stroke: The Tromsø study.

BACKGROUND: Stroke lesions might alter pain processing and modulation by affecting the widely distributed network of brain regions involved. We aimed to compare pain tolerance in stroke survivors and stroke-free persons in the general population, with and without chronic pain. METHODS: We included all participants of the sixth and seventh wave of the population-based Tromsø Study who had been tested with the cold pressor test (hand in cold water bath, 3°C, maximum time 106 s in the sixth wave and 120 s in the seventh) and who had information on previous stroke status and covariates. Data on stroke status were obtained from the Tromsø Study Cardiovascular Disease Register and the Norwegian Stroke Register. Cox regression models were fitted using stroke prior to study attendance as the independent variable, cold pressor endurance time as time variable and hand withdrawal from cold water as event. Statistical adjustments were made for age, sex, diabetes, hypertension, hyperlipidaemia, body mass index and smoking. RESULTS: In total 21,837 participants were included, 311 of them with previous stroke. Stroke was associated with decreased cold pain tolerance time, with 28% increased hazard of hand withdrawal (hazard ratio [HR] 1.28, 95% CI 1.10-1.50). The effect was similar in participants with (HR 1.28, 95% CI 0.99-1.66) and without chronic pain (HR 1.29, 95% CI 1.04-1.59). CONCLUSIONS: Stroke survivors, with and without chronic pain, had lower cold pressor pain tolerance, with possible clinical implications for pain in this group. SIGNIFICANCE: We found lower pain tolerance in participants with previous stroke compared to stroke-free participants of a large, population-based study. The association was present both in those with and without chronic pain. The results may warrant increased awareness by health professionals towards pain experienced by stroke patients in response to injuries, diseases and procedures.

Gray matter volume and pain tolerance in a general population: the Tromsø study.

ABSTRACT: As pain is processed by an extensive network of brain regions, the structural status of the brain may affect pain perception. We aimed to study the association between gray matter volume (GMV) and pain sensitivity in a general population. We used data from 1522 participants in the seventh wave of the Tromsø study, who had completed the cold pressor test (3°C, maximum time 120 seconds), undergone magnetic resonance imaging (MRI) of the brain, and had complete information on covariates. Cox proportional hazards regression models were fitted with time to hand withdrawal from cold exposure as outcome. Gray matter volume was the independent variable, and analyses were adjusted for intracranial volume, age, sex, education level, and cardiovascular risk factors. Additional adjustment was made for chronic pain and depression in subsamples with available information on the respective item. FreeSurfer was used to estimate vertexwise cortical and subcortical gray matter volumes from the T1-weighted MR image. Post hoc analyses were performed on cortical and subcortical volume estimates. Standardized total GMV was associated with risk of hand withdrawal (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.71-0.93). The effect remained significant after additional adjustment for chronic pain (HR 0.84, 95% CI 0.72-0.97) or depression (HR 0.82, 95% CI 0.71-0.94). In post hoc analyses, positive associations between standardized GMV and pain tolerance were seen in most brain regions, with larger effect sizes in regions previously shown to be associated with pain. In conclusion, our findings indicate that larger GMV is associated with longer pain tolerance in the general population.

Exploring the incremental utility of circulating biomarkers for robust risk prediction of incident atrial fibrillation in European cohorts using regressions and modern machine learning methods.

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.

Data from national health registers as endpoints for the Tromsø Study: Correctness and completeness of stroke diagnoses.

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.

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. METHODS: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014-000096-80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). FINDINGS: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9-81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88-1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74-2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53-8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67-1·94; p=0·64). INTERPRETATION: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. FUNDING: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health.

Sex-specific time trends in incident atrial fibrillation and the contribution of risk factors: the Tromsø Study 1994-2016.

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.

Decompressive hemicraniectomy for space-occupying brain infarction: Nationwide population-based registry study.

OBJECTIVE: We analyzed data from the Norwegian Stroke Registry (NSR) to study access to and outcomes of decompressive hemicraniectomy for brain infarction in a nationwide routine clinical setting. We also discretionary assessed whether the outcomes were comparable with those achieved in randomized controlled trials (RCTs), and whether the use was in accordance with guidelines. METHODS: The NSR is a nationwide (population 5.3 million) clinical quality registry. We included all stroke-cases operated in 2017 through 2019, and retrieved data on baseline characteristics, treatment and functional outcome after three months (dichotomized modified Rankin Scale score; favorable (0-3) or unfavorable (4-6)). Crude treatment rates and the expected proportion of patients transferred from a local hospital to a stroke-center for the operation were estimated, based on the total population's distribution of residency. RESULTS: The 68 cases were 17 (25%) women and 51 (75%) men with a median National Institute of Health Stroke Scale (NIHSS) score on admission of 14.0 (inter-quartile range (IQR) 11.0) and a median time from onset to hemicraniectomy of 34.3 (IQR 40.9) hours. The crude treatment rate varied between regions from 0.29 to 1.40 operations per 100,000 population per year, and the proportion transferred from a local hospital (50%) was lower than expected (68%). A favorable outcome was achieved in 20/52 (38.5%) cases. CONCLUSIONS: The findings indicate gender- and geographic-inequalities in access. Among operated cases, outcomes were comparable with those reported from RCTs, and the use in accordance with recommendations in the current guidelines from the American Stroke Association.

Outcomes after coronary angiography for unstable angina compared to stable angina, myocardial infarction and an asymptomatic general population.

Background: The outcomes of real-world unstable angina (UA) in the high-sensitivity troponin era are unclear. We aimed to investigate the outcomes of UA referred to coronary angiography compared to stable angina (SA), non-ST-segment elevation myocardial infarction (NSTEMI), STEMI and a general population. Methods: We included the 9,694 patients with no prior coronary artery disease (CAD) referred to invasive or CT coronary angiography from 2013 to 2018 in Northern Norway (51% SA, 12% UA, 23% NSTEMI and 14% STEMI), and 11,959 asymptomatic individuals recruited from the Tromsø Study. We used Cox models to estimate the hazard ratios (HR) for all-cause mortality and major adverse cardiovascular events (MACE), defined as cardiovascular death, MI or obstructive CAD. Results: The median follow-up time was 2.8 years. The incidence rate of death was 8.5 per 1000 person-years (95 % confidence interval [CI] 8.0-9.0) in the general population, 9.7 (95 % CI 8.3-11.5) in SA, 14.9 (95 % CI 11.4-19.6) in UA, 29.7 (95 % CI 25.6-34.3) in NSTEMI and 36.5 (95 % CI 30.9-43.2) in STEMI. In multivariable adjusted analyses, compared with UA, SA had a 38 % lower risk of death and a non-significant lower risk of MACE (HR 0.62, 95 % CI 0.44-0.89; HR 0.86, 95 % CI 0.66-1.11). NSTEMI had a 2.4-fold higher risk of death (HR 2.39, 95 % CI 1.38-4.14) and a 1.6-fold higher risk of MACE (HR 1.62, 95 % CI 1.11-2.38) compared tox UA during the first year after coronary angiography, but a similar risk thereafter. There was no difference in the risk of death for UA with non-obstructive CAD and obstructive CAD (HR 0.78, 95 % CI 0.39-1.57). Conclusion: UA had a higher risk of death but a similar risk of MACE compared to SA and a lower 1-year risk of death and MACE compared to NSTEMI.

Macular Layer Thickness and Effect of BMI, Body Fat, and Traditional Cardiovascular Risk Factors: The Tromsø Study.

Purpose: The purpose of this study was to investigate associations between cardiovascular risk factors and the thickness of retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), and outer retina layers (ORL). Methods: In this population-based study, we included participants from the Tromsø Study: Tromsø6 (2007 to 2008) and Tromsø7 (2015 to 2016). Persons with diabetes and/or diagnosed glaucoma were excluded from this study. Retinal thickness was measured on optical coherence tomography (Cirrus HD-OCT) macula-scans, segmented on RNFL, GCIPL, and ORL and associations were analyzed cross-sectionally (N = 8288) and longitudinally (N = 2595). We used directed acyclic graphs (DAGs) for model selection, and linear regression to adjust for confounders and mediators in models assessing direct effects. Factors examined were age, sex, blood pressure, daily smoking, serum lipids, glycated hemoglobin, body mass index (BMI), total body fat percentage (BFP), and the adjustment variables refraction and height. Results: The explained variance of cardiovascular risk factors was highest in GCIPL (0.126). GCIPL had a strong negative association with age. Women had thicker GCIPL than men at higher age and thinner ORL at all ages (P < 0.001). Systolic blood pressure was negatively associated with RNFL/GCIPL (P = 0.001/0.004), with indication of a U-shaped relationship with GCIPL in women. The negative association with BMI was strongest in men, with significant effect for RNFL/GCIPL/ORL (P = 0.001/<0.001/0.019) and in women for GCIPL/ORL (P = 0.030/0.037). BFP was negatively associated with GCIPL (P = 0.01). Higher baseline BMI was associated with a reduction in GCIPL over 8 years (P = 0.03). Conclusions: Cardiovascular risk factors explained 12.6% of the variance in GCIPL, with weight and blood pressure the most important modifiable factors.

Joint effect of myocardial infarction and obesity on the risk of venous thromboembolism: The Tromsø Study.

BACKGROUND: Myocardial infarction (MI) is associated with an increased risk of venous thromboembolism (VTE). Obesity is a recognized risk factor for both MI and VTE. Whether obesity further increases the risk of VTE in MI patients is scarcely investigated. AIM: To study the joint effect of MI and obesity on the risk of VTE. METHODS: Study participants (n = 29 410) were recruited from three surveys of the Tromsø Study (conducted in 1994-1995, 2001, and 2007-2008) and followed up through 2014. All incident MI and VTE cases during follow-up were recorded. Cox regression models with MI as a time-dependent variable were used to estimate hazard ratios (HRs) of VTE (adjusted for age and sex) by combinations of MI exposure and obesity status. Joint effects were assessed by calculating relative excess risk and attributable proportion (AP) due to interaction. RESULTS: During a median of 19.6 years of follow-up, 2090 study participants experienced an MI and 784 experienced a VTE. Among those with MI, 55 developed a subsequent VTE, yielding an overall incidence rate (IR) of VTE of 5.3 per 1000 person-years (95% confidence interval [CI]: 4.1-6.9). In the combined exposure group (MI+/Obesity+), the IR was 11.3 per 1000 person-years, and the adjusted HR indicated a 3-fold increased risk of VTE (HR 3.16, 95% CI: 1.99-4.99) compared to the reference group (MI-/Obesity-). The corresponding AP was 0.46 (95% CI: 0.17-0.74). CONCLUSIONS: The combination of MI and obesity yielded a supra-additive effect on VTE risk of which 46% of the VTE events were attributed to the interaction.

Racial and Ethnic Differences in the Association Between Classical Cardiovascular Risk Factors and Common Carotid Intima-Media Thickness: An Individual Participant Data Meta-Analysis.

Background The major risk factors for atherosclerotic cardiovascular disease differ by race or ethnicity but have largely been defined using populations of European ancestry. Despite the rising prevalence of cardiovascular disease in Africa there are few related data from African populations. Therefore, we compared the association of established cardiovascular risk factors with carotid-intima media thickness (CIMT), a subclinical marker of atherosclerosis, between African, African American, Asian, European, and Hispanic populations. Methods and Results Cross-sectional analyses of 34 025 men and women drawn from 15 cohorts in Africa, Asia, Europe, and North America were undertaken. Classical cardiovascular risk factors were assessed and CIMT measured using B-mode ultrasound. Ethnic differences in the association of established cardiovascular risk factors with CIMT were determined using a 2-stage individual participant data meta-analysis with beta coefficients expressed as a percentage using the White population as the reference group. CIMT adjusted for risk factors was the greatest among African American populations followed by Asian, European, and Hispanic populations with African populations having the lowest mean CIMT. In all racial or ethnic groups, men had higher CIMT levels compared with women. Age, sex, body mass index, and systolic blood pressure had a significant positive association with CIMT in all races and ethnicities at varying magnitudes. When compared with European populations, the association of age, sex, and systolic blood pressure with CIMT was weaker in all races and ethnicities. Smoking (beta coefficient, 0.39; 95% CI, 0.09-0.70), body mass index (beta coefficient, 0.05; 95% CI, 0.01-0.08) and glucose (beta coefficient, 0.13; 95% CI, 0.06-0.19) had the strongest positive association with CIMT in the Asian population when compared with all other racial and ethnic groups. High-density lipoprotein-cholesterol had significant protective effects in African American (beta coefficient, -0.31; 95% CI, -0.42 to -0.21) and African (beta coefficient, -0.26; 95% CI, -0.31 to -0.19) populations only. Conclusions The strength of association between established cardiovascular risk factors and CIMT differed across the racial or ethnic groups and may be due to lifestyle risk factors and genetics. These differences have implications for race- ethnicity-specific primary prevention strategies and also give insights into the differential contribution of risk factors to the pathogenesis of cardiovascular disease. The greatest burden of subclinical atherosclerosis in African American individuals warrants further investigations.

Wake-up stroke and unknown-onset stroke; occurrence and characteristics from the nationwide Norwegian Stroke Register.

Introduction: Population-based knowledge of the characteristics of wake-up stroke and unknown-onset stroke is limited. We compared occurrence and characteristics of ischaemic and haemorrhagic wake-up stroke, unknown-onset stroke and known-onset stroke in a nationwide register-based study. Patients and methods: We included patients registered in the Norwegian Stroke Register from 2012 through 2019. Age, sex, risk factors, clinical characteristics, acute stroke treatment and discharge destination were compared according to stroke type and time of onset. Results: Of the 60,320 patients included, 11,451 (19%) had wake-up stroke, 11,098 (18.4%) had unknown time of onset and 37,771 (62.6%) had known symptom onset. The proportion of haemorrhagic stroke was lower among wake-up stroke patients (1107/11,451, 9.7%, 95% CI: 9.1-10.2) than for known-onset stroke (5230/37,771, 13.8%, 95% CI: 13.5-14.2) and for unknown-onset stroke (1850/11,098, 16.7%, 95% CI: 16.0-17.4). Mild stroke (NIHSS <5) was more frequent in ischaemic wake-up stroke (5364/8308, 64.6%, 95% CI: 63.5-65.5) than in known-onset (16,417/26,746, 61.4%, 95% CI: 60.8-62.0) and unknown-onset stroke (3242/5853, 55.4%, 95% CI: 54.1-56.7), while baseline characteristics were otherwise similar to known-onset stroke. Unknown-onset stroke patients were more often female, lived alone and had more severe strokes compared to wake-up stroke and known-onset stroke patients. Unknown-onset stroke patients were more often in need of community-based health care on discharge and had a higher in-hospital mortality. Discussion and conclusions: Ischaemic wake-up strokes shared baseline characteristics with known-onset strokes, but tended to be milder. Ischaemic unknown-onset stroke patients differed significantly from wake-up stroke, emphasising the importance of considering them as separate entities.