Finnish flow diverter study : 8 years of experience in the treatment of acutely ruptured intracranial aneurysms

Background Flow diversion of acutely ruptured intracranial aneurysms (IAs) is controversial due to high treatment-related complication rates and a lack of supporting evidence. We present clinical and radiological results of the largest series to date. Methods This is a nationwide retrospective study of acutely ruptured IAs treated with flow diverters (FDs). The primary outcome was the modified Rankin Scale (mRS) score at the last available follow-up time. Secondary outcomes were treatment-related complications and the aneurysm occlusion rate. Results 110 patients (64 females; mean age 55.7 years; range 12-82 years) with acutely ruptured IAs were treated with FDs between 2012 and 2020 in five centers. 70 acutely ruptured IAs (64%) were located in anterior circulation, and 47 acutely ruptured IAs (43%) were blister-like. A favorable functional outcome (mRS 0-2) was seen in 73% of patients (74/102). Treatment-related complications were seen in 45% of patients (n=49). Rebleeding was observed in 3 patients (3%). The data from radiological follow-ups were available for 80% of patients (n=88), and complete occlusion was seen in 90% of aneurysms (79/88). The data from clinical follow-ups were available for 93% of patients (n=102). The overall mortality rate was 18% (18/102). Conclusions FD treatment yields high occlusion for acutely ruptured IAs but is associated with a high risk of complications. Considering the high mortality rate of aneurysmal subarachnoid hemorrhage, the prevention of rebleeding is crucial. Thus, FD treatment may be justified as a last resort option.Peer reviewe

Finnish flow diverter study : 8 years of experience in the treatment of acutely ruptured intracranial aneurysms

Background Flow diversion of acutely ruptured intracranial aneurysms (IAs) is controversial due to high treatment-related complication rates and a lack of supporting evidence. We present clinical and radiological results of the largest series to date. Methods This is a nationwide retrospective study of acutely ruptured IAs treated with flow diverters (FDs). The primary outcome was the modified Rankin Scale (mRS) score at the last available follow-up time. Secondary outcomes were treatment-related complications and the aneurysm occlusion rate. Results 110 patients (64 females; mean age 55.7 years; range 12-82 years) with acutely ruptured IAs were treated with FDs between 2012 and 2020 in five centers. 70 acutely ruptured IAs (64%) were located in anterior circulation, and 47 acutely ruptured IAs (43%) were blister-like. A favorable functional outcome (mRS 0-2) was seen in 73% of patients (74/102). Treatment-related complications were seen in 45% of patients (n=49). Rebleeding was observed in 3 patients (3%). The data from radiological follow-ups were available for 80% of patients (n=88), and complete occlusion was seen in 90% of aneurysms (79/88). The data from clinical follow-ups were available for 93% of patients (n=102). The overall mortality rate was 18% (18/102). Conclusions FD treatment yields high occlusion for acutely ruptured IAs but is associated with a high risk of complications. Considering the high mortality rate of aneurysmal subarachnoid hemorrhage, the prevention of rebleeding is crucial. Thus, FD treatment may be justified as a last resort option.Peer reviewe

Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure : a Mendelian randomization study in the FINRISK cohort

Aims Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and previous studies several single-nucleotide poly-morphisms (SNPs) at the NPPA-NPPB locus associated with natriuretic peptides have been identified. We investigated the causal relationship between natriuretic peptides and AF as well as HF using a Mendelian randomization approach. Methods and results N-terminal pro B-type natriuretic peptide (NT-proBNP) (N= 6669), B-type natriuretic peptide (BNP) (N= 6674), and mid-regional pro atrial natriuretic peptide (MR-proANP) (N= 6813) were measured in the FINRISK 1997 cohort. N=30 common SNPs related to NT-proBNP, BNP, and MR-proANP were selected from studies. We performed six Mendelian randomizations for all three natriuretic peptide biomarkers and for both outcomes, AF and HF, separately. Polygenic risk scores (PRSs) based on multiple SNPs were used as genetic instrumental variable in Mendelian randomizations. Polygenic risk scores were significantly associated with the three natriuretic peptides. Polygenic risk scores were not significantly associated with incident AF nor HF. Most cardiovascular risk factors showed significant confounding percentages, but no association with PRS. A causal relation except for small causal betas is unlikely. Conclusion In our Mendelian randomization approach, we confirmed an association between common genetic variation at the NPPA-NPPB locus and natriuretic peptides. A strong causal relationship between natriuretic peptides and incidence of AF as well as HF at the community-level was ruled out. Therapeutic approaches targeting natriuretic peptides will therefore very likely work through indirect mechanisms.Peer reviewe

Combined Influence of Waist and Hip Circumference on Risk of Death in a Large Cohort of European and Australian Adults

Background - Waist circumference and hip circumference are both strongly associated with risk of death; however, their joint association has rarely been investigated. Methods and Results - The MONICA Risk, Genetics, Archiving, and Monograph (MORGAM) Project was conducted in 30 cohorts from 11 countries; 90 487 men and women, aged 30 to 74 years, predominantly white, with no history of cardiovascular disease, were recruited in 1986 to 2010 and followed up for up to 24 years. Hazard ratios were estimated using sex‐specific Cox models, stratified by cohort, with age as the time scale. Models included baseline categorical obesity measures, age, total and high‐density lipoprotein cholesterol, systolic blood pressure, antihypertensive drugs, smoking, and diabetes mellitus. A total of 9105 all‐cause deaths were recorded during a median follow‐up of 10 years. Hazard ratios for all‐cause death presented J‐ or U‐shaped associations with most obesity measures. With waist and hip circumference included in the same model, for all hip sizes, having a smaller waist was strongly associated with lower risk of death, except for men with the smallest hips. In addition, among those with smaller waists, hip size was strongly negatively associated with risk of death, with ≈20% more people identified as being at increased risk compared with waist circumference alone. Conclusions - A more complex relationship between hip circumference, waist circumference, and risk of death is revealed when both measures are considered simultaneously. This is particularly true for individuals with smaller waists, where having larger hips was protective. Considering both waist and hip circumference in the clinical setting could help to best identify those at increased risk of death

Temporal relations between atrial fibrillation and ischaemic stroke and their prognostic impact on mortality

AimsLimited 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 resultsAcross 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 P ConclusionThe 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.</p

Cardiac Troponin I and Incident Stroke in European Cohorts Insights From the BiomarCaRE Project

Background and Purpose: Stroke is a common cause of death and a leading cause of disability and morbidity. Stroke risk assessment remains a challenge, but circulating biomarkers may improve risk prediction. Controversial evidence is available on the predictive ability of troponin concentrations and the risk of stroke in the community. Furthermore, reports on the predictive value of troponin concentrations for different stroke subtypes are scarce. Methods: High-sensitivity cardiac troponin I (hsTnI) concentrations were assessed in 82 881 individuals (median age, 50.7 years; 49.7% men) free of stroke or myocardial infarction at baseline from 9 prospective European community cohorts. We used Cox proportional hazards regression to determine relative risks, followed by measures of discrimination and reclassification using 10-fold cross-validation to control for overoptimism. Follow-up was based upon linkage with national hospitalization registries and causes of death registries. Results: Over a median follow-up of 12.7 years, 3033 individuals were diagnosed with incident nonfatal or fatal stroke (n=1654 ischemic strokes, n=612 hemorrhagic strokes, and n=767 indeterminate strokes). In multivariable regression models, hsTnI concentrations were associated with overall stroke (hazard ratio per 1-SD increase, 1.15 [95% CI, 1.10-1.21]), ischemic stroke (hazard ratio, 1.14 [95% CI, 1.09-1.21]), and hemorrhagic stroke (hazard ratio, 1.10 [95% CI, 1.01-1.20]). Adding hsTnI concentrations to classical cardiovascular risk factors (C indices, 0.809, 0.840, and 0.736 for overall, ischemic, and hemorrhagic stroke, respectively) increased the C index significantly but modestly. In individuals with an intermediate 10-year risk (5%-20%), the net reclassification improvement for overall stroke was 0.038 (P=0.021). Conclusions: Elevated hsTnI concentrations are associated with an increased risk of incident stroke in the community, irrespective of stroke subtype. Adding hsTnI concentrations to classical risk factors only modestly improved estimation of 10-year risk of stroke in the overall cohort but might be of some value in individuals at an intermediate risk.</div

Quantitative and semiquantitative imaging techniques in detecting joint inflammation in patients with rheumatoid arthritis:phase-shift water-fat MRI method for fat suppression at 0.23 T, contrast-enhanced dynamic and static MRI, and quantitative ^99mTc-nanocolloid scintigraphy

Abstract The purpose of this study was to evaluate the value of 0.23T low-field magnetic resonance imaging (MRI) and nanocolloid (NC) scintigraphy in assessing joint pathology associated with rheumatoid arthritis (RA). Fat suppression methods combined with contrast media enhancement aid in distinguishing enhancing inflamed tissue from the surrounding fat, especially in the imaging of arthritic joints. The feasibility and image quality of a phase-shift water-fat MRI method for fat suppression at low-field 0.23T open configuration MR scanner was evaluated. The technique was combined with contrast-enhanced imaging to assess the conspicuity of synovial hypertrophy in the joints of 30 RA patients. Improved conspicuity and delineation of synovitis was detected with this method. However, because of a great amount of manual post processing, future development is needed to make this method more feasible. Contrast-enhanced MRI and NC scintigraphy may provide objective and quantitative information about the inflammatory activity in arthritic joints. The value of quantitative and semiquantitative measures of inflammation derived from NC scintigraphy and low-field MRI of the wrist joint of 28 early RA patients was evaluated. Furthermore, it was investigated whether these parameters have predictive value of further erosive development during two years of follow-up. Strong correlations were detected between the NC scintigraphy and MRI measures, and these parameters were associated with laboratory markers of inflammation. During the two-year follow-up, the initial MRI and NC scintigraphy measures were closely related with the progression of wrist joint erosions. Small erosive-like bone defects can occasionally be found in wrist MRI of patients without clinically overt arthritis. The prevalence of these lesions was studied in bilateral wrist MRI examinations of 31 healthy persons. Small lesions resembling erosions were detected in 14 out of 31 subjects. Altogether 24 of the 930 wrist bones evaluated showed such lesions (3%). Thus small changes resembling erosions can be found in the wrist MRI of healthy subjects; the significance of these findings must always be interpreted with reference to the clinical picture. In conclusion, early RA patients with high local inflammatory activity, as detected by NC scintigraphy and MRI are at risk of developing further bone damage. Furthermore, in the follow-up of early RA patients, if clinically sustained response is not achieved, these methods help to identify patients who need more intensive drug treatment

CHANCES cohort descriptions, assessment of the availability and quality of data, and definitions of variables

The Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES) is a collaborative large scale integrating project funded by the European Commission in 2010-2015 within the Seventh Framework Programme. The aim of CHANCES was to combine and integrate on-going cross-sectional and cohort studies in order to produce evidence on ageing-related health characteristics and determinants in Europe. One of the tasks in CHANCES was to harmonize data from the large number of cohorts for joint data analysis. The data harmonization was seen as a challenging task as the group of participating cohorts was fairly heterogeneous compared to groups of cohorts, such as MORGAM on which we had previous experience. Eventually, the harmonization of the CHANCES cohorts was clearly more successful that many of could anticipate in the beginning. This was largely facilitated by the enthusiastic young researchers of the Partners of CHANCES and the use of a Wiki server, hosted by the National Institute for Health and Welfare of Finland (THL). All CHANCES investigators from the different centres had a writing and editing access to the CHANCES Wiki space, and this was taken into wide use for colleting information from the cohorts, and preparing documents. Three groups of such documents, outlined in the beginning of the project period were descriptions of the cohorts, assessment of the availability, quality and comparability of the data from the cohorts, and definitions of variable for joint analysis. Later, the data conversion rules that were used to derive the joint CHANCES variables from the data available locally for each cohort were documented. The current publication is an HTML-export of these documents from the CHANCES Wiki space. Cohort descriptions, Data assessment and Definitions of variables are three key reference documents for those who plan and conduct analysis of the CHANCES data and interpret the results. These documents are meant to serve as key methodological references in the publications of results derived from the CHANCES data

Association of Repeatedly Measured High-Sensitivity-Assayed Troponin I with Cardiovascular Disease Events in a General Population from the MORGAM/BiomarCaRE Study

Abstract BACKGROUND High-sensitivity troponin I (hs-cTnI) concentrations reflect myocardial stress. The role of hs-cTnI in predicting long-term changes in the risk of cardiovascular disease (CVD) in general populations is not clearly defined. METHODS We investigated whether the change in 3 repeated measures of hs-cTnI collected 5 years apart in a prospective Danish study (3875 participants, initially aged 30–60 years, 51% female, disease free at baseline) improves 10-year prediction of incident CVD compared to using a single most recent hs-cTnI measurement. The change process was modelled using a joint (longitudinal and survival) model and compared to a Cox model using a single hs-cTnI measure adjusted for classic CVD risk factors, and evaluated using discrimination statistics. RESULTS Median hs-cTnI concentrations changed from 2.6 ng/L to 3.4 ng/L over 10 years. The change in hs-cTnI predicts 10-year risk of CVD (581 events); the joint model gave a hazard ratio of 1.31 per interquartile difference in hs-cTnI (95% CI 1.15–1.48) after adjustment for CVD risk factors. However, the joint model performed only marginally better (c-index improvement 0.0041, P = 0.03) than using a single hs-cTnI measure (c-index improvement 0.0052, P = 0.04) for prediction of CVD, compared to a model incorporating CVD risk factors without hs-cTnI (c-index 0.744). CONCLUSIONS The change in hs-cTnI in 5-year intervals better predicts risk of CVD in the general population, but the most recent measure of hs-cTnI, (at 10 years) is as effective in predicting CVD risk. This simplifies the use of hs-cTnI as a prognostic marker for primary prevention of CVD in the general population. </jats:sec