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1.
  • Börschel, Christin S., et al. (författare)
  • Risk prediction of atrial fibrillation and its complications in the community using hs troponin I
  • 2023
  • Ingår i: European Journal of Clinical Investigation. - : John Wiley & Sons. - 0014-2972 .- 1365-2362. ; 53:5
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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2.
  • Camen, Stephan, et al. (författare)
  • Cardiac Troponin I and Incident Stroke in European Cohorts : Insights From the BiomarCaRE Project
  • 2020
  • Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 51:9, s. 2770-2777
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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3.
  • Camen, Stephan, et al. (författare)
  • Risk Factors, Subsequent Disease Onset, and Prognostic Impact of Myocardial Infarction and Atrial Fibrillation
  • 2022
  • Ingår i: Journal of the American Heart Association. - : American Heart Association. - 2047-9980 .- 2047-9980. ; 11:7
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Although myocardial infarction (MI) and atrial fibrillation (AF) are frequent comorbidities and share common cardiovascular risk factors, the direction and strength of the association of the risk factors with disease onset, subsequent disease incidence, and mortality are not completely understood.METHODS AND RESULTS: In pooled multivariable Cox regression analyses, we examined temporal relations of disease onset and identified predictors of MI, AF, and all-cause mortality in 108 363 individuals (median age, 46.0 years; 48.2% men) free of MI and AF at baseline from 6 European population-based cohorts. During a maximum follow-up of 10.0 years, 3558 (3.3%) individuals were diagnosed exclusively with MI, 1922 (1.8%) with AF but no MI, and 491 (0.5%) individuals developed both MI and AF. Association of sex, systolic blood pressure, antihypertensive treatment, and diabetes appeared to be stronger with incident MI than with AF, whereas increasing age and body mass index showed a higher risk for incident AF. Total cholesterol and daily smoking were significantly related to incident MI but not AF. Combined population attributable fraction of cardiovascular risk factors was >70% for incident MI, whereas it was only 27% for AF. Subsequent MI after AF (hazard ratio [HR], 1.68; 95% CI, 1.03–2.74) and subsequent AF after MI (HR, 1.75; 95% CI, 1.31–2.34) both significantly increased overall mortality risk.CONCLUSIONS: We observed different associations of cardiovascular risk factors with both diseases indicating distinct pathophysiological pathways. Subsequent diagnoses of MI and AF significantly increased mortality risk.
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4.
  • Camen, Stephan, et al. (författare)
  • Temporal relations between atrial fibrillation and ischaemic stroke and their prognostic impact on mortality
  • 2020
  • Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 22:4, s. 522-529
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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5.
  • Cameron, Adrian J., et al. (författare)
  • Combined Influence of Waist and Hip Circumference on Risk of Death in a Large Cohort of European and Australian Adults
  • 2020
  • Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980 .- 2047-9980. ; 9:13
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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6.
  • Chadalavada, Sucharitha, et al. (författare)
  • Diabetes and heart failure associations in women and men : Results from the MORGAM consortium
  • 2023
  • Ingår i: Frontiers in Cardiovascular Medicine. - 2297-055X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Diabetes and its cardiovascular complications are a growing concern worldwide. Recently, some studies have demonstrated that relative risk of heart failure (HF) is higher in women with type 1 diabetes (T1DM) than in men. This study aims to validate these findings in cohorts representing five countries across Europe.Methods: This study includes 88,559 (51.8% women) participants, 3,281 (46.3% women) of whom had diabetes at baseline. Survival analysis was performed with the outcomes of interest being death and HF with a follow-up time of 12 years. Sub-group analysis according to sex and type of diabetes was also performed for the HF outcome.Results: 6,460 deaths were recorded, of which 567 were amongst those with diabetes. Additionally, HF was diagnosed in 2,772 individuals (446 with diabetes). A multivariable Cox proportional hazard analysis showed that there was an increased risk of death and HF (hazard ratio (HR) of 1.73 [1.58–1.89] and 2.12 [1.91–2.36], respectively) when comparing those with diabetes and those without. The HR for HF was 6.72 [2.75–16.41] for women with T1DM vs. 5.80 [2.72–12.37] for men with T1DM, but the interaction term for sex differences was insignificant (p for interaction 0.45). There was no significant difference in the relative risk of HF between men and women when both types of diabetes were combined (HR 2.22 [1.93–2.54] vs. 1.99 [1.67–2.38] respectively, p for interaction 0.80).Conclusion: Diabetes is associated with increased risks of death and heart failure, and there was no difference in relative risk according to sex.
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7.
  • Csengeri, Dora, et al. (författare)
  • Alcohol consumption, cardiac biomarkers, and risk of atrial fibrillation and adverse outcomes
  • 2021
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:12, s. 1170-1177
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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8.
  • Di Castelnuovo, Augusto, et al. (författare)
  • NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) and the Risk of Stroke Results From the BiomarCaRE Consortium
  • 2019
  • Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 50:3, s. 610-617
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose: NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a risk factor for atrial fibrillation and a marker of cardiac function used in the detection of heart failure. Given the link between cardiac dysfunction and stroke, NT-proBNP is a candidate marker of stroke risk. Our aim was to evaluate the association of NT-proBNP with stroke and to determine the predictive value beyond a panel of established risk factors. Methods: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe-Consortium, we analyzed data of 58 173 participants (50% men; mean age 52 y) free of stroke from 6 community-based cohorts. NT-proBNP measurements were performed in the central Biomarkers for Cardiovascular Risk Assessment in Europe laboratory. The outcomes considered were total stroke and subtypes of stroke (ischemic/hemorrhagic). Results: During a median follow-up time of 7.9 years, we observed 1550 stroke events (1176 ischemic). Increasing quarters of the NT-proBNP distribution were associated with increasing risk of stroke (P for trend < 0.0001; multivariable Cox regression analysis adjusted for risk factors and cardiac diseases). Individuals in the highest NT-proBNP quarter (NTproBNP > 82.2 pg/mL) had 2-fold (95% CI, 75%-151%) greater risk of stroke than individuals in the lowest quarter (NTproBNP < 20.4 pg/mL). The association remained unchanged when adjusted for interim coronary events during followup, and though it was somewhat heterogeneous across cohorts, it was highly homogenous according to cardiovascular risk profile or subtypes of stroke. The addition of NT-proBNP to a reference model increased the C-index discrimination measure by 0.006 (P=0.0005), yielded a categorical net reclassification improvement of 2.0% in events and 1.4% in nonevents and an integrated discrimination improvement of 0.007. Conclusions: In European individuals free of stroke, levels of NT-proBNP are positively associated with risk of ischemic and hemorrhagic stroke, independently from several other risk factors and conditions. The addition of NT-proBNP to variables of established risk scores improves prediction of stroke, with a medium effect size.
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9.
  • Haller, Paul M., et al. (författare)
  • Biomarker-based prediction of fatal and non-fatal cardiovascular outcomes in individuals with diabetes mellitus
  • 2023
  • Ingår i: European Journal of Preventive Cardiology. - 2047-4873 .- 2047-4881. ; 30:12, s. 1218-1226
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: The role of biomarkers in predicting cardiovascular outcomes in high-risk individuals is not well established. We aimed to investigate benefits of adding biomarkers to cardiovascular risk assessment in individuals with and without diabetes. 'METHODS AND RESULTS: We used individual-level data of 95 292 individuals of the European population harmonized in the Biomarker for Cardiovascular Risk Assessment across Europe consortium and investigated the prognostic ability of high-sensitivity cardiac troponin I (hs-cTnI), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP). Cox-regression models were used to determine adjusted hazard ratios of diabetes and log-transformed biomarkers for fatal and non-fatal cardiovascular events. Models were compared using the likelihood ratio test. Stratification by specific biomarker cut-offs was performed for crude time-to-event analysis using Kaplan-Meier plots. Overall, 6090 (6.4%) individuals had diabetes at baseline, median follow-up was 9.9 years. Adjusting for classical risk factors and biomarkers, diabetes [HR 2.11 (95% CI 1.92, 2.32)], and all biomarkers (HR per interquartile range hs-cTnI 1.08 [95% CI 1.04, 1.12]; NT-proBNP 1.44 [95% CI 1.37, 1.53]; hs-CRP 1.27 [95% CI 1.21, 1.33]) were independently associated with cardiovascular events. Specific cut-offs for each biomarker identified a high-risk group of individuals with diabetes losing a median of 15.5 years of life compared to diabetics without elevated biomarkers. Addition of biomarkers to the Cox-model significantly improved the prediction of outcomes (likelihood ratio test for nested models P < 0.001), accompanied by an increase in the c-index (increase to 0.81).CONCLUSION: Biomarkers improve cardiovascular risk prediction in individuals with and without diabetes and facilitate the identification of individuals with diabetes at highest risk for cardiovascular events.
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10.
  • Magnussen, Christina, et al. (författare)
  • Sex Differences and Similarities in Atrial Fibrillation Epidemiology, Risk Factors, and Mortality in Community Cohorts Results From the BiomarCaRE Consortium (Biomarker for Cardiovascular Risk Assessment in Europe)
  • 2017
  • Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 136:17, s. 1588-1597
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Atrial fibrillation (AF) is a common cardiac disease in aging populations with high comorbidity and mortality. Sex differences in AF epidemiology are insufficiently understood.Methods: In N=79 793 individuals without AF diagnosis at baseline (median age, 49.6 years; age range, 24.1–97.6 years; 51.7% women) from 4 community-based European studies (FINRISK, DanMONICA, Moli-sani Northern Sweden) of the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), we examined AF incidence, its association with mortality, common risk factors, biomarkers, and prevalent cardiovascular disease, and their attributable risk by sex. Median follow-up time was 12.6 (to a maximum of 28.2) years.Results: Fewer AF cases were observed in women (N=1796; 4.4%), than in men (N=2465; 6.4%). Cardiovascular risk factor distribution and lipid profile at baseline were less beneficial in men than in women, and cardiovascular disease was more prevalent in men. Cumulative incidence increased markedly after the age of 50 years in men and after 60 years in women. The lifetime risk was similar (>30%) for both sexes. Subjects with incident AF had a 3.5-fold risk of death in comparison with those without AF. Multivariable-adjusted models showed sex differences for the association of body mass index and AF (hazard ratio per standard deviation increase, 1.18; 95% confidence interval [CI], 1.12–1.23 in women versus 1.31; 95% CI 1.25–1.38 in men; interaction P value of 0.001). Total cholesterol was inversely associated with incident AF with a greater risk reduction in women (hazard ratio per SD, 0.86; 95% CI, 0.81–0.90 versus 0.92; 95% CI, 0.88–0.97 in men; interaction P value of 0.023). No sex differences were seen for C-reactive protein and N-terminal pro B-type natriuretic peptide. The population-attributable risk of all risk factors combined was 41.9% in women and 46.0% in men. About 20% of the risk was observed for body mass index.Conclusions: Lifetime risk of AF was high, and AF was strongly associated with increased mortality both in women and men. Body mass index explained the largest proportion of AF risk. Observed sex differences in the association of body mass index and total cholesterol with AF need to be evaluated for underlying pathophysiology and relevance to sex-specific prevention strategies.
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