25 research outputs found
Scandinavian society for the study of diabetes Abstracts Seventh Meeting
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46039/1/125_2005_Article_BF01219478.pd
Genetic variation of platelet glycoprotein VI and the risk of venous thromboembolism
Clinical epidemiolog
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Discovery of novel plasma biomarkers for future incident venous thromboembolism by untargeted synchronous precursor selection mass spectrometry proteomics
Essentials Discovery of predictive biomarkers of venous thromboembolism (VTE) may aid risk stratification. A case-control study where plasma was sampled before the occurrence of VTE was established. We generated untargeted plasma proteomic profiles of 200 individuals by use of mass spectrometry. Assessment of the biomarker potential of 501 proteins yielded 46 biomarker candidates.AbstractBackground Prophylactic anticoagulant treatment may substantially reduce the incidence of venous thromboembolism (VTE) but entails considerable risk of severe bleeding. Identification of individuals at high risk of VTE through the use of predictive biomarkers is desirable in order to achieve a favorable benefit-to-harm ratio. Objective We aimed to identify predictive protein biomarker candidates of VTE. Methods We performed a case-control study of 200 individuals that participated in the Tromsø Study, a population-based cohort, where blood samples were collected before the VTE events occurred. Untargeted tandem mass tag-synchronous precursor selection-mass spectrometry (TMT-SPS-MS3)-based proteomic profiling was used to study the plasma proteomes of each individual. Results Of the 501 proteins detected in a sufficient number of samples to allow multivariate analysis, 46 proteins were associated with VTE case-control status with P-values below the 0.05 significance threshold. The strongest predictive biomarker candidates, assessed by statistical significance, were transthyretin, vitamin K-dependent protein Z and protein/nucleic acid deglycase DJ-1. Conclusions Our untargeted approach of plasma proteome profiling revealed novel predictive biomarker candidates of VTE and confirmed previously reported candidates, thereby providing conceptual support for the validity of the study. A larger nested case-control study will be conducted to validate our findings
Impact of Chronic Inflammation, Assessed by hs-CRP, on the Association between Red Cell Distribution Width and Arterial Cardiovascular Disease: The Tromsø Study
Red cell distribution width (RDW), a measure of variability in size of circulating
erythrocytes, is associated with arterial cardiovascular disease (CVD), but the
underlying mechanism remains unclear. We aimed to investigate the impact of
chronic inflammation as measured by high sensitivity CRP (hs-CRP) on this
relationship, and explore whether RDW could be a mediator in the causal pathway
between inflammation and arterial CVD. Baseline characteristics, including RDW and
hs-CRP were obtained from 5,765 individuals attending a population-based cohort
study. We followed participants from inclusion in the fourth survey of the Tromsø
Study (1994/95) until December 31st 2012. Multivariable Cox-regression models were
used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for incident
myocardial infarction (MI) and ischemic stroke across quintiles of hs-CRP and RDW.
Subjects with hs-CRP in the highest quintile had 44% higher risk of MI (HR: 1.44,
95% CI 1.14-1.80), and 64% higher risk of ischemic stroke (HR: 1.64, 95% CI 1.20-
2.24) compared to subjects in the lowest quintile. RDW mediated 7.2% (95% CI 4.0-
30.8%) of the association between hs-CRP and ischemic stroke. Subjects with RDW
in the highest quintile had 22% higher risk of MI (HR: 1.22, 95% CI 0.98-1.54) and
44% higher risk of ischemic stroke (HR: 1.44, 95% CI 1.06-1.97) compared to
subjects in the lowest quintile. These risk estimates were slightly attenuated after
adjustments for hs-CRP. Our findings suggest that chronic inflammation is not a
primary mechanism underlying the relationship between RDW and arterial CVD
The Role of Stroke as a Trigger for Incident Venous Thromboembolism: Results from a Population-based Case-Crossover Study
Stroke is associated with a short-term increased risk of subsequent venous thromboembolism (VTE). It is unclear to what extent this association is mediated by strokerelated complications that are potential triggers for VTE, such as immobilization and
infection. We aimed to investigate the role of acute stroke as a trigger for incident VTE
while taking other concomitant VTE triggers into account. We conducted a populationbased case-crossover study with 707 VTE patients. Triggers were registered during the
90 days before a VTE event (hazard period) and in four preceding 90-day control
periods. Conditional logistic regression was used to estimate odds ratios with 95%
confidence intervals (CIs) for VTE according to triggers. Stroke was registered in 30 of
the 707 (4.2%) hazard periods and in 6 of the 2,828 (0.2%) control periods, resulting in a
high risk of VTE, with odds ratios of 20.0 (95% CI: 8.3–48.1). After adjustments for
immobilization and infection, odds ratios for VTE conferred by stroke were attenuated
to 6.0 (95% CI: 1.6–22.1), and further to 4.0 (95% CI: 1.1–14.2) when other triggers
(major surgery, red blood cell transfusion, trauma, and central venous catheter) were
added to the regression model. A mediation analysis revealed that 67.8% of the total
effect of stroke on VTE risk could be mediated through immobilization and infection.
Analyses restricted to ischemic stroke yielded similar results. In conclusion, acute
stroke was a trigger for VTE, and the association between stroke and VTE risk appeared
to be largely mediated by immobilization and infection
Atherosclerotic risk factors and risk of myocardial infarction and venous thromboembolism; Time-fixed versus time-varying analyses. The Tromsø Study
Background: Single measurements of modifiable risk factors may underestimate associations with outcomes in cohorts. We aimed to compare risk estimates of myocardial infarction (MI) and
venous thromboembolism (VTE) by atherosclerotic risk factors during long follow-up using
time-fixed analyses without and with correction for regression dilution and time-varying
analyses.
Methods: The study included 5970 subjects enrolled in the fourth survey of the Tromsø Study (1994/95). Blood pressure, lipid levels, body mass index (BMI), diabetes and smoking status were
measured at baseline, and subjects still alive at the fifth (2001/02, n = 5179) and sixth
(2007/08, n = 4391) survey were re-measured. Incident events of MI (n = 714) and VTE (n =
214) were recorded until December 2010. Time-fixed and time-varying Cox regression models
were used to estimate hazard ratios (HR) for MI and VTE adjusted for age and sex.
Results: Variations in BMI, blood pressure and lipid levels were small, and did not alter the risk estimates
when time-varying analyses were compared to time-fixed analyses. For MI, variables
that changed considerably over time yielded the greatest changes in risk estimates (HR for
smoking changed from 1.80 (95% CI 1.55–2.10) to 2.08 (95% CI 1.78–2.42)). For VTE, only
BMI was associated with increased risk in both time-fixed and time-varying analysis, but the risk estimates weakened in the time-varying analysis. Correction of time-fixed HRs with
Rosner´s method tended to overestimate risk estimates compared to time-varying analysis.<p