| 1. |
- Bergström, Petra, et al.
(författare)
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Association of NFE2L2 and KEAP1 haplotypes with amyotrophic lateral sclerosis.
- 2014
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Ingår i: Amyotrophic lateral sclerosis & frontotemporal degeneration. - : Informa UK Limited. - 2167-9223 .- 2167-8421. ; 15:1-2, s. 130-137
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron syndrome influenced by oxidative stress. The transcription factor Nrf2 and its repressor Keap1 constitute an important defence system in cellular protection against oxidative stress. Here we hypothesize that common genetic variations in the genes NFE2L2 and KEAP1, encoding Nrf2 and Keap1, may influence the risk and phenotype of ALS. Five hundred and twenty-two Swedish patients with sporadic ALS (SALS) and 564 Swedish control subjects were studied. Eight tag SNPs in NFE2L2 and three tag SNPs in KEAP1 were genotyped by allelic discrimination and three functional NFE2L2 promoter SNPs were genotyped by sequencing. One NFE2L2 haplotype (GGGAC) was associated with decreased risk of SALS (OR = 0.62 per allele, p = 0.003) and one haplotype in KEAP1 (CGG) was associated with later SALS onset (+3.4 years per allele, p = 0.015). When stratified by subgroup, one haplotype in NFE2L2, GAGCAGA including three functional promoter SNPs associated with high Nrf2 protein expression, was associated with 4.0 years later disease onset per allele in subgroup ALS (p = 0.008). In conclusion, these results suggest that variations in NFE2L2 and KEAP1, encoding two central proteins in cellular oxidative stress defence, may influence SALS pathogenesis.
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| 2. |
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| 3. |
- Bjurman, Christian, 1983, et al.
(författare)
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Assessment of a multimarker strategy for prediction of mortality in older heart failure patients: a cohort study
- 2013
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 3:3
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Primarily to develop a multimarker score for prediction of 3-year mortality in older patients with decompensated heart failure (HF). DESIGN: Prospective cohort study. SETTING: Secondary care. Single centre. PATIENTS AND BIOMARKERS: 131 patients, aged >/=65 years, with decompensated HF were included. Assessment of biomarkers was performed at discharge. PRIMARY OUTCOME MEASURE: 3-year mortality. RESULTS: Mean age was 73+/-11 years; mean left ventricular ejection fraction , 43+/-14%; 53% were male. The 3-year mortality was 53.4%. The following N-terminal brain natriuretic peptide (NTproBNP) levels could optimally stratify mortality: <2000 ng/l (n=39), 30.8% mortality; 2000-8000 ng/l (n=58), 51.7% mortality; and >8000 ng/l (n=34), 82.4% mortality. However, in the 2000-8000 ng/l range, NTproBNP levels had low-prognostic capacity, based on the area under the receiver operating characteristic curve (AUC=0.53; 95% CI 0.40 to 0.67). In this group, multivariate analysis identified age, cystatin C (CysC), and troponin T (TnT) levels as independent risk factors. A risk score based on these three risk factors separated a high-risk and low-risk groups within the NTproBNP range of 2000-8000 ng/l. The score exhibited a significantly higher AUC (0.75; 95% CI 0.62 to 0.86) than NTproBNP alone (p=0.03) in this NTproBNP group and had similar prognostic capacity as NTproBNP in patients below or above this NTproBNP range (p=0.57). Net reclassification improvement and integrated discriminatory improvement in the group with NTproBNP levels between 2000 and 8000 ng/l was 54% and 23%, respectively, and in the whole cohort 22% and 11%, respectively. CONCLUSIONS: Our results suggested that, to assess risk in HF, older patients required significantly higher levels of NTproBNP than younger patients. Furthermore, a risk score that included TnT and CysC at discharge, and age could improve risk stratification for mortality in older patients with HF in particular when NTproBNP was moderately elevated.
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| 4. |
- Bjurman, Christian, 1983, et al.
(författare)
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Cystatin C in a composite risk score for mortality in patients with infective endocarditis: a cohort study
- 2012
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 2:4
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To develop a multimarker prognostic score for infective endocarditis (IE). DESIGN: Retrospective case-control. SETTING: Secondary care. Single centre. PARTICIPANTS: 125 patients with definite IE. PRIMARY OUTCOME MEASURES: 90-day and 5-year mortality. RESULTS: Mean age was 62.7+/-17 years. The 90-day and 5-year mortality was 10.4% and 33.6%, respectively. CysC levels at admission and over 20% increases in CysC levels during 2 weeks of treatment were prognostic for 90-day and 5-year mortality independent of creatinine estimated glomerular filtration rate. In multivariate analyses, CysC (OR 5.42, 95% CI 1.90 to 15.5, p=0.002) and age (OR 1.06, 95% CI 1.02 to 1.10, p=0.002) remained prognostic for 5-year mortality. NT-proBNP, TnT, C reactive protein and interleukin 6 were also linked to prognosis. A composite risk scoring system using levels of CysC, NT-proBNP, age and presence of mitral valve insufficiency was able to separate a high-risk and a low-risk group. CONCLUSIONS: CysC levels at admission and increase in CysC after 2 weeks of treatment were independent prognostic markers for both 90-day and 5-year mortality in patients with IE. A multimarker composite risk scoring system including CysC identified a high-risk group.
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| 5. |
- Bjurman, Christian, 1983, et al.
(författare)
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Small changes in Troponin T levels are common in patients with non-ST-elevation myocardial infarction and are linked to higher mortality
- 2013
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 62:14, s. 1231-1238
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To examine the extent of change in Troponin T levels in patients with non-ST-elevation myocardial infarction (NSTEMI).BACKGROUND:Changes in cardiac troponin levels are required for the diagnosis of NSTEMI, according to the new universal definition of acute myocardial infarction. A relative change of 20-230 % and an absolute change of 7- 9 ng/L have been suggested as cut-off points.METHOD:In a clinical setting, where a change in cTnT was not mandatory for the diagnosis of NSTEMI, serial samples of cTnT were measured with a high-sensitive cTnT (hs-cTnT) assay, and 37 clinical parameters were evaluated in 1178 patients with a final diagnosis of NSTEMI presenting <24h after symptom onset.RESULTS:After six hours of observation, the relative change in the hs-cTnT level remained <20 % in 26 % and the absolute change <9 ng/L in 12 % of the NSTEMI patients. A relative hs-cTnT change <20% was linked to higher long-term mortality across quartiles (p=0.002) and in multivariate analyses (HR 1.61 (1.17-2.21) p=0.004), whereas 30-day mortality was similar across quartiles of relative hs-cTnT changeCONCLUSION:Because stable hs-TnT levels are common in patients with a clinical diagnosis of NSTEMI in our hospital, a small hs-cTnT change may not be useful to exclude NSTEMI, particularly as these patients show both short-term and long-term mortality at least as high as patients with large changes in hs-cTnT.
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| 6. |
- DuttaRoy, Smita, 1971, et al.
(författare)
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The effects of age on circulating vascular markers and cardiac prognostic markers, before and after 2 months home-based high-frequency exercise training in patients with stable coronary artery disease
- 2014
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Ingår i: European Heart Journal. European Society of Cardiology, 30 August - 3 September 2014, Barcelona. - 0195-668X .- 1522-9645. ; 35:Supplement: 1
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: Vascular endothelial growth factor (VEGF) and stromal derived factor (SDF-1) play an important role in angiogenesis. Relaxin-2 (Rlx-2) has both angiogenic and vasodilatory properties, while endothelin-1 (ET-1) is a potent vasocontrictor.VEGF, SDF-1 and Rlx-2-levels have shown to be positively modulated by exercise training, while the effect of exercise on (Rlx-2) is not known. Age is a known risk factor for morbidity and mortality in coronary artery disease (CAD). We wanted to investigate how age affects levels of these vascular factors and known prognostic cardiac markers before and after high frequency exercise training (HFE), in patients with CAD. Methods: Patients with stable CAD (age 48-80 years) were randomized to HFE (aerobic exercise 70% of max, 30 minutes, 5 times/week and resistance exercise 3 times/week), performed at home for 8 weeks, or usual lifestyle (ctrl). Serum and plasma was collected from 21 controls and 24 HFE-patients and analyzed at baseline and after 8 weeks. VEGF, SDF-1, Rlx-2 and ET-1were analyzed with enzymelinked immunoadsorbent assay (ELISA). TnT and NT-pro-BNP were analyzed on Cobas e602 (Roche). Correlation was calculated using the statistical software Graph Pad Prism 6. Pearson’s r was calculated to determine correlation between the factors prior to exercise, while Spearman’s r was used for the analysis on the exercise induced effects of the HFE-group. The exercise-induced effect on cardiac biomarkers was determined by comparing % change (from baseline to 8 weeks) between HFE and Ctrl using Mann-Whitney U-test. Results: At baseline, there was a significant positive correlation between age and TnT (r=0.38, p<0.05) and a non-significant positive correlation between age and NT-proBNP (r=0.36, p=0.06), while no correlation was found between age and levels of vascular markers (VEGF r=-0,14, SDF-1 r=-0,13, ET-1 r=0,08, Rlx-2 r=0,06, p=ns for all). As we have previously shown, home-based HFE decreased VEGF (2,6+29% (ctrl) and -3,9 +13% (HFE), p<0,05), but the other studied factors were not significantly affected. We found no correlation between age and changes in cardiac markers after exercise. Conclusions: Elderly patients with stable CAD have higher levels of TnT and NT-proBNP, indicating a higher degree of underlying CAD. This may also reflect their higher mortality in CAD. HFE-training may lower VEGF in patients with stable CAD. Interestingly, there seems to be no difference in the respone response to exercise in cardiac biomarkers, between younger and older CAD patients
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| 9. |
- Hammarsten, Ola, et al.
(författare)
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Evaluation of a Sensitive Copeptin Assay for Clinical Measurement
- 2012
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Ingår i: The Open Clinical Chemistry Journal. - : Bentham Science Publishers Ltd.. - 2588-7785 .- 1874-2416. ; 5:1, s. 21-26
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: Background: Copeptin, a marker of vasopressin production, has been introduced for earlier diagnosis of acute myocardial infarction and other clinical emergencies. We evaluated the analytical performance of a new generation copeptin assay in an inter-laboratory trial. Methods: Precision, linearity range, carry-over contamination, the limit of blank and an inter-laboratory comparison trial for the copeptin US KRYPTOR assay were performed on the B·R·A·H·M·S KRYPTOR compact PLUS. Results: The intra-assay imprecision (CVs) was 12.6–2.2% and total imprecision over five days was 12.3-4.3% between 3.1 and 18.2 pmol/L. The assay had excellent linearity between 7-222 pmol/L. The limit of blank was 2.5 pmol/L and the limit of detection was 3.2 pmol/L, but was dependent on the analyte-free material used. No significant difference between sample type, such as serum or different types of plasma or reagent lots, was noted. The copeptin results remained unchanged upon five repeated freeze-thaw cycles. A set of patient samples with a mean copeptin concentration of 2.1-61 pmol/L run at two separate sites showed close correlation (r2=0.99, slope=1.01, intercept=0.35), indicating comparable results across laboratories. Conclusion: The new ultrasensitive copeptin KRYPTOR assay shows excellent inter-lab precision, opening up the possibility for international guidelines to exclude acute myocardial infarction.
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| 10. |
- Hammarsten, Ola, et al.
(författare)
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Long-time quality assessment of the Elecsys Troponin T hs assay
- 2013
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120. ; 46:12, s. 1055-1057
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Tidskriftsartikel (refereegranskat)abstract
- Recently, Roche announced a problem with the calibrators for their high sensitive cardiac troponin T (hscTnT) assay. We have monitored the performance of the assay since its introduction into clinical use in December 2009 and we're in a unique position to provide quantitative information concerning the effects of this problem. Our data document that the measured cTnT concentration in the hscTnT assay dropped by 5.8 ng/L around the 99th percentile before its recalibration in May 2012. Thus, the hscTnT levels in our hospital have been underestimated around this cut-off value since its introduction. The approach we used may be one that other laboratories should consider.
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