| 1. |
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| 2. |
- Welsh, P., et al.
(författare)
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Prognostic importance of emerging cardiac, inflammatory, and renal biomarkers in chronic heart failure patients with reduced ejection fraction and anaemia: RED-HF study
- 2018
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Ingår i: European journal of heart failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 20, s. 268-277
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To test the prognostic value of emerging biomarkers in the Reduction of Events by Darbepoetin Alfa in Heart Failure (RED-HF) trial. METHODS AND RESULTS: Circulating cardiac [N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT)], neurohumoral [mid-regional pro-adrenomedullin (MR-proADM) and copeptin], renal (cystatin C), and inflammatory [high-sensitivity C-reactive protein (hsCRP)] biomarkers were measured at randomization in 1853 participants with complete data. The relationship between these biomarkers and the primary composite endpoint of heart failure hospitalization or cardiovascular death over 28 months of follow-up (n = 834) was evaluated using Cox proportional hazards regression, the c-statistic and the net reclassification index (NRI). After adjustment, the hazard ratio (HR) for the composite outcome in the top tertile of the distribution compared to the lowest tertile for each biomarker was: NT-proBNP 3.96 (95% CI 3.16-4.98), hsTnT 3.09 (95% CI 2.47-3.88), MR-proADM 2.28 (95% CI 1.83-2.84), copeptin 1.66 (95% CI 1.35-2.04), cystatin C 1.92 (95% CI 1.55-2.37), and hsCRP 1.51 (95% CI 1.27-1.80). A basic clinical prediction model was improved on addition of each biomarker individually, most strongly by NT-proBNP (NRI +62.3%, P < 0.001), but thereafter was only improved marginally by addition of hsTnT (NRI +33.1%, P = 0.004). Further addition of biomarkers did not improve discrimination further. Findings were similar for all-cause mortality. CONCLUSION: Once NT-proBNP is included, only hsTnT moderately further improved risk stratification in this group of chronic heart failure with reduced ejection fraction patients with moderate anaemia. NT-proBNP and hsTnT far outperform other emerging biomarkers in prediction of adverse outcome.
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| 3. |
- Gullestad, L., et al.
(författare)
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Galectin-3 predicts response to statin therapy in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)
- 2012
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 33:18, s. 2290-2296
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Tidskriftsartikel (refereegranskat)abstract
- To investigate whether plasma galectin-3, a mediator of fibrogenesis, can identify patients with chronic heart failure (HF) for whom statins are effective. Patients with ischaemic systolic HF enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) were randomly assigned to 10 mg/day of rosuvastatin or placebo. Galectin-3 was measured in plasma. The primary outcome was cardiovascular death, myocardial infarction, or stroke. Of 1492 patients, 411 had a primary event during a median follow-up of 32.8 months. There was an interaction between baseline galectin-3 and rosuvastatin on the primary endpoint (P-value for interaction 0.036). Among patients with below the median plasma concentrations of galectin-3 (19.0 ng/mL), those assigned to rosuvastatin had a lower primary event rate [hazard ratio (HR) 0.65; 95 confidence interval (CI), 0.460.92; P 0.014], lower total mortality (HR 0.70; 95 CI, 0.500.98; P 0.038), and lower event rate of all-cause mortality and HF hospitalizations (HR 0.72; 95 CI, 0.540.98; P 0.017) compared with placebo, but no benefit was observed in patients with higher levels of galectin-3. The combination of concurrently low concentrations of galectin-3 and N-terminal pro-B-type natriuretic peptide (102.7 pmol/L) identified patients with a large benefit with rosuvastatin (HR 0.33; 95 CI, 0.160.67; P 0.002). Patients with systolic HF of ischaemic aetiology who have galectin-3 values 19.0 ng/mL may benefit from rosuvastatin treatment. However, the data from this post hoc analysis should be interpreted with caution since the overall results of the CORONA study did not show a significant effect on the primary endpoint.
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| 4. |
- Gullestad, L., et al.
(författare)
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The predictive value of galectin-3 for mortality and cardiovascular events in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)
- 2012
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 164:6, s. 878-883
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Tidskriftsartikel (refereegranskat)abstract
- Background Galectin-3 is a new biomarker involved in inflammation and fibrogenesis and could therefore contribute to myocardial remodeling. We examined the prognostic value of baseline galectin-3 in a substudy involving approximately 30% of participants in the CORONA study. Methods Patients (n = 1462) aged >60 years with systolic, ischemic heart failure (HF) were randomized to 10 mg/d rosuvastatin or placebo. The primary composite end point was cardiovascular death, nonfatal myocardial infarction, or stroke (n = 408). Results In the unadjusted analysis, galectin-3 was associated with all end points considered, except hospitalization for worsening of HF. In multivariable analyses, adjusting for other clinical and biochemical predictor variables, galectin-3 was significantly associated with the primary end point (hazard ratio [HR] 1.53 [1.10-2.12], P = .011) as well as all-cause (HR 1.61 [1.20-2.29], P = .002) and cardiovascular mortality (HR 1.70 [1.19-2.42], P = .003), sudden death (HR 1.83 [1.14-2.94], P = .012), and the coronary end point (HR 1.48 [1.03-2.12], P = .035). However, when N-terminal pro-brain natriuretic peptide was added to the model, galectin-3 association with the end points was markedly attenuated and no longer significant. Conclusions Galectin-3 is not associated with outcome in older patients with advanced chronic systolic HF of ischemic etiology when adjusting for N-terminal pro-brain natriuretic peptide and may therefore have limited use in the prognostication of elderly patients with systolic HF in clinical practice. (Am Heart J 2012;164:878-83.)
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| 5. |
- Jansson, AM, et al.
(författare)
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Multimarker Risk Assessment Including Osteoprotegerin and CXCL16 in Acute Coronary Syndromes.
- 2012
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Lippincott Williams & Wilkins. - 1079-5642 .- 1524-4636. ; 32:12, s. 3041-3049
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Tidskriftsartikel (refereegranskat)abstract
- Objective-: CXCL16 and osteoprotegerin (OPG) both predict mortality in acute coronary syndromes. We hypothesized that a combination of CXCL16 and OPG concentrations would add prognostic information to the Global Registry of Acute Coronary Events (GRACE) score in patients hospitalized for acute coronary syndromes. Methods and Results-: We assessed the associations between circulating OPG and soluble CXCL16 levels, obtained within 24 hours of admission (day 1) and after 3 months, and mortality, heart failure and reinfarction in 1322 patients admitted with acute coronary syndromes. After adjustment for the GRACE score, medication, diabetes mellitus and sex, the combination of high values (fourth quartile) for OPG and CXCL16 at baseline was associated with increased short-term (3 months) cardiovascular mortality (hazard ratio, 3.28; 95% CI, 1.84-5.82; P<0.0001). The combined high values were also significantly associated with the long-term (median 91 months) prognosis after adjustment, with hazard ratios 2.18 for cardiovascular mortality (95% CI, 1.62-2.92; P<0.0001), and 2.22 for heart failure (95% CI, 1.67-2.96; P<0.0001). These long-term associations remained significant after further adjustment for left ventricular ejection fraction, C-reactive protein, and pro B-type natriuretic peptide. For 635 patients with blood samples within 24 hours and at 3 months, the combination of high CXCL16 and OPG values (fourth quartile) in the early or stable phase was of a similar order associated with mortality and morbidity beyond 3 months. Conclusion-: Circulating CXCL16 and OPG are independent predictors of long-term mortality and heart failure development in acute coronary syndromes patients, even after extensive adjustments. Their combination gives more information than either marker alone.
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| 6. |
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| 7. |
- Otterdal, K, et al.
(författare)
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Rickettsia conorii is a potent complement activator in vivo and combined inhibition of complement and CD14 is required for attenuation of the cytokine response ex vivo.
- 2016
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Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 22:8, s. 734.e1-734.e6
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Tidskriftsartikel (refereegranskat)abstract
- Mediterranean spotted fever caused by Rickettsia conorii is a potentially lethal disease characterized by vascular inflammation affecting multiple organs. Studies of R. conorii so far have focused on activation of inflammatory cells and their release of inflammatory cytokines, but complement activation has not been investigated in R. conorii-infected patients. Here, we performed a comprehensive analysis of complement activation markers and the soluble cross-talking co-receptor CD14 (sCD14) in plasma from R. conorii-infected patients. The clinical data were supplemented with ex vivo experiments where the cytokine response was characterized in human whole blood stimulated with R. conorii. Complement activation markers at the level of C3 (C3bc, C3bBbP) and terminal pathway activation (sC5b-9), as well as sCD14, were markedly elevated (p <0.01 for all), and closely correlated (p <0.05 for all), in patients at admission compared with healthy matched controls. All tested markers were significantly reduced to baseline values at time of follow up. Rickettsia conorii incubated in human whole blood was shown to trigger complement activation accompanied by release of the inflammatory cytokines interleukin-1β (IL-1β), IL-6, IL-8 and tumour necrosis factor. Whereas inhibition of either C3 or CD14 had only a minor effect on released cytokines, combined inhibition of C3 and CD14 resulted in significant reduction, virtually to baseline levels, of the four cytokines (p <0.05 for all). Our data show that complement is markedly activated upon R. conorii infection and complement activation is, together with CD14, responsible for a major part of the cytokine response induced by R. conorii in human whole blood.
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| 8. |
- Vergaro, Giuseppe, et al.
(författare)
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Circulating levels and prognostic cut-offs of sST2, hs-cTnT, and NT-proBNP in women vs. men with chronic heart failure
- 2022
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Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 9:4, s. 2084-2095
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Tidskriftsartikel (refereegranskat)abstract
- Aims To define plasma concentrations, determinants, and optimal prognostic cut-offs of soluble suppression of tumorigenesis-2 (sST2), high-sensitivity cardiac troponin T (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in women and men with chronic heart failure (HF). Methods and results Individual data of patients from the Biomarkers In Heart Failure Outpatient Study (BIOS) Consortium with sST2, hs-cTnT, and NT-proBNP measured were analysed. The primary endpoint was a composite of 1 year cardiovascular death and HF hospitalization. The secondary endpoints were 5 year cardiovascular and all-cause death. The cohort included 4540 patients (age 67 +/- 12 years, left ventricular ejection fraction 33 +/- 13%, 1111 women, 25%). Women showed lower sST2 (24 vs. 27 ng/mL, P < 0.001) and hs-cTnT level (15 vs. 20 ng/L, P < 0.001), and similar concentrations of NT-proBNP (1540 vs. 1505 ng/L, P = 0.408). Although the three biomarkers were confirmed as independent predictors of outcome in both sexes, the optimal prognostic cut-off was lower in women for sST2 (28 vs. 31 ng/mL) and hs-cTnT (22 vs. 25 ng/L), while NT-proBNP cut-off was higher in women (2339 ng/L vs. 2145 ng/L). The use of sex-specific cut-offs improved risk prediction compared with the use of previously standardized prognostic cut-offs and allowed to reclassify the risk of many patients, to a greater extent in women than men, and for hs-cTnT than sST2 or NT-proBNP. Specifically, up to 18% men and up to 57% women were reclassified, by using the sex-specific cut-off of hs-cTnT for the endpoint of 5 year cardiovascular death. Conclusions In patients with chronic HF, concentrations of sST2 and hs-cTnT, but not of NT-proBNP, are lower in women. Lower sST2 and hs-cTnT and higher NT-proBNP cut-offs for risk stratification could be used in women.
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| 9. |
- Vergaro, Giuseppe, et al.
(författare)
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NT-proBNP for Risk Prediction in Heart Failure : Identification of Optimal Cutoffs Across Body Mass Index Categories
- 2021
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Ingår i: JACC. Heart failure. - : American College of Cardiology. - 2213-1779 .- 2213-1787. ; 9:9, s. 653-663
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThe goal of this study was to assess the predictive power of N-terminal pro–B-type natriuretic peptide (NT-proBNP) and the decision cutoffs in heart failure (HF) across body mass index (BMI) categories.BackgroundConcentrations of NT-proBNP predict outcome in HF. Although the influence of BMI to reduce levels of NT-proBNP is known, the impact of obesity on prognostic value remains uncertain.MethodsIndividual data from the BIOS (Biomarkers In Heart Failure Outpatient Study) consortium were analyzed. Patients with stable HF were classified as underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), and mildly (BMI 30-34.9 kg/m2), moderately (BMI 35-39.9 kg/m2), or severely (BMI ≥40 kg/m2) obese. The prognostic role of NT-proBNP was tested for the endpoints of all-cause and cardiac death.ResultsThe study population included 12,763 patients (mean age 66 ± 12 years; 25% women; mean left ventricular ejection fraction 33% ± 13%). Most patients were overweight (n = 5,176), followed by normal weight (n = 4,299), mildly obese (n = 2,157), moderately obese (n = 612), severely obese (n = 314), and underweight (n = 205). NT-proBNP inversely correlated with BMI (β = –0.174 for 1 kg/m2; P < 0.001). Adding NT-proBNP to clinical models improved risk prediction across BMI categories, with the exception of severely obese patients. The best cutoffs of NT-proBNP for 5-year all-cause death prediction were lower as BMI increased (3,785 ng/L, 2,193 ng/L, 1,554 ng/L, 1,045 ng/L, 755 ng/L, and 879 ng/L, for underweight, normal weight, overweight, and mildly, moderately, and severely obese patients, respectively) and were higher in women than in men.ConclusionsNT-proBNP maintains its independent prognostic value up to 40 kg/m2 BMI, and lower optimal risk-prediction cutoffs are observed in overweight and obese patients.
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| 10. |
- Aamodt, A. H., et al.
(författare)
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Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19
- 2021
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 268, s. 3574-3583
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Tidskriftsartikel (refereegranskat)abstract
- Objective To test the hypotheses that blood biomarkers for nervous system injury, serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. Methods Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa), NfL and GFAp. Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects. Results In total, 21% (n = 10) of the patients were admitted to an intensive care unit, and the overall mortality rate was 13% (n = 6). Non-survivors had higher serum concentrations of NfL (p < 0.001) upon admission than patients who were discharged alive both in adjusted analyses (p = 2.6 x 10(-7)) and unadjusted analyses (p = 0.001). The concentrations of NfL in non-survivors increased over repeated measurements; whereas, the concentrations in survivors were stable. The GFAp concentration was also significantly higher in non-survivors than survivors (p = 0.02). Conclusion Increased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.
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| 15. |
- Arora, S., et al.
(författare)
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The Effect of Everolimus Initiation and Calcineurin Inhibitor Elimination on Cardiac Allograft Vasculopathy in De Novo Recipients: One-Year Results of a Scandinavian Randomized Trial
- 2015
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135. ; 15:7, s. 1967-1975
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Tidskriftsartikel (refereegranskat)abstract
- Early initiation of everolimus with calcineurin inhibitor therapy has been shown to reduce the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant recipients. The effect of de novo everolimus therapy and early total elimination of calcineurin inhibitor therapy has, however, not been investigated and is relevant given the morbidity and lack of efficacy of current protocols in preventing CAV. This 12-month multicenter Scandinavian trial randomized 115 de novo heart transplant recipients to everolimus with complete calcineurin inhibitor elimination 7-11 weeks after HTx or standard cyclosporine immunosuppression. Ninety-five (83%) patients had matched intravascular ultrasound examinations at baseline and 12 months. Mean (SD) recipient age was 49.9 +/- 13.1 years. The everolimus group (n=47) demonstrated significantly reduced CAV progression as compared to the calcineurin inhibitor group (n=48) (Maximal Intimal Thickness 0.03 +/- 0.06 and 0.08 +/- 0.12mm, Percent Atheroma Volume 1.3 +/- 2.3 and 4.2 +/- 5.0%, Total Atheroma Volume 1.1 +/- 19.2mm(3) and 13.8 +/- 28.0mm(3) [all p-values0.01]). Everolimus patients also had a significantly greater decline in levels of soluble tumor necrosis factor receptor-1 as compared to the calcineurin inhibitor group (p=0.02). These preliminary results suggest that an everolimus-based CNI-free can potentially be considered in suitable de novo HTx recipients.
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| 16. |
- Arora, Satish, et al.
(författare)
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Virtual Histology Assessment of Cardiac Allograft Vasculopathy Following Introduction of Everolimus—Results of a Multicenter Trial
- 2012
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Ingår i: American Journal of Transplantation. - : Wiley-Blackwell. - 1600-6135 .- 1600-6143. ; 12:10, s. 2700-2709
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Tidskriftsartikel (refereegranskat)abstract
- In this 12-month multicenter Scandinavian study, 78 maintenance heart transplant (HTx) recipients randomized to everolimus with reduced calcineurin inhibitor (CNI) exposure or continued standard CNI-therapy underwent matched virtual histology (VH) examination to evaluate morphological progression of cardiac allograft vasculopathy (CAV). Parallel measurement of a range of inflammatory markers was also performed. A similar rate of quantitative CAV progression was observed in the everolimus (n = 30) and standard CNI group (n = 48) (plaque index 1.9 +/- 3.8% and 1.6 +/- 3.9%, respectively; p = 0.65). However, VH analysis revealed a significant increase in calcified (2.4 +/- 4.0 vs. 0.3 +/- 3.1%; p = 0.02) and necrotic component (6.5 +/- 8.5 vs. 1.1 +/- 8.6%; p = 0.01) among everolimus patients compared to controls. The increase in necrotic and calcified components was most prominent in everolimus patients with time since HTx andgt;5.1 years and was accompanied by a significant increase in levels of von Willebrand (vWF) factor (p = 0.04) and vascular cell adhesion molecule (VCAM) (p = 0.03). Conversion to everolimus and reduced CNI is associated with a significant increase in calcified and necrotic intimal components and is more prominent in patients with a longer time since HTx. A significant increase in vWF and VCAM accompanied these qualitative changes and the prognostic implication of these findings requires further investigation.
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| 21. |
- Caidahl, K, et al.
(författare)
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Osteoprotegerin: a biomarker with many faces
- 2010
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Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636. ; 30:9, s. 1684-1686
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 22. |
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| 24. |
- Gravning, J., et al.
(författare)
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Prognostic Effect of High-Sensitive Troponin T Assessment in Elderly Patients With Chronic Heart Failure Results From the CORONA Trial
- 2014
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Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 7:1, s. 96-103
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Tidskriftsartikel (refereegranskat)abstract
- Background The incremental prognostic value of high-sensitive troponin T (hs-cTnT) in heart failure (HF) beyond that of high-sensitivity C-reactive protein and amino-terminal probrain natriuretic peptide is debated. We examined the prognostic value of hs-cTnT in a subgroup of patients from the Controlled Rosuvastatin Multinational Trial in HF (CORONA) study. Methods and Results Hs-cTnT as a risk factor for the primary end point (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke; n=356), as well as all-cause mortality (n=366), cardiovascular mortality (n=299), and the composite of cardiovascular mortality and hospitalization from worsening of HF (n=465), was investigated in 1245 patients (60 years; New York Heart Association [NYHA] class II-IV, ischemic systolic HF) randomly assigned to 10 mg rosuvastatin or placebo. In multivariable analyses, adjusting for left ventricular ejection fraction, NYHA class, age, body mass index, diabetes mellitus, sex, intermittent claudication, heart rate, estimated glomerular filtration rate, apolipoprotein B/apolipoprotein A-1 ratio, amino-terminal probrain natriuretic peptide, high-sensitivity C-reactive protein, and hs-cTnT (both dichotomized according to the 99th percentile and as a continuous variable) was associated with all end points (primary end point: hazard ratio, 1.87 and 1.51, respectively, per SD change; P<0.001; all other end points: hazard ratio, 1.39-1.70). However, improved discrimination as assessed by C-statistics was only seen for the primary end point and all-cause mortality. Conclusions Elevated hs-cTnT levels provide strong and independent prognostic information in older patients with chronic ischemic HF. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00206310.
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| 30. |
- Larsson, Lisa, 1976, et al.
(författare)
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Beneficial effect on cardiac function by intravenous immunoglobulin treatment in patients with dilated cardiomyopathy is not due to neutralization of anti-receptor autoantibody
- 2004
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Ingår i: Autoimmunity. - 0891-6934. ; 37:6-7, s. 489-493
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Tidskriftsartikel (refereegranskat)abstract
- Anti-beta1-adrenoceptor (beta1AR) autoantibodies have been shown to be pathophysiologically important in idiopathic dilated cardiomyopathy (DCM). Treatment with intravenous immunoglobulin (IVIG) has shown beneficial effects in both DCM and ischemic cardiomyopathy. However, the underlying mechanism has not been clarified. In the present study, we therefore examined whether the improvement of cardiac function was due to neutralization of functional beta1AR autoantibodies by anti-idiotypic antibodies. Autoantibodies against the beta1AR was analysed in sera from patients with DCM and coronary artery disease (CAD) treated with IVIG or placebo before, 6 and 12 months. Six month after treatment, DCM patients showed increase in beta1AR autoantibodies, mostly in IgG1 and IgG2, whereas in CAD patients mostly in IgG2. No changes in beta1AR autoantibodies after 12 months were detected. In summary, our results indicate that improvement of cardiac function by IVIG is not due to neutralization of beta1AR autoantibodies.
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| 31. |
- Latini, R., et al.
(författare)
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Pentraxin-3 in chronic heart failure: the CORONA and GISSI-HF trials
- 2012
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 14:9, s. 992-999
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Tidskriftsartikel (refereegranskat)abstract
- Pentraxin-3 (PTX3) is a component of the humoral arm of innate immunity which can regulate inflammatory processes. Since the role of inflammation in the progression of chronic heart failure (HF) is debated, we investigated the prognostic value of PTX3 and the effect of a statin in two large populations of patients with HF. Plasma levels of PTX3 were measured at randomization and after 3 months in 1457 patients enrolled in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) and 1233 patients enrolled in the GISSI-Heart Failure trial (GISSI-HF). The relationships between baseline PTX3 levels or their changes over time and mortality were evaluated with multivariable Cox proportional hazard models including clinical factors, high sensitivity C-reactive protein (hsCRP), and N-terminal pro brain natriuretic peptide (NT-proBNP). PTX3 concentration [median (Q1Q3) 5.34 (3.557.64) ng/mL, n 2690] was higher in females, in older patients, and those with lower body mass index. Baseline elevated PTX3 was associated with a higher risk of all-cause mortality [759 events, hazard ratio (HR) for 1 SD increase 1.20, 95 confidence interval (CI) 1.121.30, P 0.0001], cardiovascular mortality (587 events, HR 1.27, 95 CI 1.171.38, P 0.0001), or hospitalization for worsening HF (720 events, HR 1.21, 95 CI 1.121.30, P 0.0001), and marginally improved discrimination. Three-month changes in PTX3 were associated with fatal events after adjustment for hsCRP or NT-proBNP. Rosuvastatin lowered hsCRP levels but significantly raised PTX3. In two independent clinical trials that enrolled patients with chronic HF, PTX3 was consistently associated with outcomes. The opposite effects of a statin on hsCRP and PTX3 call for further investigation. NCT00336336 (GISSI-HF), NCT00206310 (CORONA).
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| 37. |
- Nymo, S. H., et al.
(författare)
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Inflammatory cytokines in chronic heart failure: interleukin-8 is associated with adverse outcome. Results from CORONA
- 2014
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 16:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- Aim We investigated the ability of prototypical inflammatory cytokines to predict clinical outcomes in a large population of patients with chronic systolic heart failure (HF). Methods and results Serum levels of tumour necrosis factor-alpha (TNF-alpha), soluble TNF receptors type I and II (sTNF-RI and sTNF-RII), and the chemokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) were analysed in 1464 patients with chronic ischaemic systolic HF in the CORONA study, aged >= 60 years, in NYHA class II-IV, and related to the primary endpoint (n = 320), as well as any coronary event (n = 255), all-cause mortality (n = 329), cardiovascular (CV) mortality (n = 268), and the composite endpoint hospitalization from worsening heart failure (WHF) or CV mortality (n = 547). TNF-alpha, sTNF-RI, sTNF-RII, and IL-8, but not MCP-1, were independent predictors of all endpoints except the coronary endpoint in multivariable models including conventional clinical variables. After further adjustment for estimated glomerular filtration rate, the ApoB/ApoA-1 ratio, NT-proBNP, and high-sensitivity C-reactive protein, only IL-8 remained a significant predictor of all endpoints (except the coronary endpoint), while sTNF-RI remained independently associated with CV mortality. Adding IL-8 to the full model led to a significant improvement in net reclassification for all-cause mortality and CV hospitalization, but only a borderline significant improvement for the primary endpoint, CV mortality, and the composite endpoint WHF hospitalization or CV mortality. Conclusion Our study supports a relationship between IL-8 and outcomes in patients with chronic HF. However, the clinical usefulness of IL-8 as a biomarker in an unselected HF population is at present unclear.
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| 38. |
- Nymo, S. H., et al.
(författare)
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The association between neutrophil gelatinase-associated lipocalin and clinical outcome in chronic heart failure: Results from CORONA
- 2012
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 271, s. 436-443
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To study the prognostic value of neutrophil gelatinase-associated lipocalin (NGAL) in chronic heart failure (HF) of ischaemic aetiology. Background. Neutrophil gelatinase-associated lipocalin is a marker of kidney injury as well as matrix degradation and inflammation and has previously been shown to be increased in HF. We investigated whether serum NGAL levels could provide prognostic information in chronic HF. Methods. We assessed NGAL as a predictor of primary outcomes (cardiovascular death, nonfatal stroke and nonfatal myocardial infarction, n=307) and all-cause mortality (n=321), cardiovascular mortality (n=259) and hospitalization (n=647) as well as the number of hospitalizations during follow-up for all (n=1934) and CV causes (n=1204) in 1415 patients with chronic HF (≥60years, New York Heart Association class II-IV, ischaemic systolic HF) in the CORONA population, randomly assigned to 10mg rosuvastatin or placebo. Results. Multivariate analysis revealed that NGAL added significant information when adjusting for clinical variables, but was no longer significant when further adjusting for apolipoprotein A-1 (ApoA-1), glomerular filtration rate (GFR), C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). However, belonging to the highest NGAL tertile was associated with more frequent hospitalization, even after adjusting for clinical variables, GFR and ApoA-1, but not after adjusting for CRP and NT-proBNP. There was no interaction between rosuvastatin treatment and NGAL. Conclusion. Neutrophil gelatinase-associated lipocalin added no significant information to NT-proBNP and GFR in a multivariate model for primary and secondary end-points. © 2012 The Association for the Publication of the Journal of Internal Medicine.
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- Nymo, St., et al.
(författare)
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Serum neutrophil gelatinase-associated lipocalin (NGAL) concentration is independently associated with mortality in patients with acute coronary syndrome.
- 2018
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Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 262, s. 79-84
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Tidskriftsartikel (refereegranskat)abstract
- Circulating neutrophil gelatinase-associated lipocalin (NGAL) concentration increases in cardiovascular disease, but the long-term prognostic value of NGAL concentration has not been evaluated in acute coronary syndrome (ACS). We examined the association between NGAL concentration and prognosis in patients with ACS after non-ST-elevation myocardial infarction (NSTEMI) or STEMI.NGAL concentration was measured in blood from 1121 consecutive ACS patients (30% women, mean age 65years) on the first morning after admission. After adjustment for 14 variables, NGAL concentration predicted long-term (median 167months) mortality (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.10-1.61, P=0.003) for quartile (q) 4 of NGAL concentration. NGAL concentrations also predicted long-term mortality (HR=1.63, 95% CI 1.31-2.03, P<0.001, N=741) when adjusting for Global Registry of Acute Coronary Events (GRACE) score, left ventricular ejection fraction (LVEF), and pro-B-type natriuretic peptide (proBNP) and C-reactive protein (CRP) concentrations. With these adjustments, NGAL concentration predicted long-term mortality in NSTEMI patients (HR=2.02, 95% CI 1.50-2.72, P<0.001) but not in STEMI patients (HR=1.32, 95% CI 0.95-1.83, P=0.100). In all patients, the combination of NGAL concentration and GRACE score yielded an HR of 5.56 (95% CI 4.37-7.06, P<0.001) for q4/q4 for both variables.NGAL concentration in ACS is associated with long-term prognosis after adjustment for clinical confounders. Measuring circulating NGAL concentration may help to identify patients-particularly those with NSTEMI-needing closer follow-up after ACS.
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- Otterdal, Kari, et al.
(författare)
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High serum CXCL10 in Rickettsia conorii infection is endothelial cell mediated subsequent to whole blood activation.
- 2016
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Ingår i: Cytokine. - : Elsevier BV. - 1043-4666 .- 1096-0023. ; 83, s. 269-274
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The pathophysiological hallmark of Rickettsia conorii (R. conorii) infection comprises infection of endothelial cells with perivascular infiltration of T-cells and macrophages. Although interferon (IFN)-γ-induced protein 10 (IP-10)/CXCL10 is induced during vascular inflammation, data on CXCL10 in R. conorii infection is scarce.METHODS: Serum CXCL10 was analyzed in two cohorts of southern European patients with R. conorii infection using multiplex cytokine assays. The mechanism of R. conorii-induced CXCL10 release was examined ex vivo using human whole blood interacting with endothelial cells.RESULTS: (i) At admission, R. conorii infected patients had excessively increased CXCL10 levels, similar in the Italian (n=32, ∼56-fold increase vs controls) and the Spanish cohort (n=38, ∼68-fold increase vs controls), followed by a marked decrease after recovery. The massive CXCL10 increase was selective since it was not accompanied with similar changes in other cytokines. (ii) Heat-inactivated R. conorii induced a marked CXCL10 increase when whole blood and endothelial cells were co-cultured. Even plasma obtained from R. conorii-exposed whole blood induced a marked CXCL10 release from endothelial cells, comparable to the levels found in serum of R. conorii-infected patients. Bacteria alone did not induce CXCL10 production in endothelial cells, macrophages or smooth muscle cells.CONCLUSIONS: We show a massive and selective serum CXCL10 response in R. conorii-infected patients, likely reflecting release from infected endothelial cells characterized by infiltrating T cells and monocytes. The CXCL10 response could contribute to T-cell infiltration within the infected organ, but the pathologic consequences of CXCL10 in clinical R. conorii infection remain to be defined.
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- Shahini, Negar, et al.
(författare)
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The alternative complement pathway is dysregulated in patients with chronic heart failure
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- The complement system, an important arm of the innate immune system, is activated in heart failure (HF). We hypothesized that HF patients are characterized by an imbalance of alternative amplification loop components; including properdin and complement factor D and the alternative pathway inhibitor factor H. These components and the activation product, terminal complement complex (TCC), were measured in plasma from 188 HF patients and 67 age- and sex- matched healthy controls by enzyme immunoassay. Our main findings were: (i) Compared to controls, patients with HF had significantly increased levels of factor D and TCC, and decreased levels of properdin, particularly patients with advanced clinical disorder (i.e., NYHA functional class IV), (ii) Levels of factor D and properdin in HF patients were correlated with measures of systemic inflammation (i.e., C-reactive protein), neurohormonal deterioration (i.e., Nt-proBNP), cardiac function, and deteriorated diastolic function, (iii) Low levels of factor H and properdin were associated with adverse outcome in univariate analysis and for factor H, this was also seen in an adjusted model. Our results indicate that dysregulation of circulating components of the alternative pathway explain the increased degree of complement activation and is related to disease severity in HF patients.
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