| 1. |
- James, Stefan K, et al.
(författare)
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An acute inflammatory reaction induced by myocardial damage is superimposed on a chronic inflammation in unstable coronary artery disease
- 2005
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 149:4, s. 619-626
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Inflammation plays an important role in unstable coronary artery disease (CAD). We assessed the kinetics of inflammatory markers from symptom onset in patients with unstable CAD and their relation to myocardial damage.METHODS:Serial measurements of inflammatory mediators were performed in consecutive patients with unstable CAD enrolled at selected sites in the FRISC II (n = 558) and the GUSTO IV (n = 404) trials. The time from symptom onset was calculated for every serum sample (total 4400 samples).RESULTS:Median levels of interleukin 6 and C-reactive protein reached their peaks at 36 to 42 hours and at 48 to 54 hours, respectively, from symptom onset and returned to early postsymptom levels within 6 weeks. The early increase occurred almost exclusively in patients with baseline troponin T elevation (>0.01 microg/L). In contrast, median levels of fibrinogen increased continuously up to 120 hours after symptom onset, independently of myocardial damage. At 6 months, fibrinogen levels were still higher than in the early phase after symptom onset. The median levels of interleukin 6, C-reactive protein, and fibrinogen were still higher at 6 months than in healthy controls matched for age and sex to a population with unstable CAD.CONCLUSIONS:An early acute inflammatory reaction induced by myocardial damage seems to be superimposed on a chronic inflammatory condition, both of which might influence long-term outcome in unstable CAD.
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| 2. |
- James, Stefan, 1964-, et al.
(författare)
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The antibody configurations of cardiac troponin I assays may determine their clinical performance
- 2006
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 52:5, s. 832-837
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous studies have shown superior clinical performance of the cardiac troponin I (cTnI) assay from Beckman-Coulter Diagnostics. This assay had a unique combination of monoclonal antibodies with 2 monoclonal antibodies directed against epitopes near the NH(2) terminus of the heart-specific region of troponin I. The approach has been adopted by the new cTnI assay from Abbott Diagnostics. The aim of our study was to investigate whether this approach affects the clinical performance of cTnI assays. METHODS: Cardiac troponin concentrations were measured in a random sample of patients with unstable coronary artery disease included in the GUSTO IV trial (n = 696) by the AccuTnI (Beckman-Coulter Diagnostics), Architect cTnI (Abbott Diagnostics), Immulite 2500 cTnI (Diagnostics Products Corporation), and Elecsys 2010 cTnT (Roche Diagnostics) assays and related to the 1-year mortality. The primary cutoff concentrations were based on the 99th percentile upper reference limits and an imprecision (CV) < or =10%. RESULTS: The sensitivities of the AccuTnI and Architect cTnI assays in identifying patients who died within 1 year were equal and were significantly higher (P <0.05) than those of the Immulite 2500 cTnI and the Elecsys cTnT assays. The concordance between the AccuTnI and Architect cTnI assays was 97%, but concordances between the Architect cTnI and the Elecsys cTnT assays were 89%-92% with more at-risk patients (P <0.01 to P <0.001) identified by the Architect cTnI assay. CONCLUSIONS: The Architect cTnI assay has clinical performance similar to that of the AccuTnI, probably as a result of the inclusion of a monoclonal antibody against troponin I epitope 41-49 in the assay
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| 3. |
- Johnston, Nina, et al.
(författare)
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Early invasive treatment benefits patients with renal dysfunction in unstable coronary artery disease
- 2006
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 152:6, s. 1052-1058
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Tidskriftsartikel (refereegranskat)abstract
- Background: Few studies have investigated the effects of an early revascularization in relation to renal function in patients with unstable coronary artery disease (CAD). Methods: Patients (n = 2457) with unstable CAD randomized to a noninvasive or invasive treatment strategy in the Fast Revascularisation during InStability in Coronary artery disease (FRISC-II) trial were stratified according to tertiles of creatinine clearance (CrCl < 69 mL/min, CrCl 69-90 mL/min, CrCl > 90 mL/min) and followed for 2 years regarding death and/or myocardial infarction (MI). Results: In the noninvasive cohort, the rate of death or MI at 2 years was 22.4% at CrCl < 69 mL/min, 14.6% at CrCl 60-90 mL/min, and 11.6% at CrCl > 90 mL/min. In the invasive cohort, the rate of death or MI was reduced to 14.6% (P = .003) at CrCl < 69 mL/min and to 9.9% (P = .048) at CrCl 69 to 90 mL/min, but no significant reduction (11.2%) at CrCl > 90 mL/min. In a logistic regression analysis adjusting for other important covariables, CrCl < 69 mL/min remained independently associated with the risk of the combined end point in the noninvasively treated group (odds ratio, 1.96; 95% confidence interval, 1.12-3.42) but not in the invasively treated group (odds ratio, 1.09; 95% confidence interval, 0.56-2.14). When the interaction term for treatment strategy and CrCl group was included in the analysis, the interaction between treatment strategy and CrCl <90 mL/min was independently associated with the risk of future MI (P = .006). Conclusion: In unstable CAD, an early invasive treatment strategy reduces the long-term risk of future death and MI in patients with mildly to moderately reduced CrCl.
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| 4. |
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| 5. |
- Johnston, Nina, et al.
(författare)
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Improved identification of patients with coronary artery disease by the use of new lipid and lipoprotein biomarkers
- 2006
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 97:5, s. 640-5
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Tidskriftsartikel (refereegranskat)abstract
- Increasing attention is being directed toward new lipid and lipoprotein biomarkers as risk factors for coronary artery disease, although limited information is available on the diagnostic accuracy of these new biomarkers for the identification of patients with coronary artery disease. In the present study, levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, lipoprotein-associated phospholipase A2 (Lp-PLA2), and oxidized LDL/HDL cholesterol were determined in 431 apparently healthy men and women without clinical evidence of coronary artery disease who were matched for age and gender with 490 men and women with coronary artery disease who participated in the Second Fragmin and Fast Revascularization During Instability in Coronary Artery Disease (FRISC-II) trial. Diagnostic accuracy was determined by receiver-operating characteristic curve analysis by measuring the area under the curve. The diagnostic accuracies of each lipid or lipoprotein biomarker (in descending order of area under the curve) were 0.867 for oxidized LDL/HDL cholesterol (95% confidence interval [CI] 0.844 to 0.890), 0.826 for oxidized LDL (95% CI 0.800 to 0.852), 0.775 for 1/HDL cholesterol (95% CI 0.745 to 0.805), 0.764 for total/HDL cholesterol (95% CI 0.733 to 0.795), 0.631 for triglycerides (95% CI 0.594 to 0.667), 0.597 for Lp-PLA2 (95% CI 0.558 to 0.615), 0.577 for LDL cholesterol (95% CI 0.539 to 0.615), and 0.520 for total cholesterol (95% CI 0.482 to 0.537). In conclusion, these findings indicate that the ratio of oxidized LDL to HDL cholesterol was a more potent biomarker for discriminating between subjects with and without coronary artery disease than traditionally measured lipids and lipoproteins and Lp-PLA2.
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| 6. |
- Johnston, Nina, 1961-
(författare)
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Low-Density Lipoprotein Oxidation and Renal Dysfunction : New Markers of Poor Prognosis in Patients with Unstable Coronary Artery Disease
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In patients with unstable coronary artery disease (CAD) biochemical markers are emerging as useful tools in clinical management. In this thesis we studied the use of markers of low-density lipoprotein (LDL) oxidation and renal function.Our study populations consisted of unstable CAD patients included in the Fast Revascularisation during Instability in Coronary artery disease (FRISC)-II trial and healthy controls. Patients were followed for 2 years regarding death and myocardial infarction (MI).Using receiver operating characteristic curve analysis, we found that oxidized low-density lipoprotein (OxLDL), especially when combined with high-density lipoprotein, compared to traditionally measured lipids/lipoproteins, and a new lipoprotein marker, lipoprotein associated-phospholipase A2, was better at discriminating between healthy controls and CAD patients. In patients, OxLDL was found to be an independent prognostic marker associated with an increased risk of MI, of particular use in patients with no evidence of myocardial necrosis. In our study on the effects of an early invasive treatment strategy in unstable CAD patients with mild to moderate renal dysfunction (i.e. creatinine clearance <90mL/min) we found that in patients randomized to invasive treatment, the rates of death/MI and MI alone were significantly lower than in patients randomized to non-invasive treatment. In patients treated invasively, no detrimental effects were seen on renal function at follow-up at 6 months. In healthy controls, we investigated new markers of renal (cystatin C) and cardio-renal function (N-terminal probrain natriuretic peptide, [NT-proBNP]) regarding reference levels and physiological determinants. We found that cystatin C is influenced by age whereas NT-proBNP is influenced by age and gender.Our studies suggest that OxLDL and renal dysfunction are associated with a poor prognosis in unstable CAD patients and that these markers demonstrate potential for clinical use. In the search for new markers related to renal function we have contributed with reference levels of cystatin C and NT-proBNP.
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| 7. |
- Johnston, Nina, et al.
(författare)
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Oxidized low-density lipoprotein as a predictor of outcome in patients with unstable coronary artery disease
- 2006
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 113:2, s. 167-173
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prognostic value of circulating oxidized low-density lipoprotein (OxLDL) in patients with unstable coronary artery disease (CAD) is unknown. Methods: Plasma levels of OxLDL were measured in 433 patients with unstable CAD included in FRISC-II (Fragmin and fast Revascularisation in Instability in Coronary artery disease trial) and in 233 of these patients at follow-up 4-7 weeks later. Mortality and myocardial infarction (MI) at 2 years of follow-up was related to above (n 226) or below (n =207) the median level of OxLDL (76 U/L) at study entry. Results: After adjustment for other well-known predictors of risk, OxLDL levels > 76 U/L were associated with a higher risk for recurrent MI (Odds Ratio [95% CI]: 1.90 [1.05-3.39]). When patients were divided according to troponin T (TnT) status, the prognostic value of OxLDL was most evident in the TnT negative group with a risk of MI of 16.9% in patients with elevated OxLDL compared to 1.7% (p = 0.004) in those without. No association was found between levels of OxLDL and mortality. At follow-up levels of OxLDL were similar to levels during the acute phase unless patients were treated with statins in which levels were significantly lower. Conclusions: Elevated levels of OxLDL may identify patients with unstable CAD, at increased risk for future MI independent of other risk variables, particularly those without evidence of myocardial damage. OxLDL levels appear to be similar in patients during the unstable and stable phase of CAD unless statin therapy is initiated.
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| 8. |
- Kempf, Tibor, et al.
(författare)
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Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay
- 2007
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 53:2, s. 284-291
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Growth-differentiation factor 15 (GDF15) is a member of the transforming growth factor beta (TGF-beta) cytokine superfamily. There has been increasing interest in using circulating GDF15 as a biomarker in patients, for example those with cardiovascular disease. METHODS: We developed an IRMA that uses a polyclonal, affinity chromatography-purified goat antihuman GDF15 IgG antibody, assessed the preanalytic characteristics of GDF15, and determined circulating GDF15 concentrations in 429 apparently healthy elderly individuals and 153 patients with chronic heart failure (CHF). RESULTS: The assay had a detection limit of 20 ng/L, an intraassay imprecision of < or =10.6%, and an interassay imprecision of < or =12.2%. Specificity was demonstrated with size-exclusion chromatography, parallel measurements with polyclonal and monoclonal anti-GDF15 antibody, and lack of cross-reactivity with TGF-beta. The assay was not appreciably influenced by the anticoagulant matrix or unrelated biological substances. GDF15 was stable at room temperature for 48 h and resistant to 4 freeze-thaw cycles. Apparently healthy, elderly individuals presented with a median GDF15 concentration of 762 ng/L (25th-75th percentiles, 600-959 ng/L). GDF15 concentrations were associated with age and with cystatin C and C-reactive protein concentrations. CHF patients had increased GDF15 concentrations that were closely related to disease severity. CONCLUSION: The IRMA can detect GDF15 in human serum and plasma with excellent sensitivity and specificity. The reference limits and confounding variables defined for apparently healthy elderly individuals and the favorable preanalytic characteristics of GDF15 are expected to facilitate future studies of GDF15 as a biomarker in various disease settings, including CHF.
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| 9. |
- Lindahl, Bertil, et al.
(författare)
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Serial analyses of N-terminal pro-B-type natriuretic peptide in patients with non-ST-segment elevation acute coronary syndromes : a Fragmin and fast Revascularisation during In Stability in Coronary artery disease (FRISC)-II substudy
- 2005
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 45:4, s. 533-541
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:The aim of this research was to describe N-terminal part of the pro-B-type natriuretic peptide (NT-proBNP) levels over time in non-ST-segment elevation acute coronary syndromes (NSTEACS), to elucidate factors associated with changes of NT-proBNP levels, and to examine association with long-term mortality.BACKGROUND:The NT-proBNP levels are associated with mortality. Long-term temporal changes of NT-proBNP levels and their relation to other factors have not been examined.METHODS:The NT-proBNP was analyzed at randomization and at 48 h, after 6 weeks, 3 and 6 months in NSTEACS patients enrolled in the Fragmin and fast Revascularisation during InStability in Coronary artery disease (FRISC)-II trial. The NT-proB-type natriuretic peptide was analyzed at least three time points in 1,216 patients.RESULTS:The median NT-proBNP level, which at randomization was 529 ng/l, decreased throughout the whole sampling period to 238 ng/l at six months. Elevated troponin T, C-reactive protein, and female gender were associated with higher reduction rates, and high age, diabetes, previous myocardial infarction, treatment with diuretics, and nitrates on admission with lower reduction rates. At each time point, the NT-proBNP level was predictive of the two-year mortality. However, the adjusted odds ratio increased for each time point.CONCLUSIONS:The initial rise of NT-proBNP in NSTEACS is mainly reversible. Factors associated with less reversibility are related to chronically impaired left ventricular function, and factors associated with greater reversibility are related to the acute myocardial damage. The NT-proBNP level measured during a chronic, relatively stable phase is a better predictor of mortality than during an acute unstable phase. The clinical setting and timing of measurement will be important to consider when using NT-proBNP for risk assessment.
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| 10. |
- Mälarstig, Anders, et al.
(författare)
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Genetic variations in the tissue factor gene are associated with clinical outcome in acute coronary syndrome and expression levels in human monocytes
- 2005
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 25:12, s. 2667-2672
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Tissue factor (TF) has, among other factors, a prominent role in acute coronary syndrome (ACS). Our goal was to investigate whether single nucleotide polymorphisms (SNP) in the TF gene (F3) are associated with plasma TF, risk, and outcome in patients with ACS. Moreover, we wanted to investigate the impact of associated TF SNPs on mRNA production in human monocytes. METHODS AND RESULTS: In 725 patients with ACS [Fragmin and Fast Revascularization during Instability in Coronary Artery Disease II (FRISC-II) study] and 376 controls, 13 SNPs were genotyped and plasma TF measured. Thereafter, the 5466 A>G and the -1812 C>T were genotyped among all of the FRISC-II participants (n=3143) and assessed concerning clinical outcome. Associated SNPs were genotyped in 92 healthy blood donors for comparison of TF activity and TF mRNA expression. None of the SNPs were associated with patient/control status. The 5466 A>G SNP was associated with cardiovascular death (odds ratio, 1.8; P=0.025). The CG haplotype by -1812 C>T and 5466 A>G was associated with a 3-fold increased risk of death (P<0.001). TF mRNA and basal TF activity was significantly lower among 5466 AG carriers, whereas the increase in monocyte TF activity on lipopolysaccharide stimulation was significantly stronger (P=0.04). CONCLUSIONS: The 5466 AG genotype is a novel predictor of cardiovascular death in ACS and may act through a high TF response.
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