| 1. |
- Jernberg, Tomas, et al.
(author)
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BNP eller NT-proBNP bör analyseras vid misstänkt hjärtsvikt : Riktlinjer för analys och tolkning
- 2006
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In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 103:17, s. 1289-1292, 1295
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Journal article (peer-reviewed)abstract
- Available data indicate that the use of B-type natriuretic peptide (BNP) or N-terminal-proBNP (NT-proBNP) improve the diagnostics of suspected heart failure as compared to the currently used clinical diagnosis. The increased use of these diagnostic aids is therefore desirable. Since the predictive values are less than 100 procent and the levels are affected by many other factors but heart failure, the results of such measurement should not be used in isolation, but together with a proper clinical judgement. BNP and NT-proBNP are strongly related to the prognosis of most heart diseases, but we are still missing sufficient scientific proof to recommend the measurement of these hormones routinely for monitoring and therapy control.
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| 2. |
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| 3. |
- Jernberg, Tomas, et al.
(author)
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Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease
- 2006
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 27:10, s. 1166-1173
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Journal article (peer-reviewed)abstract
- AIMS: This study was designed to compare the degree of inhibition of platelet aggregation (IPA) of prasugrel with that of clopidogrel in stable aspirin-treated patients with coronary artery disease (CAD). METHODS AND RESULTS: Subjects (n=101) were randomly assigned to the following loading dose (LD) (day 1)/maintenance dose (MD) (days 2-28) combinations: prasugrel, 40 mg/5 mg; 40 mg/7.5 mg; 60 mg/10 mg; 60 mg/15 mg; or clopidogrel, 300 mg/75 mg. Turbidometric platelet aggregation was measured at multiple timepoints during the study. At 4 h after dosing, with 20 microM ADP, both prasugrel LDs achieved significantly higher mean IPA levels (60.6% and 68.4 vs. 30.0%, respectively; all P<0.0001) and lower percentage (3 vs. 52%, P<0.0001) of pharmacodynamic non-responders (defined as IPA <20%) than clopidogrel. Prasugrel 10 and 15 mg MDs achieved consistently higher mean IPA than clopidogrel 75 mg at day 28 (all P<0.0001). At pre-MD on day 28, there were no non-responders in the 10 and 15 mg prasugrel group, compared with 45% in the clopidogrel group (P=0.0007). CONCLUSION: In this population, prasugrel (40-60 mg LD and 10-15 mg MD) achieves greater IPA and a lower proportion of pharmacodynamic non-responders compared with the approved clopidogrel dosing.
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| 4. |
- Johnston, Nina, et al.
(author)
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Early invasive treatment benefits patients with renal dysfunction in unstable coronary artery disease
- 2006
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In: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 152:6, s. 1052-1058
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Journal article (peer-reviewed)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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| 6. |
- Johnston, Nina, et al.
(author)
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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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In: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 97:5, s. 640-5
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Journal article (peer-reviewed)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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| 7. |
- Johnston, Nina, 1961-
(author)
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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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Doctoral thesis (other academic/artistic)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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| 8. |
- Johnston, Nina, et al.
(author)
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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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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 113:2, s. 167-173
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Journal article (peer-reviewed)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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| 9. |
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| 10. |
- Lindahl, Bertil, et al.
(author)
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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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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 45:4, s. 533-541
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Journal article (peer-reviewed)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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