| 1. |
- Alehagen, Urban, et al.
(författare)
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Association of Copeptin and N-Terminal proBNP Concentrations With Risk of Cardiovascular Death in Older Patients With Symptoms of Heart Failure
- 2011
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Ingår i: JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION. - : Ama American Medical Association. - 0098-7484. ; 305:20, s. 2088-2095
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Tidskriftsartikel (refereegranskat)abstract
- Context Measurement of plasma concentrations of the biomarker copeptin may help identify patients with heart failure at high and low risk of mortality, although the value of copeptin measurement in elderly patients is not fully known. Objective To evaluate the association between plasma concentrations of copeptin, a surrogate marker of vasopressin, combined with concentrations of the N-terminal fragment of the precursor to B-type natriuretic peptide (NT-proBNP), and mortality in a cohort of elderly patients with symptoms of heart failure. Design, Setting, and Participants Primary health care population in Sweden enrolling 470 elderly patients with heart failure symptoms between January and December 1996. Clinical examination, echocardiography, and measurement of peptide concentrations were performed, with follow-up through December 2009. Main Outcome Measures All-cause mortality and cardiovascular mortality. Results After a median follow-up of 13 years, there were 226 deaths from all causes, including 146 deaths from cardiovascular causes. Increased concentration of copeptin was associated with increased risk of all-cause mortality (fourth quartile vs first quartile: 69.5% vs 38.5%, respectively; hazard ratio [HR], 2.04 [95% confidence interval {CI}, 1.38-3.02]) and cardiovascular mortality (fourth quartile vs first quartile: 46.6% vs 26.5%; HR, 1.94 [95% CI, 1.20-3.13]). The combination of elevated NT-proBNP concentrations and elevated copeptin concentrations also was associated with increased risk of all-cause mortality (copeptin fourth quartile: HR, 1.63 [95% CI, 1.08-2.47]; P=.01; NT-proBNP fourth quartile: HR, 3.17 [95% CI, 2.02-4.98]; Pandlt;.001). Using the 2 biomarkers simultaneously in the evaluation of cardiovascular mortality, there was a significant association for copeptin in the presence of NT-proBNP (log likelihood trend test, P=.048) and a significant association for NT-proBNP (fourth quartile: HR, 4.68 [95% CI 2.63-8.34]; Pandlt;.001). Conclusion Among elderly patients with symptoms of heart failure, elevated concentrations of copeptin and the combination of elevated concentrations of copeptin and NT-proBNP were associated with increased risk of all-cause mortality.
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| 2. |
- Alehagen, Urban, et al.
(författare)
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Pro-A-Type Natriuretic Peptide, Proadrenomedullin, and N-Terminal Pro-B-Type Natriuretic Peptide Used in a Multimarker Strategy in Primary Health Care in Risk Assessment of Patients With Symptoms of Heart Failure
- 2013
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Ingår i: Journal of Cardiac Failure. - : Elsevier. - 1071-9164 .- 1532-8414. ; 19:1, s. 31-39
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Use of new biomarkers in the handling of heart failure patients has been advocated in the literature, but most often in hospital-based populations. Therefore, we wanted to evaluate whether plasma measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP), midregional pro A-type natriuretic peptide (MR-proANP), and midregional proadrenomedullin (MR-proADM), individually or combined, gives prognostic information regarding cardiovascular and all-cause mortality that could motivate use in elderly patients presenting with symptoms suggestive of heart failure in primary health care. less thanbrgreater than less thanbrgreater thanMethods and Results: The study included 470 elderly patients (mean age 73 years) with symptoms of heart failure in primary health care. All participants underwent clinical examination, 2-dimenstional echocardiography, and plasma measurement of the 3 propeptides and were followed for 13 years. All mortality was registered during the follow-up period. The 4th quartiles of the biomarkers were applied as cutoff values. NT-proBNP exhibited the strongest prognostic information with andgt;4-fold increased risk for cardiovascular mortality within 5 years. For all-cause mortality MR-proADM exhibited almost 2-fold and NT-proBNP 3-fold increased risk within 5 years. In the 5-13-year perspective, NT-proBNP and MR-proANP showed significant and independent cardiovascular prognostic information. NT-proBNP and MR-proADM showed significant prognostic information regarding all-cause mortality during the same time. In those with ejection fraction (EF) andlt;40%, MR-proADM exhibited almost 5-fold increased risk of cardiovascular mortality with 5 years, whereas in those with EF andgt;50% NT-proBNP exhibited andgt;3-fold increased risk if analyzed as the only biomarker in the model. If instead the biomarkers were all below the cutoff value, the patients had a highly reduced mortality risk, which also could influence the handling of patients. less thanbrgreater than less thanbrgreater thanConclusions: The 3 biomarkers could be integrated in a multimarker strategy for use in primary health care. (J Cardiac Fail 2013;19:31-39)
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| 3. |
- Alehagen, Urban, et al.
(författare)
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Prognostic Assessment of Elderly Patients with Symptoms of Heart Failure by Combining High-Sensitivity Troponin T and N-Terminal Pro-B-Type Natriuretic Peptide Measurements
- 2010
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Ingår i: CLINICAL CHEMISTRY. - : American Association for Clinical Chemistry; 1999. - 0009-9147 .- 1530-8561. ; 56:11, s. 1718-1724
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful biomarker in heart failure assessment, whereas measurement of cardiac troponin is central in the diagnosis of patients with acute coronary syndromes. This report examined the prognostic use of combining high-sensitivity cardiac troponin T (hs-cTnT) and NT-proBNP measurements in elderly patients presenting to a primary care center with symptoms associated with heart failure. METHODS: A total of 470 elderly patients (age range 65-86 years) presenting with symptoms of heart failure were recruited from primary healthcare. In addition to clinical examination and echocardiography, hs-cTnT and NT-proBNP plasma concentrations were measured. All patients were followed for 10 years, and cardiovascular mortality was registered. RESULTS: By use of the hs-cTnT assay, 80.4% of the population had plasma concentrations above the lower detection limit of the assay. Of those displaying a plasma concentration of hs-cTnT andgt;99th percentile of a healthy population, 43% also had an NT-proBNP concentration in the fourth quartile (andgt;507 ng/L). In the multivariate analysis, we observed a 2.5-fold increased risk for cardiovascular mortality in individuals with a plasma NT-proBNP concentration andgt;507 ng/L (P andlt; 0.0001). Conversely, patients with hs-cTnT andgt;99th percentile displayed an approximately 2-fold increased risk for cardiovascular mortality (P = 0.0002). Combining the 2 biomarkers, NT-proBNP concentrations andgt;507 ng/L with hs-cTnT andgt;99th percentile increased the risk 3-fold, even after adjustment for clinical variables such as age, sex, impaired estimated glomerular filtration rate, and anemia (P andlt; 0.0001). CONCLUSIONS: hs-cTnT and NT-proBNP measurements combined provide better prognostic information than using either biomarker separately in elderly patients with symptoms associated with heart failure.
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| 4. |
- Goetze, Jens P., et al.
(författare)
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Cholecystokinin in plasma predicts cardiovascular mortality in elderly females
- 2016
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Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 209, s. 37-41
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cholecystokinin (CCK) and gastrin are related gastrointestinal hormones with documented cardiovascular effects of exogenous administration. It is unknown whether measurement of endogenous CCK or gastrin in plasma contains information regarding cardiovascular mortality. Methods: Mortality risk was evaluated using Cox proportional hazard regression and Kaplan-Meier analyses. Elderly patients in a primary care setting with symptoms of cardiac disease, i.e. shortness of breath, peripheral edema, and/or fatigue, were evaluated (n = 470). Primary care patients were followed for 13 years (from 1999); the 5-year all-cause and cardiovascular mortality was used as end point. Results: In univariate analysis, patients in the 4th CCK quartile had an increased risk of 5-year cardiovascular mortality (hazard ratio 3.9, 95% confidence interval: 2.1-7.0, p < 0.0001). In multivariate analysis including established factors associated with cardiovascular mortality, CCK concentrations in the 4th quartile were still associated with increased 5-year cardiovascular mortality risk (HR 3.1, 95% C.I.: 1.7-5.7, p = 0.0004), even when including 4th quartile NT-proBNP concentrations in the same model. We observed a marked difference between the genders, where CCK concentrations in the 4th quartile were associated with a higher 5-year cardiovascular mortality in female patients (HR 8.99, 95% C.I.: 3.49-102.82, p = 0.0007) compared to men (1.47, 95% C.I.: 0.7-3.3, p = 0.35). In contrast, no significant information was obtained from 4th quartile gastrin concentrations on 5-year cardiovascular mortality risk. Conclusions: CCK in plasma is an independent marker of cardiovascular mortality in elderly female patients. The study thus introduces measurement of plasma CCK in gender-specific cardiovascular risk assessment. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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| 5. |
- Goetze, Jens P, et al.
(författare)
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Chromogranin A as a biomarker in cardiovascular disease
- 2014
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Ingår i: Biomarkers in Medicine. - : Future Medicine. - 1752-0363 .- 1752-0371. ; 8:1, s. 133-140
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Forskningsöversikt (refereegranskat)abstract
- Chromogranin A is known as an important marker of neuroendocrine tumors. In cardiovascular medicine, however, chromogranin A measurement has only recently gained interest, since increased concentrations in the circulation are associated with risk of clinical worsening and death in patients with acute coronary syndromes or chronic heart failure. In this article, we summarize the current clinical data on chromogranin A as a biomarker in cardiovascular disease from high-risk conditions; for example, obesity, hypertension and diabetes, to overt heart failure. Biological activity of the various chromogranin A fragments, including the intact precursor itself, will not be covered in the present review. Instead, we highlight the complexity of chromogranin A as a plasma marker, where the protein is extensively and variably processed to a plethora of peptide fragments. Current immunological methods for clinical measurement differ dramatically with respect to both epitope choice and clinical validation.
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| 6. |
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| 7. |
- Goetze, Jens P, et al.
(författare)
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Plasma chromogranin A is a marker of death in elderly patients presenting with symptoms of heart failure
- 2014
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Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 3:1, s. 47-56
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular risk assessment remains difficult in elderly patients. We examined whether chromogranin A (CgA) measurement in plasma may be valuable in assessing risk of death in elderly patients with symptoms of heart failure in a primary care setting. A total of 470 patients (mean age 73 years) were followed for 10 years. For CgA plasma measurement, we used a two-step method including a screening test and a confirmative test with plasma pre-treatment with trypsin. Cox multivariable proportional regression and receiver-operating curve (ROC) analyses were used to assess mortality risk. Assessment of cardiovascular mortality during the first 3 years of observation showed that CgA measurement contained useful information with a hazard ratio (HR) of 5.4 (95% CI 1.7–16.4) (CgA confirm). In a multivariate setting, the corresponding HR was 5.9 (95% CI 1.8–19.1). When adding N-terminal proBNP (NT-proBNP) to the model, CgA confirm still possessed prognostic information (HR: 6.1; 95% CI 1.8–20.7). The result for predicting all-cause mortality displayed the same pattern. ROC analyses in comparison to NT-proBNP to identify patients on top of clinical variables at risk of cardiovascular death within 5 years of follow-up showed significant additive value of CgA confirm measurements compared with NT-proBNP and clinical variables. CgA measurement in the plasma of elderly patients with symptoms of heart failure can identify those at increased risk of short- and long-term mortality.
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| 8. |
- Hunter, Ingrid, et al.
(författare)
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N-Terminal Pro-Atrial Natriuretic Peptide Measurement in Plasma Suggests Covalent Modification
- 2011
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Ingår i: Clinical Chemistry. - : American Association for Clinical Chemistry. - 0009-9147 .- 1530-8561. ; 57:9, s. 1327-1330
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The N-terminal fragment of cardiac-derived pro-B-type natriuretic peptide is a glycosylated polypeptide. It is unknown whether N-terminal proatrial natriuretic peptide (proANP) fragments are also covalently modified. We therefore evaluated the clinical performance of 2 distinctly different proANP assays on clinical outcome. METHODS: We examined 474 elderly patients with symptoms of heart failure presenting in a primary healthcare setting. Samples were analyzed with an automated immunoluminometric midregion proANP (MR-proANP) assay and a new processing-independent assay (PIA) developed in our laboratory. The results were compared with Bland-Altman plots, and clinical performance was assessed by generating ROC curves for different clinical outcomes. RESULTS: Despite linear regression results indicating a good correlation (r = 0.85; P less than 0.0001), the PIA measured considerably more proANP than the MR-proANP assay (mean difference, 663 pmol/L; SD, 478 pmol/L). In contrast, the clinical performances of the 2 assays [as assessed by the area under the ROC curve (AUC)] in detecting left ventricular dysfunction were similar [proANP PIA, 0.71 (95% CI, 0.63-0.79); MR-proANP assay, 0.74 (95% CI, 0.66-0.81); P = 0.32]. The prognostic ability to report cardiovascular mortality during a 10-year follow-up revealed AUC values of 0.66 (95% CI, 0.60-0.71) for the proANP PIA and 0.69 (95% CI, 0.63-0.74) for the MR-proANP assay (P = 0.08, for comparing the 2 assays). CONCLUSIONS: Our data suggest that N-terminal proANP fragments in patient plasma differ from the calibrator peptides used but that the difference does not affect ROC curves in an elderly cohort of patients with mild to moderate heart failure. We suggest that human N-terminal proANP fragments can be covalently modified.
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| 9. |
- Mylin, Anne K., et al.
(författare)
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N-terminal pro-C-type natriuretic peptide in serum associated with bone destruction in patients with multiple myeloma
- 2015
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Ingår i: Biomarkers in Medicine. - : Future Medicine. - 1752-0363 .- 1752-0371. ; 9:7, s. 679-689
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine whether N-terminal proCNP concentrations in serum is associated with bone destruction in patients with multiple myeloma. Materials and methods: N-terminal proCNP and biochemical bone markers were measured in 153 patients. Radiographic bone disease and skeletal-related events were evaluated at specific time-points. Results: N-terminal proCNP concentrations increased with age. High N-terminal proCNP concentrations were associated with high-risk disease and renal impairment. Renal function explained 22% of the variation. N-terminal proCNP concentrations correlated with serum bone ALP and serum PINP, but lacked association with bone resorption markers, radiographic bone disease and skeletal-related events. Conclusion: Serum N-terminal proCNP are associated with bone formation activity in patients with multiple myeloma, but should be interpreted with caution in patients with renal impairment.
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| 10. |
- Timm, Annette, et al.
(författare)
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Comparison of automated von Willebrand factor activity assays.
- 2015
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Ingår i: Thrombosis Research. - : Elsevier BV. - 1879-2472 .- 0049-3848.
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Tidskriftsartikel (refereegranskat)abstract
- Von Willebrand Disease (VWD) is the most common inherited bleeding disorder. Measurement of von Willebrand factor (VWF) activity in plasma is often based on platelet agglutination stimulated by the ristocetin cofactor activity. Novel assays, based on latex beads with recombinant glycoprotein Ib instead of platelets, have recently been developed but it is unclear whether these can improve the diagnostic capability for VWD.
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