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ABSTRACT: Background: TSP-1 is a vasoconstrictive protein, which is released from both endothelium and cardiomyocytes during ischemia and promotes platelet aggregation and adhesion to subendothelial layers in atherosclerotic lesions. During myocardial ischemia and reperfusion, TSP-1 disturbs local microcirculation by disrupting both NO-signaling as well as VEGF-pathways by activation of CD47 and CD36. Furthermore, activation of TGF-ß might induce excessive fibrosis after infarction. It was assumed that TSP-1 is washed out after successful coronary reperfusion. In this study, we examined circulating TSP-1 post emergency PCI as a risk factor for major adverse cardiac events after STEMI with and without ventricular fibrillation. Methods: TSP-1 levels in platelet poor plasma were measured in 54 patients after ST-elevation myocardial infarction. Major adverse cardiac events were monitored for 426 days. Results: Patients with decreased TSP levels after coronary stenting showed a significantly higher risk for MACE than patient with higher TSP levels (TSP-1[d0]: n = 46, no MACE = 16.38 ± 1.98 ug/mL vs. MACE 7.11 ± 1.54 ug/mL; p = 0.003). Kaplan-Meyer-analysis for MACE showed a better outcome above 10 ug/mL (p = 0.02). For MACE later than 3 months post-STEMI, the corresponding Kaplan-Meier-analysis yielded a p-value of 0.01. The number needed to diagnose for late MACE was 2.158. Conclusion: Low plasma levels of TSP1 after PCI are associated with MACE. Due to its procoagulant effects and dysregulation of microvascular tone, adequately powered prospective studies are warranted to test the impact of TSP-1 on cardiac microcirculation, endothelial function and remodeling. TSP-1 might serve as a new diagnostic and therapeutic approach in cardiovascular disease.
Clinical hemorheology and microcirculation 06/2012; · 3.40 Impact Factor
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ABSTRACT: To investigate effects of ethanol on activity markers of atherosclerosis in an in vitro endothelial cell model.
After 24 h incubation with ethanol (0.0095%), human umbilical vein endothelial cells were stimulated for 1 h with lipopolysaccharide, and were then incubated in direct contact with activated platelets. Following this incubation, the expression of CD40L and CD62P on platelets, and the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), urokinase plasminogen activator receptor (uPAR), and membrane-type 1 matrix metalloproteinase (MT1-MMP) on endothelial cells were measured by flow cytometry.
The increased expression of VCAM-1 and uPAR on endothelial cells by proinflammatory stimulation with activated platelets was significantly reduced through pre-incubation with ethanol (P < 0.05). Furthermore, platelets in direct contact with ethanol and with endothelial cells pre-incubated in ethanol showed a significant reduction in their CD40L expression (P < 0.05). Ethanol had no significant effect on ICAM-1 and MT1-MMP expression on endothelial cells.
Ethanol directly attenuates platelet activation and has significant endothelial cell-mediated effects on selected markers of atherosclerosis in vitro. These findings underline possible protective effects of ethanol on atherosclerosis.
World journal of cardiology. 06/2012; 4(6):201-5.
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International journal of cardiology 01/2012; 155(2):291-3. · 7.08 Impact Factor
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ABSTRACT: In addition to their cholesterol lowering ability, statins have proven pleiotropic effects in the cardiovascular system. Chronic inflammation with interactions between platelets and endothelial cells leads to an upregulation of activity markers of atherosclerosis. The purpose of this study was to investigate the effects of simvastatin and atorvastatin on platelets and endothelial cells in an in vitro endothelial cell model.
After a 24 h incubation period with either simvastatin or atorvastatin (1 μmol/L), human umbilical vein endothelial cells were stimulated for 1 h with lipopolysaccharide (LPS), and were then incubated in direct contact with activated platelets. Platelet surface expression of CD40L and CD62P and expression of ICAM-1, VCAM-1, uPAR and MT1-MMP on endothelial cells were measured by flow cytometry. Supernatants were analyzed by ELISA for soluble MMP-1. The increased expression of VCAM-1 and uPAR on endothelial cells by stimulation with LPS and by direct contact with activated platelets was significantly reduced to a similar extent through pre-incubation with both atorvastatin and simvastatin (p < 0.05). Platelets without endothelial cell contact, but in direct contact with either statin, showed similar significant reductions in surface expression of CD40L (p < 0.005).
These effects may explain the ability of statins to reduce the progression of atherosclerosis in addition to their cholesterol-lowering properties.
Cardiology journal 01/2012; 19(1):20-8. · 1.31 Impact Factor
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Anadolu kardiyoloji dergisi: AKD = the Anatolian journal of cardiology 12/2011; 11(8):741-2. · 0.44 Impact Factor
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ABSTRACT: An upregulation of platelet CD40 ligand (CD40L) and CD62P has been described in atherosclerotic cardiovascular diseases and among patients with acute cerebral ischemia. Correlation between platelet and monocyte activation and the etiology of ischemic stroke were examined in 41 patients with acute ischemic stroke. Compared to 10 controls, all patients with stroke showed a significantly elevated platelet expression of CD40L (P < .001) and had significantly higher amounts of platelet-monocyte aggregates (P = .002). Plasma levels of interleukin 7 were significantly lower in patients with stroke compared to controls (P = .006). Patients with small artery disease had a significantly higher platelet CD40L expression than patients with cardioembolic stroke (P = .029). Plasma levels of soluble CD40L were significantly higher in patients with large artery disease compared to patients with cardioembolic stroke (P = .047). In conclusion, patients with acute ischemic stroke show an upregulation of platelet CD40L and an activation of cellular coagulation with highest activation in the large artery disease subgroup.
Clinical and Applied Thrombosis/Hemostasis 07/2011; 18(1):87-91. · 1.33 Impact Factor
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ABSTRACT: Interactions between platelets and endothelial cells under inflammatory conditions lead to an increased expression of various activity markers of atherosclerosis in the vessel wall. The purpose of this study was to investigate possible protective effects of nicotinic acid in an in vitro endothelial cell model.
After a 24-hour incubation period with nicotinic acid (1 mmol/l), human umbilical vein endothelial cells were stimulated for 1 h with lipopolysaccharide and were then incubated in direct contact with activated platelets. Following this incubation, the expression of CD40L and CD62P on platelets and the expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, uPAR, and MT1-MMP on endothelial cells were measured by flow cytometry. Supernatants were analyzed by ELISA for soluble MCP-1 and MMP-1.
The increased expression of VCAM-1 on endothelial cells by proinflammatory stimulation with activated platelets was significantly reduced through preincubation with nicotinic acid (P<.05). Furthermore, platelets in direct contact with preincubated endothelial cells showed a significant reduction in their CD62P and CD40L expression when compared to platelets incubated with untreated endothelial cells (P<.05). Treatment with nicotinic acid did not have a significant effect on ICAM-1, uPAR, and MT1-MMP expression on endothelial cells. Levels of soluble MCP-1 and MMP-1 in supernatants were lower after preincubation with nicotinic acid.
Nicotinic acid inhibits platelet activation after platelets contacted nicotinic acid treated endothelial cells and inhibits VCAM-1 expression on human endothelial cells under inflammatory conditions. These findings suggest a possible pleiotropic therapeutic relevance of nicotinic acid in atherosclerosis.
Cardiovascular pathology: the official journal of the Society for Cardiovascular Pathology 05/2011; 21(2):89-95. · 1.63 Impact Factor
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ABSTRACT: In a recently published genome-wide association study (GWAS), three single nucleotide polymorphisms (SNPs) (rs2824292, rs1353342, rs12090554) were significantly associated with increased susceptibility for ventricular fibrillation (VF) during acute myocardial infarction (AMI). The association of rs2824292 could be confirmed in a second cohort. Both cohorts were from the Netherlands. We aimed to replicate this association in a German cohort of AMI patients with or without VF.
We included a German cohort of 90 individuals with AMI and VF (cases) and 167 AMI individuals without VF and used Taqman assays for SNP typing.
None of the loci showed evidence for a statistically significant association with VF. The observed genotype frequencies of the three loci were in Hardy-Weinberg equilibrium, which essentially excludes genotyping errors.
In contrast to the data from the Netherlands, we could not detect a significant association of the rs2824292 locus and risk of VF during AMI in our German cohort. Differences in recruitment and clinical phenotypes between the Dutch and German cohorts may underlie different genotype associations.
Clinical Chemistry and Laboratory Medicine 05/2011; 49(7):1237-9. · 2.15 Impact Factor
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Elif Elmas,
Christina Doesch,
Stephan Fluechter,
Miriam Freundt,
Christel Weiss,
Siegfried Lang, Thorsten Kälsch,
Dariush Haghi,
Jana Papassotiriou,
Jan Kunde,
Stefan O Schoenberg,
Martin Borggrefe,
Theano Papavassiliu
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ABSTRACT: We aimed to determine the diagnostic performance of biomarkers in predicting myocardial fibrosis assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) in patients with hypertrophic cardiomyopathy (HCM). LGE CMR was performed in 40 consecutive patients with HCM. Left and right ventricular parameters, as well as the extent of LGE were determined and correlated to the plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), carboxy-terminal pro-endothelin-1 (CT-proET-1), carboxy-terminal pro-vasopressin (CT-proAVP), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8). Myocardial fibrosis was assumed positive, if CMR indicated LGE. LGE was present in 26 of 40 patients with HCM (65%) with variable extent (mean: 14%, range: 1.3-42%). The extent of LGE was positively associated with MR-proANP (r = 0.4; P = 0.01). No correlations were found between LGE and MR-proADM (r = 0.1; P = 0.5), CT-proET-1 (r = 0.07; P = 0.66), CT-proAVP (r = 0.16; P = 0.3), MMP-9 (r = 0.01; P = 0.9), TIMP-1 (r = 0.02; P = 0.85), and IL-8 (r = 0.02; P = 0.89). After adjustment for confounding factors, MR-proANP was the only independent predictor associated with the presence of LGE (P = 0.007) in multivariate analysis. The area under the ROC curve (AUC) indicated good predictive performance (AUC = 0.882) of MR-proANP with respect to LGE. The odds ratio was 1.268 (95% confidence interval 1.066-1.508). The sensitivity of MR-proANP at a cut-off value of 207 pmol/L was 69%, the specificity 94%, the positive predictive value 90% and the negative predictive value 80%. The results imply that MR-proANP serves as a novel marker of myocardial fibrosis assessed by LGE CMR in patients with HCM.
The international journal of cardiovascular imaging 04/2011; 27(4):547-56. · 2.15 Impact Factor
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ABSTRACT: Patients with Takotsubo cardiomyopathy (TC) often present with symptoms similar to those of myocardial infarction (MI). We analyzed blood concentrations of mediators of inflammation and platelet- and monocyte-activity markers in patients with TC and MI for significant differences. Clinical data of patients with TC (n = 16) and acute MI (n = 16) were obtained. Serial blood samples were taken at the time of hospital admission (t(0)), after 2-4 days (t(1)) and after 4-7 weeks (t(2)), respectively. Plasma concentrations of interleukin (IL)-6, IL-7, soluble CD40 ligand (sCD40L), and monocyte chemotactic protein 1 (MCP-1) were determined with an ELISA. Tissue factor binding on monocytes, platelet-activation marker CD62P, platelet CD40-ligand (CD40L), and platelet-monocyte aggregates were measured using flow cytometry. Expression of CD62P on platelets and IL-6 plasma levels were significantly lower in patients with TC compared to MI at the time of hospital admission. IL-7 plasma levels were significantly elevated in patients with TC compared to patients with MI at 2-4 days after hospital admission. No significant differences were observed concerning sCD40L and MCP-1 plasma levels, tissue factor binding on monocytes, CD40L expression on platelets, and platelet-monocyte aggregates at any point in time. Our results indicate that inflammatory mediators and platelet-activity markers contribute to the differences in the pathogenesis of MI and TC.
Heart and Vessels 03/2011; 27(2):186-92. · 2.05 Impact Factor
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ABSTRACT: Inflammatory conditions contribute to increased expression of various activity markers in platelets and endothelial cells, leading to atherosclerotic changes in the vascular wall. The objective of this study was to investigate possible protective effects of 1α,25-dihydroxyvitamin D3 in an endothelial cell model.
After a 24-hour incubation with 1α,25-dihydroxyvitamin D3, human umbilical vein endothelial cells were stimulated with lipopolysaccharide (LPS) and incubated in direct contact with platelets. The expression of CD40L and CD62P in platelets, the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (VCAM-1), the urokinase receptor uPAR and membrane type 1 matrix metalloproteinase (MT1-MMP) in endothelial cells and endothelial cell reactive oxygen species generation were measured by flow cytometry. Endothelial nitric oxide synthase was analyzed by Western blot.
The increased expression of VCAM-1 and MT1-MMP in endothelial cells by proinflammatory stimulation with LPS and by direct contact with activated platelets was significantly reduced through preincubation with 1α,25-dihydroxyvitamin D3. Platelets in direct contact with preincubated endothelial cells showed significantly reduced CD62P expression when compared to platelets incubated with untreated endothelial cells.
1α,25-Dihydroxyvitamin D3 attenuates platelet activation and the expression of VCAM-1 and MT1-MMP in human endothelial cells and could have early therapeutic relevance in atherosclerotic diseases.
Cardiology 01/2011; 118(2):107-15. · 1.71 Impact Factor
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ABSTRACT: The P-Selectin Gene Polymorphism Val168Met.
Ventricular fibrillation (VF) in the setting of acute myocardial infarction (AMI) is the leading cause of sudden cardiac death (SCD). Family history of SCD is described as risk factor for primary VF during acute AMI. Genetic factors may be associated with primary VF. We examined polymorphisms in genes related to the activation and adhesion of blood platelets in patients with and without VF in the setting of AMI and among healthy controls.
Two hundred and forty patients with a history of AMI and 475 healthy controls were studied. Seventy-three patients (30%) had primary VF during AMI. By using PCR techniques with sequence-specific primers (PCR-SSP), we genotyped 5 single nucleotide polymorphisms (SNPs) in P-selectin (SELP) (V168M, S290N, N592D, V599L, T715P), 2 SNPs (M62I, S273F) in P-selectin glycoprotein ligand-1 (SELPLG), 5 SNPs in CD40LG (-3459A>G, -122A>C, -123A>C, 148T>C, intr4-13T>C), the H558R SNP in SCN5A, and rs2106261 in ZFHX3. In addition, length polymorphisms in SELPLG (36bp-tandem repeat) and CD40LG (CA-repeat) were genotyped by PCR methods. Results were evaluated by 2-sided t-tests, chi-square tests, and logistic regression analysis.
None of the gene polymorphisms showed significant differences between AMI patients and healthy controls. Among patients with a history of VF, however, the SELP 168M variant showed a significantly higher prevalence (14/73 patients; 19.2%) as compared with patients without VF (13/167 patients; 7.8%; P < 0.01). This association remained significant in a logistic regression analysis after adjustment for age and gender (P = 0.013; odds ratio 2.8; 95% confidence interval 1.2-6.3).
This is the first description of an association of the SELP gene variant 168M with primary VF during acute MI. This variant may be a candidate polymorphism for evaluating the susceptibility for VF in the setting of acute MI.
Journal of Cardiovascular Electrophysiology 11/2010; 21(11):1260-5. · 3.06 Impact Factor
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ABSTRACT: Since Wegener's granulomatosis (WG) represents a relapsing disease, efforts have been made to reliably predict relapses using blood tests. Followup measures such as conventionally determined C-reactive protein (CRP), antineutrophil cytoplasmic antibody (C-ANCA) titer, and proteinase-3 (PR3) ELISA are applied. We evaluated whether during remission elevated highly sensitive CRP (hsCRP) precedes relapse as a marker of subclinical inflammation and thus might improve clinical assessment.
We investigated 227 sera of 57 patients with WG: 74 sera collected from patients in remission who subsequently relapsed (before relapse), 30 sera collected during relapse, and 123 sera from patients in remission without relapse. We also distinguished between major and minor relapse. hsCRP, conventionally determined CRP (CRP), C-ANCA, PR3-ELISA, and erythrocyte sedimentation rate (ESR) were measured using commercial kits, and levels were correlated to clinical status.
Only hsCRP and ANCA titer, but not CRP levels, were higher in sera from patients who subsequently relapsed versus those who did not, indicating patients at risk. Levels of hsCRP, CRP, and ESR were higher in sera collected during relapse than in the sera before relapse. hsCRP, conventional CRP, and ESR were also higher in samples collected during major relapse than before major relapse. Looking at the levels just before relapse compared to previous levels during remission, none of these measures rose directly before the clinical manifestation of the relapse.
Our study provides evidence for an additional value of hsCRP in the clinical assessment of patients with WG.
The Journal of Rheumatology 11/2010; 37(11):2319-25. · 3.69 Impact Factor
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Tom Oberheiden,
Christian Blahak,
Xuan Duc Nguyen,
Marc Fatar,
Elif Elmas,
Nicole Morper,
Carl-Erik Dempfle,
Hansjörg Bäzner,
Michael Hennerici,
Martin Borggrefe, Thorsten Kälsch
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ABSTRACT: Platelets and monocytes play a pivotal role in the initiation and progression of large-vessel atherosclerosis. An up-regulation of various platelet and coagulation activation markers has been described in cardiovascular diseases and in patients with acute cerebral ischemia. In the present study the role of platelets and cellular coagulation activation in cerebral small-vessel disease (cSVD) was assessed. In 24 patients with cSVD but without established large-vessel disease, whole blood samples were obtained. Patients were divided into three subgroups (Fazekas 1, 2 and 3) according to extent of cSVD based on morphological magnetic resonance imaging criteria. Surface expression of CD40L and CD62P on platelets, tissue-factor exposition on monocytes and platelet-monocyte aggregates were measured with flow cytometry. Plasma levels of soluble CD40L, interleukin (IL)-6 and IL-7 were assessed by ELISA. Patients with cSVD show a significantly elevated expression of platelet CD40L (P < 0.001) and CD62P (P < 0.023), significantly elevated amounts of platelet-monocyte aggregates (P < 0.004), a significantly enhanced tissue-factor exposition on monocytes (P < 0.019) and significantly lower plasma levels of IL-7 compared to 10 healthy controls. However, this platelet and monocyte activation did not correlate with the severity of cSVD. Patients with cSVD show an up-regulation of the platelet CD40L and CD62P system and an activation of cellular coagulation which might contribute to the initiation and progression of cSVD.
Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 09/2010; 21(8):729-35. · 1.25 Impact Factor
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ABSTRACT: The widespread use of primary coronary intervention (PCI) has significantly improved the prognosis of men presenting with acute coronary syndromes, but the cardiovascular event rate among women has either levelled off or increased. The purpose of the present prospective study was to compare the clinical outcome of women and men presenting with ST-elevation myocardial infarction (STEMI) undergoing primary PCI with concomitant usage of GP IIb/IIIa inhibitors.
Between January 2006 and December 2007, 297 consecutive patients presenting with STEMI were prospectively included in this single center investigation. Overall, 82 (27.6%) women and 215 (72.4%) men were treated by PCI with additional bare metal stent implantation and a GP IIb/IIIa inhibitor.
Women were significantly older (65 ± 10 vs 60 ± 12 years, p = 0.04), presented with a smaller reference luminal diameter (2.83 ± 0.51 vs 2.94 ± 0.43, p = 0.03) and had a higher prevalence of hypertension (68% vs 53%, p = 0.025) and obesity (30% vs 18%, p = 0.03). The incidence of major adverse cardiac events (MACE, defined as death, re-myocardial infarction, target lesion revascularization and coronary artery bypass graft) during long-term follow-up was similar in women and men (20% vs 26%, p = 0.29). Age, C-reactive protein, platelet count and cardiogenic shock were identified as independent predictors for MACE, whereas gender was not predictive.
In this study, female gender did not emerge as an independent predictor for MACE, but women presenting with STEMI had a higher cardiovascular risk profile; this emphasizes the need for a more extensive therapeutic strategy. Combination therapy with primary PCI and GP IIb/IIIa inhibitors might mitigate gender-related differences in clinical outcomes.
Cardiology journal 01/2010; 17(6):580-6. · 1.31 Impact Factor
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ABSTRACT: AIMS: Sudden cardiac death (SCD) is frequently caused by ventricular fibrillation (VF) occurring in the course of acute myocardial infarction (AMI). It has not been investigated yet, to what extent markers of coagulation activation and inflammation differ between patients with and without VF in the acute phase of AMI.
International journal of cardiology 07/2009; 145(1):118-9. · 7.08 Impact Factor
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ABSTRACT: Percutaneous coronary intervention (PCI) with stent implantation is considered to be the standard treatment in patients presenting with ST-elevation myocardial infarction (STEMI). According to the American Heart Association (AHA)/American College of Cardiology (ACC) guidelines for STEMI, there is a class IIa recommendation (treatment reasonable) for platelet glycoprotein (GP) IIb/IIIa inhibitors. This study aims to compare the clinical outcome of patients with and without diabetes, presenting with STEMI undergoing primary PCI with concomitant usage of GP IIb/IIIa inhibitors in real clinical practice.
Over the course of three years (2004-2006) 394 consecutive patients presenting with STEMI were included in this single centre experience. There were 95 patients (24%) with, and 299 patients (76%) without, diabetes. A GP IIb/IIIa inhibitor was administered to all patients without contraindications (316 patients, 80%).
Patients with diabetes were significantly older, more often suffered from hypertension and had a higher incidence of obesity. The rate of administration of GP IIb/IIIa inhibitors was similar in both groups (74% vs. 82%, p = 0.14). The in-hospital incidence of major adverse cardiac events (MACE, defined as death, re-myocardial infarction, target lesion revascularisation and coronary artery bypass graft) was similar in both patient groups (18 [19%] diabetics vs. 51 [17%] non-diabetics, p = 0.65). Hypertension, age and obesity were identified as predictors for MACE, whereas diabetes was not predictive.
In this single centre experience, in diabetic and non-diabetic patients presenting with STEMI, combination therapy with primary PCI and GP IIb/IIIa inhibitors might have contributed to a similar clinical outcome.
Cardiology journal 02/2009; 16(3):234-40. · 1.31 Impact Factor
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ABSTRACT: An important role in the acceleration of vascular disease has been previously suggested for advanced glycation end products. N(epsilon)-(carboxymethyl)lysine (CML) is an advanced glycation end product formed on protein by combined non-enzymatic glycation and glycoxidation reactions. CML reacts with the receptor of advanced glycation end products inducing impairment of endothelium dependent relaxation and is a marker of oxidative stress.
A total of 40 patients with acute myocardial infarction (17 patients with ST-elevation myocardial infarction, 23 patients with non-ST-elevation myocardial infarction) and 40 patients with stable coronary artery disease were included consecutively in this study. During coronary angiography, peripheral venous blood sample was taken for measuring CML.
Serum levels of CML were significantly increased in patients with acute myocardial infarction [17.9+/-10.7 vs. 6.6+/-3.1 arbitrary units (AU)/mg protein, p<0.001]. A cut-off value of CML>9.5 AU/mg protein was associated with an odds ratio of acute myocardial infarction of 39.7 [95% confidence interval (CI): 11.1-142, p<0.001], a sensitivity of 0.85 (95% CI: 0.70-0.94) and a specificity of 0.88 (95% CI: 0.73-0.96).
CML levels are significantly elevated in patients presenting with acute myocardial infarction. These results suggest the involvement of endothelial dysfunction (through receptor interaction) and oxidative stress in acute myocardial infarction.
Clinical Chemistry and Laboratory Medicine 01/2009; 47(4):446-51. · 2.15 Impact Factor
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ABSTRACT: Fibrinogen concentration influences mechanical and functional properties of the clot. The purpose of the present study was to identify threshold concentrations of fibrinogen resulting in relevant changes in whole blood clot elastic modulus and platelet contractile force, as well as plasma prothrombin time and activated partial thromboplastin time. We measured clot elastic modulus, platelet contractile force, and other hemostasis parameters in whole blood samples from 552 patients admitted to a surgical intensive care unit. Platelet contractile force and clot elastic modulus were measured using the Hemodyne apparatus. Fibrinogen levels were between less than 0.10 and 9.44 g/l, with a mean of 2.41 g/l. Mean platelet count was 203 x 10(9) l(-1), with a range of 16 x 10(9) l(-1) to 682 x 10(9) l(-1). High levels of fibrinogen result in improved mechanical stability and improved interaction of platelets with the fibrin network. Clot elastic modulus and platelet contractile force are correlated positively with plasma fibrinogen concentration. However, there was no threshold concentration or ceiling effect concerning the mechanical properties of the clots. In contrast, clotting time assays such as prothrombin time, thrombin time, or activated partial thromboplastin time are influenced by the fibrinogen concentration only at levels below 1 g/l. In linear regression analysis, clot elastic modulus was mainly influenced by fibrinogen concentration (F = 185.4, P < 0.0001), whereas platelet contractile force was influenced by fibrinogen (F = 197.0, P < 0.0001) and platelet count (F = 104.7, P < 0.0001). The present data show that 1 g/l is a threshold fibrinogen concentration for an effect on coagulation assays such as prothrombin time, thrombin time, or activated partial thromboplastin time, but increasing fibrinogen concentrations above this level results in further continuous improvement of mechanical properties of the whole blood clot.
Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 12/2008; 19(8):765-70. · 1.25 Impact Factor
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ABSTRACT: In ambulatory patients with coronary artery disease (CAD) we aimed to evaluate the diagnostic performance of mid-regional pro-adrenomedullin (MR-proADM) for the detection or exclusion of impaired left ventricular ejection fraction (LVEF).
MR-proADM levels were measured in blood samples taken from 102 outpatients with CAD classified according to the New York Heart Association (NYHA) and Canadian Cardiovascular society (CCS) I-II. Increased levels of MR-proADM correlated with impaired LVEF (r=-0.21, p=0.046). The optimal threshold of MR-proADM for identification of impaired LVEF <50% was 0.54 nmol/L with an area under the ROC curve (AUC) of 0.64 (p=0.06). In univariate and multivariate calculation, MR-proADM >0.54 nmol/L remained associated with left ventricular dysfunction even after adjusting for age and gender. The negative predictive value (NPV) for MR-proADM <or=0.54 nmol/L was 88%, the specificity was 66%.
We showed that MR-proADM is related to impaired LVEF. With an NPV of 88% MR-proADM might be a supportive tool to exclude negatively tested outpatients with CAD from further LVEF-diagnosis with moderate reliability.
International journal of cardiology 08/2008; 128(1):107-11. · 7.08 Impact Factor
