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Biomedical subjects

S Blankenberg

Publications and source records attributed to S Blankenberg.

At least 19 recordsLinked to original sources
PubMed2007

Prognostic value of plasma tissue factor and tissue factor pathway inhibitor for cardiovascular death in patients with coronary artery disease: the AtheroGene study.

BACKGROUND: Tissue factor (TF) and its specific inhibitor, tissue factor pathway inhibitor (TFPI), are important contributors to the initiation of the coagulation process. OBJECTIVES: To compare plasma levels of soluble TF (sTF) and free-TFPI (f-TFPI) between patients with stable angina pectoris (SAP) and acute coronary syndrome (ACS) and to assess the impact of the two variables on long-term prognosis. PATIENTS/METHODS: Patients with SAPs (n = 1146) and acute coronary syndrome (n = 523) from the AtheroGene study were included and followed for 2.3 years. Because of the strong impact of unfractionated heparin (UFH) on f-TFPI levels, but not on sTF levels, patients having received UFH before blood drawing were excluded from the analyses on f-TFPI (n = 226). RESULTS: On admission, no significant differences in sTF levels were observed between SAP and ACS patients. By comparison to patients with stable angina, f-TFPI levels significantly increased in patients with acute unstable angina and further increased in patients presenting with non-ST-elevation myocardial infarction and ST-elevation myocardial infarction (P < 10(-4)). Among the 1669 individuals with a coronary artery disease, 56 died from a cardiovascular cause. In prospective analyses, high sTF levels were independently associated with an increased risk of cardiovascular death in individuals with ACS (fully adjusted hazard ratio associated with one quartile increase = 2.06; 95% confidence interval 1.24-3.45; P = 0.006) but not in those with SAP (hazard ratio = 1.07; 95% confidence interval 0.78-1.46; P = 0.67). In SAP and ACS patients, high f-TFPI levels were not independently associated with an increased risk of cardiovascular death. CONCLUSIONS: Plasma sTF levels were predictive of cardiovascular mortality in individuals with ACS, whereas f-TFPI levels were associated with the severity of myocardial damage on admission but were not independently related to outcome.

Aged↗
PubMed2006

Haemostatic factors and the risk of cardiovascular death in patients with coronary artery disease: the AtheroGene study.

OBJECTIVE: To get a better insight into the role of hemostasis in coronary artery disease (CAD), we assessed the impact of von Willebrand factor (vWF), fibrinogen, thrombin-antithrombin (TAT) complexes, D-dimers, and plasmin-antiplasmin (PAP) complexes on the risk of cardiovascular event in a prospective cohort of CAD patients. METHODS AND RESULTS: The prospective Atherogene cohort includes 1057 individuals with an angiographically proven coronary artery disease at baseline. After a median follow-up of 6.6 years, 135 individuals died from a cardiovascular cause and 97 had a nonfatal cardiovascular event. Higher levels of all 5 hemostatic markers at baseline were associated with an increased risk of cardiovascular death, but not of nonfatal event. Except for vWF, these associations remained significant after adjustment for conventional cardiovascular risk factors and C-reactive protein (CRP) levels (P for trend according to increasing tertiles=0.20, 0.011, 0.026, 0.019, and 0.01 for vWF, fibrinogen, TAT, D-Dimer, and PAP, respectively). When including the 5 hemostatic markers in a stepwise Cox regression analysis where conventional risk factors and CRP were forced into the model, fibrinogen and D-dimers remained independently associated with the risk of cardiovascular death. Adjusted hazard ratios (95% CI) associated with one SD increase of fibrinogen and D-dimers were 1.27 (1.04 to 1.55) and 1.29 (1.09 to 1.53), respectively. CONCLUSIONS: In patients with coronary artery disease, fibrinogen and D-dimer levels are independent predictors of subsequent cardiovascular death. Our data support a role of impaired coagulation/fibrinolysis process in the complications of coronary artery disease.

Aged↗
PubMed2004

[Acute coronary syndrome (without ST-elevation)].

Antithrombotic therapy in acute coronary syndrome without ST-segment elevation should be initiated with aspirin 100 mg/day (loading dose 250-500 mg) and Clopidogrel 75 mg/day (loading dose 300 mg). In addition, anticoagulation with unfractionated heparin or low molecular weight heparin should be started. A GP IIb/IIIa receptor blocker can be given either upfront (Eptifibatide/Tirofiban) or directly in the cathlab preceding PCI (Abciximab). Aspirin should be given in the chronic phase lifelong, Clopidogrel for at least nine months. An invasive strategy is recommended in high-risk patients within 48 hours.

Acute Disease↗
PubMed2004

[Genet(h)ics: the philosophical concept of the discourse ethics and consequences for the research community].

The research community is increasingly confronted with the problem of ethic responsibility. Ethic reflection might be integrated as a part of one's own research projects. This question is discussed against the background of Jürgen Habermas' discourse ethics, which considers the diverse state of being in the modern age as the basis. In this situation, the process of understanding ("Verständigungsprozess") the norms assumed to be valid receives extraordinary significance, since this process of understanding itself inheres authorizing function for the norms. Taking this philosophicial approach seriously, researchers have the specific responsibility not to perform the ethical judgement based on facts alone. Since researchers might be predestined to envisage the ethical implication of their own research at an early stage, they have the possibility to activate the process of understanding about relevant ethical norms themselves as early as possible.

Biomedical Research↗
PubMed2004

[Genetic variation of the cholesterol ester transfer protein gene and the prevalence of coronary artery disease. The AtheroGene case control study].

BACKGROUND: Various functional polymorphisms of the cholesteryl ester transfer protein ( CETP) gene influence CETP activity and the concentration of high-density lipoprotein (HDL) cholesterol. Beside other functional variants mainly the promoter polymorphism CETP/C-629A is currently discussed as a risk factor of coronary artery disease (CAD). We evaluated in a large case-control study the impact of various CETP genotypes and haplotypes on HDL concentration and the prevalence of CAD. METHODS AND RESULTS: In 1214 patients with documented CAD as well as 754 population controls we determined the CETP/C-629A, TaqIB, I405V, R451Q, and A373P polymorphisms. All genotypes have an impact on the HDL concentration; univariate genotype and haplotype analyses demonstrate a significant effect of A-allel carriers on the elevation of HDL concentration. In addition, among all genotypes determined, the C-629A polymorphism is associated with the prevalence of CAD in a codominant fashion. Homozygous A-allel carriers reveal a relative risk of 0.6 (95% CI 0.44-0.82; P = 0.005) compared to the wild type. Adjustment for classical risk factors did not alter this association significantly, whereas after controlling for HDL concentration no independent significance between CETP/C-629A genotype and prevalence of CAD was observed anymore. CONCLUSION: CETP genotypes have an significant but moderate impact on systemic HDL-cholesterol concentration. The A-allel of the CETP/C-629A polymorphism is associated with a reduced CAD risk. This risk reduction is probably mediated by elevated HDL-concentration. Whether genotyping of the CETP/C-629A polymorphism provides information over and above that obtained by HDL-cholesterol measurement has to be further investigated in various prospective studies.

Carrier Proteins↗
PubMed2004

[Immunactivation in chronic heart failure. Inflammatory mediators].

Inflammatory cytokines are thought to contribute to the development and progression of chronic heart failure (CHF). It has been shown that especially tumor necrosis factor-alpha (TNF) is activated in patients with CHF and exerts detrimental effects on the myocardium. Recent studies have demonstrated that circulating levels of TNF, soluble TNF receptors 1 and 2 and interleukin-6 are strong prognostic markers. The results of two randomized studies directly antagonizing TNF in CHF patients were rather disappointing. Nevertheless, TNF antagonism remains a therapeutic option and should be focussed on patients with systemic immune activation, particularly at times of exacerbation.

Adjuvants, Immunologic↗
PubMed2004

[Influence of impaired fasting glucose on the incidence and prognosis of atherosclerosis in various vascular regions].

UNLABELLED: Patients with cardiovascular disease have a poorer diagnosis if they are diabetic. The risk for cardiovascular events is already increased in individuals with impaired fasting glucose (IFG). The aim of this study was to evaluate the impact of diabetes mellitus (DM) and IFG on the incidence of atherosclerotic manifestations and on the long-term prognosis of patients with atherosclerosis in various vascular regions. METHODS: In a prospective study we included 906 patients (72.5% men, mean age 62 +/- 9 years) preceding heart catheterization. All patients were evaluated for the presence of peripheral stenosis by carotid duplex sonography (pathologic: stenosis >50%) and evaluation of the ankle-brachial index (pathologic <0.9). Blood samples were drawn from each subject after an overnight fasting period and serum glucose was evaluated. RESULTS: Patients were compared with regard to the presence of DM (known DMor fasting glucose > or =126 mg/dL, N = 283, 31.2%) or IFG (fasting glucose >110 and <126 mg/dL, N = 89, 9.8%). Patients with IFG and DM had a higher prevalence of atherosclerotic manifestations in the coronary, carotid and peripheral vessels. Diabetics had the highest prevalence of atherosclerotic manifestations in multiple vascular regions (=advanced atherosclerosis). Cardiovascular events (death, myocardial infarction and stroke) after a median follow-up of 4.1 years were evaluated in 901 patients (99.4%). Presence of IFG and DM significantly increased the incidence of cardiovascular events (event rate: no DM 10.9%, IFG 13.6%, DM 23.4%, P < 0.0001). Moreover, patients with advanced atherosclerosis suffered significantly more often from cardiovascular events (event rate: no stenosis 4.1%, coronary artery disease without peripheral stenosis 9.7%, advanced atherosclerosis 23.9%). Prognosis was worst in patients with DM and advanced atherosclerosis with an event rate of 35%.Patients with cardiovascular disease have a poorer prognosis if they are diabetic. The risk for cardiovascular events is already increased in individuals with impaired fasting glucose (IFG). The aim of this study was to evaluate the impact of diabetes mellitus (DM) and IFG on the incidence of atherosclerotic manifestations and on the long-term prognosis of patients with atherosclerosis in various vascular regions.

Aged↗
PubMed2003

SELPLG gene polymorphisms in relation to plasma SELPLG levels and coronary artery disease.

P-selectin and P-selectin glycoprotein ligand (SELPLG, selectin P ligand) constitute a receptor/ligand complex that is likely to be involved in the development of atherosclerosis and its complications. While the genetic variability of P-selectin has already been investigated in depth, that of the SELPLG gene has not yet been extensively explored. The coding and regulatory sequences of the SELPLG were screened and nine polymorphisms were identified. The identified polymorphisms were genotyped in the AtheroGene study, a case-control study of coronary artery disease (CAD). Haplotype analysis revealed that two polymorphisms of SELPLG, the M62I and the VNTR, independently influenced plasma SELPLG levels. Conversely, haplotypes of SELPLG were not associated with CAD risk.

Adult↗
PubMed2002

The superiority of TIMI frame count in detecting coronary flow changes after coronary stenting compared to TIMI Flow Classification.

AIMS: We compared the qualitative Thombolysis in Myocardial Infarction (TIMI) Flow Classification with a new quantitative method, the TIMI Frame Count, to investigate the differences of both systems in detecting coronary flow changes after stent implantation. METHODS: TIMI flow grades and corrected TIMI frame counts (CTFC) were determined in 102 patients before, after stent implantation and at 6-month angiography. Analysis of the CTFC in patients with TIMI flow grades 3 and 2 demonstrated that for CTFC values lower than 30 frames, all patients had TIMI flow grade 3, while for CTFC values greater than 69 frames no patient had TIMI grade 3 flow. For CTFC values between 30 and 69 frames, TIMI grades 3 and 2 flow overlap. Comparing changes in TIMI flow grades and the CTFC before and after stent implantation (after stent implantation and at 6 month angiography), CTFC detects flow changes in 46% (40%) of the patients, which were not detected with TIMI Flow Classification. CONCLUSION: The TIMI Flow Classification grading system is not able to separate clearly between completely perfused and partially perfused coronary artery vessels. The quantitative TIMI Frame Count method is superior to the qualitative TIMI Flow Classification in detecting coronary flow changes.

Adult↗
PubMed2001

Circulating cell adhesion molecules and death in patients with coronary artery disease.

BACKGROUND: Vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, and E-selectin mediate adhesion and transmigration of leukocytes to the vascular endothelial wall and may promote plaque growth and instability. In a prospective study, we evaluated the effect of soluble adhesion molecules on the risk of future cardiovascular events among patients with angiographically documented coronary artery disease (CAD). Methods and Results- -We obtained baseline samples from a prospective cohort of 1246 patients with CAD. Besides various markers of inflammation, soluble VCAM-1 (sVCAM-1), sICAM-1, and sE-selectin were determined. Follow-up information on cardiovascular events was obtained (mean, 2.7; maximum, 4.1 years). Independently higher levels of sVCAM-1 (1932 versus 1128 ng/mL; P<0.0001), sICAM-1 (353 versus 287 ng/mL; P=0.015), and sE-selectin (81 versus 63 ng/mL; P=0.003) were observed in patients with future death from cardiovascular causes. In a multivariate model, fatal risk was 2.1-fold (1.1 to 4.0) higher in patients within the top quartile of baseline sVCAM-1 concentrations compared with lower quartiles. This association was present independent of general inflammatory response as reflected by low or high C-reactive protein (hs-CRP) levels. In a model that simultaneously controlled for all inflammatory and soluble adhesion markers determined, only sVCAM-1 remained independently significant for future fatal cardiovascular events, with a 2.8-fold increase in risk (P=0.003). CONCLUSIONS: Soluble adhesion molecules sVCAM-1, sICAM-1, and sE-selectin were significantly related to future death from cardiovascular causes among patients with documented CAD. Especially sVCAM-1 added to the predictive value of classic risk factors and hs-CRP in determining the risk of future cardiovascular death.

Aged↗
PubMed2001

Impact of viral and bacterial infectious burden on long-term prognosis in patients with coronary artery disease.

BACKGROUND: The number of infectious pathogens to which an individual has been exposed (infectious burden) may correlate with coronary artery disease (CAD). In a prospective study, we evaluated the effect of 8 pathogens and the aggregate pathogen burden on the risk for future fatal cardiac events among patients with angiographically documented CAD. Methods and Results-In 1018 patients, IgG or IgA antibodies to herpes simplex virus types 1 and 2, cytomegalovirus, Epstein-Barr virus, Haemophilus influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori were determined. Moreover, highly sensitive C-reactive protein was measured. Follow-up information on cardiovascular events was obtained (mean 3.1 years, maximum 4.3 years). Seropositivities to Epstein-Barr virus (P=0.001), H pylori (P=0.002), and herpes simplex virus type 2 (P=0.045) were independently associated with the future risk of cardiovascular death. An increasing number for pathogen burden was significantly predictive of the long-term prognosis (P<0.0001). Infectious burden divided into 0 to 3, 4 or 5, and 6 to 8 seropositivities was associated with an increasing mortality of 3.7%, 7.2%, and 12.6%, respectively. Patients seropositive to >5 pathogens compared with those seropositive to <4 pathogens had a 5.1 (1.4 to 18.3) higher risk of future cardiac death. This result was mainly driven by the pathogen burden of seropositivities to Herpesviridae (P<0.0001). The prognostic impact of total or viral pathogen burden was independent of the C-reactive protein level. CONCLUSIONS: These results support the hypothesis that the number of infectious pathogens to which an individual has been exposed independently contributes to the long-term prognosis in patients with documented CAD.

Antibodies, Bacterial↗
PubMed2001

Cytomegalovirus infection with interleukin-6 response predicts cardiac mortality in patients with coronary artery disease.

BACKGROUND: Prospective data relating previous exposure to cytomegalovirus (CMV) to the risk of cardiac mortality are controversial. We investigated the effect of previous exposure to CMV infection on the risk of future cardiac disease-related death in relation to an underlying inflammatory response. METHODS AND RESULTS: coronary angiography was performed in 1134 subjects, and 989 patients with documented coronary artery disease were studied prospectively. CMV-IgG titers and interleukin (IL)-6 levels were measured before angiography. Increasing titers of CMV correlated with the elevation of IL-6 levels (P<0.001) after adjustment for possible confounders. All patients were followed up for a median of 3.1 years (maximum 4.3 years). During follow-up, 96 patients died, 70 of cardiac disease. Overall, CMV seropositivity was not related to cardiac mortality after adjustment for confounding variables (P=0.19). In contrast, in patients with elevated IL-6 levels (>/=11.9 pg/mL, median level), CMV seropositivity was independently associated with a 3.2-fold (95% CI 1.4 to 7.3, P=0.007) increase in risk of future cardiac death, whereas in individuals without IL-6 elevation, previous CMV infection had no effect on cardiac mortality. CONCLUSIONS: MV seropositivity in patients with an inflammatory response is independently associated with future cardiac mortality, whereas this association is lost in patients who do not demonstrate an inflammatory response. These data support the hypothesis that the atherosclerotic effects of CMV are mediated through an underlying inflammatory response.

Aged↗
PubMed2001

[The role of inflammation and infection in acute coronary syndrome].

UNLABELLED: INFLAMMATORY PROCESS: Within the vessel wall is considered to be crucial for initiation and progression of atherosclerosis. As response to endothelial injury a focal inflammatory response arises which can lead to plaque vulnerability and rupture and a consecutive acute coronary syndrome. Systemic markers of inflammation like C-reactive protein (CRP) or interleukin (IL) 6 are elevated in stable angina and acute coronary syndrome and are associated with future cardiovascular events even in initially healthy people. Alongside classical risk factors infectious agents like cytomegalovirus or Chlamydia pneumoniae are discussed to be involved in the local and systemic inflammatory response. Seroepidemiological studies revealed disparate results of the association between antibody titers against Chlamydia pneumoniae or cytomegalovirus and prevalence of coronary artery disease or future cardiovascular events. In animal models Chlamydia pneumoniae and cytomegalovirus increase accelerated neointimal response, however, molecular mechanisms are not entirely clear. CONCLUSION: Whereas local and systemic inflammatory processes play a crucial role in atherogenesis and prognosis the causal role of infection in atherogenesis remains controversial.

Acute Disease↗
PubMed2001

Comparison of diagnostic performance of cardiac troponin I on the IMMULITE system with other automated troponin I assays in minor myocardial damage.

An analytical and clinical evaluation of cardiac troponin I (cTnI) on the IMMULITE system is presented. The assay results were compared with those of the Stratus II and the Dimension RxL-HM. A between-run imprecision CV < 20% was found at a cTnI concentration of 0.23 microg/L (functional limit of detection). On the basis of a reference study including 215 patients without ischemic heart disease (97.5th percentile: 0.294 microg/L) and 36 patients clinically classified as having stable angina pectoris (<0.22 microg/L) a preliminary cutoff level of 0.3 microg/L was defined. Assay linearity, sample stability, influence of sample material and method comparison studies were performed. In patients with Duchenne's disease, chronic hemodialysis treatment, pulmonary embolism, coronary artery bypass surgery and minimally cardiac surgery the cTnI results of the IMMULITE agreed better with the Dimension RxL-HM than with the Stratus II data. Of 142 samples from patients with unstable angina 67 samples were classified as cTnI positive with the IMMULITE, 76 with the Dimension RxL-HM, and 62 with the Stratus II. In conclusion, the new assay is sensitive for the determination of cTnI and easy to perform within 45 min.

Adult↗
PubMed2001

Association between P-selectin gene polymorphisms and soluble P-selectin levels and their relation to coronary artery disease.

P-selectin is a cellular adhesion molecule that mediates the interaction of activated endothelial cells or platelets with leukocytes. Increased levels of soluble P-selectin have been reported in various cardiovascular disorders. We measured serum soluble P-selectin levels as well as 3 polymorphisms of the P-selectin gene (C-2123G, A-1969G, and Thr715Pro) in a large cohort of patients with documented coronary artery disease (n=869) and a healthy control group (n=334). The 3 P-selectin polymorphisms were strongly associated with P-selectin levels and altogether explained 7.3% and 18.6% of the P-selectin variability in patients and controls, respectively. Genotype distributions did not significantly differ between patients and controls. P-selectin levels were increased in patients younger than 55 years of age compared with controls (135.2 vs 114.3 ng/mL, P<0.01). On the contrary, patients older than 65 years of age had significantly lower P-selectin levels than did controls (121.5 vs 134.7 ng/mL, P<0.02). In intermediate age groups, P-selectin levels did not significantly differ between the 2 groups. In conclusion, this study revealed a strong association between P-selectin gene polymorphisms and serum P-selectin levels and a complex age-dependent relation between soluble P-selectin levels and coronary artery disease, which suggests that this molecule might have different roles in the atherothrombotic process.

Cohort Studies↗
PubMed2000

Are morphological or functional changes in the carotid artery wall associated with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, or herpes simplex virus infection?

BACKGROUND AND PURPOSE: Chronic infection with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus (CMV), and herpes simplex virus (HSV) has been implicated in the pathogenesis of atherosclerosis. The carotid intima-media thickness (IMT) can be taken to indicate early atherosclerosis, the presence of a carotid stenosis is a marker of a manifest carotid atherosclerosis, and an increase in arterial stiffness is used as marker of structural and functional changes in an atherosclerotic vessel wall. METHODS: In 504 patients (75% men; mean age 62.9 [SD 10] years), we measured the IMT and the elastic pressure modulus (EP; n=445) of the common carotid artery and the prevalence of a internal or external carotid artery stenosis. Blood samples were taken, and antibodies against C pneumoniae, H pylori, CMV, and HSV types 1 and 2 were evaluated. Statistical evaluation was performed with regression procedures and multivariate logistic regression analyses. RESULTS: Seropositivity for C pneumoniae was an independent predictor for a combined end point of highest category of IMT and carotid artery stenosis (OR 1.8, 95% CI 1.1 to 3.1; adjusted) for IgG titers. Independently, CMV increased the risk for the combined end point (OR 1.7, 95% CI 1.1 to 2.8; adjusted) for IgG titers and for IgA titers (OR 2.3, 95% CI 1.1 to 4. 9; adjusted). We found a significant correlation between IgG antibodies against CMV and EP; HSV type 2 IgG titers were associated with IMT and carotid stenosis, but the latter results were no longer significant after adjustment. There was no association with H pylori or HSV type 1. CONCLUSIONS: We found a significant association of IgG antibodies against C pneumoniae and CMV with early and advanced carotid atherosclerosis. CMV was also correlated to functional changes of the carotid artery, but this could not be confirmed after adjustment.

Arteriosclerosis↗
PubMed2000

Analytical and clinical evaluation of troponin I determination on dimension RXL-HM.

The evaluation of cardiac troponin I (cTnI) on the Dimension RxL-HM analyzer is presented. The one-step enzyme immunoassay is based on two cTnI specific monoclonal antibodies. Performed on a separate module of the analyzer, assay-time is 17 minutes. Using as criterion a between-run impression CV <20% the functional limit of detection was set at 0.1 microg/l. Cutoff level for minor myocardial damage of 0.1 microg/l was found. In Duchenne's dystrophy, patients showed increased cardiac Troponin T (cTnT) but no increased cTnI. In patients with a history of coronary heart disease undergoing chronic hemodialysis, cTnT and cTnI were increased. In different patients with submassive pulmonary embolism, increased cTnI was determined. In coronary artery bypass surgery without perioperative myocardial infarction, patients with extracorporeal circulation showed significantly higher cTnI at 24 h after surgery than those with minimal cardiac surgery. In patients with unstable angina, increased cTnI was found more often than on Stratus analyzer. In conclusion, the new assay is a very sensitive cTnI assay, fast and easy to perform in parallel to enzyme and substrate assays.

Adult↗