CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-α levels

2004

SummaryMonocytes play a central role in the inflammatory disease atherosclerosis. CD14+CD16+ monocytes are considered proinflammatory monocytes, as they have an increased capacity to produce proinflammatory cytokines, such as TNF-α, and are elevated in various inflammatory diseases. We hypothesized that patients with coronary artery disease (CAD) have increased levels of CD14+CD16+ monocytes, and that CD14+CD16+ monocytes are associated with inflammation markers. We investigated CD14+CD16+ monocytes in 247 patients with CAD and 61 control subjects using flow cytometry. In addition serum concentrations of TNF-α, IL-6, and Hs-CRP were assessed. Patients with CAD had higher levels of CD14+CD16…

Different calculations of ankle-brachial index and their impact on cardiovascular risk prediction.

2008

Background— An ankle-brachial index (ABI; ratio of ankle and brachial systolic blood pressure) <0.9 indicates peripheral arterial disease (PAD) and is a strong predictor of cardiovascular events. The aim of the present study was to address the prognostic value of different methods of ABI calculation. Methods and Results— In 831 patients admitted with chest pain for diagnostic heart catheterization, blood pressure of both anterior and posterior tibial arteries was measured. ABI was calculated for each leg with the higher of the 2 ankle pressures (current definition of the American Heart Association) or with the lower of the 2 ankle pressures (modified definition) in relation to the highe…

Serum uric acid as an independent predictor of mortality in patients with angiographically proven coronary artery disease.

2002

It is a matter of controversy as to whether uric acid is an independent predictor of mortality in patients with coronary artery disease (CAD) or whether it represents only an indirect marker of adverse outcome by reflecting the association between uric acid and other cardiovascular risk factors. Therefore, we studied the influence of uric acid levels on mortality in patients with CAD. In 1,017 patients with angiographically proven CAD, classic risk factors and uric acid levels were determined at enrollment. A follow-up over a median of 2.2 years (maximum 3.1) was performed. Death from all causes was defined as an end point of the study. In CAD patients with uric acid levels303 micromol/L (5…

Influence of HMG-CoA reductase inhibitors on markers of coagulation, systemic inflammation and soluble cell adhesion.

2002

Abstract Background: Beneath its lipid-lowering properties additional non-lipid effects of statin therapy are discussed. We therefore examined the impact of statins on laboratory markers of coagulation, inflammation and soluble cell adhesion to further explore these effects in 950 hospitalised patients with angiographically proven CAD. Methods and results: Although no significant differences were found in total cholesterol, LDL and HDL and triglyceride levels a statistically lower value in 277 statin-treated patients was found for von Willebrand factor [162(130/224) vs. 208(154/283)%, P =0.0001], leukocyte count [6.9(5.8/8.4) vs. 7.3(6.1/9.4)/nl, P =0.0005], high sensitive CRP [4.3(1.8/10.8…

Inflammation, atherosclerotic burden and cardiovascular prognosis.

2006

The aim of this study was to evaluate the impact of various inflammatory markers on atherosclerotic burden and cardiovascular prognosis.In a prospective study 720 patients preceding coronary angiography were enrolled. In all patients carotid and leg arteries were examined using sonographic methods and C-reactive protein, fibrinogen, interleukin-18 (IL-18) and interleukin-6 have been determined. Patients were compared with regard to atherosclerotic burden: no clinically significant stenosis (N=57, 7.9%), coronary artery disease only (N=362, 50.3%), coronary artery disease with peripheral atherosclerosis (=multi-vascular atherosclerosis, N=301, 41.8%).Follow-up data after a median of 6.5 year…

Resistin, acute coronary syndrome and prognosis results from the AtheroGene study

2006

Resistin, an adipocyte and macrophage derived cytokine, causes insulin resistance and glucose intolerance. We investigated the impact of resistin as a diagnostic marker in patients with acute coronary syndrome and its prognostic value for future cardiovascular events.Resistin levels were determined in 1153 patients with stable angina (SAP), 380 patients with unstable angina, 278 patients with non-ST-elevation myocardial infarction (NSTEMI) and 111 patients with ST-elevation myocardial infarction (STEMI). All patients have been followed up for a median follow-up of 2.6 years. During follow-up, 70 patients died from cardiovascular causes.Compared to SAP, resistin levels (5.1 ng/mL in SAP) wer…

Factors Correlating with Restenosis after PTCA

1991

Since its introduction in 1977 [7, 8], PTCA has been widely used in patients with coronary artery disease. Restenosis with recurrence of angina remains the major problem, limiting the long-term success after PTCA. Reported restenosis rates vary from 17% to 47% [9–19, 22–26]. In larger series [12, 15, 26] a restenosis rate of about 30% was constantly found, irrespective of the definition of restenosis in use.

Cystatin C and cardiovascular mortality in patients with coronary artery disease and normal or mildly reduced kidney function: results from the Ather…

2009

Aims Chronic kidney disease is associated with increased risk of cardiovascular disease. Cystatin C is a promising marker to reliably mirror renal function. The role of cystatin C in patients with coronary artery disease (CAD) and normal or mildly reduced kidney function is the subject of current investigation. Methods and results In 2162 patients, over the whole spectrum of CAD, baseline cystatin C concentrations were measured. Patients with an estimated glomerular filtration rate of ≤60 mL/min per 1.73 m2 ( n = 295) were excluded. In patients with complete follow-up information ( n = 1827), 66 cardiovascular deaths were registered during a median follow-up of 3.65 years. Logarithmically t…

Die Rolle von Inflammation und Infektion bei akutem Koronarsyndrom

2001

Ein entzundlicher Prozess innerhalb der Gefaswand wird heute weitgehend als Ursache fur Beginn und Progression der Atherosklerose angesehen. Als Reaktion auf eine Endothelzellverletzung kommt es zu einer fokalen Entzundungsreaktion, die eine Vulnerabilitat der Plaque mit moglicher Ruptur und schlieslich das klinische Bild eines akuten Koronarsyndroms zur Folge haben kann.

Response to Letter Regarding Article, “Different Calculations of Ankle Brachial Index and Their Impact on Cardiovascular Risk Prediction”

2009

We thank Jaquinandi et al for their interest in our publication. We want to stress that the patient population of the AtheroGene study is not comparable with the patient populations reported in the articles from Lee et al and Kreitner et al, which included only patients with known advanced peripheral arterial disease.1,2 The AtheroGene study includes primarily patients with coronary artery disease, no patient had rest pain or peripheral ulcers and only 52 patients (6.3%) had intermittent claudication.3 In addition, …

Comparative impact of multiple biomarkers and N-terminal pro-brain natriuretic peptide in the context of conventional risk factors for the prediction…

2006

Background— Individual markers of inflammation may add incremental predictive value in the context of conventionally available risk factors. We evaluated the ability of 9 inflammatory biomarkers, microalbuminuria, and N-terminal pro-brain natriuretic peptide (Nt-proBNP) to improve cardiovascular risk prediction beyond that obtained from traditional risk factors in a secondary-prevention population. Methods and Results— We measured biomarkers representing the acute-phase reaction (C-reactive protein, fibrinogen, and interleukin-6), proinflammatory pathways (soluble tumor necrosis factor receptor-1 and -2, soluble interleukin-1 receptor antagonist, and interleukin-18), endothelial activation…

Prognostic use of soluble fms-like tyrosine kinase-1 and placental growth factor in patients with coronary artery disease.

2015

Background: Intention of the study is to assess the cardiovascular mortality of patients with coronary artery disease (CAD) with the biomarkers of angiogenesis PlGF and its endogenous inhibitor sFlt-1. Methods: The cohort included n = 1848 patients with CAD and 282 subjects without CAD. In 85 patients cardiovascular mortality, as combination of fatal myocardial infarction or any cardiac death, during a median follow-up duration of 3.9 years was reported. Results: In Kaplan–Meier curve analysis PlGF in rising thirds was not predictive regarding outcome (p = 0.54), the same was shown for sFlt-1 (p = 0.44). Cox regression for the fully adjusted model provided a hazard ratio (HR) of 0.8 (p = 0…

Predictors of leptin concentration and association with cardiovascular risk in patients with coronary artery disease: results from the AtheroGene stu…

2016

AbstractContext: Leptin is produced in white adipose tissue, but also in human coronary atherosclerotic lesions.Objective: The aim of this study is to assess the prognostic value of leptin in patients with proven coronary artery disease (CAD) (N = 1907).Methods: AtheroGene is a contemporary CAD cohort study (N = 3229). Median follow-up time was 3.8 (Quartile 1/3 with 2.8/4.9) years.Results: Leptin concentration was associated with a hazard ratio (HR) for the fully adjusted model of HR = 1.32 in women but was not significant in men. The endpoint cardiovascular death and non-fatal myocardial infarction was observed in 167 patients.Conclusion: In women with known CAD, increased leptin concentr…

Interleukin-18 Is a Strong Predictor of Cardiovascular Death in Stable and Unstable Angina

2002

Background — Interleukin (IL)-18 plays a central role in orchestrating the cytokine cascade and accelerates atherosclerosis and plaque vulnerability in animal models. However, epidemiological data evaluating the role of IL-18 levels in atherosclerosis are lacking. Methods and Results — In a prospective study of 1229 patients with documented coronary artery disease, we measured baseline serum concentrations of IL-18 and other markers of inflammation. During the follow-up period (median, 3.9 years), 95 patients died of cardiovascular causes. Median serum concentrations of IL-18 were significantly higher among patients who had a fatal cardiovascular event than among those who did not (68.4 ve…

Fondaparinux and enoxaparin in comparison to unfractionated heparin in preventing thrombus formation on mechanical heart valves in an ex vivo rabbit …

2003

SummaryThe aim of the present study was to investigate the efficacy of three different parenterally administered anticoagulants for the prevention of thrombus formation on artificial heart valves in an experimental rabbit model.Unfractionated heparin was administered intravenously in group I (n = 10), Enoxaparin subcutaneously in group II (n = 10), fondaparinux intravenously in group III (n = 10), and no medication was administered to group IV (n = 9). Leaflets from Sulzer Carbomedics bileaflet mechanical heart valves were placed in a flow chamber. The flow chamber was filled with blood in a continuous circulation between the carotid artery and the jugular vein.In group IV the flow chamber …

Herpesvirus DNA (Epstein-Barr virus, herpes simplex virus, cytomegalovirus) in circulating monocytes of patients with coronary artery disease

2005

Background -The underlying mechanism of the chronic inflammatory process in atherosclerosis is still unknown. As a possible trigger, several studies in recent years have suggested that different viruses and bacteria are associated with atherosclerotic diseases. Methods - We applied polymerase chain reaction to analyse whether Epstein-Barr virus (EBV), herpes simplex virus (HSV), and cytomegalovirus (CMV) DNA could be detected in CD14 + cells from 184 patients with angiographically documented coronary artery disease (CAD) (74 patients with stable angina (SAP), 51 patients with unstable angina (UAP), and 59 patients with myocardial infarction (Ml)) and from 52 healthy controls. Results - In t…

Clopidogrel and aspirin in the prevention of thromboembolic complications after mechanical aortic valve replacement (CAPTA)

2003

Axel Schlitt*, Ralf S. von Bardeleben, Anne Ehrlich, Antje Eimermacher, Dirk Peetz, Manfred Dahm, Hans J. Rupprecht Department of Medicine II, Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany Coordination Center for Clinical Studies, Johannes Gutenberg-University Mainz, Mainz, Germany Clinic for Clinical Chemistry and Laboratory Medicine, Johannes Gutenberg-University Mainz, Mainz, Germany Department of Cardiothoracic and Vascular Surgery, Johannes Gutenberg-University Mainz, Mainz, Germany

Glutathione Peroxidase 1 Activity and Cardiovascular Events in Patients With Coronary Artery Disease

2003

Along with superoxide dismutase, glutathione peroxidase 1 is one of the cellular antioxidant enzymes that have a key role in controlling reactive oxygen species. It uses glutathione to reduce hydrogen peroxide to water and lipid peroxides to their respective alcohols. There are suggestions from in vitro and animal studies that these enzymes could protect against atherosclerosis. This prospective study examined the possibility that relatively high activity of antioxidant enzymes protects against cardiovascular events. The study population included 636 patients suspected of having coronary artery disease who were followed for a median period of 4.7 years. Stable angina was present in 510 pati…

Circulating Cell Adhesion Molecules and Death in Patients With Coronary Artery Disease

2001

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 even…

Abciximab Facilitates the Rate and Extent of Thrombolysis

1999

Background —The TIMI 14 trial tested the hypothesis that abciximab, the Fab fragment of a monoclonal antibody directed to the platelet glycoprotein (GP) IIb/IIIa receptor, is a potent and safe addition to reduced-dose thrombolytic regimens for ST-segment elevation MI. Methods and Results —Patients (n=888) with ST-elevation MI presenting <12 hours from onset of symptoms were treated with aspirin and randomized initially to either 100 mg of accelerated-dose alteplase (control) or abciximab (bolus 0.25 mg/kg and 12-hour infusion of 0.125 μg · kg −1 · min −1 ) alone or in combination with reduced doses of alteplase (20 to 65 mg) or streptokinase (500 000 U to 1.5 MU). Control patients recei…

Association of soluble endothelial protein C receptor plasma levels and PROCR rs867186 with cardiovascular risk factors and cardiovascular events in …

2012

Abstract Background Blood coagulation is an essential determinant of coronary artery disease (CAD). Soluble Endothelial Protein C Receptor (sEPCR) may be a biomarker of a hypercoagulable state. We prospectively investigated the relationship between plasma sEPCR levels and the risk of cardiovascular events (CVE). Methods We measured baseline sEPCR levels in 1673 individuals with CAD (521 with acute coronary syndrome [ACS] and 1152 with stable angina pectoris [SAP]) from the AtheroGene cohort. During a median follow up of 3.7 years, 136 individuals had a CVE. In addition, 891 of these CAD patients were genotyped for the PROCR rs867186 (Ser219Gly) variant. Results At baseline, sEPCR levels wer…

Variations in acoustical beam properties of intracoronary Doppler catheters.

1993

The limitations of coronary angiography in assessing the functional significance of coronary obstructions is well known. While the critical variable of coronary blood flow cannot be readily measured, intraluminal Doppler sonography offers useful related functional information on blood flow velocity. In order to fully evaluate Doppler signals it is essential to have exact knowledge of the transducer transmission characteristics and of the ultrasound beam topology. In an experimental set-up, the transmitter-receiver characteristics of five commonly used Doppler catheters were investigated. In comparing the beam characteristics we found inhomogeneities in the lateral beam spread. At a penetrat…

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

2001

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 …

Impact of inflammatory markers on cardiovascular mortality in patients with metabolic syndrome.

2008

Recent investigations suggest the inclusion of inflammatory markers in the definition of the metabolic syndrome (MS). The aim of this study was to address the role of C-reactive protein, fibrinogen, interleukin-6 (IL-6) and IL-18 (IL-18) on cardiovascular prognosis in accordance to MS.A total of 1263 patients with documented coronary artery disease were prospectively included. We defined MS (MS yes: N=533, 42.2%) as the presence of at least three of the following criteria: triglyceridesor=150 mg/dl; low high-density lipoprotein cholesterol (men:40 mg/dl women:50 mg/dl); body mass index greater than 30 kg/m; blood pressureor=130/85 mmHg; fasting glucoseor=100 mg/dl. In addition, we determine…

Plasma PAF-acetylhydrolase in patients with coronary artery disease: results of a cross-sectional analysis.

2003

Inflammation underlies both onset and perpetuation of atherosclerosis. Plasma lipoproteins transport the platelet-activating factor-acetylhydrolase (PAF-AH) with potentially anti-inflammatory activities. Our aim was to determine whether PAF-AH activity was associated with inflammatory markers and with coronary artery disease (CAD). PAF-AH activity and a panel of inflammatory mediators were measured in plasma of 496 patients with CAD and in 477 controls; 276 patients presented with stable angina pectoris and 220 with acute coronary syndrome (ACS). Individuals within the highest quartile of PAF-AH activity had an 1.8-fold increase in CAD risk [95% confidence interval (CI), 1.01 to 3.2; P = 0.…

Midregional Proadrenomedullin for Prediction of Cardiovascular Events in Coronary Artery Disease: Results from the AtheroGene Study

2011

Abstract BACKGROUND Midregional proadrenomedullin (MR-proADM) is a newly identified prognostic marker in heart failure. We evaluated the prognostic impact of MR-proADM in a cohort of patients with symptomatic coronary artery disease according to their clinical presentation. METHODS We measured baseline MR-proADM concentrations in 2240 individuals from the prospective AtheroGene study and evaluated the prognostic impact on future fatal and nonfatal cardiovascular events during a follow-up period of 3.6 (1.6) years. RESULTS The sample comprised 1355 individuals with stable angina pectoris (SAP) and 885 with acute coronary syndrome (ACS). A cardiovascular event occurred in 192 people. Individu…

Ectasia and Aneurysm of the Right Coronary Artery Resulting From a Shunt to the Coronary Sinus

1998

A 65-year-old woman presented with a systolic-diastolic murmur. Further MRI investigations as well as angiography revealed an arteriovenous shunt to the coronary sinus via an enlarged right coronary artery (Figure 1A⇓ and 1B⇓). The distal part of this coronary artery was transformed to a large coronary aneurysm of such extent that the left atrium was compressed …

Analysis of risk factors for restenosis after PTCA

1990

To identify risk factors for restenosis, we evaluated data in 473 patients with single-vessel percutaneous transluminal coronary angioplasty (PTCA) and control angiography after 6 months. Restenosis, defined as (1) loss greater than 50% of the initial gain, and (2) stenosis greater than 50% was found in 138 patients (29.2%). Univariate analysis revealed eight factors related to restenosis: (1) duration of symptoms less than 1 month (P = 0.005), (2) unstable angina (P = 0.004), (3) high-grade stenosis before PTCA (P = 0.014), (4) large residual stenosis after PTCA (P = 0.001), (5) insufficient improvement of stenosis (P = 0.042), (6) prolonged single inflation time (P = 0.017), (7) prolonged…

Prognostic value of tissue inhibitor of metalloproteinase-1 for cardiovascular death among patients with cardiovascular disease: results from the Ath…

2005

Aims Metalloproteinases are proteolytic enzymes, which decompose the extracellular matrix, influence cardiac remodelling, and are inhibited by tissue inhibitor of metalloproteinases (TIMPs). Little is known about the prognostic impact of the TIMP-1/matrix metalloproteinase complex in patients with future cardiovascular death. Methods and results In 1979 patients with suspected coronary artery disease (CAD), TIMP-1 has been determined at baseline. Among 1945 (98.4%) patients with a mean follow-up period of 2.6±1.2 years, 75 patients died because of cardiovascular causes. Mean concentrations of TIMP-1 were higher among patients who experienced a fatal cardiovascular event than among those who…

Cardioprotective Effects of the Na + /H + Exchange Inhibitor Cariporide in Patients With Acute Anterior Myocardial Infarction Undergoing Direct PTCA

2000

Background —Activation of Na + /H + exchange in myocardial ischemia and/or reperfusion leads to calcium overload and myocardial injury. Experimental studies have shown that Na + /H + exchange inhibitors can attenuate Ca 2+ influx into cardiomyocytes. We therefore performed a multicenter, randomized, placebo-controlled clinical trial to test the hypothesis that inhibition of Na + /H + exchange limits infarct size and improves myocardial function in patients with acute anterior myocardial infarction (MI) treated with direct PTCA. Methods and Results —One hundred patients were randomized to receive placebo (n=51) or a 40-mg intravenous bolus of the Na + /H + exchange inhibitor cariporide (HOE…

Multiple marker approach to risk stratification in patients with stable coronary artery disease

2010

Aims Multimarker approaches for risk prediction in coronary artery disease have remained inconsistent. We assessed multiple biomarkers representing distinct pathophysiological pathways in relation to cardiovascular events in stable angina. Methods and results We investigated 12 biomarkers reflecting inflammation [C-reactive protein, growth-differentiation factor (GDF)-15, neopterin], lipid metabolism (apolipoproteins AI, B100), renal function (cystatin C, serum creatinine), and cardiovascular function and remodelling [copeptin, C-terminal-pro-endothelin-1, mid-regional-pro-adrenomedullin (MR-proADM), mid-regional-pro-atrial natriuretic peptide (MR-proANP), N-terminal-pro-B-type natriuretic …

Glutathione Peroxidase-1 and Homocysteine for Cardiovascular Risk Prediction

2005

Objectives This prospective study was designed to evaluate the effect of joint determination of two important contrary biomarkers—homocysteine and glutathione peroxidase (GPx)-1—on cardiovascular risk stratification. Background Homocysteine plasma levels have been associated with cardiovascular risk. Experimental data suggest that antioxidative GPx-1 activity modulates cardiovascular risk associated with homocysteine. Methods In 643 patients with coronary artery disease, we performed a prospective study to assess the risk of homocysteine plasma levels and GPx-1 activity on long-term cardiovascular risk with a median follow-up of 7.1 years. Results Both homocysteine and GPx-1 were among the …

Impact of Viral and Bacterial Infectious Burden on Long-Term Prognosis in Patients With Coronary Artery Disease

2001

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 cardiovascul…

Further evaluation of plasma sphingomyelin levels as a risk factor for coronary artery disease

2006

Abstract Background Sphingomyelin (SM) is the major phospholipid in cell membranes and in lipoproteins. In human plasma, SM is mainly found in atherogenic lipoproteins; thus, high levels of SM may promote atherogenesis. Methods We investigated in a median follow up of 6.0 years the association of SM with the incidence of a combined endpoint (myocardial infarction and cardiovascular death) in stable and unstable patients, and its relation to other marker of atherosclerosis in 1,102 patients with angiographically documented CAD and 444 healthy controls. Results and discussion Logistic regression analysis showed that SM categorized by median was associated with an elevated risk for CAD (HR 3.2…

Serum selenium and prognosis in cardiovascular disease: results from the AtheroGene study

2010

Experimental data suggest a protective role of the essential trace element selenium against cardiovascular disease (CVD), whereas epidemiological data remains controversial. We aimed to investigate the impact of serum selenium concentration in patients presenting with stable angina pectoris (SAP) or acute coronary syndrome (ACS) on long term prognosis.Baseline selenium concentration was measured in 1731 individuals (852 with SAP, and 879 with ACS). During a median follow-up of 6.1 years, 190 individuals died from cardiovascular causes.In those ACS patients who subsequently died of cardiac causes, selenium levels were lower compared to survivors (61.0microg/L versus 71.5microg/L; P0.0001). I…

Coronary thrombolysis with tissue-type plasminogen activator (t-PA)

1985

Coronary thrombolysis is presently under intensive investigation as a treatment for acute myocardial infarction for two main reasons. Firstly it is now well established that acute myocardial infarction is often associated with thrombotic occlusion of an atherosclerotic coronary artery [1]. Secondly it has been shown that administration of thrombolytic agents can reopen an occluded coronary artery in the majority of patients [2, 3] and that reperfusion of ischemic myocardial tissue is generally well tolerated. Coronary thrombolysis is however not a goal in itself but is employed to prevent necrosis and dysfunction of jeopardized myocardial cells. There is ample evidence in animals that the i…

Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease.

2003

Background—Matrix metalloproteinase (MMP)-9 secretion by macrophages and other inflammatory cells accelerates atherosclerotic progression and destabilizes vulnerable plaque in animal models. However, epidemiological data evaluating the prognostic impact of circulating concentrations and functional genetic variations of MMP-9 are lacking.Methods and Results—In a prospective study of 1127 patients with documented coronary artery disease, we measured baseline plasma MMP-9 levels and determined the MMP-9/C-1562T and MMP-9/R279Q genotypes. During the follow-up period (mean of 4.1 years), 97 patients died from cardiovascular (CV) causes. Median concentrations of MMP-9 were significantly higher am…

Combined medical and mechanical recanalization in acute myocardial infarction

1985

A technique of combined medical and mechanical recanalization was employed in 96 patients with acute transmural myocardial infarction. The mean time between onset of symptoms and admission to hospital was 170 +/- 65 min (X +/- SD). After 10 +/- 16 min, 250,000 U streptokinase was administered intravenously for 20 min. Intracoronary thrombolysis was commenced within 38 +/- 14 min. First coronary angiograms demonstrated reperfusion, an open vessel in 25/96 patients (26%). In 15/71 patients (21%) reperfusion occurred during thrombolysis therapy, before mechanical recanalization could be performed. Recanalization was achieved mechanically in 37/71 patients (52%) with occluded coronary vessels. …

B-Type Natriuretic Peptide and the Risk of Cardiovascular Events and Death in Patients With Stable Angina

2006

B-Type Natriuretic Peptide and the Risk of Cardiovascular Events and Death in Patients With Stable Angina: Results From the AtheroGeneStudyRenate Schnabel, Edith Lubos, Hans J. Rupprecht, Christine...

Analysis of N-terminal-pro-brain natriuretic peptide and C-reactive protein for risk stratification in stable and unstable coronary artery disease: r…

2004

Aims N-terminal-pro-brain natriuretic peptide (Nt-proBNP) is a reliable risk predictor in acute coronary artery disease (CAD). Little is known about patients with stable angina pectoris (SAP). We aimed to investigate the prognostic impact of Nt-proBNP in a population with CAD especially focussing on patients with SAP. Methods and results We obtained baseline samples from a prospective cohort of 904 consecutive patients with CAD. Cardiovascular events were registered during followup (median 2 years; maximum 3.7 years). Baseline Nt-proBNP was significantly higher among individuals with cardiovascular events compared with those without (711.5 vs. 238.8 pg/mL; P , 0.0001). A similar association…

Common genetic variation of the cholesteryl ester transfer protein gene strongly predicts future cardiovascular death in patients with coronary arter…

2003

OBJECTIVES We sought to evaluate the association between cholesteryl ester transfer protein (CETP) genotypes and the risk of future cardiovascular mortality in patients with coronary artery disease (CAD). BACKGROUND Polymorphisms of the CETP gene influence CETP activity and high-density lipoprotein (HDL) cholesterol concentration and might affect the long-term prognosis and response to statin therapy in patients with CAD. METHODS We used serum samples and deoxyribonucleic acid collected at baseline from a prospective cohort of 1,211 patients with CAD prospectively followed up (median follow-up of 4.1 years), 82 of whom experienced a fatal cardiovascular event. The CETP/C-629A and I405V poly…

Substantial Reduction of Platelet Adhesion by Heparin-Coated Stents

2001

Although optimized antiplatelet medication has improved the clinical outcome after coronary stenting, vessel occlusion and restenosis still remain a relevant clinical problem. Platelets play a key role in this process. Therefore, the authors compared the platelet adhesion on different stent surface modifications (electropolished without coating or coated with carbon, carbon and additional heparin, silicon carbide, or heparin alone) to investigate their role in reducing platelet adhesion. All stents and additional stainless steel plates were incubated in heparinized whole blood with radiolabeled platelets. After washing the stents and plates four times, radioactivity caused by the adhesion o…

Association of adiponectin with adverse outcome in coronary artery disease patients: results from the AtheroGene study

2008

In primary prevention, the adipocytokine adiponectin seems to be protective against diabetes mellitus and cardiovascular disease. Data in patients with manifest coronary artery disease (CAD) are scant stimulating the investigation of the association of adiponectin concentrations and cardiovascular outcome in a prospective CAD cohort.In 1890 consecutive patients with documented CAD [1130 with stable angina (SAP) and 760 with acute coronary syndrome (ACS)] baseline concentrations of adiponectin were measured by enzyme-linked immuno assay. During a median follow-up of 2.5 years cardiovascular events were registered (cardiovascular deaths 70; non-fatal myocardial infarction 46). Baseline adipon…

Impact of C-reactive protein and fibrinogen on cardiovascular prognosis in patients with stable angina pectoris: the AtheroGene study.

2006

Aims C-reactive protein and fibrinogen have been extensively studied and shown to be predictive for a first cardiovascular event in healthy individuals. We evaluated the potential clinical use of C-reactive protein and fibrinogen in patients already suffering from coronary artery disease (CAD). Methods and results In a substudy of the prospective Athero Gene registry, we assessed in 1806 patients with documented CAD and stable angina pectoris, the risk of cardiovascular death and non-fatal myocardial infarction ( n =183) over a median follow-up of 3.5 (maximum 7.7) years according to baseline levels of C-reactive protein and fibrinogen. C-reactive protein and fibrinogen were associated with…

Impact of pathogen burden in patients with coronary artery disease in relation to systemic inflammation and variation in genes encoding cytokines.

2003

The number of infectious pathogens to which an individual has been exposed (pathogen burden) has been linked to the development and the prognosis of coronary artery disease (CAD). The interaction among infection, genetic host susceptibility, and CAD remains unclear. This study was aimed at evaluating the modulation of the association between CAD and pathogen burden, by serum levels of inflammatory markers and polymorphisms of the interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha genes. Immmunoglobulin (Ig) G or IgA antibodies to 8 pathogens were determined in 991 patients with CAD and 333 control subjects. Serum levels of high-sensitivity C-reactive protein, fibrinogen, IL-6, and TNF…

Serum sphingomyelin levels are related to the clearance of postprandial remnant-like particles.

2005

It is known that sphingomyelin (SM) content is higher in apolipoprotein B-containing particles (BLps) than in high density lipoproteins and that BLp levels, including chylomicrons and their remnant particles, are positively related to atherosclerosis. To evaluate the relationship between serum SM and postprandial remnant particle levels, we determined SM, triglyceride (TG), and cholesterol levels in serum and in remnant-like particles (RLPs) before and 3, 5, 7, and 10 h after a high-fat meal in 31 healthy subjects. We found that serum SM, like serum TG, was increased to its maximum 3 h after fat loading and then gradually decreased to basal levels after 10 h. More important, we determined t…

Prognostic value of lipoproteins and their relation to inflammatory markers among patients with coronary artery disease

2005

Abstract Background Lipoproteins and their subfractions are associated with the incidence of atherosclerotic diseases. In patients with coronary artery disease (CAD), low serum concentrations of high density lipoprotein (HDL) and high low-density lipoproteins (LDL) are correlated to myocardial infarction and cardiovascular death. There is growing evidence indicating that those lipoprotein factors are related to the inflammatory process in atherogenesis. Methods We investigated in a median follow up of 3.9 years the association of HDL, apolipoprotein A-I (apoA-I), LDL, apolipoprotein B (apoB), and triglycerides with the incidence of a combined endpoint (myocardial infarction and cardiovascul…

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

2016

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation o…

Impact of infectious burden on extent and long-term prognosis of atherosclerosis.

2002

Background — Recent findings suggest a causative role of infections in the pathogenesis of atherosclerosis. In hypothesizing an association between infectious agents and the development of atherosclerosis, we would expect a correlation to the extent of atherosclerosis. Moreover, this effect could be multiplied by the number of pathogens to which an individual had been exposed. Methods and Results — In 572 patients, IgG or IgA antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, Hemophilus influenzae , Chlamydia pneumoniae , Mycoplasma pneumoniae , and Helicobacter pylori were measured. The extent of atherosclerosis was determined by coronary angiography, carotid…

Comparison of antiplatelet effects of aspirin, ticlopidine, or their combination after stent implantation.

1998

Background —This study was performed to analyze the influence of either aspirin, ticlopidine, or their combination on platelet activation and aggregation parameters after stent implantation. Methods and Results —Sixty-one patients with successful implantation of a single Palmaz-Schatz stent in a native coronary artery were randomly assigned to either group A (aspirin 300 mg/d+ticlopidine 2×250 mg/d), group B (ticlopidine 2×250 mg/d), or group C (aspirin 300 mg/d). Platelet activation was evaluated on days 1, 7, and 14 by flow cytometry measurement of expression of CD62p (p-selectin) and the binding of fibrinogen to the platelet surface glycoprotein IIb/IIIa receptor. Platelet aggregation w…

Glutathione Peroxidase-1 Activity, Atherosclerotic Burden, and Cardiovascular Prognosis

2007

Recent findings suggest that erythrocyte intracellular glutathione peroxidase-1 (GPX-1) activity is related inversely to future cardiovascular events. The aim of this study is to evaluate the association of GPX-1 activity to extent of atherosclerosis, as well as its long-term prognosis in context with atherosclerotic burden. In a prospective study, we included 508 patients before coronary angiography. Atherosclerosis of carotid and leg arteries was documented using sonographic methods. Blood samples were drawn after an overnight fasting period, and GPX-1 activity was determined in washed erythrocytes. GPX-1 activity tended to decrease with increasing numbers of atherosclerotic vascular beds…

Asymmetric Dimethylarginine and the Risk of Cardiovascular Events and Death in Patients With Coronary Artery Disease

2005

As a competitive inhibitor of endothelial nitric oxide synthase, asymmetric dimethylarginine (ADMA) has been related to atherosclerotic disease. Little is known about the prognostic impact of baseline ADMA determination. In a prospective cohort of 1908 patients with coronary artery disease, we assessed baseline serum concentration of ADMA in 1874 consecutive patients with coronary artery disease. One hundred fourteen individuals developed the primary end point of death from cardiovascular causes or nonfatal myocardial infarction during a mean follow-up of 2.6±1.2 years. Median concentrations of ADMA levels were higher among individuals who subsequently developed the primary end point than …

Relation of markers of inflammation (C-reactive protein, fibrinogen, von Willebrand factor, and leukocyte count) and statin therapy to long-term mort…

2002

We evaluated a possible interaction between statins and inflammation in 1,246 patients with angiographically diagnosed coronary artery disease. Four different inflammatory markers were determined: high, sensitive C-reactive protein (hs-CRP) (p = 0.001), fibrinogen (p = 0.006), von Willebrand factor (p = 0.006), and leukocyte count (p = 0.03); these levels were significantly higher among the 88 patients who died of cardiac causes during follow-up (median 2.9 years) than among survivors. In a multivariate backward stepwise Cox regression mode, only hs-CRP was evaluated to be a significant predictor of death from coronary artery disease. This prediction was lost in statin-treated patients. Com…

Monocyte-derived dendritic cells of patients with coronary artery disease show an increased expression of costimulatory molecules CD40, CD80 and CD86…

2007

Background Atherosclerosis is a disease triggered by diverse exogenous stimuli and sustained by chronic inflammatory processes. Dendritic cells (DCs) are key regulatory antigen-presenting cells and play a crucial role in regulating the adaptive and innate immune system in any chronic inflammatory process. DCs are present in atherosclerotic lesions in the areas of the highest T-cell density. So far, their role in atherosclerosis has not been fully elucidated. We investigated the phenotypic properties of DCs in patients with coronary artery disease (CAD) in comparison to healthy individuals. Methods Peripheral blood monocytes were isolated from 50 patients with CAD and 19 healthy individuals …

Impact of Metabolic Syndrome on Atherosclerotic Burden and Cardiovascular Prognosis

2007

Patients with metabolic syndrome (MS) are at increased risk of cardiovascular atherosclerosis. The aim of this study was to evaluate the impact of MS on cardiovascular prognosis in context with atherosclerotic burden. A total of 811 patients with coronary heart disease (CHD) were included and carotid and leg arteries were examined using sonographic methods. Patients with low (CHD only, n = 428, 52.8%) or high atherosclerotic burden (CHD and peripheral atherosclerosis, n=383, 47.2%) were compared. Patients withor=3 of the following criteria: triglyceridesor=150 mg/dl, high-density lipoprotein cholesterol40 mg/dl (men) and50 mg/dl (women), body mass index30 kg/m2, blood pressureor=130/85 mm H…

PLTP activity is a risk factor for subsequent cardiovascular events in CAD patients under statin therapy: the AtheroGene study.

2009

Phospholipid transferprotein (PLTP) mediates both net transfer and exchange of phospholipids between different lipoproteins. Although many studies have investigated the role of PLTP in atherogenesis, the role of PLTP in atherosclerotic diseases is unclear. We investigated the association of serum PLTP activity with the incidence of a combined endpoint (myocardial infarction and cardiovascular death) and its relation to other markers of atherosclerosis in 1,085 patients with angiographically documented coronary artery disease (CAD). In the median follow-up of 5.1 years, 156 patients had suffered from the combined endpoint of myocardial infarction or cardiovascular death including 47 of 395 p…

B-Type Natriuretic Peptide and the Risk of Cardiovascular Events and Death in Patients With Stable Angina Results From the AtheroGeneStudy

ObjectivesThe aim of this study was to assess the predictive value of the cardiac hormone B-type natriuretic peptide (BNP) for long-term outcome in a large cohort of stable angina patients.BackgroundRecent data suggest a role of BNP in stable ischemic heart disease beyond its known value in heart failure and acute coronary syndromes.MethodsIn 1,085 patients with coronary artery disease (CAD) baseline levels of BNP were prospectively associated with cardiovascular (CV) events during a mean follow-up of 2.5 years.ResultsBNP concentrations were significantly elevated in patients with future CV events (median [25th/75th interquartile range] 119.2 [43.6/300.4] pg/ml vs. 36.2 [11.3/94.6] pg/ml; p…