Gerd Rippin

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

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 levels <303 micromol/L (5.1 mg/dl) (lowest quartile) compared with those with uric acid levels >433 micromol/L (7.1 mg/dl) (highest quartile), the mortality rate increased from 3.4% to 17.1% (fivefold increase). After adjustment for age, both sexes demonstrated an increased risk for death with increasing uric acid levels (female patients: hazard ratio [HR] 1.30, 95% confidence intervals [CI] 1.14 to 1.49, p < or = 0.001; male patients: HR 1.39 [95% CI 1.21 to 1.59], p < or = 0.001). In multivariate Cox regression analysis performed with 12 variables that influence overall mortality-including diuretic use-elevated levels of uric acid demonstrated an independent, significant positive relation to overall mortality (HR 1.23 [95% CI 1.11 to 1.36], p <0.001) in patients with CAD. Thus, uric acid is an independent predictor of mortality in patients with CAD.

Relation of Markers of Inflammation (C-Reactive Protein, Fibrinogen, von Willebrand Factor, and Leukocyte Count) and Statin Therapy to Long-Term Mortality in Patients With Angiographically Proven Coronary Artery Disease

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. Compared with patients receiving statin medication, patients without statins did not have increased cardiac mortality (even when low-density lipoprotein [LDL] levels were >125 mg/dl) when hs-CRP levels were not elevated. In contrast, patients without statins and elevated hs-CRP (top quartile) had a 2.3-fold increase in risk for fatal coronary events, independent of LDL levels. In conclusion, only elevated hs-CRP was selected as an independent predictor of death. Statin therapy is associated with elevated hs-CRP, with a risk reduction for fatal coronary events, independent of LDL levels; this, in part, may be explained by the anti-inflammatory effects on atherosclerosis.

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—CMV 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.

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.

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

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) vs. 7.6(2.8/20.0) mg/dl, P=0.0001], interleukin-6 [9.5(5.1/18.7) vs. 14.4(7.2/28.1) mg/dl, P=0.0001] and soluble p-selectin [112.6(82.0/146.0) vs. 127.8(93.8/162.4) mg/dl, P=0.001] compared to 673 patients without statin therapy. This result was confirmed in a subgroup of 510 patients matched for age, gender and percentage of acute coronary syndromes. CONCLUSIONS In statin treated patients significantly lower levels of coagulation, systemic inflammation and soluble cell adhesion markers were found. Therefore the effect of statin therapy may also be mediated by additional non-lipid-lowering effects.

Marginal integrity of different resin-based composites for posterior teeth: an in vitro dye-penetration study on eight resin-composite and compomer-/adhesive combinations with a particular look at the additional use of flow-composites

OBJECTIVE To determine improvements in marginal adaptation of resin-based composite restorative systems by means of flow-composites (Solitaire 2/Gluma Solid Bond, Solitaire 2/Flow Line/Gluma Solid Bond, Point 4/Optibond Solo Plus, Point 4/Revolution/Optibond Solo Plus) and to determine the equality of simplified bonding systems (Solitaire 2/Gluma Comfort Bond, Tetric Ceram/Tetric Flow/Excite, Dyract AP/Prime & Bond NT/NRC, Pertac II/Prompt-L-Pop) in marginal gap formation. METHODS The marginal dye penetration (2% methylene-blue) was investigated separately for the approximal boxes of Class II mod-cavities with one cervical margin of the approximal box within enamel, the other within cementum. The surface analysis determined the percentage of dye-penetrated cervical and lateral margins of the approximal boxes, while the in depth investigation reported the mean dye penetration (mm) at both different cervical margins. RESULTS After thermocycling (5000 x , 5-55 degrees C) the percentage of dye penetration at the cervical cementum margins ranged from 16.5 +/- 5.9% (Solitaire/Flow Line/Gluma Solid Bond) to 82.8 +/- 5.7% (Pertac II/Prompt L-Pop), for the cervical enamel margins from 10.1 +/- 5.2% (Dyract AP/NRC/P & B NT) to 72.7 +/- 7.9% (Pertac II/Prompt L-Pop), and for the lateral enamel margins of the approximal boxes from 4.8 +/- 2.3% (Dyract AP/NRC/P & B NT) to 53.9 +/- 6.8% (Pertac II/Prompt L-Pop). In the in-depth dye penetration investigation the mean dye penetration ranged from 0.2 +/- 0.2 mm (Point 4/Revolution/Optibond Solo Plus) to 1.7 +/- 0.2 mm (Pertac II/Prompt L-Pop) at the cementum margins. At the enamel margins only Pertac II/Prompt L-Pop and Solitaire 2/Gluma Solid Bond showed mean in depth dye-penetrations deeper than 0.1 mm. SIGNIFICANCE Pertac II/Prompt-L-Pop showed a statistically significant (significance level alpha = 0.05, Wilcoxon test) higher percentage of dye-penetrated margins than most of the other restorative systems.

Comparison of image compression viability for lossy and lossless JPEG and Wavelet data reduction in coronary angiography.

Background: Lossless or lossy compression of coronary angiogram data can reduce the enormous amounts of data generated by coronary angiographic imaging. The recent International Study of Angiographic Data Compression (ISAC) assessed the clinical viability of lossy Joint Photographic Expert Group (JPEG) compression but was unable to resolve two related questions: (A) the performance of lossless modes of compression in coronary angiography and (B) the performance of newer lossy wavelet algorithms. This present study seeks to supply some of this information. Methods: The performance of several lossless image compression methods was measured in the same set of images as used in the ISAC study. For the assessment of the relative image quality of lossy JPEG and wavelet compression, the observers ranked the perceived image quality of computer-generated coronary angiograms compressed with wavelet compression relative to the same images with JPEG compression. This ranking allowed the matching of compression ratios for wavelet compression with the clinically viable compression ratios for the JPEG method as obtained in the ISAC study. Results: The best lossless compression scheme (LOCO-I) offered a mean compression ratio (CR) of 3.80:1. The quality of images compressed with the lossy wavelet-based method at CR = 10:1 and 20:1 was comparable to JPEG compression at CR = 6:1 and 10:1, respectively. Conclusion: The study has shown that lossless compression can exceed the CR of 2:1 usually quoted. For lossy compression, the range of clinically viable compression ratios can probably be extended by 50 to 100% when applying wavelet compression algorithms as compared to JPEG compression. These results can motivate a larger clinical study.

Dose-adjusted thrombosis prophylaxis in trauma surgery according to levels of D-Dimer.

In 234 trauma surgery patients, thrombosis prophylaxis with Nadroparin-Calcium low-molecular-weight heparin (LMWH) was adjusted according to levels of D-Dimer. Basic prophylaxis was 2,850 IU per day. If D-Dimer concentrations rose above 2 mg/L after the fourth postoperative (p.o.) day, LMWH was administered twice a day. Color Doppler ultrasound was performed between the fifth and seventh p.o. days. Patients were divided into a high-risk (group 1: hip, femur, or knee replacement surgery, n=102) and a moderate-risk group (group 2: other surgery of the knee, tibia, fibula, or foot, n=132). Group 1 showed significantly higher D-Dimer levels than group 2 (p<0.001). Measurement of D-Dimer on days 2 and 4 p.o. showed a sensitivity of 100% and a specificity of 72.8% in identifying patients at risk (i.e., D-Dimer>2 mg/L after day 4 p.o.). The overall deep vein thrombosis (DVT) rate in group 1 was 3.9%, and the rate of proximal DVT was 1.96%. In group 2, one distal DVT (0.8%) occurred. The results show that D-Dimer is a useful marker to monitor p.o. coagulation activation and to manage LMWH prophylaxis in trauma surgery patients.

Tenascin expression patterns and cells of monocyte lineage: relationship in human gliomas.

Stromal extracellular matrix (ECM) components are thought to play an important role in regulating invasion of human gliomas. Macrophages and microglial cells may heavily influence the integrity of the extracellular compartment of gliomas, and the affected ECM may play a key role in regulating migratory activity of both tumor cells and macrophages/microglia. The aim of this investigation was to study immunohistochemically the expression patterns of four ECM components: fibronectin, laminin, collagen IV, and tenascin (TN) in human gliomas, with special attention to TN. Our main goal was to study the possible correlation between TN expression and macrophagic/microglial infiltration in gliomas. Altogether, 90 gliomas were studied. Tumors included 46 glioblastomas, 19 anaplastic gliomas, 22 low grade gliomas, and 3 pilocytic astrocytomas. Vascular TN prevailed in perinecrotic areas of glioblastomas, whereas interstitial TN was more often expressed distant from necrosis and in the ECM of anaplastic and low grade gliomas. Double staining with CD68 and anti-TN antibodies showed that macrophagic/microglial density was significantly higher in TN-positive areas of most of the glioblastomas and anaplastic gliomas, whereas microglial percentage from total number of CD68-positive cells was in most of the cases significantly higher in TN-negative areas. In addition, we saw a morphologically spatial correlation between higher densities of macrophagic/microglial infiltration and TN expression in perinecrotic areas in glioblastomas. Attachment of macrophages to TN-positive basement membrane zones of newly formed stromal blood vessels was evident. On the basis of our results, we conclude that TN may play a crucial role in regulating trafficking of cells of monocyte lineage in human gliomas.

Effect of the Atrial Blanking Time On the Detection of Atrial Fibrillation in Dual Chamber Pacing

NOWAK, B., et al.: Effect of the Atrial Blanking Time On the Detection of Atrial Fibrillation in Dual Chamber Pacing. Patients with paroxysmal atrial fibrillation (PAF) and dual chamber pacemakers frequently have short postventricular atrial blanking times and sensitive atrial sensing thresholds used to provide reliable detection and mode switching during AF. However, short atrial blanking times increase the risk of atrial sensing of ventricular far‐field signals. We evaluated if the length of the atrial blanking time influences the detection of AF. The study included ten patients with a VDDR (n = 7) or DDDR system (n = 3), who presented with AF at 18 follow‐up visits. Bipolar atrial sensing was programmed to the most sensitive value. Atrial blanking times were programmed from 100 to 200 ms in 25‐ms steps in each patient. Using marker annotation, the following parameters were measured at ten consecutive ventricular beats: VAF = the interval between ventricular stimulus and first sensing of AF; AFS = the number of atrial‐sensed events between two ventricular events; and XAF = the interpolated number of atrial‐sensed events during atrial blanking time. The intervals between ventricular events and between atrial‐sensed event markers showed no significant differences for the five blanking times tested. There was no significant influence of the atrial blanking time onto the measured parameters (least square means ± standard error) with VAF between 281 ± 12 and 300 ± 12 ms (P = NS), AFs between 3.4 ± 0.2 and 3.6 ± 0.2 beats (P = NS) and XAF between 1.84 ± 0.12 and 2.03 ± 0.12 beats (P = NS). At ventricular rates < 100/min, the atrial sensing of AF in dual chamber pacemakers demonstrated no evidence for deterioration by an increase of the atrial blanking time from 100 to 200 ms. Thus, the risk of ventricular far‐field sensing may be reduced without compromising atrial sensing.