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The use of β-receptor blockers in peripheral arterial disease is controversial for their impact on vasomotor tone. The β-blocker nebivolol possesses vasodilating, endothelium-dependent, NO-releasing properties that might be beneficial in peripheral arterial disease. The aim of the study was to evaluate the effects and tolerability of nebivolol in comparison with metoprolol in these patients. A total of 128 patients with intermittent claudication and essential hypertension were included and double-blind randomized to receive 5 mg of nebivolol (N=65) or 95 mg of metoprolol (N=63) once daily. End points were changes in ankle-brachial index, initial and absolute claudication distance, endothelial function assessed by flow-mediated dilatation of the brachial artery, blood pressure, and quality of life using the claudication scale questionnaire. End point analysis was possible in 109 patients (85.2%). After the 48-week treatment period, ankle-brachial index and absolute claudication distance improved significantly in both patient groups ( P P =0.003) and 16.6% after metoprolol ( P =0.12) treatment. Quality of life was not influenced by either treatment, and there was no relevant change in flow-mediated dilatation in patients treated with nebivolol or metoprolol ( P =0.16). Both drugs were equally effective in lowering blood pressure. In conclusion, β-blocker therapy was well tolerated in patients with intermittent claudication and arterial hypertension during a treatment period of ≈1 year. In the direct comparison, there was no significant difference between nebivolol and metoprolol.

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.

Inflammatory mechanisms play an important role in all stages of the atherosclerotic process.1 Various studies implicate that certain infectious agents represent candidates that trigger these inflammatory responses.2 An association of viral infection with atherosclerosis was first reported in the 1970s, when experimental infection of germ-free chickens with an avian herpes virus was found to produce arterial disease.3 Although several infectious pathogens have been detected within the atherosclerotic plaque, including Chlamydia pneumoniae , Cytomegalovirus, and Helicobacter pylori , the precise role of these pathogens in causing atherosclerosis or in aggravating the atherosclerotic process remains to be established.4 In addition, a pathogen resident in an atherosclerotic vessel wall may be just an “innocent bystander” rather than a causally relevant agent, and atherosclerotic arteries might be simply more susceptible to infections. Although multiple seroepidemiological studies could demonstrate associations between atherosclerosis and antibodies against different pathogens, other studies did not.2,5 More important, recent secondary prevention studies failed to prevent cardiovascular events by administering antibiotics.6,7 Because several types of pathogens may contribute to the multifaceted process of atherosclerosis, it seems to be unlikely that a single microbe causes atherosclerosis. Instead, the total pathogen burden of infection at various sites may affect atherosclerosis progression.5,8 Various mechanisms and hypotheses have been proposed to explain possible interactions between pathogen agents and the atherosclerotic vessel wall.5 These include induction of specific antibodies or alteration of circulating cytokines, acute phase proteins, and white blood cells. Results from several studies also point to a significant role of immune responses contributing to atherogenesis.5,9 One of the auto antigens discussed as a possible immune target is the heat shock protein (HSP), which is synthesized in cells exposed to inflammation, infection, or oxidative stress.9 HSP has been detected on endothelial cells, macrophages, and smooth …

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, …

Chronic kidney disease is associated with an increased risk of cardiovascular disease. Cystatin C is a promising marker to reliably detect renal function. The role of cystatin C in patients with coronary artery disease and maintained renal function is less well established. In 2082 consecutive patients with documented coronary artery disease (CAD) (1267 with stable angina (SAP) and 815 with acute coronary syndrome (ACS)) baseline concentrations of cystatin C were measured if MDRD estimated glomerular filtration rate (GFR) was >30ml/min/1.73m 2 . During a median follow-up of 3.65 years cardiovascular mortality was documented (n=90). The median age of the study cohort was 63 years, 78.0% were of male gender. Age, sex, body mass index (BMI), and current smoking were predictors of cystatin C baseline concentration. GFR showed a strong negative association and the biomarkers Nt-proBNP and CRP were positively related to cystatin C measurements. Kaplan-Meier survival analysis showed a stepwise decrease in cardiovascular survival across quartiles of cystatin C baseline concentration (p log rank

Introduction: Selenium is an essential trace element with important antioxidative properties. The aim of this study was to evaluate the relative risk of cardiovascular mortality according to increasing concentrations of selenium and a possible protective effect of high selenium concentrations against oxidative stress in patients with established coronary artery disease. Methods: In this substudy of the prospective Athero Gene survey, 1867 patients were included. These patients could be stratified according to the diagnosis into stable angina pectoris (SAP, n=852), acute coronary syndrome (ACS, n=879) and exclusion of relevant coronary artery disease (NoCAD, n=123). Results: Low selenium concentration is associated with an increased relative risk for cardiovascular mortality. When the collective with ACS is stratified into tertiles of rising selenium concentration, the survival curves according to the Kaplan-Meier-Method (Log-Rank Test: P=0.0001) reveal an adverse outcome. In contrast, in patients with SAP was no association between the selenium concentration and outcome (P=0.35) had been observed. In a fully adjusted Cox proportional hazards model encompassing classical risk factors, medication and laboratory markers, thirds of increasing selenium concentration were associated with a protective effect in patients with ACS (tertiles: HR: 0.362, 95% CI: 0.149–0.878, P=0.025). In a Cox backward-stepwise regression analysis encompassing sixteen variables of cardiovascular risk prediction, one increment increase in selenium concentration decreased the risk of cardiovascular mortality in patients with ACS (HR:0.746, 95%CI: 0.602–0.926; P-Value: 0.008). Conclusion : Increased selenium concentration is related to an improved outcome after the acute event. This data encourages the concept of selenium administration in patients with ACS.

The quotient between ankle and brachial blood pressure (ankle brachial index =ABI) is widely used for peripheral arterial disease (PAD) screening. Guidelines on ABI measurement do not uniformly define whether the higher or the lower ankle pressure should be applied to the calculation. We hypothesized that considering the lowest ankle pressure as numerator and the highest brachial pressure as denominator would increase the prognostic impact. Methods: In 831 patients preceding coronary angiography, ABI was calculated for both legs according to the current definition of the American Heart Association (highest ankle pressure/ highest arm pressure) and according to an extended definition (lowest ankle pressure/ highest arm pressure). For each patient the lowest ABI from both legs was used for further evaluation. 15 patients with an ABI >1.5 were excluded. PAD was defined, if an ABI of less than 0.9 could be detected in one leg with each ABI definition. Results: Using the current ABI definition 204 patients (25.0%) and using the extended definition 292 patients (35.8%) with PAD could be identified. Follow-up data (median 6.6 years) was available for 812 patients (99.5%) and 157 patients (19.3%) suffered from cardiovascular events (death, infarction, stroke). Event rate was significantly higher in patients with PAD (current ABI definition: PAD yes / no=28.1% / 16.3%, P0.9 using the current and >0.9 using the extended ABI definition. Hazard ratio (95% confidence interval) was 1.5 (1.1–2.1) for patients with PAD using the current ABI definition (P=0.02) and 1.7 (1.2–2.3) for patients with PAD using the extended ABI definition (P=0.004) compared to patients without PAD. In addition, including ABI as continuous variable improved the area under the ROC curve from 0.68 (0.63– 0.73) for a basic model to 0.70 (0.65– 0.75) for a basic model plus ABI based on current definition and 0.71 (0.66 – 0.76) for a basic model plus ABI based on extended definition. Conclusion: Using the highest ankle pressure the real PAD prevalence is underestimated and a group of patients at risk is overlooked. Therefore we recommend the use of the lowest ankle pressure for ABI calculation.

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 among those who did not (0.70 versus 0.63 μmol/L; P P for trend, P P =0.002) and ADMA (hazard ratio, 1.90; 95% confidence interval, 1.3 to 2.8; P =0.001) as the strongest risk predictors. High levels of baseline ADMA independently predict future cardiovascular risk. ADMA has prognostic value beyond traditional risk factors and novel biomarkers and might guide therapeutic strategies.