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Anemia is associated with the cardiovascular outcome in healthy subjects but its impact on outcome in patients with cardiovascular disease has not yet been fully understood. Therefore, we assessed the long-term influence of hemoglobin on all-cause and cardiovascular mortality in patients with atherosclerotic disease. We prospectively studied 1,065 of 1,286 consecutive patients with asymptomatic carotid narrowing. During a median follow-up of 6.2 years, corresponding to 5,551 overall person-years, 275 patients (25.8%) died. Continuous measures of hemoglobin displayed a significant inverse effect on all-cause mortality and cardiovascular mortality (adjusted hazard ratio [HR] for increase of 1 SD of hemoglobin 0.73, 95% confidence interval [CI] 0.64 to 0.83; p <0.001) and adjusted HR 0.76, 95% CI 0.64 to 0.89; p = 0.001, respectively). The cumulative 6-year survival rate was 61%, 79%, 80%, and 81% in the first, second, third, and fourth quartile of hemoglobin (log-rank p <0.001). Patients within the first quartile (<12.9 g/dl) had a significantly increased risk of all-cause mortality (adjusted HR 1.93, 95% CI 1.46 to 2.54, p <0.001) and cardiovascular mortality (adjusted HR 1.68, 95% CI 1.19 to 2.36, p = 0.003) compared to patients with greater levels. In conclusion, our study has demonstrated a significant association with hemoglobin levels and all-cause and cardiovascular mortality in patients with carotid narrowing. Nevertheless, additional research, in terms of randomized controlled trials, is needed to warrant these findings and to evaluate potential therapeutic interventions. [Copyright &y& Elsevier]

The article presents information about novel techniques for the percutaneous treatment of peripheral artery disease. It mentions several techniques including percutaneous transluminal angioplasty (PSM), bare metal stents (BMS) and drug-eluting balloons (DEB). It also states several diseases to be treated by novel techniques including revascularization of chronic obstructive arterial disease of the aortoiliac, femoropopliteal, and below the knee segments.

Background: Multidetector CT angiography (CTA) is a non-invasive imaging technique for evaluation of peripheral vascular disease. CTA might be particularly useful for assessment of intermediate- and long-term morphological outcome after endovascular treatment. Validation of CTA vs. the current imaging standard, colour Doppler ultrasonography (CDUS), for quantification of native and in-stent re-stenosis in the superficial femoral artery (SFA) is required. Methods: Seventy randomized patients who underwent stent implantation (n=47) or balloon angioplasty (n=23) underwent 6-month follow-up with CDUS and CTA. CTA was compared with CDUS in both sub-groups of patients in terms of binary re-stenosis (>50% lumen narrowing) and re-occlusion. Agreement between CTA and CDUS was assessed using Kappa (κ) statistics with 95% confidence intervals, and correlation coefficients. Results: Binary re-stenosis was detected in 16/70 (22.9%) patients by CTA and 17/70 (24.3%) patients by CDUS (κ=0.88, 95% CI: 0.80-0.96). Re-stenosis rates after balloon angioplasty were 39.1% (9/23) on CTA and CDUS (κ=0.82, 95% CI: 0.66-0.98), and after stent implantation 14.9% (7/47) on CTA and 17.0% (8/47) on CDUS (κ=0.92, 95% CI: 0.84-1.00). Re-occlusions were detected in 3/70 (4.3%) patients by both CTA and CDUS (κ=0.65; 95% CI 0.54-0.76). Significant correlations (r=0.85, p<0.001) were noted between degree of re-stenosis on CTA and peak velocity ratio on CDUS. The correlation coefficient was higher in patients after balloon angioplasty (r=0.94, p<0.001) than in patients after stent implantation (r=0.71, p<0.001). Conclusion: CTA and CDUS show excellent agreement for evaluation of native and in-stent re-stenosis after endovascular treatment of SFA obstructions. CTA is an appropriate non-invasive imaging modality for follow-up after endovascular therapy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Multidetector CT angiography (CTA) is a non-invasive imaging technique for evaluation of peripheral vascular disease. CTA might be particularly useful for assessment of intermediate- and long-term morphological outcome after endovascular treatment. Validation of CTA vs. the current imaging standard, colour Doppler ultrasonography (CDUS), for quantification of native and in-stent re-stenosis in the superficial femoral artery (SFA) is required. Methods: Seventy randomized patients who underwent stent implantation (n =47) or balloon angioplasty (n =23) underwent 6-month follow-up with CDUS and CTA. CTA was compared with CDUS in both sub-groups of patients in terms of binary re-stenosis (>50% lumen narrowing) and re-occlusion. Agreement between CTA and CDUS was assessed using Kappa (κ) statistics with 95% confidence intervals, and correlation coefficients. Results: Binary re-stenosis was detected in 16/70 (22.9%) patients by CTA and 17/70 (24.3%) patients by CDUS (κ =0.88, 95% CI: 0.80–0.96). Re-stenosis rates after balloon angioplasty were 39.1% (9/23) on CTA and CDUS (κ =0.82, 95% CI: 0.66–0.98), and after stent implantation 14.9% (7/47) on CTA and 17.0% (8/47) on CDUS (κ =0.92, 95% CI: 0.84–1.00). Re-occlusions were detected in 3/70 (4.3%) patients by both CTA and CDUS (κ =0.65; 95% CI 0.54–0.76). Significant correlations (r =0.85, p <0.001) were noted between degree of re-stenosis on CTA and peak velocity ratio on CDUS. The correlation coefficient was higher in patients after balloon angioplasty (r =0.94, p <0.001) than in patients after stent implantation (r =0.71, p <0.001). Conclusion: CTA and CDUS show excellent agreement for evaluation of native and in-stent re-stenosis after endovascular treatment of SFA obstructions. CTA is an appropriate non-invasive imaging modality for follow-up after endovascular therapy. [Copyright &y& Elsevier]

Background A single-nucleotide polymorphism (SNP) in the palladin gene (PALLD, rs7439293) has recently been reported to be associated with coronary heart disease (CHD) in two case-control studies as well as in a large population-based cohort (Atherosclerosis Risk in Communities study, ARIC). Its clinical relevance, however, has not been evaluated prospectively. We investigated whether the risk allele (A) of PALLD rs7439293 (G>A) is associated with the occurrence of future major cardiovascular events (MACE) in a cohort of patients with prevalent carotid atherosclerosis. Materials and methods A total of 1283 consecutive patients with neurologically asymptomatic carotid atherosclerosis were included in the study and prospectively followed for a median of 3.5 years (interquartile range 3-4 years). We analysed whether the risk allele is associated with progression of carotid atherosclerosis after a 6-9-month period as measured by duplex Doppler sonography. Patients were then followed for the occurrence of a first MACE, a composite of myocardial infarction, stroke, coronary revascularization and death. Results After a median of 7.5 months (interquartile range 6-9 months), progression of carotid stenosis was observed in 103 (8.1%) patients. Cardiovascular events occurred in 337 (30%) patients after a median follow-up of 3.5 years. The risk allele of PALLD was neither associated with progressive carotid atherosclerosis (P = 0.21) nor with MACE (P = 0.58). Adjusted hazard ratios for a first MACE in heterozygous and homozygous carriers were 0.83 (95% CI 0.58-1.18) and 0.94 (95% CI 0.65-1.35) compared to wild type, respectively. Conclusions The A-allele of PALLD rs7439293 was not associated with progressive carotid atherosclerosis as measured by duplex Doppler sonography nor did it represent a risk factor for adverse cardiovascular outcome among patients with prevalent carotid atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Chronic and acute infections are associated with an increased risk of stroke. The inflammatory response can be influenced by functional polymorphisms in components of the immune system. We hypothesized that these polymorphisms may also modulate the risk of ischemic cerebrovascular events. Methods: We determined the frequency of polymorphisms in tumor necrosis factor-α[( TNF-α) G(–376)A, G(–244)A, G(–238)A, G(–308)A], Toll-like receptor 4 [( TLR4) Gly299Asp and Thr399Ile], interleukin-1-receptor antagonist [( IL-1-RA) intron 2 variable-number tandem repeat], monocyte differentiation antigen CD14 receptor C(–260)T, and interleukin-6 [( IL-6) G(–174)C] genes in 404 patients with acute stroke or transient ischemic attack before the age of 60 years and in 415 healthy individuals. We also tested for interactions between genotypes, recent febrile episodes and stroke risk. Results: None of the polymorphisms was associated with an increased risk of stroke after adjustment for age and gender. Following multivariate adjustment, carriers of the TNF-α (–308)A allele, the IL-1-RA 2* allele or the IL-6 (–174)C allele appeared to have an increased risk of stroke in association with a febrile episode prior to strokes. Conclusion: In our study none of the investigated polymorphisms of the inflammatory system was associated with the risk of acute cerebrovascular events before the age of 60 years. However, post-hoc analyses indicate that some polymorphisms seem to contribute to the risk of stroke in combination with fever. Clin Chem Lab Med 2006;44:918–23. [ABSTRACT FROM AUTHOR]

Abstract: Background: Acute Stanford type A aortic dissection is associated with substantial perioperative morbidity and mortality. A sepsis-like state may lead to antithrombin (AT) III consumption and deficiency. The impact of preoperative AT III activity on outcome in patients undergoing emergency surgery is yet unknown. Methods: We measured preoperative AT III activity in 99 consecutive patients undergoing emergency aortic surgery for Stanford type A aortic dissection during a 4-year period in a retrospective study. Cardiovascular co-morbidities, risk factors and surgical data were recorded and patients were followed for 30-day mortality, and occurrence of multiple organ failure (MOF). Results: During the first 30 days, 15 patients (15%) died, and 8 patients (8%) had MOF. Median AT III levels (IQR) in 30-day non-survivors versus survivors were 64% (52–72) versus 90% (75–97) (p <0.001), and in patients with versus without MOF were 66% (52.3–77.3) versus 88% (72–96) (p =0.018), respectively. Adjusted odds ratios for 30-day mortality and MOF for AT III activity (per % increments) were 0.92 (p =0.007), and 0.96 (p =0.012), respectively, indicating a significant inverse relationship between AT III activity and outcome. Conclusion: There is a strong inverse association between preoperative AT III activity and adverse outcome in patients undergoing surgical repair of acute Stanford type A aortic dissection. Larger studies are necessary to determine a cut-off value for AT III and to assess whether patients with low AT III levels benefit targeted therapeutic interventions. [Copyright &y& Elsevier]

: ObjectivesWe investigated the association of the heme oxygenase-1 (HO-1) promoter genotype with the inflammatory response and restenosis after balloon angioplasty.: BackgroundHeme oxygenase-1, which is induced by balloon angioplasty, can inhibit neointima formation and vascular remodeling. A dinucleotide repeat in the HO-1 gene promoter shows a length polymorphism that modulates HO-1 gene transcription. Short (<25 guanosine thymidine [GT]) repeats are associated with a 10-fold greater up-regulation of HO-1 than are longer repeats.: MethodsWe studied 381 consecutive patients who underwent femoropopliteal balloon angioplasty (n = 210) and comparison groups with femoropopliteal stenting (n = 68) and lower limb angiography (n = 103). C-reactive protein (CRP) was measured at baseline, 24, and 48 h. We evaluated patency at six months by duplex sonography and assessed the association of the length of GT repeats in the HO-1 gene promoter with postintervention CRP and restenosis.: ResultsRestenosis within six months was found in 74 patients (35%) after balloon angioplasty and in 21 patients (31%) after stenting. After balloon angioplasty, carriers of the short length (<25 GT) dinucleotide repeats had a lower postintervention CRP at 24 h (p = 0.009) and 48 h (p < 0.001) and a reduced risk for restenosis (adjusted relative risk 0.43, 95% confidence interval: 0.24 to 0.71, p < 0.001) compared with patients with longer alleles. After stenting or angiography, we found no association between the HO-1 genotype with CRP or restenosis.: ConclusionsThe HO-1 promoter genotype that controls the degree of HO-1 up-regulation in response to stress stimuli is associated with the postintervention inflammatory response and the restenosis risk after balloon angioplasty. [Copyright &y& Elsevier]

Objective: To investigate long-term clinical and morphological outcome of patients with subclavian–axillary vein thrombosis treated with systemic thrombolysis compared to anticoagulation in a retrospective, nonrandomised study. Methods: We studied 95 consecutive inpatients with subclavian–axillary vein thrombosis treated either with systemic urokinase thrombolysis and subsequent oral anticoagulation (n=33) or with anticoagulation only (n=62). Anticoagulation was performed with heparin and phenprocoumon. Patients were followed for median 40 months (IQR 14 to 94) for symptomatic upper extremity post-thrombotic syndrome and for venous recanalisation by duplex ultrasound. Results: Primary technical success rate of the systemic thrombolysis was 88% (n=29) with seven peri-intervention bleeding complications (21%). No complication was observed in patients with anticoagulation only (p<0.0001). At the time of follow-up, duplex sonography showed a thrombotic subclavian vein in 40 of 83 patients (48%), but only 9 of 95 patients (10%) had a symptomatic upper extremity post-thrombotic syndrome. Patients with systemic thrombolysis exhibited a 60% adjusted reduced risk for a thrombotic subclavian vein at the time of follow-up compared to patients with anticoagulation only (95% CI: 0.2 to 0.9, p=0.03). However, the frequency of symptomatic post-thrombotic syndrome after thrombolysis and anticoagulation was similar (adjusted p=0.6). Conclusion: Systemic thrombolysis of subclavian–axillary vein thrombosis has an acceptable primary technical success rate and improves venous recanalisation rates compared to anticoagulation. However, the high rate of complications during thrombolysis and the lack of clinical benefit suggest that conservative treatment may be favoured. [Copyright &y& Elsevier]

Study objective: To assess the safety and the accuracy of a 4 h stepwise diagnostic approach relying on clinical judgement in unselected patients with acute chest pain. Design: Prospective cohort study. Setting: Emergency department (ED) of a tertiary care university hospital. Patients: 1288 unselected patients presenting with acute chest pain. Interventions: After history and physical examination, clinical judgement (step I), governed the need for further patient evaluation: baseline 12 lead electrocardiogramm (ECG) and laboratory examinations (step II), serial 12 lead ECG and laboratory examinations after 4 h (step III), and 4 h troponin T measurement (step IV) to exclude or to confirm a coronary origin of chest pain. Patients were followed clinically for 6 months for future occurrence of cardiac events (myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA), CABG, cardiac death), any death and for accuracy of the ED diagnosis in non-coronary chest pain patients. Measurements and results: Chest pain was diagnosed to be coronary in origin in 381 and non-coronary in 907 patients, respectively. Cardiac events occurred during follow up in 240 (19%) of 1288 patients, in 233 of 381 (61%) with presumed coronary and seven of 907 (1%) with presumed non-coronary chest pain. Sensitivity, specificity, positive predictive value and negative predictive value for correct detection of coronary chest pain were 97, 86, 61 and 99%, respectively. In non-coronary chest pain patients the agreement between the ED diagnosis and the final diagnosis was good (κ=0.71, 95% confidence interval (CI) 0.67–0.75). Conclusions: The 4 h stepwise approach guided by clinical judgement was safe for ruling out impending cardiac events in unselected patients with acute chest pain. However, more extensive evaluation is necessary for accurate rule-in of coronary chest pain. [Copyright &y& Elsevier]

Objective: Vascular inflammation is a hallmark in the development of abdominal aortic aneurysms (AAA). Heme oxygenase-1 (HO-1) is a novel vascular anti-inflammatory factor. A (GT)n dinucleotide repeat in the HO-1 gene promoter shows a length polymorphism that modulates the level of gene transcription. Short (<25 GT) repeats are associated with an increased HO-1 upregulation in response to inflammatory stimuli than are longer repeats. We hypothesised that patients with AAA had less frequently short repeats in the HO-1 gene promoter compared to patients with coronary (CAD) or peripheral artery disease (PAD), or healthy controls. Methods: 70 consecutive patients with atherosclerotic AAA, each 70 age- and sex-matched patients with CAD and PAD as well as 61 unmatched healthy atherosclerosis-free controls for a total of 271 individuals were studied. The frequency of carriers of short repeats in the HO-1 gene promoter was determined and compared between the groups. Results: In the AAA group, 29 patients (41%) were carriers of short (GT)n repeats compared to 47 patients (67%) in the CAD group, 44 patients (63%) in the PAD group and 35 healthy controls (59%). Patients with AAA were less frequently carriers of short repeats compared to age- and sex-matched patients with CAD (OR=0.38, p=0.006) and PAD (OR=0.35, p=0.01). Healthy controls exhibited short alleles more frequently than patients with AAA (p=0.04), but comparable to CAD (p=0.3) and PAD patients (p=0.7). Conclusion: Patients with AAA were less frequently carriers of short (<25 GT) repeats in the HO-1 gene promoter than patients with atherosclerosis or healthy subjects. This suggests that short alleles, and thus, facilitated upregulation of HO-1, may be a protective anti-inflammatory factor against the development of AAA. [Copyright &y& Elsevier]

Presents an editorial regarding the role of brain natriuretic peptide, C-reactive protein, and urinary albumin levels in predicting cardiovascular risk in older patients. Use of prognostic biomarkers in predicting cardiovascular risk; Reference to an article in the April 6, 2005, issue of the journal in which Kistorp and colleagues assess the ability of N-amino terminal fragment of the prohormone brain natriuretic peptide to predict mortality in older persons.

Background: Experimental and clinical data indicate a major influence of diabetes on atherogenesis. We aimed to assess whether the effect of diabetes on long-term mortality in asymptomatic patient with carotid stenosis is contingent upon the degree of the carotid atherosclerotic burden. Methods: 1065 patients with neurological asymptomatic carotid atherosclerosis as evaluated by duplex sonography were prospectively followed for cause-specific mortality. Results: During a median of 11.8 years, a total of 549 deaths, including 362 cardiovascular deaths, were recorded. Diabetes and glycohemoglobin A1c (Hba1c) levels were significantly associated with mortality. Diabetes displayed an independent risk for all-cause (adjusted HR 1.62; 95% CI 1.35–1.94) and cardiovascular death (adjusted HR 1.75, 95% CI 1.40–2.19). The adjusted hazard ratio per increase of 1% of Hba1c levels was 1.21 (P < 0.01) for all-cause and 1.31 (P < 0.01) for cardiovascular mortality, respectively. Patients with diabetes mellitus and a higher degree of carotid stenosis and were at great risk of adverse outcome. Only 21% of the asymptomatic diabetic patients with carotid narrowing over 50% survived, whereas 62% of the patients without diabetes and with carotid atherosclerosis below 50% were still alive after 12-years of follow-up. The high risk for all-cause and cardiovascular death of these patients remained significant after adjustment for various established cardiovascular risk factors in multivariable regression analysis (adjusted hazard ratio 2.4, P < 0.001; compared to patients without diabetes and < 50% carotid atherosclerosis). Conclusion: Diabetic patients with carotid stenosis ≥ 50% are at exceptional high risk for all-cause and cardiovascular death. Thus, routinely ultrasound investigation of the carotid arteries might be a valuable prognostic tool for patients with diabetes mellitus. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Local Delivery of Paclitaxel to Inhibit Retinosis During Angioplasty of the Leg" by G. Tepe, T. Zeller and T. Albrecht in the February 14, 2008 issue.

A response by Martin Schillinger and Erich Minar to letters to the editor about their article on the superiority of primary stenting with nitinol stents over balloon angioplasty in patients with peripheral-artery disease in the May 4, 2006 issue of the "New England Journal of Medicine" is presented.

Background: Because stent implantation for disease of the superficial femoral artery has been associated with high rates of late clinical failure, percutaneous transluminal angioplasty is preferred for endovascular treatment, and stenting is recommended only in the event of suboptimal technical results. We evaluated whether primary implantation of a self-expanding nitinol (nickel–titanium) stent yielded anatomical and clinical benefits superior to those afforded by percutaneous transluminal angioplasty with optional secondary stenting. Methods: We randomly assigned 104 patients who had severe claudication or chronic limb ischemia due to stenosis or occlusion of the superficial femoral artery to undergo primary stent implantation (51 patients) or angioplasty (53 patients). Restenosis and clinical outcomes were assessed at 6 and 12 months. Results: The mean (±SD) length of the treated segment was 132±71 mm in the stent group and 127±55 mm in the angioplasty group. Secondary stenting was performed in 17 of 53 patients (32 percent) in the angioplasty group, in most cases because of a suboptimal result after angioplasty. At 6 months, the rate of restenosis on angiography was 24 percent in the stent group and 43 percent in the angioplasty group (P=0.05); at 12 months the rates on duplex ultrasonography were 37 percent and 63 percent, respectively (P=0.01). Patients in the stent group were able to walk significantly farther on a treadmill at 6 and 12 months than those in the angioplasty group. Conclusions: In the intermediate term, treatment of superficial-femoral-artery disease by primary implantation of a self-expanding nitinol stent yielded results that were superior to those with the currently recommended approach of balloon angioplasty with optional secondary stenting. (ClinicalTrials.gov number, NCT00281060.) N Engl J Med 2006;354:1879-88. [ABSTRACT FROM AUTHOR]

Background and Objective Platelets play a pivotal role in atherothrombosis and are potentially involved in the pathogenesis of atherosclerosis. We investigated whether mean platelet volume ( MPV) predicts clinical outcome and progression of atherosclerosis in patients with asymptomatic carotid artery disease. Methods We studied 1006 of 1268 prospectively collected consecutive patients with asymptomatic carotid atherosclerosis who were evaluated by duplex sonography. Patients were followed up clinically for the occurrence of a major adverse cardiovascular event ( MACE), a composite of myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke and death. Results During a median follow-up of 3·1 years (interquartile range, 2·5-3·5), a total of 316 (31·5%) MACEs were recorded. Increased levels of MPV were significantly associated with increased risk of the occurrence of MACEs (adjusted hazard ratio [ HR] for an increase in one standard deviation [ SD] of MPV 1·22, confidence interval [ CI] 1·05-1·35, P < 0·01). Patients with MPV levels above 11·8 femtolitre (= fifth quintile) had a significantly higher event rate (41·3% vs. 29·3%, P < 0·001) with an adjusted HR for MACEs of 1·65 (95% CI 1·26-2·16, P < 0·001) compared with patients with MPV levels in the first to fourth quintile. No significant association was found between baseline MPV levels with either baseline degree or progression during a 6-month follow-up of carotid stenosis. Conclusion Mean platelet volume was independently and significantly associated with adverse cardiovascular outcome in patients with asymptomatic carotid atherosclerosis. [ABSTRACT FROM AUTHOR]

Abstract: Background: Inflammation is associated with atherosclerotic disease. In this context, it has been shown that an increased neutrophil count is a risk factor for cardiovascular events in patients with coronary and peripheral artery disease. However, the impact of neutrophils on long-term mortality in patients with carotid atherosclerosis is not yet fully understood. Methods: We prospectively studied 853 of 1268 consecutive patients with neurologically asymptomatic carotid stenosis for all-cause and cardiovascular death, respectively. Results: During a median follow-up time of 6.3 years (IQR 5.8–6.7 years) a total of 203 deaths (23.8%), including 134 cardiovascular deaths (15.7%), were recorded. An increase of 1 G/L of neutrophil count indicated an increased risk for all-cause mortality of 1.20 (CI [95%] 1.10–1.31, P < 0.001) and of cardiovascular death of 1.30 (CI 1.17–1.45, P < 0.001), respectively. For the second to the fourth quartile of the neutrophil count, adjusted hazard ratios for all-cause mortality were 1.12 (CI, 0.71–1.75), 1.46 (CI, 0.96–2.21), and 1.76 (CI, 1.15–2.69; P = 0.03 for trend); and 1.41 (CI, 0.80–2.49), 1.53 (CI, 0.88–2.68), and 2.54 (CI, 1.49–4.33; P < 0.01 for trend) for cardiovascular mortality, compared to the lowest quartile, respectively. Patients with baseline carotid stenosis of more than 50% and/or increased neutrophil count (≥median), had a 1.9–2.4 fold increase in risk of (CV-) death, compared to patients with carotid narrowing of less than 50% and/or neutrophil count less than the median (P < 0.001). After adjusting for cardiovascular risk factors, only neutrophils, but not eosinophils, basophils, monocytes, lymphocytes, or the total leukocyte count showed a significant association with long-term mortality. No significant association was found between white blood cell subtypes with either baseline degree or progression during a 6 month follow-up of carotid stenosis. Conclusion: The baseline neutrophil count was an independent predictor for all-cause and cardiovascular mortality in neurologically asymptomatic patients with carotid stenosis. Thus, the measurement of neutrophils could provide prognostic information on outcome in patients at risk. [Copyright &y& Elsevier]

Eur J Clin Invest 2012; 42 (9): 921-926 Abstract Background Humoral mediators of inflammation, in particular the complement system, have been described to play an important role in atherogenesis. Previously, we found a single-nucleotide polymorphism (SNP) in the complement 5 gene ( C5 rs17611, A>G) independently associated with stroke. Up to now, the impact of C5 rs17611 on the progression of atherosclerosis and cardiovascular outcome in patients with asymptomatic atherosclerosis was unclear. Materials and Methods We investigated C5 rs17611 in a cohort of 1065 consecutive patients with asymptomatic carotid atherosclerosis. All patients were prospectively followed for the progression of carotid atherosclerosis and the development of a first major cardiovascular event (MACE), respectively. Results Three hundred and thirty-seven patients (31·6%) experienced a MACE during a median follow-up of 3·0 years. The homozygous GG genotype of the C5 rs17611 was significantly associated with adverse cardiovascular outcome (adjusted HR: 1·36 [95% CI, 1·07-1·73]; P = 0·01). After stratification for sex, C5 rs17611 CC was found to be an independent risk factor for MACE in men (HR 1·50 [95% CI, 1·12-1·83]). No association of C5 rs17611 with progression of carotid stenosis, observed in 93 (8·7%) patients, was detectable. Performance of ELISA indicated a significant association of the C5 rs17611 variant with C5a plasma levels. Conclusion The C5 rs17611 GG genotype is associated with increased C5a plasma levels and represents a risk factor for adverse cardiovascular outcome in male patients with carotid atherosclerosis. [ABSTRACT FROM AUTHOR]

Abstract: Background: The formation of abdominal aortic aneurysm (AAA) is caused by a destructive remodeling of the extracellular matrix in the vascular wall. Proteoglycan content and biosynthesis have been shown to be altered in AAA. Xylosyltransferase I (XT-I) is the initial and rate-limiting enzyme in the biosynthesis of the proteoglycan-linked glycosaminoglycan chains. A familial predisposition to AAA is well recognized. Thus, variations in the XT-I coding gene XYLT1 might be risk factors for AAA formation. Methods: We performed genotyping of two genetic variations in the XYLT1 gene which, have been already linked to proteoglycan-associated diseases, in 129 AAA patients and 129 age- and sex-matched healthy controls. Results: The T-allele of the polymorphism c.343G>T (p.A115S) was found to be significantly more frequent in AAA patients compared to the healthy control group, demonstrating that carriers of the T-allele have a 5-fold increased risk of developing AAA (odds ratio 4.87, 95%-CI 1.38–17.19; p =0.011). Conclusions: Our results show that XT-I polymorphisms potentially confer to the genetic susceptibility of AAA. [Copyright &y& Elsevier]

Background: Acute Stanford type A aortic dissection (AAD) is associated with substantial perioperative mortality and morbidity. Objective: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a prognostic biomarker of outcome in cardiovascular disease. Its predictive power in patients undergoing emergency surgery for acute type A aortic dissection is yet unknown. Methods: We prospectively measured pre-operative NT-proBNP in 104 patients (39 female, 35%; median age 61 years) undergoing emergency surgery for AAD during a 6-year study period. European System for Cardiac Operative Risk Evaluation risk scores were recorded and patients were followed for 30-day mortality and major adverse events (MAEs) as defined by the need for rethoracotomy, occurrence of postoperative heart failure, neurologic deficit, lung failure, renal failure, or sepsis. Results: Median logistic European System for Cardiac Operative Risk Evaluation in the cohort was 12 (interquartile range 7 to 19). During the first 30 days, 23 patients (22%) died, and 53 patients (51%) experienced MAEs. Median (interquartile range) NT-proBNP levels in survivors versus nonsurvivors were 328 pg/ml (157 to 569) versus 2,240 pg/ml (515 to 4,734; p < 0.001), and in patients without versus with MAEs, 227 pg/ml (107 to 328) and 719 pg/ml (442 to 2,287; p < 0.001), respectively. Adjusted odds ratios for increasing tertiles of NT-proBNP compared with the lowest tertile were 0.98 (95% confidence interval [CI] 0.18 to 5.33; p = 0.98) and 11.67 (95% CI 2.61 to 52.09; p = 0.001) for 30-day mortality and 9.07 (95% CI 2.58 to 31.83; p = 0.001) and 50.21 (95% CI 10.85 to 232.45; p < 0.001) for MAEs, respectively, indicating a significant association between pre-operative NT-proBNP levels and outcome. Conclusions: Pre-operative NT-proBNP predicts outcome in patients undergoing surgery of AAD. [Copyright &y& Elsevier]

There exists no systematic evaluation of liver function in renal allograft recipients undergoing C2-monitoring with Neoral® [cyclosporine A (CsA)-microemulsion]. In the present cohort analysis, we compared the hepatic profiles of C2-monitored ( n = 80), C0-monitored ( n = 81), and non-CsA-treated renal allograft recipients ( n = 29), transplanted between 1/1999 and 2/2004 in our institution. While the C2-targets were set in accordance with ( n = 72) or below ( n = 8) the consensus on Neoral® (1500 ± 200 ng/ml), non-CsA-patients received FK506 ( n = 29), partially in combination with rapamycin ( n = 13) as primary immunosuppression. Analysis of maximum hepatic laboratory parameters and also repeated measures byanova within 30 days post-transplant revealed highly significant elevations of direct, indirect and total bilirubin, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and lactate dehydrogenase ( P < 0.001) in the C2-group, in comparison with the C0- and the non-CsA-group. Bilirubin-levels were by far the most affected of all hepatic parameters, and correlated with C2-levels ( r2 = 0.62). Seventeen CsA-patients had excessive bilirubin-elevations (>4 mg/dl) and were therefore considered to be ‘CsA-sensitive’ [14 C2-patients (17% of all C2-patients), 3 C0-patients (4% of all C0-patients)]. Bilirubin- and the other parameter elevations in these patients were reversible upon withdrawal or lowering of CsA. Most ‘CsA-sensitive’ patients ( n = 12, 70%) displayed pre-transplant hepatic impairment, indicating a pre-existing liver instability. Collectively, our data emphasize the need for increased awareness toward individual predispositions for CsA-sensitivity. [ABSTRACT FROM AUTHOR]

Background: The heme oxygenase-1 (HO-1) isoenzyme has recently been suggested to protect transplants from ischemia–reperfusion and immunologic injury. Inducibility of this enzyme is modulated by a (GT)n dinucleotide length polymorphism in the HO-1 gene promoter. Short (class S) repeats are associated with greater up-regulation of HO-1 than are long repeats. In the present study, we investigated the impact of the promoter polymorphism on the development of cardiac allograft vasculopathy (CAV) in human heart transplants. Methods: We enrolled 152 recipients of a heart allograft with at least 1 year survival post-transplantation in this retrospective study. The HO-1 genotype was assessed using genomic DNA isolated from paraffin-embedded allograft biopsy specimens. Patients were followed angiographically for CAV. Angiographic vessel-wall abnormalities were defined as CAV, and a stenosis of more than 50% in at least 1 vessel area was defined as severe CAV. Results: Eighty-seven patients (57%) had received a heart from a donor with at least 1 class S allele. Within the mean follow-up period of 9 years, 95 patients (63%) showed signs of CAV, among which 60 patients (40%) developed severe CAV. The frequency of CAV and severe CAV was not significantly different between class S allele recipients and non-recipients (CAV, 57/87 vs 38/65, p = 0.12; severe CAV, 35/87 vs 25/65, p = 0.30). Conclusion: In contrast to recent findings in renal allografts and vascular injury, the HO-1 gene promoter polymorphism does not show an association with the development of CAV in heart transplants. [Copyright &y& Elsevier]

Abdominal aortic aneurysm (AAA) is characterized by dilatation of arterial walls, which is accompanied by degradation of elastin and collagen molecules. Biochemical and environmental factors are known to be relevant for AAA development, and familial predisposition is well recognized. A connective tissue disorder that is also associated with fragmentation of elastic fibers is Pseudoxanthoma elasticum (PXE). PXE is caused by mutations in the ABCC6 gene and mainly affects dermal, ocular and all vascular tissues. To investigate whether variations in ABCC6 are found in AAA patients and to determine mutations in PXE patients, we analyzed seven selected ABCC6 exons of 133 AAA and 54 PXE patients subjected to mutational analysis. In our cohort of AAA patients, we found five ABCC6 alterations, which result in missense or silent amino acid variants. The allelic frequencies of these sequence variations were not significantly different between AAA patients and healthy controls. Therefore, we suggest that alterations in ABCC6 are not a genetic risk factor for AAA. Mutational screening of the PXE patients revealed 19 different ABCC6 variations, including two novel PXE-causing mutations. These results expand the ABCC6 mutation database in PXE. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Heme oxygenase-1 (HO-1) has been demonstrated to exert potent anti-oxidant and anti-inflammatory effects in the context of atherosclerotic vascular disease, and therefore was referred to as a potential vascular protective factor. A (GT)n dinucleotide repeat polymorphism in the HO-1 promoter has been shown to modulate HO-1 gene expression. Short (<25) GT repeats were associated with HO-1 up-regulation, and therefore may influence susceptibility to ischaemic vascular events. We investigated the association of HO-1 repeat length with the risk of cerebrovascular events in a case control study and assessed possible interrelations with vascular risk factors.We determined the number of GT repeats in the HO-1 promoter in 399 patients with ischaemic cerebrovascular events and 398 healthy controls and compared the frequencies of short (<25) repeat (class S) and long (≥25) repeat (class L) alleles after adjustment for potentially confounding factors.Genotype distributions of S/S, S/L and L/L in patients were 9.8% (n=39), 45.1% (n=180) and 45.1% (n=180), which was similar to the distribution in controls with 11.5% (n=46), 44.5% (n=177) and 44.0% (n=175). In the presence of vascular risk factors, the HO-1 genotype became functionally relevant: in patients without hyperlipidemia the S/S genotype exerted a protective effect on the development of ischaemic cerebrovascular events (OR 0.2; 95% CI 0.1–0.6), while this effect was no longer present in hyperlipidemic patients.Short (<25 GT) repeats in the HO-1 gene promoter confer a reduced risk for cerebrovascular events in individuals with normal plasma lipid levels. This may explain controversial findings in different populations. [Copyright &y& Elsevier]

Recently, inflammation has received considerable attention in the pathogenesis of both type 2 diabetes and atherosclerosis. The interleukin-1 receptor antagonist (IL-1ra) is a major modulator of the interleukin-1 pro-inflammatory pathway. We studied the relationship between a variable number tandem repeat (VNTR) polymorphism in intron 2 of the IL-1ra gene (IL1RN) and coronary artery disease (CAD) in patients with and without type 2 diabetes, following 787 consecutive patients admitted for suspected CAD. According to the current criteria of the American Diabetes Association, 250 patients had type 2 diabetes. In this group of patients, allele 2 carriers (n = 108) had an increased prevalence of CAD compared with noncarriers (85.2 vs. 73.2%), a difference that remained significant in a multivariate logistic regression model (odds ratio 2.2, 95% CI 1.1-4.3, P = 0.02). No association of CAD with allele 2 carrier status was present among nondiabetic patients (n = 537). Enzyme-linked immunosorbent assays showed decreased baseline plasma levels of IL-1ra in patients with type 2 diabetes, which may in part explain the role of the IL1RN VNTR in these patients. [ABSTRACT FROM AUTHOR]

Von Willebrand factor (VWF) plays an important role in thrombogenesis and mediates platelet adhesion particularly under high shear stress. Such conditions are generally found in stenotic arteries and can eventually cause myocardial infarction or stroke. We aimed to study whether levels of VWF antigen (VWF:Ag) predict future major adverse cardiovascular events (MACE) in patients suffering from carotid artery stenosis. Patients with atherosclerotic carotid artery disease defined by the presence of nonstenotic plaques or any degree of carotid stenosis were prospectively enrolled. Concentrations of VWF were measured by enzyme immunoassay. VWF:Ag levels were more stable after 4 freeze-thaw cycles, when compared to VWF activity, and we showed similar concentrations of VWF in citrated plasma and serum (±4%). Levels of VWF:Ag predicted future cardiovascular events in 811 patients with carotid stenosis independent of known cardiovascular risk factors. Patients with VWF:Ag concentrations in the 4th quartile had a 44% event rate after an average 3-year follow up and a hazard ratio of 2.15 (95% confidence interval 1.46–3.16; p < 0.001). High concentrations of VWF:Ag predict major cardiovascular events in patients with carotid stenosis, and given their high event rate may be useful for risk stratification of such patients. Image 1 • The predictive value of VWF for MACE is unknown in patients with asymptomatic carotid stenosis. • This large cohort study investigated the predictive value of VWF for MACE in 811 patients with carotid stenosis. • VWF levels within the highest quartile were independently associated with a 2.1-fold increase in MACE. • This cohort study in 811 patients with carotid stenosis showed that high VWF-levels predicted MACE, which may be useful for risk stratification. [ABSTRACT FROM AUTHOR]

Background Inflammatory responses are pivotal in the initiation and development of premature atherosclerotic lesions. Galectin-3 represents a valuable biomarker for both progression and destabilization of atherosclerotic lesions. This study aims to assess the involvement of galectin-3 in premature myocardial infarction. Design In this multicentre case-control study, we assessed circulating galectin-3 levels in 144 patients comprising 72 consecutive survivors of acute myocardial infarction (≤ 40 years) and 72 hospital controls frequency matched for age, gender and centre. Results Patients with acute myocardial infarction showed significantly higher galectin-3 levels as compared to controls in the acute phase of acute myocardial infarction (2552 ± 1992 vs. 1666 ± 829 pg/mL; P < 0·001) as well as in the stable phase 1 year after the index event (3692 ± 1774 vs. 1666 ± 829 pg/mL; P < 0·001). Circulating galectin-3 was significantly and independently associated with premature myocardial infarction in the logistic regression analysis (acute phase: adj. OR per 1- SD change 2·03, 95% CI 1·30−3·19; P = 0·002; stable phase: adj. OR of 6·54 (95% CI 2·56−16·68; P < 0·001). Moreover, we observed a significant correlation between circulating galectin-3 and leucocyte count ( r = 0·35, P < 0·001), non- HDL cholesterol ( r = 0·23, P = 0·014) and HDL cholesterol ( r = −0·29, P = 0·002). Conclusion We demonstrated that elevated levels of circulating galectin-3 are strongly associated with premature myocardial infarction. Galectin-3 might serve as link between dyslipidaemia as driving force of plaque formation with inflammation as initiator of plaque rupture in patients with premature acute myocardial infarction. [ABSTRACT FROM AUTHOR]

Background Red cell distribution width (RDW) is associated with morbidity and mortality in chronic cardiac disease. The aim of the present study was to investigate the role of RDW as a predictor of adverse outcome in patients with carotid atherosclerosis. Materials and methods We prospectively studied 1065 of 1286 consecutive patients with neurological asymptomatic carotid artery stenosis as assessed by duplex Doppler sonography. The study end points were all-cause mortality and cardiovascular mortality respectively. Results During a median follow-up time of 6·2 years (interquartile range 5·9-6·6), corresponding to 5551 overall person-years, 275 patients (25·8%) died. Of them, 182 patients (66·2%) died due to cardiovascular causes. RDW was significantly associated with adverse outcome. In a continuous multivariate Cox regression analysis, the adjusted hazard ratio for each per cent increase in RDW was 1·39 (95% CI 1·27-1·53; P < 0·001) for all-cause and 1·43 (95% CI 1·28-1·60; P < 0·001) for cardiovascular mortality respectively. Kaplan-Meier estimates showed a gradual relationship between increasing quartiles of RDW and death (log rank P < 0·001). Adjusted hazard ratios for all-cause death ranged from 0·89 to 1·94 for the highest vs. the lowest quartile ( P < 0·001 for trend) and for cardiovascular death from 1·08 to 2·34 for the highest vs. the lowest quartile ( P < 0·001 for trend) respectively. Conclusions Red cell distribution width was significantly and independently associated with all-cause and cardiovascular death in patients with asymptomatic carotid atherosclerosis. [ABSTRACT FROM AUTHOR]

Background There is growing evidence that the predictive value of HDL cholesterol levels for cardiovascular risk stratification is limited in patients with coronary artery disease ( CAD). HDL function seems to be a more sensitive surrogate of cardiovascular risk estimation than simple serum levels. Therefore, we aimed to assess whether impaired antioxidant HDL function is involved in the development of premature acute myocardial infarction ( AMI). Methods In this multicentre case-control study, we compared the antioxidant function of HDL, measured by the HDL inflammatory index ( HII), and HDL particle size in 184 patients comprising 92 patients with AMI at a very young age (≤40 years of age) and 92 age- and gender-matched controls. Results Antioxidant capacities of HDL were significantly impaired in the acute phase of AMI ( HII of 1·50 [ IQR 1·10-1·74] vs. 0·56 [ IQR 0·41-0·86] in controls, P < 0·001 as well as in the chronic stable phase 1 year after the event ( HII of 0·85 [ IQR 0·72-1·03] vs. 0·56 [ IQR 0·41-0·86], P < 0·001) compared to controls. Moreover, HDL function in the stable phase remained significantly associated with premature MI in adjusted logistic regression analysis with an OR of 2·24 per SD increase of HII (95% CI 1·28-3·91; P = 0·005). Analyses of HDL size revealed a significant correlation between all HDL subfractions and HDL function in controls, whereas this correlation was lost for large and intermediate HDL in AMI patients. Conclusion Impaired antioxidant function of HDL is independently associated with the development of premature AMI. The maintenance of HDL function might evolve into a significant therapeutic target, especially in patients with premature CAD. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2012; 42 (6): 631-636 Abstract Background Low-density lipoprotein (LDL) cholesterol lowering has been established as one of the principal targets in preventive cardiology. Recently, assessment of LDL particle size and number as well as other lipid moieties has been presented as a more reliable method to quantify atherogenicity of the lipoprotein fractions. Thus, it was our aim to assess the influence of different lipoprotein fractions on premature myocardial infarction (≤ 40 years of age). Methods and results We enrolled 302 patients into our multicentre case-control study, including 102 patients with myocardial infarction and 200 age-, gender- and centre-matched controls. The LDL and HDL Lipoprint ® System were used for lipid subfraction quantification. The lipid risk factors most strongly associated with premature acute myocardial infarction (AMI) in the adjusted model were non-HDL C (OR 5·02, 95% CI 2·75-9·15, P-value = 0·001), LDL-C (OR 4·35, 95% CI 2·5-7·57, P-value = 0·001), VLDL-C (OR 3·66, 95% CI 2·14-6·28, P-value = 0·001), large IDL-C (OR 3·15, 95% CI 1·94-5·12, P-value = 0·001), large LDL-C (OR 3·67, 95% CI 2·19-6·15, P-value = 0·001) and intermediate LDL-C (OR 1·96, 95% CI 1·25-3·06, P-value = 0·003). In contrast, small dense LDL was not significantly associated with premature myocardial infarction. Conclusion Non-HDL cholesterol is most strongly associated with premature coronary artery disease and could serve as preferred risk predictor and therapeutic target in this young patient population (≤ 40 years). Besides, VLDL, LDL-C, large LDL, intermediate LDL and large IDL were significantly associated with premature myocardial infarction. Furthermore, our data suggest that risk prediction using small dense LDL particles might not be useful in young AMI survivors. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2012; 42 (5): 463-469 Abstract Background Myeloperoxidase (MPO) is involved in a multitude of inflammatory processes involving oxidative modification of soluble components and cellular surfaces. Thus, MPO plays a key role in promoting atherosclerosis via oxidative stress by modification of both high- and low-density lipoprotein and production of other bioactive molecules. A polymorphism (MPO 463G>A, rs2333227) results in different expression rates of MPO. We aimed to assess whether MPO could be of clinical use as a risk marker for vascular disease in a high-risk group. Material and methods Plasma MPO levels of 406 patients suffering from peripheral arterial disease (PAD) were measured on an Abbott Architect i2000sr and grouped into patients with high (>115 ng/mL) and low (< 115 ng/mL) MPO levels. Genotyping of rs2333227 was performed on an ABI TaqMan 7900HT RT-PCR thermocycler. Results The relative risk of major adverse cardiovascular events (MACE) for patients with high plasma MPO is 1·2 (95%CI: 1·038-1·377, P < 0·05), initial event-free periods in male patients are significantly longer in patients with MPO <115 ng/mL (mean = 875 days compared with mean = 734 days, P < 0·05) In smokers, an increased hazard ratio was computed for patients with high MPO levels (HR = 3·127, 95%CI: 1·258-7·772, P < 0·05). Effects of MPO [-463A] allele on initial MACE-free intervals did not persist after multivariate analysis. Conclusions Hence, we suggest consideration of plasma MPO for risk stratification of MACE in patients with PAD. In contrast, MPO-463G>A is not an independent risk factor for MACE in patients suffering from PAD. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Besides its effects on glucose and lipid metabolism, the Wnt pathway has been increasingly implicated in the regulation of proliferation, migration and survival of vascular cells. In addition, defective Wnt signaling has been identified in a family with autosomal dominant early coronary artery disease. The aim of this study was to investigate whether premature coronary artery disease is associated with features of decreased Wnt signaling. Methods and results: We prospectively enrolled 100 consecutive young survivors of myocardial infarction (MI≤40years of age) from two high-volume cardiac catheterization centers and 100 sex and age matched hospital controls. We determined serum levels of Wnt-1 and its antagonist Dkk-1 by ELISA. MI patients showed significantly lower Wnt-1 levels as compared to controls (151ng/mL, IQR 38–473ng/mL vs. 233ng/mL, IQR 62–1756; p <0.005) whereas Dkk-1 was not different at baseline. Wnt-1 levels remained stable over time, whereas Dkk-1 significantly increased at one-year follow-up from 3557, IQR 2306–5810pg/mL to 4973, IQR 3293–7093pg/mL (p <0.001). In the stable phase of the disease, Wnt-1 levels were lower (p <0.005) and Dkk-1 levels were significantly higher (p <0.001) as compared to controls. Wnt-1 at follow-up was associated with glucose, HbA1c, non-HDL-, HDL-cholesterol and triglyceride levels but no other features of the metabolic syndrome. Conclusion: This study establishes an association between low Wnt-1 and high Dkk-1 serum levels and premature myocardial infarction. Wnt-1 is associated with markers of glucose and lipid metabolism. Further research elucidating the role of Wnt pathways in premature coronary artery disease and metabolic syndrome is warranted. [Copyright &y& Elsevier]

Objective: The aim of this study was to assess whether visualisation of in-stent changes can be improved with high-resolution, steady-state, blood pool contrast-enhanced MR angiography compared with first-pass MR angiography. Intra-arterial digital subtraction angiography (DSA) served as the reference standard.Methods: Twenty patients after stent placement in the superficial femoral artery (SFA) underwent MRA prior to reintervention. MRA of the SFA includes first-pass MRA as well as 3D high-resolution MRA in the steady state (SS-MRA) after injection of Gadofosveset trisodium. Sensitivity and specificity values for the detection of significant in-stent lesions by means of SS-MRA were calculated at the proximal, middle and distal stent segments in comparison to DSA. Kappa statistics were used to determine agreement between the two techniques.Results: Sensitivity and specificity values for the detection of significant stenosis with SS-MRA reached 95% in the proximal, 100% in the middle and 100% in the distal stent segment. Kappa coefficients between SS-MRA and DSA were 0.789, 0.797 and 0.859 for the proximal, middle and distal segments, whereas the Kappa coefficients for FP-MRA were 0,211, 0,200 and 0,594 in these segments, respectively.Conclusion: Detection of in stent stenosis is significantly improved using SS MRA, in comparison to state-of-the-art FP-MRA. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Acute myocardial infarction (AMI) at young age is a rare disease with a poor prognosis. Bone metabolism parameters such as 1,25 (OH)2 vitamin D3, 25 (OH) vitamin D3 and osteocalcin have been recently implicated in the development of coronary heart disease (CHD). We evaluated the role of these serum markers in a study population of very young AMI survivors (≤40years). Methods and results: We prospectively enrolled 302 subjects into our multi-center case control study, including 102 young myocardial infarction patients (≤40years) and 200 control subjects who were frequency-matched on gender and age in an approximate 2:1 ratio per case patient. In the adjusted logistic regression analysis, we used baseline laboratory measurements for the first analysis (acute phase analysis) and measurements from one-year follow-up visits (stable phase analysis). In both, elevated levels of 25 (OH) vitamin D3 (acute phase: OR per IQR 2.02, 95% CI 1.13–3.58, p=0.017; stable phase: OR 4.07, 95% CI 1.8–9.21, p=0.001) and 1,25 (OH)2 vitamin D3 (acute phase: OR 2.82, 95% CI 1.7–4.7, p<0.001; stable phase: OR 4.57, 95% CI 2.31–9.05, p<0.001) were associated with premature AMI. Conversely, osteocalcin was inversely associated with premature myocardial infarction (acute phase: OR 0.53, 95% CI 0.28–1.03, p=0.059; stable phase: OR 0.26, 95% CI 0.12–0.6, p<0.001). The observed associations were independent of the acute phase of myocardial infarction. Conclusion: In our study, elevated levels of 25 (OH) vitamin D3 and 1,25 (OH)2 vitamin D3, as well as decreased levels of osteocalcin were associated with myocardial infarction in very young patients. The precise mechanism and implications of these findings will have to be elucidated in future studies. [Copyright &y& Elsevier]

Abstract: Background: We aimed to investigate the correlation of infrared thermography (IT) with laser Doppler perfusion imager (LDPI) among patients with primary Raynaud''s phenomenon and healthy controls. Methods: Forty-seven individuals were included: we examined 25 patients with primary Raynaud''s phenomenon and 22 age and gender matched healthy controls. IT of the volar surface of the subjects'' left hands was performed to record skin temperature while skin perfusion of the same area was determined using LDPI. All measurements were obtained at room temperature (baseline measurements) and following standardized cold provocation. Results: Good correlation of baseline measurements was found between IT and LDPI in primary Raynaud patients and healthy controls (r =0.868, p <0.0001 vs. r =0.790, p <0.0001). Following cold challenge, correlation was weaker in both groups (r =0.742 vs. r =0.766, p <0.0001). Correlation after cold provocation was statistically significant among patients with primary Raynaud''s phenomenon in contrast to controls (Chi Quadrat, p =0.023 vs. p =0.306). Conclusion: A significant correlation was found between IT and LDPI in primary Raynaud patients and in healthy controls (r =0.868 and r =0.742, both p <0.0001). Following cold provocation, correlation decreases in both groups. Thus, at room temperature IT might substitute for skin perfusion measured by LDPI. [Copyright &y& Elsevier]

Abstract: Background: Recurrent disease (restenosis) after endovascular treatment of the superficial femoral artery (SFA) remains a major problem. We evaluated the efficacy of beta-endovascular brachytherapy using the CORONA centering catheter in patients with SFA restenosis in a single-arm Phase II trial. Methods and results: A total of 28 patients (mean age 70 years; 16 female, 12 male) with recurrent SFA stenosis were treated, and in-stent restenosis was present in 17 patients (61%). Brachytherapy was performed with strontium-90 beta source using a 7-French CO2-filled one-segment centering catheter. New stents had to be applied in two cases. Mean interventional length was 129 mm (range 20–240 mm). A dose of 14 Gy in vessel radius (postinterventional) plus 2 mm was applied in 24 patients and 18.4 Gy in four patients. Treatment time was 7 min 32 s per radiation segment. No major adverse events occurred. Patients were followed by ankle-brachial index and duplex sonography for a median of 42 months. Cumulative restenosis rates at 1, 2, and 3 years were 9%, 28%, and 40%, respectively. Target vessel revascularization was performed in seven cases (25%). Conclusions: In comparison to literature data, the treatment of SFA restenosis with beta brachytherapy may improve long-term patency. [Copyright &y& Elsevier]

Abstract: Objectives: We hypothesized that high sensitivity C-reactive protein (hs-CRP) and the presence of renal artery stenosis (RAS) might conjointly predict future major adverse cardiovascular events (MACE) in patients with peripheral artery disease (PAD). Background: Clinical outcome in PAD is determined by the extent of atherosclerosis affecting additional vascular beds and the activity of the atherosclerotic process reflected by inflammatory serum markers. Data on the predictive value of hs-CRP on outcome in PAD patients with RAS is limited. Methods: We prospectively enrolled 447 PAD patients who were admitted to our institution for angioplasty. Preintervention hs-CRP was assessed and renal angiograms were obtained. Patients were then followed clinically for the occurrence of MACE for median 15.6 months. Serum creatinine was obtained in all patients at 12 months. Results: Incidental RAS ≥60% at baseline was found in 68 patients (15.2%), MACE were recorded in 111 patients during follow-up. Hs-CRP was significantly associated with the occurrence of MACE (p <0.001) and with 12 months creatinine levels (p =0.005). Adjusted hazard ratios for MACE for increasing quartiles of hs-CRP as compared to the lowest quartile were 1.11 (95% CI 0.53–2.35), 1.06 (95% CI 0.50–2.26) and 2.79 (95% CI 1.47–5.28). Analyzing joint effects of hs-CRP and RAS, we observed no significant interaction. Conclusion: Hs-CRP predicts cardiovascular and renal outcome in PAD patients irrespective of the presence of RAS. Patients with hs-CRP levels above 0.88mg/dL were at particularly high risk for MACE. [Copyright &y& Elsevier]

The authors investigated the incidence of critical limb ischemia (CLI) in 187 patients with intra-aortic balloon pump (IABP) support during a 6-year study period and determined risk factors and long-term outcome (median 5 years) after discharge from a cardiac intensive care unit. Cardiogenic shock following acute myocardial infarction was the predominant cause of IABP support. CLI occurred in 10% of the patients after IABP implantation. Nevertheless, in light of the overall high mortality in this patient population, CLI seems not a primary concern. Furthermore, its incidence significantly decreased during recent years. Duration of IABP support was a significant predictor for CLI. [ABSTRACT FROM AUTHOR]

Summary: Background: No accurate, independent biomarker has been identified that could reliably predict neurological outcome early after cardiac arrest. We speculated that brain natriuretic peptide (BNP) measured at hospital admission may predict patient outcome. Methods: BNP-levels were measured in 155 comatose cardiac arrest survivors (108 male, 58 years [IQR 49–68]) (median time to ROSC 11min; IQR 20–30) during a 6-year study period. Cardiovascular co-morbidities and resuscitation history were assessed according to the Utstein-style and patients were followed for 6-month neurological outcome measured by cerebral performance category (CPC) and survival. Results: Seventy patients (45%) suffered from unfavourable neurological outcome and 79 deaths (51%) occurred during the first 6 months. BNP was significantly associated with an adverse neurological outcome and mortality, independent of the prearrest health condition and cardiac arrest characteristics (median 60pg/ml; IQR 10–230). Adjusted odds ratios for poor neurological outcome at 6 months were 1.14 (95% CI 0.51–2.53), 1.76 (95% CI 0.80–3.88) and 2.25 (95% CI 1.05–4.81), for increasing quartiles of BNP as compared to the lowest quartile. Adjusted odds ratios for mortality until 6 months were 1.09 (95% CI 0.35–3.40), 2.81 (0.80–9.90) and 4.7 (1.27–17.35) compared to the lowest quartile, respectively. Conclusion: Brain natriuretic peptide levels on admission predict neurological outcome at 6 months and survival after cardiac arrest. [Copyright &y& Elsevier]

Objectives: We investigated the effect of myeloperoxidase (MPO) on progression of carotid stenosis in states of high and low high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) levels. Background: Myeloperoxidase is pivotally involved in the pathogenesis of atherosclerosis. In vitro data suggest that MPO exerts deleterious effects via oxidative modulation of lipoproteins. Methods: We prospectively studied 1,019 of 1,268 consecutive patients who were asymptomatic with respect to carotid artery disease. Patients underwent serial carotid ultrasound investigations at baseline and after a follow-up interval of median 7.5 months (range 6 to 9 months), categorizing carotid arteries as 0% to 29%, 30% to 49%, 50% to 69%, 70% to 89%, or 90% to 99% stenosed or occluded. The MPO, HDL-C, and LDL-C levels were measured at baseline, grouped by medians, and correlated with progression of carotid atherosclerosis. Results: Progression of carotid atherosclerosis was found in 100 of 1,019 patients (9.8%). Myeloperoxidase (p = 0.014) but not HDL-C (p = 0.95) or LDL-C (p = 0.30) were associated with progressive disease. However, MPO ≥310 ng/ml was significantly associated with progressive disease (adjusted odds ratio [OR] 2.57, 95% confidence interval [CI] 1.39 to 4.75) only in patients with HDL-C levels <49 mg/dl. Otherwise, in patients with higher HDL-C levels (≥49 mg/dl), MPO ≥310 ng/ml did not predict disease progression (adjusted OR 1.42, 95% CI 0.72 to 2.78). No interaction of MPO with LDL-C was observed. Conclusions: Myeloperoxidase was associated with progression of carotid atherosclerosis in patients with HDL cholesterol levels below 49 mg/dl. [Copyright &y& Elsevier]

Background: Because stent implantation for disease of the superficial femoral artery has been associated with high rates of late clinical failure, percutaneous transluminal angioplasty is preferred for endovascular treatment, and stenting is recommended only in the event of suboptimal technical results. We evaluated whether primary implantation of a self-expanding nitinol (nickel-titanium) stent yielded anatomical and clinical benefits superior to those afforded by percutaneous transluminal angioplasty with optional secondary stenting. Methods: We randomly assigned 104 patients who had severe claudication or chronic limb ischemia due to stenosis or occlusion of the superficial femoral artery to undergo primary stent implantation (51 patients) or angioplasty (53 patients). Restenosis and clinical outcomes were assessed at 6 and 12 months. Results: The mean (+/-SD) length of the treated segment was 132+/-71 mm in the stent group and 127+/-55 mm in the angioplasty group. Secondary stenting was performed in 17 of 53 patients (32 percent) in the angioplasty group, in most cases because of a suboptimal result after angioplasty. At 6 months, the rate of restenosis on angiography was 24 percent in the stent group and 43 percent in the angioplasty group (P=0.05); at 12 months the rates on duplex ultrasonography were 37 percent and 63 percent, respectively (P=0.01). Patients in the stent group were able to walk significantly farther on a treadmill at 6 and 12 months than those in the angioplasty group. Conclusions: In the intermediate term, treatment of superficial-femoral-artery disease by primary implantation of a self-expanding nitinol stent yielded results that were superior to those with the currently recommended approach of balloon angioplasty with optional secondary stenting. (ClinicalTrials.gov number, NCT00281060.). [ABSTRACT FROM AUTHOR]

Abstract: On waiting lists, transplant candidates are routinely screened for potentially harmful complement-fixing alloantibodies using complement-dependent cytotoxicity (CDC) panel-reactive antibody (PRA) testing. We have recently developed a novel cell-independent assay for assessment of complement-activating panel reactivity ([C4d]FlowPRA), which is based on selective flow-cytometric detection of alloantibody-triggered C4 complement split product deposition to human leukocyte antigen (HLA)-coated FlowPRA beads. Serum specimens selected from 120 transplant candidates were evaluated by [C4d]FlowPRA (HLA class I vs II) in comparison with FlowPRA IgG alloantibody screening (HLA class I vs II), a method detecting both complement- and noncomplement-activating alloantibodies, and with CDC-PRA on separated T (T-CDC) or B cells (B-CDC, evaluation on platelet-absorbed sera). For each assay, ≥10% PRA reactivity was considered positive. Comparing complement-dependent PRA assays with standard FlowPRA, the specificity calculated for [C4d]FlowPRA (HLA class I: 92%; class II: 100%) was found to be superior to that of CDC testing (T-CDC-PRA: 79%; B-CDC-PRA: 86%). Because noncomplement-activating alloreactivities were not detected for both techniques, low sensitivities were calculated ([C4d]FlowPRA HLA class I: 61%; class II: 31%; T-CDC-PRA: 70%; B-CDC-PRA: 55%). Compared with CDC-PRA, [C4d]FlowPRA gave a high specificity (HLA class I compared with T-CDC: 89%, HLA class II compared with B-CDC: 95%) but, at least in part because of false-positive CDC results, a modest sensitivity (66% and 38%, respectively). For both HLA classes, we found a highly significant association between absolute [C4d]FlowPRA and CDC-PRA levels (p &#60; 0.0001). Our results suggest that detection of C4 split product deposition to FlowPRA beads may represent an attractive HLA-specific and time-effective alternative to CDC-PRA screening. [Copyright &y& Elsevier]

Heme oxygenase (HO) seems to be a novel protective factor with potent anti-inflammatory, anti-oxidant, and anti-proliferative effects. HO-1, the inducible isoform, is expressed in various tissues and is upregulated by multiple stimuli. However, humans differ quantitatively in their ability to mount an HO-1 response, modulated by two potentially functional polymorphisms in the HO-1 gene promoter region. From several studies it seems that the ability of a patient with certain genotypes to respond strongly in terms of upregulating HO-1 may be an important endogenous protective factor. In the present article we systematically review the hitherto published evidence that promoter polymorphisms in the HO-1 gene exert functional importance by influencing the level of HO-1 expression in different organ systems. [Copyright &y& Elsevier]

Background: Patients with renal insufficiency tend to suffer from advanced atherosclerosis and exhibit a reduced life expectancy. We investigated the association of renal impairment, traditional cardiovascular risk factors and all-cause mortality in patients with symptomatic peripheral artery disease (PAD). Methods: We studied 515 patients with advanced PAD (intermittent claudication, n = 410; critical ischemia, n = 105). Cardiovascular risk profile and calculated glomerular filtration rate (GFR) were obtained at baseline and patients were followed for median 21 months (interquartile range 12 to 25) for mortality. Results: Sixty-five patients (13%) died. Cumulative survival rates at 6, 12, and 24 months were 97%, 95%, and 89%, respectively. Adjusted hazard ratios for mortality according to decreasing quartiles of GFR were 1.2, 2.5, and 5.9 compared to the highest quartile (P<0.001). The association between renal impairment and mortality was independent of diabetes and hypertension, suggesting that decreased GFR adds to the prognostic value of traditional cardiovascular risk factors. Conclusion: Renal impairment is associated with an increased risk for mortality in patients with advanced peripheral artery disease, irrespective of the coincidence of arterial hypertension and diabetes mellitus. This suggests that impaired renal function exerts an unfavorable effect on patient’s outcome, independently of these cardiovascular and renal risk factors. [Copyright &y& Elsevier]

Background and purpose: Elevated plasma levels of interleukin-6 (IL-6) are associated with an increased risk and worse outcome of acute vascular events. A common G/C promoter polymorphism at nt (−174) of the IL-6 gene has been shown to affect basal IL-6 levels. Consequently, the IL-6 genotype may be associated with risk and outcome of ischemic stroke (IS). We investigated the statistical association between this polymorphism and cerebrovascular events, as well as the clinical outcome in patients with symptoms before the age of 60. Methods: We examined 214 patients of 60 years or less with acute ischemic stroke or transient ischemic attack (TIA) and 214 age- and sex-matched healthy control subjects for the (−174) IL-6 G/C polymorphism by mutagenic separated polymerase chain reaction (MS PCR). Clinical severity of the vascular event was evaluated by validated scales at predefined points of time. Results: In the total group of patients, the genotype and allele frequencies in the patient group (38% GG, 45% GC, 17% CC; allelic frequency: 60% G, 40% C) did not differ significantly from the control group. However, individuals homozygous for the (−174)G variant had significantly worse scores on the NIH Stroke Scale (NIHSS) already on admission and 1 week after the event. Also, patients with severe disability 1 week and 3 months after the event (Rankin Scale (RS) 4 or 5; NIH Stroke Scale≥6) were significantly more often carriers of the GG genotype. In a multivariate analysis, the IL-6 (−174)GG genotype was significantly associated with severe disability after 1 week (RS 4–5; odds ratio (OR)=3.2, 95% CI: 1.5–6.6; p=0.002; NIHSS≥6; OR=4.2, 95% CI: 1.6–11.1). Conclusions: The (−174)GG-genotype of the IL-6 gene is associated with severe stroke in young patients with acute cerebrovascular events. Further studies with larger patient groups are warranted to confirm these findings. [Copyright &y& Elsevier]

Summary. After rupture of an arteriosclerotic plaque in a coronary artery, platelets play a crucial role in the subsequent thrombus formation, leading to myocardial infarction. An increased mean platelet volume (MPV), as an indicator of larger, more reactive platelets, may represent a risk factor for myocardial infarction. However, this hypothesis is still controversial and most studies addressing the role of MPV were performed comparing patients suffering from myocardial infarction with healthy controls. We intended to identify patients at high risk of suffering myocardial infarction in a group of patients with known coronary artery disease. One hundred and eighty-five consecutive patients with stable coronary artery disease were compared with 188 individuals who had suffered myocardial infarction. Patients within the highest quintile of MPV (≥ 11·6 fl) had a significantly higher risk of experiencing a myocardial infarction compared with patients within the lowest quintile (OR = 2·6, 95% CI 1·3–5·1) in a multivariate analysis that included sex, age, body mass index, hyperlipidaemia, hypertension, smoking and diabetes mellitus. Our results indicate that patients with pre-existing coronary artery disease and an increased MPV (≥ 11·6 fl) are at higher risk of myocardial infarction. These patients can be easily identified during routine haematological analysis and could possibly benefit from preventive treatment. [ABSTRACT FROM AUTHOR]

Background and Purpose: Despite extensive research in the last decade, the role of serum amyloid A (SAA) in atherogenesis remains highly controversial. The aim of this study was therefore to assess whether SAA is associated with long‐term mortality in patients with subclinical carotid artery disease. Methods: One thousand sixty‐five patients with neurological asymptomatic carotid atherosclerosis as evaluated by duplex sonography were prospectively followed for cause‐specific mortality. Results: During a median of 11.8 years, a total of 549 deaths, including 362 cardiovascular deaths, were recorded. Patients who died within the follow‐up period had significantly higher baseline SAA serum levels compared to those who survived (12.9 vs 9.5 mg/dL; P < 0.001). In univariable Cox regression analysis, the risk of all‐cause and cardiovascular mortality significantly increased in patients with elevated serum levels of SAA (crude hazard ratio for cardiovascular mortality per increase of 1 SD of SAA levels was 1.14, 95% CI 1.08‐1.22], P < 0.0001). However, SAA lost its significance after adjusting for high‐sensitivity C‐reactive protein (hsCRP), suggesting that SAA might not be directly associated with atherogenesis, but rather be a mere reflection of the individual patient's inflammatory status. Conclusions: Serum amyloid A is not independently associated with (cardiovascular) mortality in patients with subclinical carotid atherosclerosis. [ABSTRACT FROM AUTHOR]