Same-day discharge after percutaneous coronary procedures-Structured review and comprehensive meta-analysis.

INTRODUCTION: Percutaneous coronary intervention is a well-established revascularization strategy for patients with coronary artery disease. The safety and feasibility of performing these procedures on a same-day discharge basis for selected patients has been studied in a large number of mostly nonrandomized trials. An up to date literature review should focus on trials with radial access, representing the current standard for coronary procedures in Austria and other European countries. METHODS: The aim of this consensus statement is to review the most recent evidence for the safety and feasibility of performing same-day discharge procedures in selected patients. A structured literature search was performed using prespecified search criteria, focusing on trials with radial access procedures. RESULTS: A total of 44 clinical trials and 4 large meta-analyses were retrieved, spanning 21 years of clinical evidence from 2001 to 2022. The outcome data from a wide range of clinical settings were unanimous in showing no negative effect on early (24 h) or late (30 day) major adverse events after same-day discharge coronary procedures. Based on nine prospective trials a comprehensive meta-analysis was compiled. Using 1­month major adverse events data the pooled odds ratio of same-day discharge versus overnight stay procedures was 0.66 (95% confidence interval, CI 0.35-01.24; p = 0.19; I2 0%), indicating a noninferiority in carefully selected patients. CONCLUSION: Outcome data from same-day discharge coronary intervention trials with radial access confirm the robust safety profile showing no increase in the risk of major adverse events compared to overnight stay.

Interplay of inflammatory markers and anti-SARS-CoV-2 antibodies in COVID-19 mortality: A prospective cohort study.

OBJECTIVES: Despite high global vaccination coverage, it remains unclear how vaccination and anti-SARS-CoV-2 antibodies affect immune responses and inflammation levels in patients with COVID-19. It is further unclear whether the inflammatory response differs depending on antibody levels and whether the combination of antibody and inflammation levels in COVID-19 patients affects mortality rates. METHODS: We conducted a prospective multicenter cohort study that included 1031 hospitalized COVID-19 patients from five hospitals. Anti-SARS-CoV-2-spike antibodies, interleukin-6 (IL6), and CRP were measured on hospital admission. The prespecified endpoint was all-cause in-hospital mortality. RESULTS: We observed significantly lower levels of CRP (P<0.001) and IL6 (P<0.001) in patients with antibody levels above 1200 BAU/ml. After adjusting for potential confounders, patients with high levels of inflammatory markers (CRP>6 mg/dl or IL6>100 pg/ml) combined with low levels of anti-SARS-CoV-2-spike antibodies (<1200 BAU/ml) were approximately 8 times more likely to die than patients with low inflammatory responses and high antibody levels (CRP: aHR 7.973, 95% CI 2.744-23.169, P<0.001; IL6: aHR 8.973, 95% CI 3.549-22.688, P<0.001). CONCLUSION: Hospitalized COVID-19 patients presenting with high inflammatory markers and low antibody levels exhibited the highest mortality risks. Higher antibody levels are associated with lower levels of inflammation in hospitalized COVID-19 patients.

Diagnostic Accuracy of Bone Scintigraphy for the Histopathological Diagnosis of Cardiac Transthyretin Amyloidosis-A Retrospective Austrian Multicenter Study.

We aimed to ascertain the real-world diagnostic accuracy of bone scintigraphy in combination with free light chain (FLC) assessment for transthyretin (ATTR) cardiac amyloidosis (CA) using the histopathological diagnosis derived from endomyocardial biopsy (EMB) as a reference standard. We retrospectively analyzed 102 patients (22% women) with suspected CA from seven Austrian amyloidosis referral centers. The inclusion criteria comprised the available results of bone scintigraphy, FLC assessment, and EMB with histopathological analysis. ATTR and AL were diagnosed in 60 and 21 patients (59%, 21%), respectively, and concomitant AL and ATTR was identified in one patient. The specificity and positive predictive value (PPV) of Perugini score ≥ 2 for ATTR CA were 95% and 96%. AL was diagnosed in three out of 31 patients (10%) who had evidence of monoclonal proteins and a Perugini score ≥ 2. When excluding all patients with detectable monoclonal proteins (n = 62) from analyses, the PPV of Perugini score ≥ 2 for ATTR CA was 100% and the NPV of Perugini score < 2 for ATTR CA was 79%. Conclusively, ATTR CA can be diagnosed non-invasively in the case of a Perugini score ≥ 2 and an unremarkable FLC assessment. However, tissue biopsy is mandatory in suspected CA in any other constellation of non-invasive diagnostic work-up.

2020 update of the Austrian Society of Cardiology (ÖKG) and the Austrian Society of Cardiac Surgery (ÖGHTG) on the position statement of the ÖKG and ÖGHTG for transcatheter aortic valve implantation 2011.

This position statement is an update to the 2011 consensus statement of the Austrian Society of Cardiology (ÖKG) and the Austrian Society of Cardiac Surgery (ÖGTHG) for transfemoral transcatheter aortic valve implantation.Due to a number of recently published studies, broadening of indications and recommendations of medical societies and our own national developments, the ÖKG and the ÖGHTG wish to combine the 2017 ESC/EACTS guidelines for the management of valvular heart disease with a national position paper and to focus on certain details for the application in Austria. Thus, this position statement serves as a supplement and further interpretation of the international guidelines.

Sex differences in independent factors associated with coronary artery disease.

BACKGROUND: Women undergoing coronary angiography (CA) due to chest pain are more likely to present with less extensive coronary artery disease (CAD) than men, which might be attributed to different effects of cardiovascular risk factors on coronary atherogenesis between sexes. The aim of the present study was to evaluate sex differences in independent factors associated with obstructive and non-obstructive CAD in a large consecutive cohort of patients undergoing elective CA. METHODS: Data from 7819 patients (2653 women and 5184 men), including cardiovascular risk factors, clinical presentation, CAD severity and treatment decisions were analysed. RESULTS: Women were older than men (65 ± 11 vs. 63 ± 11 years, p < 0.001); low-density lipoprotein cholesterol (LDL; 125 ± 38 vs. 122 ± 37 mg/dL, p < 0.001) and high-density lipoprotein cholesterol (HDL) cholesterol levels (62 ± 18 vs. 51 ± 15 mg/dL, p < 0.001) were higher in women; and smokers were more frequently men (14.4 vs. 20.1%, p < 0.001). Men more frequently had an obstructive CAD (41.1 vs. 65.6%, p < 0.001). Multivariable analyses revealed age, HDL cholesterol, hypercholesterolaemia, diabetes mellitus, arterial hypertension and a positive family history being associated with obstructive CAD in both sexes, whereas smoking was independently associated with obstructive CAD only in women. The association of hypercholesterolaemia with obstructive CAD was stronger in men. For non-obstructive CAD, no sex-specific associated factors could be identified. CONCLUSION: The impact of smoking and hypercholesterolaemia on coronary atherosclerosis is different between women and men. This might be taken into account when planning individual interventions to reduce cardiovascular risk.

Prasugrel vs. ticagrelor in acute coronary syndromes: which one to choose?

Acute coronary syndromes (ACS) are still associated with significant morbidity and mortality. Dual antiplatelet therapy with clopidogrel and acetyl-salicylic acid has become the standard of care for patients with ACS in the last 2 decades. However, clopidogrel has drawbacks including delayed therapeutic effect, significant interindividual variability of platelet aggregation inhibition or reduced action on thrombocytes due to interaction with other drugs or genetic polymorphisms. Consequently, new antiplatelet drugs have been developed. Two of these drugs, namely prasugrel and ticagrelor, have been approved by the European Medicines Agency (EMA) and are already available in many European countries. For each substance a "mega-trial" has been published. Both agents were clearly superior compared to clopidogrel and should be therefore preferred in patients with ACS. However, no study has directly compared efficacy as well as safety of prasugrel and ticagrelor so far. Hence, clinicians will be claimed to decide which one to choose in everyday practice. The aim of this manuscript is to summarize the current literature and to provide a guide for individual decision-making between prasugrel and ticagrelor in ACS in daily routine.

Comparison of peripheral endothelial function in shift versus nonshift workers.

Shift working is related to increased cardiovascular morbidity. Peripheral endothelial dysfunction, an inherent feature of early atherosclerosis, has been suggested as a surrogate marker of cardiovascular risk. Whether shift working is associated with peripheral endothelial dysfunction has not been investigated to date. A total of 48 male shift workers (SWs) and 47 male nonshift workers (NSWs) (mean age 43 ± 5 years) were recruited from a glass manufactory. The SWs and NSWs were matched according to age, body mass index, smoking habits, family history of premature coronary artery disease, prevalence of hypercholesterolemia and hypertension, and work place. Their sport habits were also documented. Peripheral endothelial function was assessed using the EndoPAT technique to determine the peripheral arterial tone (PAT) index. According to the study design, no difference was found in the risk factor profiles between the SWs and NSWs. Despite a greater percentage of regular physical activity among the SWs (16.7 vs 4.3%, p = 0.05), shift working was associated with a reduced PAT index compared to working only on the day shift (PAT index 1.73 ± 0.4 vs 1.94 ± 0.5, p = 0.03). In the NSW group, the participants with regular physical training (n = 16) had a greater PAT index than those without regular physical activity (n = 12; PAT index 2.28 ± 0.45 vs 1.86 ± 0.51, p = 0.03). No such difference was found in the SWs. In conclusion, SWs had a reduced PAT index compared with NSWs, suggesting endothelial dysfunction. Therefore, the known increased cardiovascular risk in those shift working might be related to endothelial dysfunction.

[Biomarker for diagnosis of rejection after heart transplantation]. / Biomarker zur Diagnose der zellulären Abstossung nach Herztransplantation.

Heart transplantation is an established therapeutic modality in patients with end-stage heart failure. In the 1st year after transplantation acute cellular rejection is still important. The diagnosis of acute cellular rejection is based on the histological evaluation of endomyocardial biopsy (EMB) specimens. EMB is an invasive procedure with a definite risk and poor tolerance in some patients. Imaging methods like echocardiography and magnetic resonance imaging as well as intracardiac ECG have been used for noninvasive diagnosis of acute cellular rejection. In addition, a large number of circulating biomarkers have been evaluated for noninvasive diagnosis of rejection. B-type natriuretic peptide, troponin and inflammatory markers are the most important biomarkers in this field. Although these parameters are useful, none of them has the potential to replace EMB as the gold standard for diagnosis of rejection. In the near future microarray technology might get important for diagnosis of acute cellular rejection. Using microarray technique gene expression profiles can be detected, which are associated with an increased risk for rejection. Ongoing studies will demonstrate, whether microarrays can at least reduce the number of EMBs.

[Myocarditis and sudden cardiac death in athletes. Diagnosis, treatment, and prevention]. / Myokarditis als Ursache des plötzlichen Herztodes bei Sportlern. Diagnose, Behandlung und Prävention.

Myocarditis is the reason for sudden cardiac death in 5-22% of athletes < 35 years of age. Actually, parvovirus B19 and human herpes virus 6 are the most important pathogens. Clinical presentation of myocarditis is heterogeneous, with all courses between asymptomatic and fulminant reported. Especially in athletes it is important to take subtle discomforts seriously and initiate further evaluation. Electrocardiogram, laboratory parameters, serologic markers, and echocardiography are helpful in diagnosis of myocarditis, but are not specific. Magnetic resonance imaging (MRI) of the heart has become an important tool in the evaluation of patients with myocarditis and allows noninvasive appraisal of myocardial inflammation using late enhancement. However, MRI is not able to assess viral persistence. Therefore, endomyocardial biopsy (EMB) remains the gold standard in diagnosis of myocarditis. When considering EMB in these athletes one should not ignore spontaneous healing in 50% of patients with myocarditis. Contrariwise, specific therapy (e.g., immunosuppression, interferon, immunoglobulins) for myocarditis is only feasible after getting results of EMB. When myocarditis is verified, athletes have to withdraw from sport for at least 6 months. Before restarting physical activity, a detailed examination is necessary and most of the patients will undergo another EMB. For prevention of myocarditis and sudden cardiac death it is recommended to stop elite sport for 4 weeks after an unspecific infection. Whether moderate sport can be started earlier is unclear.

Neopterin, CD4+CD28- lymphocytes and the extent and severity of coronary artery disease.

OBJECTIVES: Macrophages and pro-inflammatory CD3+CD4+CD28- T lymphocytes are involved in atherosclerotic plaque destabilization. Whether neopterin, a macrophage-specific activation-marker, and circulating CD3+CD4+CD28- cells are also related to the severity and extent of coronary artery disease (CAD) in stable patients is still unclear. METHODS: Coronary angiograms of 30 patients with stable angina pectoris were graded using the Gensini severity and an extent score. Patients were grouped according to the median of each score. Lymphocyte subsets were determined by FACS analysis and neopterin by radioimmunoassay. Peripheral endothelial function of the brachial artery (FMD) shown to correlate with cardiovascular risk factors was evaluated using high-resolution ultrasound. RESULTS: More extensive CAD was associated with increased neopterin levels (8.3 +/- 3.3 vs. 5.5 +/- 1.2 nmol/L, p < 0.001) and increased CD3+CD4+CD28- cells (3.1 +/- 1.6 vs. 2.0 +/- 1.2%, p < 0.05). A high Gensini severity score was associated with increased neopterin levels (7.8 +/- 2.7 vs. 6.3 +/- 1.7 nmol/L, p < 0.05), but not with CD3+CD4+CD28- cells. Neopterin correlated with both the extent (r = 0.59, p < 0.001) and the Gensini score (r = 0.57, p < 0.003). FMD was not correlated with both scores. CONCLUSIONS: Neopterin and CD3+CD4+CD28- lymphocytes are associated with CAD extent in stable patients, thereby emphasizing the inherent role of inflammation in atherogenesis itself beyond plaque destabilization. Neopterin's correlation with CAD severity might be additionally useful in identifying patients eligible for revascularization procedures.

Is there a relation between non-calcifying coronary plaques and acute coronary syndromes? A retrospective study using multislice computed tomography.

OBJECTIVES: The purpose of this study was to assess whether different coronary plaque types as classified by multislice computed tomography (CT) are retrospectively correlated with acute coronary syndromes (ACS) in an unselected study population. METHODS: Sixty-three consecutive patients were examined with 16-slice CT coronary angiography. Coronary plaque types were classified as calcifying type 1, mixed (calcifying > non-calcifying) type 2, mixed (non-calcifying > calcifying) type 3, and non-calcifying type 4. Patients who had an ACS within 17 days were included. All patients underwent invasive coronary angiography. RESULTS: Fifty-eight patients (92%) had coronary plaques evaluated by CT: 18 type 1 (31%), 10 type 2 (17%), 16 type 3 (28%) and 14 type 4 (24%). The presence of a non-calcifying plaque component (types 2-4; 40 of 63 patients, 63%) was correlated with ACS (n = 15; 24%) (p < 0.001). Only type 3 was significantly correlated with ACS (p = 0.01), but plaque types 2 and 4 were not. The diagnostic accuracy of CT for detection of stenosis >50% in proximal segments was: sensitivity 98%, specificity 90%, negative predictive value 97%, positive predictive value 97% per patient. CONCLUSIONS: Mixed calcifying/non-calcifying plaques with a predominantly non-calcifying component (type 3) as classified by multislice CT are retrospectively correlated with ACS.

Interventional and medical treatment of acute heart failure due to inflammation: four cases.

Four patients (aged 15-41 years, mean age 26.7 years) with fulminant myocarditis undergoing mechanical circulatory support are reported. All patients suffered from acute low-output syndrome refractory to inotropic support. Diagnosis was confirmed by histology and immunohistochemistry. RT-PCR (reverse transcription-polymerase chain reaction) from endomyocardial biopsy specimens revealed parvovirus B19 in two patients and a coinfection with Chlamydia pneumoniae and parvovirus B19 in one patient. Midterm support with the biventricular Thoratec system was preceded by implantation of an extracorporeal membrane oxygenation (ECMO) device in two patients. Two patients regained full cardiac function and were successfully weaned from the ventricular assist device (VAD) after 12 and 40 days. Heart transplantation was performed in another patient without evidence of myocardial recovery after 53 days. One patient died of cerebral hemorrhage on day 12 after VAD implantation. In summary, patients with life-threatening fulminant myocarditis can be successfully bridged to recovery or transplantation with mechanical circulatory support.

Countervailing effects of rapamycin (sirolimus) on nuclear factor-kappa B activities in neointimal and medial smooth muscle cells.

OBJECTIVE: Local application of rapamycin (sirolimus) by drug-eluting stents prevents lumen obliteration after angioplasty by inhibition of neointimal hyperplasia. The effects of rapamycin on neointimal smooth muscle cells (niSMC) which are responsible for the occurrence of restenosis have not been investigated so far. METHODS AND RESULTS: Rat niSMC and medial SMC (mSMC) were obtained from balloon catheter-injured arteries. The niSMC exhibited higher basal NF-kappaB activity and TNF-alpha mRNA levels. Nuclear protein binding to NF-kappaB-DNA was attenuated in niSMC by incubation with rapamycin (0.1 and 1 microg/ml) for 24 and 48 h. In contrast in mSMC, 0.1 microg/ml rapamycin had no effect and at 1 microg/ml even increased nuclear protein binding to NF-kappaB-DNA. After 12 h incubation, rapamycin (0.001-10 microg/ml) induced IkappaB-alpha protein in niSMC, whereas in mSMC it stimulated IkappaB-alpha at much lower levels. Prolonged rapamycin treatment (1 microg/ml for 72 h) had no effect on TNF-alpha mRNA level and NF-kappaB activity in niSMC, whereas it led to their increase in mSMC. Vascular endothelial growth factor (VEGF) secretion was higher in mSMC than in niSMC; rapamycin decreased VEGF levels in both cell types. Ultrastructural analysis suggested that rapamycin caused early signs of degeneration in niSMC, but enhanced protein synthesis in mSMC. CONCLUSIONS: This study shows that rapamycin influences the inflammatory phenotypes of SMC in opposite directions: it reduces the high basal NF-kappaB activity in niSMC and enhances NF-kappaB activity and TNF-alpha expression in mSMC. In addition, rapamycin inhibits VEGF production regardless of the phenotype of SMC. These findings shed light on molecular mechanisms and structural changes underlying therapeutic applications of rapamycin in prevention of restenosis, inhibition of chronic transplant arteriosclerosis and reduction of secondary malignoma formation due to immunosuppression.

Effect of atorvastatin on circulating proinflammatory T-lymphocyte subsets and soluble CD40 ligand in patients with stable coronary artery disease--a randomized, placebo-controlled study.

BACKGROUND: Coronary atherosclerosis includes an activation of circulating T lymphocytes. Statins exert anti-inflammatory effects beyond lipid lowering. Whether these properties influence systemic T lymphocytes is unclear. METHODS: To investigate the effect of atorvastatin on circulating T-lymphocyte subsets producing proinflammatory and anti-inflammatory cytokines (interferon gamma [IFN-gamma(+)], interleukin 2 [IL-2(+)], IL-4(+), and IL-10(+)) and on the T-cell-activating soluble CD40 ligand (sCD40L), 30 hypercholesterolemic patients with angiographically documented stable coronary artery disease (CAD) were randomized to placebo or atorvastatin (20 mg/d) for 3 months. Eight healthy volunteers served as controls. Levels of peripheral cytokine-producing CD4+ and CD8+ T cells and their CD28- subsets were determined by FACS. Serum soluble CD40L was measured with ELISA. RESULTS: IL-2(+) T lymphocytes and sCD40L levels were higher in patients with CAD compared with controls, whereas IFN-gamma(+) and anti-inflammatory IL-4(+) and IL-10(+) T lymphocytes were similar. Levels of IL-2(+), IFN-gamma(+), IL-4(+), and IL-10(+) T-cell subsets as well as CD28- T lymphocytes were neither changed by atorvastatin nor by placebo, whereas sCD40L was lowered only in atorvastatin-treated patients (P < .01). CONCLUSION: Circulating IL-2(+) T lymphocytes are increased in patients with stable CAD reflecting an activation of the global immune system, but are not influenced by atorvastatin therapy. The elevated levels of platelet-derived T-lymphocyte-stimulating sCD40L are decreased by atorvastatin probably reflecting an atheroprotective effect. Hence, sCD40L may be an additional biomarker to be considered when evaluating the treatment effects of statins in patients with stable CAD.

Atorvastatin affects several angiogenic mediators in human endothelial cells.

The pleiotropic effects of statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, have been recently extended to the modulation of angiogenesis. Here, to get more insight into the statins action, the authors have investigated the effect of atorvastatin on the expression of several angiogenic and inflammatory genes in human umbilical endothelial cells (HUVECs). Atorvastatin was proangiogenic at the dose of 10 nM, and antiangiogenic at the concentrations of 1 to 10 micro M. Moreover, these higher concentrations inhibited also the proliferation of HUVECs induced by vascular endothelial growth factor (VEGF). Lower doses of atorvastatin did not influence endothelial cell proliferation. Importantly, atorvastatin at the micromolar concentrations diminished the production of interleukin (IL)-8, a proinflammatory and proangiogenic chemokine, and inhibited the synthesis of urokinase plasminogen activator (uPA), a potent proinflammatory mediator. However, it decreased also the expression of plasminogen activator inhibitor-1 (PAI-1) and thrombospondin-1 (TSP-1), the inhibitors of angiogenesis. Atorvastatin stimulated the expression of angiopoietin (Ang)-2 and moderately enhanced the expression of endothelial nitric oxide synthase (eNOS), whereas heme oxygenase-1 (HO-1) was not significantly affected. In conclusion, the present findings points to other angiogenesis-related effects of atorvastatin, which may be of relevance to the beneficial influence of statins in cardiovascular system.

Effects of local gene transfer of VEGF on neointima formation after balloon injury in hypercholesterolemic rabbits.

Enhancement of the generation of nitric oxide (NO) and vascular endothelial growth factor (VEGF) are suggested to prevent restenosis after angioplasty. Accordingly, we tested whether the local delivery of L-arginine (L-Arg), a substrate for NO generation and the VEGF gene, alone or in combination, can influence neointima formation in hypercholesterolemic rabbits. Balloon injury of the iliac arteries was performed in 24 New Zealand White rabbits fed a 1% cholesterol diet for 3 weeks followed by a local infusion of: (1) pSG5VEGF165 plasmid alone (1000 microg); (2) pSG5VEGF165 (1000 microg) with L-Arg (800mg); (3) L-Arg (800mg) alone; and (4) L-Arg (800 mg) with naked pSVbeta-gal plasmid (1000 microg). The animals were kept on the hypercholesterolemic diets for a further 28 days, when vessels were taken for morphometric analysis and immunocytochemistry. Endogenous rabbit VEGF concentration in the plasma increased significantly at 7 days after injury (17.06 +/- 1.57 vs 23.01 +/- 1.9 pg/ml; p < 0.02) and remained elevated for up to 28 days (28.46 +/- 5.24; p < 0.01). Injured arteries exhibited strong immunocytochemical staining for rabbit VEGF. Rabbits that received a VEGF gene transfer revealed more prominent neointima formation, whereas treatment with L-Arg was associated with significantly less intimal thickness (p < 0.05). Local transfer of the VEGF gene does not inhibit neointima formation in hypercholesterolemic rabbits. Our results suggest that VEGF gene therapy applied locally in atherosclerotic arteries may not be beneficial.

Statins differentially regulate vascular endothelial growth factor synthesis in endothelial and vascular smooth muscle cells.

OBJECTIVES: HMG-CoA reductase inhibitors (statins) can modulate the formation of new blood vessels, but the reports on their contribution to angiogenesis are contradictory. Therefore, we investigated whether the effect of statins is dependent either on the concentration of the drug or on the cell type. METHODS AND RESULTS: Under basal conditions human vascular smooth muscle cells (HVSMC) and microvascular endothelial cells (HMEC-1) constitutively generate and release vascular endothelial growth factor (VEGF). In contrast, primary macrovascular endothelial cells (HUVEC) produce minute amounts of VEGF. Different statins (atorvastatin, simvastatin and lovastatin, 1-10 micromol/l) significantly reduced basal and cytokine-, nitric oxide- or lysophosphatidylcholine (LPC)-induced VEGF synthesis in HMEC-1 and HVSMC. Interestingly, at the same concentrations statins upregulated VEGF generation in HUVEC. Furthermore, statins exerted dual, concentration-dependent influence on angiogenic activities of HUVEC as determined by tube formation assay. At low concentrations (0.03-1 micromol/l) the pro-angiogenic activity of statins is prevalent, whereas at higher concentrations statins inhibit angiogenesis, despite increasing VEGF synthesis. CONCLUSION: Our data show that statins exert concentration- and cell type-dependent effects on angiogenic activity of endothelial cells and on VEGF synthesis. The data are of relevance for elucidating the differential activity of statins on angiogenesis in cardiovascular diseases and cancer.

HMG-CoA reductase inhibitors regulate inflammatory transcription factors in human endothelial and vascular smooth muscle cells.

OBJECTIVE: Pleiotropic atheroprotective effects of HMG-CoA reductase inhibitors may be mediated on the level of vascular gene transcription. The aim of this study was to characterize the effects of statins on the activation of transcription factors known to regulate inflammation and cell proliferation/differentiation. METHODS AND RESULTS: Simvastatin, atorvastatin, and lovastatin (0.1 to 10 micro mol/L) inhibited the binding of nuclear proteins to both the nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) DNA consensus oligonucleotides in human endothelial and vascular smooth muscle cells as assessed by electrophoretic mobility shift assay (EMSA). The inhibitory effects of statins on NF-kappaB or AP-1-dependent transcriptional activity were examined by transient transfection studies. HMG-CoA reductase inhibitors upregulated IkappaB-alpha protein levels in endothelial cells and decreased c-Jun mRNA expression in smooth muscle cells as analyzed by Western and Northern blotting, respectively. Furthermore, statins inhibited DNA binding of hypoxia-inducible factor-1alpha. Downstream effects of statins included inhibition of plasminogen activator inhibitor-1 and vascular endothelial growth factor-A mRNA levels in endothelial cells. CONCLUSIONS: HMG-CoA reductase inhibitors downregulate the activation of transcription factors NF-kappaB, AP-1, and hypoxia-inducible factor-1alpha. These findings support the concept that statins have antiinflammatory and antiproliferative effects that are relevant in the treatment of atherosclerotic diseases.

Morphologic rather than functional or mechanical sonographic parameters of the brachial artery are related to angiographically evident coronary atherosclerosis.

OBJECTIVES: The purpose of this study was to determine the relationship among coronary atherosclerosis and functional, morphologic, and mechanical parameters assessed noninvasively within the brachial artery (BA). BACKGROUND: Flow-mediated vasodilation (FMD) of the BA, intima-media thickness (IMT) of the carotid artery, and distensibility of the aorta have been correlated with the presence of coronary artery disease (CAD). METHODS: The BA was examined with high-resolution ultrasound (13 MHz) in 117 male patients, in whom coronary angiography was performed. Coronary artery disease (> or =30% diameter stenosis in > or =1 major branch) was found in 84 patients, and 33 patients had smooth coronary arteries (non-CAD). Wall cross-sectional area (WCSA) was calculated from resting diameter and IMT. RESULTS: The BA-WCSA (5.3 +/- 1.5 mm(2) vs. 4.4 +/- 1.4 mm(2), p = 0.002) and IMT (0.37 +/- 0.07 mm vs. 0.31 +/- 0.07 mm, p < 0.001) were significantly greater in patients with CAD compared with non-CAD patients. Flow-mediated vasodilation and distensibility were similar among groups. Using logistic regression analyses adjusting for age, positive family history, hypertension, hypercholesterolemia, smoking, FMD, and distensibility, only WCSA (p < 0.01) and IMT (p < 0.001) correlated independently with the presence of CAD. CONCLUSIONS: Morphologic but not functional and mechanical parameters of the BA are associated with the presence of CAD. Among BA sonographic parameters, IMT and WCSA seem to be the most accurate ones for the estimation of coronary atherosclerotic risk.