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Otmar Pachinger

Publications and source records attributed to Otmar Pachinger.

At least 55 records · Page 3Linked to original sources
PubMed2004

Accurate, simplified and rapid three-dimensional echocardiographic volume quantifications: Comparison of different algorithms in symmetric and asymmetric left ventricular geometry.

OBJECTIVE: A comparative investigation of dynamic three-dimensional freehand echocardiography (D3DFE) and magnetic resonance imaging (MRI) was conducted to determine the accuracy and rapidity of the average rotation method (ARM) and the disk summation method (DSM) for volumetric analysis. METHODS: In 15 patients with an asymmetric left ventricle and 12 normal subjects, end-diastolic and end-systolic left ventricular volumes were assessed by D3DFE and by MRI. Both DSM and ARM were used for volume determination. All echocardiographic readings were performed by two examiners blinded to each other and to the MRI results. The times needed for echocardiographic data acquisition and volumetric analysis with either algorithm were determined. RESULTS: Correlation between ARM and MRI measurements was tighter than between DSM and MRI measurements (end-diastolic volume: r=0.95, P<0.0001 versus r=0.94, P<0.0001 in asymmetric ventricles; and r=0.97, P<0.0001 versus r=0.96, P<0.0001 in symmetric ventricles; end-systolic volume: r=0.94, P<0.0001 versus r=0.93, P<0.0001 in asymmetric ventricles and r=0.96, P<0.0001 versus r=0.94, P<0.0001 in symmetric ventricles). In addition, ARM analysis was less time-consuming than DSM (6.4+/-0.4 min versus 7.6+/-0.3 min, P<0.05). CONCLUSIONS: For D3DFE, ARM is the most accurate and rapid approach to left ventricular volume determination. ARM benefits from advanced two-dimensional imaging and can be easily added to any standard transthoracic echocardiographic examination.

Adult↗
PubMed2003

Endothelial dysfunction induced by hyperhomocyst(e)inemia: role of asymmetric dimethylarginine.

BACKGROUND: Endothelial function is impaired by hyperhomocyst(e)inemia. We have previously shown that homocyst(e)ine (Hcy) inhibits NO production by cultured endothelial cells by causing the accumulation of asymmetric dimethylarginine (ADMA). The present study was designed to determine if the same mechanism is operative in humans. METHODS AND RESULTS: We studied 9 patients with documented peripheral arterial disease (6 men; 3 women; age, 64+/-3 years), 9 age-matched individuals at risk for atherosclerosis (older adults; 9 men; age, 65+/-1 years), and 5 young control subjects (younger adults; 5 men; age, 31+/-1 years) without evidence of or risk factors for atherosclerosis. Endothelial function was measured by flow-mediated vasodilatation of the brachial artery before and 4 hours after a methionine-loading test (100 mg/kg body weight, administered orally). In addition, blood was drawn at both time points for measurements of Hcy and ADMA concentrations. Plasma Hcy increased after the methionine-loading test in each group (all, P<0.001). Plasma ADMA levels rose in all subjects, from 0.9+/-0.2 to 1.6+/-0.2 micromol/L in younger adults, from 1.5+/-0.2 to 3.0+/-0.4 micromol/L in older adults, and from 1.8+/-0.1 to 3.9+/-0.3 micromol/L in peripheral arterial disease patients (all, P<0.001). Flow-mediated vasodilatation was reduced from 13+/-2% to 10+/-1% in younger adults, from 6+/-1% to 5+/-1% in older adults, and from 7+/-1% to 3+/-1% in peripheral arterial disease patients (all, P<0.001). Furthermore, we found positive correlations between plasma Hcy and ADMA concentrations (P=0.03, r=0.450), as well as ADMA and flow-mediated vasodilatation (P=0.002, r=0.623). CONCLUSIONS: Our results suggest that experimental hyperhomocyst(e)inemia leads to accumulation of the endogenous NO synthase inhibitor ADMA, accompanied by varying degrees of endothelial dysfunction according to the preexisting state of cardiovascular health.

Adult↗
PubMed2003

Plasma distribution of apoA-IV in patients with coronary artery disease and healthy controls.

Recent studies showed lower apolipoprotein A-IV (apoA-IV) plasma concentrations in patients with coronary artery disease (CAD). The actual distribution of the antiatherogenic apoA-IV in human plasma, however, is discussed controversially and it was never investigated in CAD patients. We therefore developed a gentle technique to separate the various apoA-IV-containing plasma fractions. Using a combination of precipitation of all lipoproteins with 40% phosphotungstic acid and 4 M MgCl2, as well as immunoprecipitation of all apoA-I-containing particles with an anti-apoA-I antibody, we obtained three fractions of apoA-IV: lipid-free apoA-IV (about 4% of total apoA-IV), apoA-IV associated with apoA-I (LpA-I:A-IV, 12%), and apoA-I-unbound but lipoprotein-containing apoA-IV (LpA-IV, 84%). We compared these three apoA-IV fractions between 52 patients with a history of CAD and 52 age- and sex-matched healthy controls. Patients had significantly lower apoA-IV levels when compared to controls (10.28 +/- 3.67 mg/dl vs. 11.85 +/- 2.82 mg/dl, P = 0.029), but no major differences for the three plasma apoA-IV fractions. We conclude that our gentle separation method reveals a different distribution of apoA-IV than in many earlier studies. No major differences exist in the apoA-IV plasma distribution pattern between CAD patients and controls. Therefore, the antiatherogenic effect of apoA-IV has to be explained by other functional properties of apoA-IV (e.g., the antioxidative characteristics).

Adult↗
PubMed2003

Effects of oral magnesium therapy on exercise tolerance, exercise-induced chest pain, and quality of life in patients with coronary artery disease.

Previous studies have demonstrated that magnesium supplementation improves endothelial function in patients with coronary artery disease (CAD). However, the impact on clinical outcomes, such as exercise-induced chest pain, exercise tolerance, and quality of life, has not been established. In a multicenter, multinational, prospective, randomized, double-blind and placebo-controlled trial, 187 patients with CAD (151 men, 36 women; mean +/- SD age 63 +/- 10 years, range 42 to 83) were randomized to receive either oral magnesium 15 mmol twice daily (Magnosolv-Granulat, total magnesium 365 mg provided as magnesium citrate) (n = 94) or placebo (n = 93) for 6 months. Symptom-limited exercise testing (Bruce protocol) and responses given on quality-of-life questionnaires were the outcomes measured. Magnesium therapy significantly increased intracellular magnesium levels ([Mg]i) in a substudy of 106 patients at 6 months compared with placebo (35.5 +/- 3.7 vs 32.6 +/- 2.9 mEq/L, p = 0.0151). Magnesium treatment significantly increased exercise duration time compared with placebo (8.7 +/- 2.1 vs 7.8 +/- 2.9 minutes, p = 0.0075), and lessened exercise-induced chest pain (8% vs 21%, p = 0.0237). Quality-of-life parameters significantly improved in the magnesium group. These findings suggest that oral magnesium supplementation in patients with CAD for 6 months results in a significant improvement in exercise tolerance, exercise-induced chest pain, and quality of life, suggesting a potential mechanism whereby magnesium could beneficially alter outcomes in patients with CAD.

Administration, Oral↗
PubMed2003

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.

Atorvastatin↗
PubMed2003

Activation of heat shock transcription factor 1 in atherosclerosis.

Previous work established that increased expression of heat shock proteins (HSPs) in the vessel wall might evoke proinflammatory and autoimmune reactions in the pathogenesis of atherosclerosis. The present study was designed to further scrutinize the molecular mechanisms of HSP expression involving activation of heat shock transcription factors (HSFs) in atherosclerotic lesions in animal models. Severe atherosclerotic lesions developed in the aortas of rabbits 16 weeks after feeding a 0.2% cholesterol diet. When protein extracts from the aortas were subjected to Western blot analysis, the level of HSF1 in proteins from atherosclerotic lesions of hypercholesterolemic rabbits were significantly higher than those of normal vessels. Gel mobility shift assays revealed the formation of protein-heat shock element complexes containing HSF1 in protein extracts from atherosclerotic lesion. Furthermore, triglyceride-rich lipoprotein, oxidized-triglyceride-rich lipoprotein, low-density lipoprotein, and oxidized low-density lipoprotein did not activate HSF1 in cultured smooth muscle cells, whereas HSF1 was highly activated in cells treated with tumor necrosis factor-alpha. Interestingly, mechanical stretching of smooth muscle cells resulted in HSF1 translocation from the cytoplasm to the nucleus and hyperphosphorylation followed by increased HSP70 expression. Thus, our findings provide the first evidence that HSF1 is activated and highly expressed in atherosclerotic lesions and that cytokine stimulation and disturbed mechanical stress to the vessel wall may be responsible for such activation.

Animals↗
PubMed2003

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.

Atorvastatin↗
PubMed2003

Tissue Doppler analysis is hindered in abnormal wall motion and changes in afterload.

BACKGROUND: Tissue Doppler (TD) analysis is used to estimate contractility. However, interference with hemodynamics has not been investigated. OBJECTIVE: To evaluate the effect of hemodynamic conditions and wall motion abnormalities on TD indices. METHODS: TD indices were obtained in 16 dogs and correlated with hemodynamics and wall thickening. RESULTS: An inverse relation between TD indices and systemic vascular resistance was observed when afterload-related parameters were included in the analysis (early systolic subendocardial velocity: r((multiple regression))=0.82, P<0.0001 vs. r((simple regression))=0.57, P=0.0002). Early systolic TD data were more closely related to hemodynamics than those derived from the entire systole. TD data did not correspond to the hyperkinesia of the contralateral wall in myocardial infarction, whereas the increase of gradient parameters reflected hypercontractility (P<0.05). CONCLUSION: TD indices are directly related to contractility and inversely to afterload. They do not reflect wall motion of those segments not involved in regional ischemia.

Animals↗
PubMed2003

Partial cut-off of the left ventricle: determinants and effects on volume parameters assessed by real-time 3-D echocardiography.

A total of 44 patients with coronary artery disease underwent real-time three-dimensional (3-D) echocardiography for end systolic (ES) and end diastolic (ED) left ventricular (LV) volumetric analysis to assess the effect of partial cut-off of the left ventricular (LV) apex on volumetric analysis by apical transthoracic echocardiography. Patients with LV cut-off were assigned to either group 1 (ejection fraction, (EF) < 49%) or group 2 (EF > or = 49%). Patients were additionally classified as group A if they had anterior or apical wall motion abnormalities (WMA) or group B if they had only inferoposterior or lateral WMA. Partial LV cut-offs were found in 22 subjects (50%). The estimated end diastolic cut-off volumes were as follows: 8.6 +/- 3.2 mL (group 1), 4.3 +/- 2.4 mL (group 2), 9.1 +/- 3.3 mL (group A) and 1.4 +/- 0.8 mL (group B). In group 1, more patients with LV volume cut-off were found than in group 2: chi(2) = 4.52, p < 0.05; and in group A more than in group B: chi(2) = 8.08, p < 0.01. In all, partial LV cut-off led to underestimation of LV volumes: 5.9 +/- 4.7 ml (ED) vs. 2.1 +/- 1.3 ml (ES), p <0.02. In conclusion, LV cut-offs can potentially alter the accuracy of echocardiographic volumetric analysis, particularly in anterior or apical WMA.

Adult↗
PubMed2003

Impact of aging on cardiac high-energy phosphate metabolism determined by phosphorus-31 2-dimensional chemical shift imaging (31P 2D CSI).

Previous echocardiographic and experimental animal studies have shown that cardiac function, structure, and metabolism change with age. The aim of this study was to evaluate the impact of age on left ventricular high-energy phosphate metabolism. Using a 1.5 Tesla whole-body MR scanner 31P 2D CSI (8 x 8 phase encoding steps, 320 mm field of view) was performed in 76 healthy male volunteers (41.7 +/- 13 years) without any history of coronary heart disease. Fourier interpolation, corrections for T1 saturation effects, the nucleus Overhauser effect, and the blood contamination were applied to the spectroscopic data. The volunteers were divided into two groups, younger (n = 37) and older (n = 39) than 41.7 years. In all volunteers, laboratory specimen were sampled, and transthoracal echocardiography was carried out. Significant differences in left ventricular phosphocreatine (PCr) to beta-adenosine-triphosphate (beta-ATP) ratios (2.16 vs. 1.83, p < 0.001), fasting serum glucose levels (83.3 vs. 98.7 mg/dl, p < 0.001), E/A (1.51 vs. 1.14 p < 0.001), and ejection fraction (EF, 65.3 vs. 59.9%, p = 0.005) were detected between the two groups of volunteers, younger and older than 41.7 years. Moreover, age correlated moderately to well with left ventricular PCr to beta-ATP ratios (r = -0.44), fasting serum glucose levels (r = 0.4), E/A (r = -0.7), left ventricular myocardial mass (r = -0.41), and EF (r = -0.55). In conclusion, our study shows that left ventricular PCr to beta-ATP ratios decrease moderately with age, as suggested by previous experimental animal studies. Additionally, age correlates negatively with E/A, left ventricular myocardial mass, and EF, as reported by previous echocardiography studies. The present study is the first to show the impact of age on left ventricular PCr to beta-ATP values in humans.

Adenosine Triphosphate↗
PubMed2003

The influence of high versus normal impedance ventricular leads on pacemaker generator longevity.

As pacemaker generator longevity is dependent on current consumption and resistance of the pacing lead, the use of a high impedance pacing lead theoretically results in an extension of battery longevity. Therefore, the effect of high versus standard impedance ventricular leads on generator longevity was studied. In 40 patients (21 women, age 73 +/- 13 years) with a standard dual chamber pacemaker indication, a bipolar standard impedance ventricular lead was implanted in 20 patients, the remaining patients received a bipolar high impedance lead in a randomized fashion. All patients received identical pacemaker generators and atrial leads. The estimated longevity of the generator was calculated automatically by a programmed pacemaker algorithm. After a mean follow-up of 39 +/- 4.8 months, no significant differences were observed with respect to mean pacing and sensing thresholds of the atrial and ventricular leads in both groups. However, the high impedance leads displayed a significantly higher impedance and a significantly lower current drain as compared to standard impedance leads (1,044 +/- 139 vs 585 +/- 90 Omega, and 2.2 +/- 0.4 vs 4.3 +/- 1.1 mA). The extrapolated generator longevity was significantly longer in the high impedance lead group, as compared to the standard impedance lead group (107.3 +/- 8.5 vs 97.6 +/- 9.0 months; P = 0.02). In conclusion, implantation of a high impedance lead for ventricular pacing results in a clinically relevant extension of generator longevity.

Aged↗
PubMed2003

An unusual cause of diastolic mitral regurgitation as a result of sterile perforation of the mitral valve.

We report the case of a 50-year-old man in whom a supracristal ventricular septal defect led to aortic regurgitation and, thus, to consecutive sterile perforation of the anterior mitral leaflet, culminating in the development of severe systolic and diastolic mitral regurgitation. Aortic regurgitation as a result of valve prolapse caused by a supracristal (conal) ventricular septal defect is a well-known phenomenon. The same is true for the origin of mitral jet lesions in patients with infective endocarditis of the aortic valve. As of yet, there have been no reports about the acquisition of mitral valve perforations in patients without the history of vegetations. Moreover, the occurrence of diastolic mitral regurgitation is usually associated with atrioventricular pressure reversal, a phenomenon that was not present in our patient. The unique comorbidity was easy to detect with Doppler echocardiography, supported by transesophageal 2-dimensional and dynamic 3-dimensional echocardiography for preoperative surgical treatment.

Aortic Valve Insufficiency↗
PubMed2003

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors improve myocardial high-energy phosphate metabolism in men.

PURPOSE: We intended to prove that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins have a beneficial impact on the human myocardial, high-energy, phosphate metabolism. METHODS: The present study included 18 male patients (mean age 49.8 +/- 10.3) with statin-treated, familiar hypercholesterolemia (FH) and 13 male patients with untreated FH (mean age 44.6 +/- 9.5). Twenty-six healthy male volunteers served as controls (mean age 44.2 +/- 12.1). Phosphorus-31, two-dimensional chemical shift imaging (31P 2D CSI) of the heart was performed in all subjects using a 1.5 Tesla whole-body magnetic resonance (MR) scanner. The ratios between phosphocreatine (PCr) and beta-adenosine-triphosphate (beta-ATP) were calculated for the left ventricular myocardium. Furthermore, echocardiographic evaluation and stress tests were performed in all individuals. RESULTS: The untreated patients with FH exhibited a significant decrease in left ventricular PCr to beta-ATP ratios (1.78 +/- 0.34) compared with statin-treated FH patients (2.15 +/- 0.26, p < 0.001) and healthy controls (2.04 +/- 0.26, p = 0.009). The left ventricular PCr-to-beta-ATP ratios of the treated FH patients were in the range of the healthy controls. CONCLUSIONS: Our study shows for the first time an-improvement of the high-energy, phosphate metabolism in the left ventricular myocardium of patients with statin-treated FH compared with untreated FH patients.

Adenosine Triphosphate↗
PubMed2002

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.

Adult↗
PubMed2002

[Adaptation of guidelines for the treatment of chronic heart failure in a specialized heart failure clinic].

BACKGROUND: Chronic heart failure is associated with high mortality and morbidity. In spite of a number of trials showing significant improvement in survival and reduction in hospitalization for patients who received ACE inhibitors/AT1 receptor antagonists (ACEI/ARB), beta-blockers and spironolactone, and notwithstanding the recommendations of national and international guidelines for the management of heart failure, substantial proportions of patients are not receiving this treatment. The aim of our study was to analyse 1. the efficiency of a specialized heart failure clinic in translating guidelines into clinical practice, and 2. the effect of optimized neurohormonal therapy on patient outcome. METHODS AND RESULTS: The data of patients with systolic heart failure and an ejection fraction < or = 35% referred to the Innsbruck Heart Failure and Transplantation Program between February 2000 and October 2001 were analysed. The number of patients treated with ACEI/ARB, beta-blocker and spironolactone increased significantly in the investigation period (p < 0.05). Equivalent dose for captopril and bisoprolol per patient developed from 66.4 +/- 42.8 to 96.5 +/- 41.9 mg (p < 0.001) and from 2.0 +/- 2.9 to 6.3 +/- 4.0 mg (p < 0.001), respectively. Optimization of neurohormonal therapy was associated with a significant improvement in NYHA class (2.5 +/- 0.8 vs. 1.9 +/- 0.8; p < 0.001). No relevant changes were noticed for blood pressure, serum creatinine, serum sodium, and serum potassium, whereas heart rate dropped significantly. Kaplan-Meier curves examining the time to first event of the combined end point of mortality and hospitalisation for worsening heart failure revealed a clear benefit for patients on combined neurohormonal therapy (ACEI/ARB and beta-blocker, n = 86) when compared with patients on neurohormonal monotherapy (ACEI/ARB or beta-blocker, n = 35), (p < or = 0.001). Differences remained significant (p = 0.022) after adjusting for NYHA class at referral, age, gender, etiology of the underlying cardiomyopathy, ejection fraction, and atrial fibrillation in Cox regression analysis. CONCLUSION: Guidelines for the management of chronic heart failure patients can be translated efficiently into clinical practice by a specialized heart failure clinic. Optimization of therapy is associated with an improvement in functional status and a decrease in mortality or hospitalization for worsening heart failure. Therefore the nationwide installation of specialized heart failure clinics is required.

Adrenergic beta-Antagonists↗
PubMed2002

Atorvastatin decreases vascular endothelial growth factor in patients with coronary artery disease.

OBJECTIVES: The aim of this study was to test a possible influence of atorvastatin on the production of vascular endothelial growth factor (VEGF) in patients with coronary artery disease (CAD) and in vitro. BACKGROUND: Vascular endothelial growth factor is suggested to be involved in the growth of atherosclerotic plaque by inducing its neovascularization. Hepatic hydroxymethyl glutaryl-coenzyme A reductase inhibitors (statins) are known to have atheroprotective effects beyond lipid lowering. METHODS: Blood was collected from 14 male hypercholesterolemic patients with angiographically confirmed CAD at baseline and after two months of atorvastatin therapy (20 mg/d) and from eight male control patients. In an ex vivo assay, human coronary artery smooth muscle cells (HCASMC) were incubated with the patient plasma collected before and after atorvastatin therapy. To test the direct effect of atorvastatin on VEGF synthesis in vitro, HCASMC were treated with atorvastatin (1, 3 and 10 microM). The VEGF concentration was measured by enzyme-linked immunosorbent assay. RESULTS: Atorvastatin therapy reduced VEGF plasma levels in CAD patients (from 31.1 +/- 6.1 to 19.0 +/- 3.6 pg/ml; p < 0.05). The VEGF plasma concentration tended to be higher in CAD patients before treatment compared to control patients (31.1 +/- 6.1 vs. 23.4 +/- 3.6 pg/ml; p = NS). Plasma collected before therapy induced significantly more VEGF in HCASMC compared to the plasma collected after treatment and compared to control cells. In vitro, atorvastatin decreased both the basal and the interleukin-1beta-induced VEGF release in HCASMC. CONCLUSIONS: These data suggest that atorvastatin may lower the plasma level of VEGF in CAD patients, which could represent a novel beneficial effect of this and perhaps other statins.

Anticholesteremic Agents↗
PubMed2002

Association of wall thickness of the brachial artery measured with high-resolution ultrasound with risk factors and coronary artery disease.

Intima-media thickness of the carotid and femoral arteries has been associated with coronary atherosclerosis and its clinical sequelae. The brachial artery (BA) is widely used for the assessment of flow-mediated vasodilation. The aim of this study was to examine whether BA wall thickness (WT) is associated with coronary artery disease (CAD) and risk factors. High-resolution ultrasound (13 MHz) examination of the BA was performed in 179 patients undergoing coronary angiography for the evaluation of chest pain. CAD (> or =30% diameter stenosis in > or =1 major branch) was found in 132 patients, whereas 47 patients had smooth coronary arteries. WT of the posterior BA wall (0.4 +/- 0.05 vs 0.35 +/- 0.06 mm, p <0.001) and wall index (WI) (WT/vessel diameter x 100; 16.1 +/- 0.0 vs 13.8 +/- 0.8, p <0.001) were greater in patients with than without CAD. On univariate analysis, WT and WI correlated with age, presence of CAD, systemic hypertension, maximum coronary diameter stenosis, and baseline diameter. On logistic regression analyses adjusting for age, cholesterol levels, systemic hypertension, smoking, and positive family history, WT (p <0.01) and WI (p = 0.02) remained significantly correlated with the presence of CAD. Thus, BA-WT is independently correlated with the presence of CAD. WT may provide a novel noninvasive marker of atherosclerosis that can be assessed together with flow-mediated vasodilation to yield functional and morphologic information in the same vessel.

Adult↗