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Biomedical subjects

C von Schacky

Publications and source records attributed to C von Schacky.

At least 19 recordsLinked to original sources
PubMed2001

Endothelial function of the popliteal artery in patients with coronary artery disease.

Coronary artery disease (CAD) is associated more closely with atherosclerosis in the popliteal than in the brachial artery. This case-control study aimed at clarifying whether endothelial dysfunction of patients with CAD can be detected non-invasively in the popliteal artery by means of ischemia-induced flow-mediated dilation (FMD) and cold pressor reaction (CPR), and how it compares with the brachial artery. We further investigated a new mode of evaluation of the CPR. Eleven cases with CAD were compared with 16 matched healthy controls. Popliteal and brachial arterial diameter was monitored by ultrasound for 20 min following ischemia and cold pressor. For CPR, the difference between maximum and minimum diameter was defined as maximum vasomotion. In the popliteal artery, maximum vasomotion and FMD were significantly smaller in cases than in controls, the difference being more pronounced than in the brachial artery, where only maximum vasomotion was significantly smaller. After exclusion of current smokers, only the difference in maximum vasomotion of both arteries remained significant. We conclude that maximum vasomotion may be more sensitive for detection of endothelial dysfunction than FMD. Endothelial dysfunction in patients with CAD is more pronounced in the popliteal artery than in the brachial artery.

Adult↗
PubMed2001

Effect of oral postmenopausal hormone replacement on progression of atherosclerosis : a randomized, controlled trial.

-Postmenopausal hormone replacement therapy (HRT) is associated with low cardiovascular morbidity and mortality in epidemiological studies. Yet, no randomized trial has examined whether HRT is effective for prevention of coronary heart disease (CHD) in women with increased risk. The objective of this study was to determine whether HRT can slow progression of atherosclerosis, measured as intima-media thickness (IMT) in carotid arteries. Carotid IMT is an appropriate intermediate end point to investigate clinically relevant effects on atherogenesis. This randomized, controlled, observer-blind, clinical, single-center trial enrolled 321 healthy postmenopausal women with increased IMT in >/=1 segment of the carotid arteries. For a period of 48 weeks, subjects received either 1 mg/d 17ss-estradiol continuously plus 0.025 mg gestodene for 12 days every month (standard-progestin group), or 1 mg 17ss-estradiol plus 0.025 mg gestodene for 12 days every third month (low-progestin group), or no HRT. Maximum IMT in 6 carotid artery segments (common, bifurcation, and internal, both sides) was measured by B-mode ultrasound before and after intervention. HRT did not slow IMT progression in carotid arteries. Mean maximum IMT in the carotid arteries increased by 0.02+/-0.05 mm in the no HRT group and by 0.03+/-0.05 and 0.03+/-0.05 mm, respectively, in the HRT groups (P:>0.2). HRT significantly decreased LDL cholesterol, fibrinogen, and follicle-stimulating hormone. In conclusion, 1 year of HRT was not effective in slowing progression of subclinical atherosclerosis in postmenopausal women at increased risk.

Carotid Arteries↗
PubMed2000

Impact of social support, cynical hostility and anger expression on progression of coronary atherosclerosis.

OBJECTIVES: This prospective cohort study of patients with coronary artery disease (CAD) sought to determine the impact of social support, anger expression and cynical hostility on progression of coronary atherosclerosis as shown by angiography. BACKGROUND: Low social support, high levels of expressed anger and cynical hostility are correlated to increased CAD morbidity and mortality. However, the impact of these factors, alone or together, on progression of human coronary atherosclerosis is unknown. METHODS: Of 223 patients with CAD documented by standardized angiography at baseline, 162 had a second angiogram after two years. An expert panel who had no knowledge of the patients' characteristics evaluated the films pairwise to determine disease progression. At baseline, all patients were asked to answer three self-report questionnaires: questions concerning emotional social support, the State-Trait-Anger-Expression Inventory (STAXI) and the Cook-Medley cynical hostility scale. Each patient's clinical and laboratory status was followed. RESULTS: Questionnaires and angiographic follow-up data were available for 150 patients. Bivariate analysis of the psychological variables showed a higher risk of progression only for patients who scored high on STAXI anger-out or low on social support. In the multivariate analysis, when adjusting for confounding variables and examining the interaction between psychological variables, only patients with both high anger-out and low social support were at highly increased risk for progression (odds ratio 30, confidence interval [CI] 5.5 to 165.1; RR 3.19). CONCLUSIONS: Patients with CAD and low emotional social support who express anger outwardly are at a highly increased risk of disease progression, independent of medication or other risk factors.

Anger↗
PubMed2000

Hormone replacement therapy and distensibility of carotid arteries in postmenopausal women: a randomized, controlled trial.

OBJECTIVES: The study objective was to clarify in a randomized, controlled, observer-blind trial whether hormone replacement therapy (HRT) improves elastic properties of the common carotid artery in women with signs of subclinical atherosclerosis, especially in subgroups with increased risk, and whether less progestin enhances the effect. BACKGROUND: Previous observational studies have yielded conflicting results on the influence of HRT on central arteries. Some studies reported improvement of distensibility by estrogen alone or in the subgroup of smokers. METHODS: A total of 321 postmenopausal women were randomized to 1 mg 17beta-estradiol plus 0.025 mg gestodene for 12 days every month (HRT 1), or 1 mg 17beta-estradiol plus 0.025 mg gestodene for 12 days every third month (HRT 2), or no-HRT, during 48 weeks. In 173 women, distensibility of the common carotid artery was determined before and after therapy by M-mode ultrasound and brachial blood pressure measurement. RESULTS: Change of distensibility was small and similar in the three treatment groups. In the subgroup of current smokers, HRT 2 (low progestin) increased distensibility by 32% (HRT 2: 8.2+/-11.7; HRT 1:0.6+/-6.0; no HRT: -1.8+/-6.8 x 10(-3)/kPa, p = 0.025 for no-HRT vs. HRT 2). In the subgroups with elevated blood pressure, high low density lipoprotein (LDL) cholesterol, or high age, no effect of HRT was detected. CONCLUSIONS: This randomized intervention study demonstrates that long-term HRT with estrogen and progestin does not substantially influence distensibility of central arteries. Yet, in currently smoking postmenopausal women, HRT with low progestin seems to improve distensibility; this merits further study in a specifically designed trial.

Adult↗
PubMed2000

Bone sialoprotein is a specific biochemical marker of bone metabolism in postmenopausal women: a randomized 1-year study.

Accelerated bone remodeling after the menopause is associated with increased bone loss that can be abolished using hormone replacement therapy (HRT). Biochemical markers of bone metabolism are known to correlate closely with changes in bone histomorphometry and osteodensitometry. Bone sialoprotein (BSP), a major constituent of bone matrix, is almost exclusively found in mineralized tissues and therefore considered a potential marker of bone metabolism. In 82 postmenopausal women, randomly allocated to either low-dose sequential HRT or no HRT, serum BSP was measured and compared with established specific biochemical markers of bone resorption [urinary deoxypyridinoline (DPD), pyridinoline (PYD) and amino-terminal telopeptide (NTx)] and markers of bone formation [serum osteocalcin (Oc) and bone-specific alkaline phosphatase (bALP)]. Longitudinal analysis showed a marked response of BSP levels following commencement of HRT, resulting in a 52% reduction after 12 months compared with initial values. The changes of BSP levels over time were at least as strong as in conventional markers of bone formation and resorption and paralleled their changes. A moderate to close correlation was found between BSP and both markers of bone resorption (r = 0.57 for NTx; r = 0.38 for DPD) and formation (r = 0.55 for Oc; r = 0.39 for bALP; p < 0.0001, respectively). Our data demonstrate a cause and effect relationship between commencement of HRT and a change in serum BSP. In conclusion, serum BSP circumvents some of the limitations of urinary measurements and appears valuable for the quantitative monitoring of the skeletal response to HRT in healthy postmenopausal women.

Aged↗
PubMed2000

n-3 fatty acids and the prevention of coronary atherosclerosis.

Epidemiologic studies have shown an inverse correlation between consumption of fish or other sources of dietary n-3 fatty acids and cardiovascular events. Numerous mechanisms of action for the favorable effect of dietary n-3 fatty acids on factors implicated in the pathogenesis of atherosclerosis have been described. Studies in dogs, swine, and nonhuman primates have consistently shown beneficial effects in various models of vasoocclusive diseases. Studies published currently do not indicate that dietary n-3 fatty acids prevent restenosis after percutaneous coronary angioplasty or induce regression of coronary atherosclerosis. However, in a recent study, occlusion of aortocoronary venous bypass grafts was reduced after 1 y by daily ingestion of 4 g fish-oil concentrate. In the Diet and Reinfarction Trial, 2-y overall mortality was reduced by 29% in survivors of a first myocardial infarction after consumption of n-3 fatty acid-rich fatty fish at least twice a week had been advised (Lancet 1989;2:757-61). When n-3 fatty acids were integrated into a diet resembling a traditional Mediterranean diet, 5-y cardiovascular mortality after a first myocardial infarction was reduced by 70% (Lancet 1994; 343:1454-9). Preliminary studies indicate that cardiac transplant patients could be an interesting focus of investigation. Currently, food sources rich in n-3 fatty acids are thought to be beneficial in secondary prophylaxis after a myocardial infarction. Large-scale clinical studies with endpoints such as morbidity and mortality are needed to more precisely define the role of n-3 fatty acids in primary and secondary prophylaxis of coronary atherosclerosis.

Coronary Angiography↗
PubMed2000

n-3 polyunsaturated fatty acids and the cardiovascular system.

n-3 Polyunsaturated fatty acids, mainly those contained in fish oils, are candidates for inclusion in secondary prevention programmes for coronary heart disease, based on the results of recent randomized trials in humans. Marine n-3 polyunsaturated fatty acids retard coronary atherosclerosis and appear to prevent fatal arrhythmias; and they decrease mortality subsequent to myocardial infarction.

Arteriosclerosis↗
PubMed2000

n-3 polyunsaturated fatty acids and the cardiovascular system.

n-3 Polyunsaturated fatty acids, mainly those contained in fish oils, are candidates for inclusion in secondary prevention programmes for coronary heart disease, based on the results of recent randomized trials in humans. Marine n-3 polyunsaturated fatty acids retard coronary atherosclerosis and appear to prevent fatal arrhythmias; and they decrease mortality subsequent to myocardial infarction.

Arteriosclerosis↗
PubMed1999

The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Epidemiologic studies, studies of mechanisms of action, and many animal studies indicate that dietary intake of omega-3 fatty acids has antiatherosclerotic potential. Few trials in humans have examined this potential. OBJECTIVE: To determine the effect of dietary intake of omega-3 fatty acids on the course of coronary artery atherosclerosis in humans. DESIGN: Randomized, double-blind, placebo-controlled, clinically controlled trial. SETTING: University preventive cardiology unit. PATIENTS: 223 patients with angiographically proven coronary artery disease. INTERVENTION: Fish oil concentrate (55% eicosapentaenoic and docosahexaenoic acids) or a placebo with a fatty acid composition resembling that of the average European diet, 6 g/d for 3 months and then 3 g/d for 21 months. MEASUREMENTS: The results of standardized coronary angiography, done before and after 2 years of treatment, were evaluated by an expert panel (primary end point) and by quantitative coronary angiography. Patients were followed for clinical and laboratory status. RESULTS: Pairs of angiograms (one taken at baseline and one taken at 2 years) were evaluated for 80 of 112 placebo recipients and 82 of 111 fish oil recipients. At the end of treatment, 48 coronary segments in the placebo group showed changes (36 showed mild progression, 5 showed moderate progression, and 7 showed mild regression) and 55 coronary segments in the fish oil group showed changes (35 showed mild progression, 4 showed moderate progression, 14 showed mild regression, and 2 showed moderate regression) (P = 0.041). Loss in minimal luminal diameter, as assessed by quantitative coronary angiography, was somewhat less in the fish oil group (P > 0.1). Fish oil recipients had fewer cardiovascular events (P = 0.10); other clinical variables did not differ between the study groups. Low-density lipoprotein cholesterol levels tended to be greater in the fish oil group. CONCLUSION: Dietary intake of omega-3 fatty acids modestly mitigates the course of coronary atherosclerosis in humans.

Adult↗
PubMed1999

Dietary omega-3, omega-6, and omega-9 unsaturated fatty acids and growth factor and cytokine gene expression in unstimulated and stimulated monocytes. A randomized volunteer study.

Dietary omega-3 fatty acids retard coronary atherosclerosis. Previously, we demonstrated that dietary omega-3 fatty acids reduce platelet-derived growth factor (PDGF)-A and PDGF-B mRNA levels in unstimulated, human mononuclear cells (MNCs). In a randomized, investigator-blinded intervention trial, we have now compared the effect of ingestion of 7 g/d omega-3, omega-6, or omega-9 fatty acids for 4 weeks versus no dietary intervention on PDGF-A, PDGF-B, heparin-bound epidermal growth factor (HB-EGF), monocyte chemoattractant protein-1 (MCP-1), and interleukin-10 gene expression in unstimulated MNCs and in monocytes that were adherence-activated ex vivo in a total of 28 volunteers. In unstimulated MNCs, mRNA steady-state levels of PDGF-A, PDGF-B, and MCP-1 were reduced by 25+/-10%, 31+/-13%, and 40+/-14%, respectively, after omega-3 fatty acid ingestion, as assessed by quantitative polymerase chain reaction (all P<0.05). In monocytes that were adherence-activated ex vivo for 4 and 20 hours, mRNA steady-state levels of PDGF-A, PDGF-B, and MCP-1 were reduced by 25+/-13%, 20+/-15%, and 30+/-8%, respectively (all P<0.05). Interleukin-10 and HB-EGF mRNA steady-state levels were not influenced by omega-3 fatty acid ingestion. Expression of all respective mRNAs in control volunteers or in those ingesting omega-6 or omega-9 fatty acids were not altered. We conclude that human gene expression for PDGF-A, PDGF-B, and MCP-1, factors thought relevant to atherosclerosis, is constitutive, is constant, and can be reduced only by dietary omega-3 fatty acids in unstimulated and adherence-activated monocytes.

Adult↗
PubMed1998

IGF-1, PDGF and CD18 are adherence-responsive genes: regulation during monocyte differentiation.

Unstimulated mononuclear cells express IGF-1, PDGF-A and PDGF-B mRNA, but not a number of other genes coding for growth factors or cytokines, as we demonstrated previously. The main focus of the present investigation was to compare gene expression of mononuclear cells unstimulated in suspension with gene expression of monocytes stimulated by adherence. mRNA levels of IGF-1-A and -B, PDGF-A, -B, PD-ECGF, basic FGF, acidic FGF, TGF-alpha, TGF-beta 1, and IGF-2 were sought for and quantified with our sensitive RT-PCR method (3n-PCR). The respective mRNAs of basic FGF, acidic FGF, TGF-alpha and IGF-2 were not detected, independent of the culture conditions. In suspension culture, mRNA levels of IGF-1A and -B, PDGF-A, -B, and CD18 remained unchanged. Monocyte adherence regulated IGF-1A, PDGF-A, and -B mRNA levels. In parallel, mRNA levels of the monocyte adhesion molecule CD18 increased rapidly (4.5-fold). In contrast, independent of the presence of an adherence stimulus, the mRNAs for the cytoskeletal structure protein beta-actin and PD-ECGF remained constant, whereas mRNA for growth factors TGF-beta 1 and IGF-1B, respectively, was increased. Thus, monocyte adherence selectively regulates IGF-1, PDGF-A, PDGF-B and CD18 mRNAs (adherence-responsive genes) in a coordinated manner. This led us to identify two novel consensus elements within their respective functional promoters. Both motifs, an 11 bp purine-rich sequence and a 13 bp pyrimidine-rich segment, respectively, are absent from the genes that were not specifically activated by adherence. The identified elements are potential binding sites for transcription factors that may define a common basis for the regulation of the adherence-responsive genes IGF-1A, PDGF-A, PDGF-B and CD18.

Actins↗
PubMed1998

Short term effects of omega-3 fatty acids on the radial artery of patients with coronary artery disease.

Long-term dietary omega-3 fatty acids improve coronary endothelial function in CAD patients, heart transplant recipients and diabetics. This study assessed whether short term omega-3 fatty acids affect radial artery function in CAD patients. A high resolution A-mode echotracking device (NIUS 02) was used to measure continuously, radial artery internal diameter at rest, during flow mediated vasodilation (FMD), during cold pressure test (CPT), and after sublingual glyceryl trinitrate (GTN). We studied 18 male CAD patients in a randomized, double blind, placebo controlled design. Between pre- and post-intervention measurements 24 h apart, nine subjects received 18 g fish oil concentrate (6.4 g eicosapentaenoic acid and 3.9 g docosahexaenoic acid) and nine subjects 18 g placebo. In the placebo group correlation between both baseline diameters was 0.98; P < 0.001. Pre-intervention FMD was 7.5+/-5.6%, CPT mediated vasoconstriction was 3.8+/-2.5%, and GTN induced vasodilation was 15.7+/-9.8%. Vascular responses post-intervention showed no significant difference to pre intervention, there was no significant difference between both treatment groups. The radial artery does not seem to be an immediate target for vasodilatory actions of omega-3 fatty acids.

Aged↗
PubMed1998

[Inhibition of thrombocyte aggregation after heart valve replacement].

After implantation of a mechanical cardiac valve, lifelong, full anticoagulation has been the tradition. After implantation of a biological valve, anticoagulation during 3 months subsequent to the operation is customary. This review evaluates the role of platelet inhibition after cardiac valve replacement. Platelet aggregation is inhibited effectively by aspirin in a daily dose of 100-160 mg. At this dose, episodes of severe bleeding are not significantly more frequent than during placebo, whereas patients on full anticoagulation bleed at a rate of 2% per year. After implantation of a mechanical cardiac valve, sole platelet inhibition is inferior to full anticoagulation. With a lower rate of bleeding, aspirin appears to prevent thromboembolic episodes caused by mechanical bileaflet prostheses (e.g., St. Jude) in the aortic position, and is almost as efficient as full anticoagulation. In Germany, patients with a porcine bioprosthesis, as currently in use, in the aortic position, frequently receive 100 mg aspiring per day. For patients with porcine bioprostheses in the mitral plus eventually in the aortic position in stable sinus rhythm, 100 mg aspirin per day is preferred to anticoagulation. For children with mechanical aortic valves, aspirin (2 mg/kg/day) needs to be considered an effective and convenient alternative to anticoagulation. Combining anticoagulation with 100 mg aspirin per day after implantation of a left-sided mechanical cardiac valve is pathophysiologically sound, but used to be considered as rendering the patients too bleeding-prone. Recently, total mortality and morbidity definitely have been demonstrated to be reduced by combined anticoagulation and platelet inhibition as compared to sole anticoagulation. Combining platelet inhibition with moderate anticoagulation (INR 2.0-3.0) was superior to combining it with full anticoagulation in terms of safety (INR > 3.0). Thus, current evidence favors combining moderate anticoagulation with 100 mg aspirin per day after left-sided mechanical cardiac valve replacement.

Aspirin↗
PubMed1996

The human leukotriene A4 hydrolase gene is expressed in two alternatively spliced mRNA forms.

We identified a novel short (s-) mRNA of the human leukotriene-A4 (LTA4) hydrolase using sequential reverse transcriptase PCR mapping. The s-mRNA is generated by skipping an 83 bp exon located in the 3' coding region and suggests the expression of an LTA4 hydrolase isoform with a calculated molecular mass of 59 kDa and a distinct C-terminus. Both LTA4 hydrolase mRNAs are constitutively expressed in blood cells, endothelial cells, smooth muscle cells, fibroblasts and tumour cells. The ratios of their mRNA expression levels are cell specific, with relatively high s-form mRNA expression in reticulocytes. Our data strongly suggest that the novel mRNA codes for the structurally related but distinct LTA4 hydrolase isoenzyme that has been postulated.

Alternative Splicing↗
PubMed1996

Human mononuclear cells express 12-LX: coordinated mRNA regulation with 5-LX and FLAP genes.

Lipoxygenases (LXs) catalyze formation of leukotrienes and hydroxy-eicosatetraenoic acids (HETEs), proinflammatory, and spasmogenic autacoids that are critical for host defense systems. We studied the expression and regulation of LX genes (12-LX, 5-LX, and 15-LX) and the 5-lipoxygenase activating protein (FLAP) in human mononuclear cells (MNC) and granulocytes using a quantitative reverse transcription polymerase chain reaction (RT-PCR) technique. We show that 12-LX mRNA is constitutively expressed in resting platelet-free MNC. 12-LX gene expression was upregulated by activation with lipopolysaccharide (LPS). The formation of 12-HETE was inducible with ionophore in MNC, as assessed by high-performance liquid chromatography (HPLC) and gas chromatography, and increased after LPS pretreatment. In addition to 12-LX, resting MNC expressed the genes for 5-LX and FLAP constitutively. Quantitative time course analyses of 12-LX, 5-LX, and FLAP gene expression suggested coregulation of 12-LX and FLAP mRNAs, and reciprocal regulation of 5-LX and FLAP mRNAs. During cell stimulation with LPS 5-LX mRNA levels remained unchanged, whereas FLAP gene expression increased. No 15-LX mRNA expression or 15-HETE formation was detectable in unstimulated and activated MNC. In contrast to MNC, quantitative RT-PCR mRNA analysis showed intermittent intraindividual expression of the 5-LX and FLAP genes in resting granulocytes. mRNAs for 12-LX and 15-LX were not expressed. On stimulation of granulocytes ex vivo, mRNA expression of 5-LX and FLAP was upregulated. Stimulation by LPS differed from that by ionophore A23187. Neither LPS nor ionophore induced gene expression of 12-LX or 15-LX in granulocytes. Our data indicate that resting human MNC and granulocytes express LX and FLAP genes in a cell-specific manner. Cell activation induces coordinated upregulation of 12-LX and FLAP genes in MNC, and 5-LX and FLAP genes in granulocytes, respectively. The constitutive expression of 12-LX mRNA, its upregulation on cell activation, and the formation of 12-HETE clearly indicate the presence of a functional 12-LX in human MNC.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1996

n-3 polyunsaturated fatty acids and human cytokine synthesis.

The cytokines interleukin-1 and tumor necrosis factor contribute to the pathogenesis of inflammatory diseases and, potentially, to atherogenesis. The synthesis of these cytokines in humans can be suppressed by oral intake of n-3 polyunsaturated fatty acids. This mechanism may contribute to the beneficial effect of long-term n-3 fatty acid supplementation in inflammatory diseases such as renal transplant rejection, immunoglobulin A nephropathy and rheumatoid arthritis.

Animals↗