Constitutional, biochemical and lifestyle correlates of fibrinogen and factor VII activity in Polish urban and rural populations.
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BACKGROUND: Fibrinogen and factor VII activity are known to be related to atherosclerosis and coronary heart disease, but population differences in clotting factors and modifiable characteristics that influence their levels have not been widely explored. METHODS: This paper examines correlates of plasma fibrinogen concentration and factor VII activity in 2443 men and women aged 35-64 in random samples selected from the residents in two districts in urban Warsaw (618 men and 651 women) and from rural Tarnobrzeg Province (556 men and 618 women) screened in 1987-1988, and assesses which characteristics might explain urban-rural differences. Fibrinogen and factor VII activity were determined using coagulation methods. RESULTS: Fibrinogen was 12.9 mg/dl higher in men and 14.1 mg/dl higher in women in Tarnobrzeg compared to Warsaw. Factor VII activity was higher in Warsaw (9.2% in men and 15.3% in women). After adjustment for selected characteristics, fibrinogen was higher in smokers compared to non-smokers by 28 mg/dl in men and 22 mg/dl in women. In women, a 15 mg/dl increase in HDL-cholesterol was associated with a 10 mg/dl decrease in fibrinogen (P < 0.01). After adjustment for other variables, a higher factor VII activity in Warsaw remained significant (a difference of 9.4% in men and 14.8% in women). Lower fibrinogen in Warsaw remained significant only in women (15.4 mg/dl difference). CONCLUSIONS: The study confirmed that sex, age, BMI, smoking and blood lipids are related to clotting factors. However, with the exception of gender differences and smoking, associations between clotting factors and other variables were small and of questionable practical importance. (+info)
Combined carotid endarterectomy and coronary artery bypass graft.
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Atherosclerosis is a generalized disease which afflicts a considerable number of patients in both the carotid and coronary arteries. Although the risk of stroke or death use to combined carotid endarterectomy (CEA) and coronary artery bypass graft (CABG) is thought to be higher than that of each individual operation, the combined procedure is generally preferred over staged operations to treat such patients. We performed the combined procedure safely with the aid of intraoperative portable digital subtraction angiography (DSA). This report describes our experience with the operative strategy of simultaneous CEA and CABG. Ninety CEA and 404 CABG were carried out between January 1989 and December 1997. A total of six patients received the combined procedure with the aid of intraoperative DSA; they were studied retrospectively. Postoperative mortality and morbidity after the combined procedure was 0%. In the combined procedure, neurological complications are difficult to detect after CEA because the patient must be maintained under general anesthesia and extracorporeal circulation during the subsequent CABG. However, intraoperative DSA can confirm patency of the internal carotid artery and absence of flap formation after CEA, and the CABG can be performed safely. Intraoperative portable DSA between CEA and CABG is helpful in preventing perioperative stroke in the combined procedure. (+info)
Macroscopic distribution of coronary atherosclerotic lesions in cholesterol-fed rabbits.
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In the present study we macroscopically examined a change in the distribution of coronary atherosclerosis in cholesterol-fed rabbits. Rabbits were fed a cholesterol-enriched diet for 15 weeks, then replaced by a normal diet, and were sacrificed at 15, 24, 32 and 42 weeks after the start of the experiment. The coronary atherosclerosis in the cholesterol-fed rabbits was distributed more densely in the proximal portion than in the middle and distal portions, and the lesions were severe at 24 and 32 weeks after the start of the experiment. comparison of lesions in the three portions at these time points showed that the percentages of lesion areas in the proximal portion, the middle portion and the distal portion were approximately 51%, 21 to 25% and 0.2 to 3.7%, respectively. Macroscopic observation of the coronary atherosclerotic lesions showed that the lesions formed over the vessel lumen in the proximal portion within the range of approximately 5 mm from the orifice of the left coronary artery. In the middle portion, the lesions formed predominantly around the orifices of branches as small patchy lesions from 1 to 3 mm in diameter. These findings support previous histopathological reports that suggested that the incidence of stenosis in the proximal portion was high, and the incidence of lesion occurrence in the middle and the distal portions varied. The method, macroscopical investigation of the coronary artery, is useful for analyzing coronary atherosclerosis in the rabbit. (+info)
Age-related changes in blood coagulation and fibrinolysis in mice fed on a high-cholesterol diet.
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To investigate the pathogenesis of hyperlipidemia-induced atherosclerosis, we examined age-dependent changes in platelet activity, blood coagulation and fibrinolysis in susceptibility to a high cholesterol diet (HCD) feeding in male ICR mice. Pretreatment of platelet-rich-plasma from HCD feeding mice for 3 days with epinephrine (300 microM) resulted in a marked enhancement of adenosine 5'-diphosphate (ADP: 0.1 microM) or collagen (0.7 microgram/ml)-stimulated aggregation compared with the same in control mice. Yohimbine as alpha 2-adrenergic blocker antagonized these aggregations in a dose-dependent manner. A significant increase in plasma total cholesterol and VLDL (very low-density lipoprotein)-LDL (low-density lipoprotein)-cholesterol and the liver/body weight ratio was observed in mice fed on HCD for 3 months (3-month HCD mice). In the early phase of this experiment, a significant increase in fibrinogen was observed. In the middle phase, increases in the activity of antithrombin III (ATIII) and alpha 2-plasmin inhibitor (alpha 2-Pl) followed. Plasminogen content gradually decreased in both normal diet and HCD mice throughout the experiment. The activity of plasminogen activator inhibitor (PAI) decreased in 3-month HCD mice. Morphological observation of the aortic arch from 3-month HCD mice revealed apparent atheromatous plaques not seen in control mice. These results suggest that 3-month HCD mice can be a convenient hyperlipidemia-induced atherosclerotic model and the changes in platelet activity, coagulation and fibrinolysis in the early phase may be a cause of pathologic changes in this model. (+info)
2-Isopropylidenehydrazono-4-oxo-thiazolidin-5-ylacetanilide (OPB-9195) treatment inhibits the development of intimal thickening after balloon injury of rat carotid artery: role of glycoxidation and lipoxidation reactions in vascular tissue damage.
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We have pursued the hypothesis that the carbonyl modification of proteins by glycoxidation and lipoxidation reactions plays a role in atherogenesis. Human atherosclerotic tissues with fatty streaks and uremic arteriosclerotic tissues were examined, with specific antibodies, to detect protein adducts formed with carbonyl compounds by glycoxidation or lipoxidation reactions, i.e. advanced glycation end products (AGEs) or glycoxidation products, such as carboxymethyllysine (CML) and pentosidine, and lipoxidation products, such as malondialdehyde (MDA)-lysine and 4-hydroxy-nonenal (HNE)-protein adduct. All the four adducts were identified in the proliferative intima and in macrophage-rich fatty streaks. If the carbonyl modification is not a mere result but is a contributor to atherogenesis, inhibition of glycoxidation and lipoxidation reactions might prevent vascular tissue damage. We tested this hypothesis in rats following balloon injury of their carotid arteries, a model exhibiting a remarkable intimal thickening, which are stained positive for all the four adducts. Oral administration of 2-isopropylidenehydrazono-4-oxo-thiazolidin-5-ylacetanili de (OPB-9195), an inhibitor of both glycoxidation and lipoxidation reactions, in rats following balloon injury effectively prevented the intimal thickening. These data suggest a role for the carbonyl modification of proteins by glycoxidation and lipoxidation reactions in most, if not all, types of vascular tissue damage ('carbonyl stress'), and the usefulness of inhibitors of carbonyl reactions for the treatment of vascular tissue damage. (+info)
Association of dietary protein intake and coffee consumption with serum homocysteine concentrations in an older population.
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BACKGROUND: Elevated blood concentrations of total homocysteine (tHcy) have been implicated in the pathogenesis of atherosclerotic cardiovascular disease. Previous studies identified suboptimal nutritional status and dietary intake of folate, vitamin B-6, and vitamin B-12 as determinants of elevated tHcy. OBJECTIVE: We identified other nutritional factors associated with tHcy in 260 retired schoolteachers in the Baltimore metropolitan area. DESIGN: We performed observational analyses of baseline and 2-4-mo follow-up data collected in a study designed to test the feasibility of conducting a large-scale clinical trial of vitamin supplements by mail. The study population consisted of 151 women and 109 men with a median age of 64 y. At baseline, each participant completed a food-frequency questionnaire. At follow-up, fasting serum tHcy was measured. RESULTS: In multivariable linear regression and generalized linear models, there was an independent, inverse dose-response relation between dietary protein and In tHcy (P = 0.002) and a positive, significant dose-response relation between coffee consumption and In tHcy (P for trend = 0.01). Other significant predictors of In tHcy were creatinine (positive; P = 0.0001) and prestudy use of supplemental B vitamins (inverse; P = 0.03). In stratified analyses restricted to persons receiving standard multivitamin therapy, the association of 1n tHcy with dietary protein and coffee persisted. CONCLUSIONS: These results support the hypothesis that increased protein intake and decreased coffee consumption may reduce tHcy and potentially prevent atherosclerotic cardiovascular disease and other disease outcomes. (+info)
Tenascin-C is expressed in macrophage-rich human coronary atherosclerotic plaque.
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BACKGROUND: Tenascin is a large extracellular matrix glycoprotein generally found in adult tissues undergoing active remodeling such as healing wounds and tumors. To determine the potential role of tenascin-C (TN-C) in the pathophysiology of atherosclerosis, we investigated the pattern of expression of TN-C in human coronary atherosclerotic plaques. METHODS AND RESULTS: Immunohistochemical staining and in situ hybridization demonstrated minimal and random expression of TN-C in fibrotic but lipid-poor atherosclerotic plaques. In contrast, all plaques with an organized lipid core or ruptured intimal surface strongly expressed TN-C, which was preferentially concentrated around the lipid core, shoulder regions, and ruptured area of the plaques but not in the fibrous cap. TN-C was not detected in normal arterial tissue. To identify the cellular source of TN-C, the plaques were stained with smooth muscle cell- and macrophage-specific antibodies. TN-C expression correlated with the infiltration of macrophages. Northern blot and immunoprecipitation analysis showed that macrophages expressed 7. 0-kb TN-C mRNA and 220-kDa protein. Reverse transcription-polymerase chain reaction of total RNA derived from macrophages showed that they express the small isoform of TN-C. Zymogram analysis revealed that macrophages markedly increased MMP-9 expression. CONCLUSIONS: This study demonstrates that the level of TN-C expression correlates with the degree of inflammation present, not with plaque size. In addition, cultured macrophages have the capacity to express the TN-C gene. These findings suggest the significance of macrophages in the remodeling of atherosclerotic plaque matrix composition. (+info)
Prior cytomegalovirus infection and the risk of restenosis after percutaneous transluminal coronary balloon angioplasty.
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BACKGROUND: Restenosis is a common problem after all revascularization procedures in atherosclerotic coronary arteries. Reactivated human cytomegalovirus (CMV) has been detected in tissues of restenotic vascular lesions and was hypothesized to be a contributing pathogenic factor. Recent data suggest an association of restenosis after optimal coronary atherectomy with CMV serostatus, and a possible role of antiviral therapy was discussed. We therefore tested the hypothesis that prior CMV infection might be a risk factor for restenosis after conventional coronary balloon angioplasty (PTCA). METHODS AND RESULTS: We analyzed 92 consecutive patients who had been admitted for control angiography after previous PTCA within a mean interval of 6 months. Anti-CMV antibodies were measured as an indicator of prior CMV infection and latency. The coronary angiograms before PTCA, directly after, and 6 months later were analyzed quantitatively. Sixty-five percent of the patients were CMV-positive. Before PTCA, the degree (mean+/-SD) of stenosis was 69+/-10% in CMV-positive and 68+/-8.3% in CMV-negative subjects. PTCA resulted in a residual stenosis of 39% in both groups. After 6 months, the late losses of luminal diameter in the CMV-positive and -negative groups were 11+/-13% and 12+/-15%, respectively (P=0.658). In an ANCOVA with 25 potential risk factors for restenosis, CMV serostatus was not significantly associated with restenosis development. CONCLUSIONS: Our data indicate that prior CMV infection, in contrast to optimal atherectomy, is not associated with chronic restenosis after conventional coronary balloon angioplasty. The results do not support a possible benefit from antiviral therapy. (+info)