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Correlation between plasma total homocysteine and copper in patients with peripheral vascular disease

CLINICAL CHEMISTRY 2000年第3期46卷 385-391页

作者： Mansoor, MA Bergmark, C Haswell, SJ Savage, IF Evans, PH Berge, RK Svardal, AM Kristensen, O Cent Hosp Rogaland Div Clin Chem N-4003 Stavanger Norway St Gorans Univ Hosp Dept Surg S-17176 Stockholm Sweden Univ Hull Dept Chem Kingston Upon Hull HU6 7RX N Humberside England Univ Glasgow Dept Publ Hlth Glasgow G12 8QQ Lanark Scotland Univ Bergen Dept Clin Biochem N-5021 Bergen Norway Univ Bergen Dept Pharmacol N-5021 Bergen Norway

Background: Increased concentrations of both plasma total homocysteine and copper are separately associated with cardiovascular disease. Correlations between plasma total homocysteine, trace elements, and vitamins in patients with peripheral vascular disease have not been investigated. Methods: The concentrations of trace elements in plasma were determined by the multielement analytical technique of total-reflection x-ray fluorescence spectrometry. Plasma total homocysteine Tvas determined by HPLC. Results: In the univariate and multivariate regression analyses, copper was positively correlated with plasma total homocysteine in all subjects (coefficient +/- SE, 0.347 +/- 0.113;P = 0.0026 and coefficient +/- SE, 0.422 +/- 0.108;P = 0.0002, respectively), and in patients with peripheral vascular disease (coefficient a SE, 0.370 +/- 0.150;P = 0.016;and coefficient +/- SE, 0.490 +/- 0.151;P = 0.0025, respectively). Correlation between copper and plasma total homocysteine was not detected in healthy control subjects. The concentration of calcium in plasma (67.5 vs 80.8 mu g/g) was significantly lower in the patients than in the control subjects (P = 0.02). When the patients were divided into groups, the patients with suprainguinal lesions had significantly higher copper concentrations (P = 0.04) and significantly lower selenium and calcium concentrations (P = 0.01 and 0.008, respectively) than the healthy subjects. Patients had higher concentrations of autoantibodies against oxidized LDL and concentrations of thiobarbituric acid-reactive substance than the healthy subjects (P <0.0001 and P = 0.001, respectively). The concentrations of plasma total homocysteine and alpha-tocopherol were significantly higher, and the concentrations of vitamin B-6 and beta-carotene were lower in the patients than the healthy subjects. Conclusion: Our findings suggest that the atherogenicity of homocysteine may be related to copper-dependent interactions. (C) 2000 American Association for Cl

关键词：抗氧化剂/代谢动脉硬化/血液病例对照研究色谱法高压液相铜/血液高半胱氨酸/血液外周血管疾病/血液光谱法 X线发射硫巴比妥酸反应物痕量元素/血液复合维生素B/血液女(雌)性人类男(雄)性中年人

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Clinical efficacy of an automated high-sensitivity C-reactive protein assay

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CLINICAL CHEMISTRY 1999年第12期45卷 2136-2141页

作者： Rifai, N Tracy, RP Ridker, PM Childrens Hosp Dept Lab Med Boston MA 02115 USA Harvard Univ Sch Med Dept Pathol Boston MA 02115 USA Univ Vermont Lab Clin Biochem Res Burlington VT 05446 USA Harvard Univ Brigham & Womens Hosp Sch Med Div Prevent Med Boston MA 02115 USA Harvard Univ Brigham & Womens Hosp Sch Med Div Cardiovasc Dis Boston MA 02115 USA Harvard Univ Brigham & Womens Hosp Sch Med Dept Med Boston MA 02115 USA

Background: Prospective studies have shown that C-reactive protein (CRP) can be used to predict risk of future cardiovascular events. High-sensitivity methods for CRP (hs-CRP) measurement are needed for this purpose. Methods: We compared the clinical efficacy of an automated and commercially available latex-enhanced assay (Latex) for hs-CRP (Dade Behring) to a validated inhouse ELISA, previously shown to predict future peripheral arterial disease (PAD) in asymptomatic populations. Using a prospective, nested, case-control design, we measured baseline hs-CRP concentrations in 144 apparently healthy men who subsequently developed symptomatic PAD and 144 age- and smoking habit-matched controls who remained free of vascular disease over the follow-up period of 60 months. Results: The two hs-CRP assays correlated highly (r = 0.95;P <0.001), and all but two participants were classified into concordant quartiles or varied by only one quartile, The median hs-CRP of the case group was significantly higher than that of controls when measured by either the ELISA (1.34 vs 0.99 mg/L;P = 0.034) or the Latex method (1.80 vs 1.20 mg/L;P = 0.042). Furthermore, for both ELISA and the Latex method, the calculated relative risks of developing PAD increased significantly with each increasing quartile of hs-CRP. The calculated interquartile increase in relative risk of PAD was 31% (95% confidence interval, 5.2-62.2%;P = 0.01) for ELISA and 34% (95% confidence interval, 8.2-66.1%;P = 0.007) for the Latex method. Conclusions: Our findings indicate that the Latex method is equally as efficacious as the validated ELISA in classifying patients into cutoff points established by prospective studies for risk stratification for coronary and cerebrovascular disease. (C) 1999 American Association for Clinical Chemistry.

关键词：抗氧化剂/治疗应用阿司匹林/治疗应用 C反应蛋白质/分析病例对照研究双盲法酶联免疫吸附测定免疫测定/方法胶乳心肌梗死/血液心肌梗死/预防和控制外周血管疾病/血液外周血管疾病/预防和控制血小板聚集抑制剂/治疗应用前瞻性研究危险因素敏感性与特异性卒中/血液卒中/预防和控制 β胡萝卜素/治疗应用老年人老年人 80以上人类男(雄)性中年人

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Inverse association between carotid intima-media thickness and the antioxidant lycopene in atherosclerosis

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AMERICAN HEART JOURNAL 2002年第3期143卷 467-474页

作者： Gianetti, J Pedrinelli, R Petrucci, R Lazzerini, G De Caterina, M Bellomo, G De Caterina, R CNR Inst Clin Physiol Lab Thrombosis & Vasc Res I-56100 Pisa Italy Univ Pisa Cardiothorac Dept Pisa Italy Univ Pisa Dept Radiol Pisa Italy Univ Naples Federico II Dept Clin Biochem Naples Italy A Avogadro Univ Eastern Piedmont Dept Med Sci Novara Italy Univ G DAnnunzio Chair Cardiol Chieti Italy

Background Antioxidants may prevent atherosclerosis by interfering with endothelial activation, which involves the expression of endothelial adhesion molecules. The aim of this study was to explore the relationship between plasma levels of some lipid-soluble antioxidants (gamma-tocopherol, gamma-tocopherol, lycopene, beta-carotene, and ubiquinone), carotid maximum intimamedia thickness (IMTmax), an index of atherosclerotic extension/severity, and soluble adhesion molecules (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], and E-selectin), which are taken as a reflection of vascular cell expression of adhesion molecules. Methods We studied 11 healthy control subjects, 11 patients with uncomplicated hypertension (UH), and 11 patients with essential hypertension plus peripheral vascular disease (PVD) who were matched for age, sex, smoking habit, and body mass index. Results Patients with PVD had elevated IMTmax (2.7 [1.1-3.1 ] mm, median [range]) compared with both patients with UH(1.2 [0.8-2.4] mm) and control subjects (1.0 [0.6-2] mm). In patients with PVD, soluble (s)VCAM-1 and sICAM-1 were also significantly higher than in the 2 other categories. Plasma levels of lycopene had a trend toward lower values in patients with PVD compared with other groups (P = .13). A statistically significant correlation was found between lycopene and IMTmax (r = 0.42, P = .014) at univariate analysis, which persisted at multivariate analysis (P < .05) and was independent of low-density lipoprotein cholesterol, creatinine clearance, and plasma insulin. Plasma lycopene did not significantly correlate with any of the soluble adhesion molecules tested. Conclusions We conclude that the inverse relationship of plasma lycopene with IMTmax is compatible with a protective role of this natural dietary antioxidant in atherosclerosis, although the mechanism of protection does not apparently involve a decrease in endothelial activation measured through solubl

关键词：方差分析抗氧化剂/分析动脉硬化/血液动脉硬化/病理学生物学标记/血液类胡萝卜素类/血液颈动脉疾病/血液颈动脉疾病/病理学 E选择素/血液高血压/血液胞间黏附分子1/血液外周血管疾病/血液外周血管疾病/病理学泛醌/血液血管细胞黏附分子1/血液 α生育酚/血液 β胡萝卜素/血液 γ生育酚/血液女(雌)性人类男(雄)性中年人

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Intravenous prostaglandin E₁ reduces soluble vascular cell adhesion molecule-1 in peripheral arterial obstructive disease

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AMERICAN HEART JOURNAL 2001年第4期142卷 733-739页

作者： Gianetti, J De Caterina, M de Cristofaro, T Ungaro, B Biol, D Del Guercio, R De Caterina, R CNR Inst Clin Physiol Lab Thrombosis & Vasc Res I-56100 Pisa Italy Univ G dAnnunzio Dept Cardiol Chieti Italy Univ Naples 2 Dept Internal Med Naples Italy Univ Naples Federico II Dept Biochem Naples Italy Univ Naples Federico II Dept Med Biotechnol Naples Italy

Objectives Elevated levels of soluble (s) vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1, pointing to activation of cells involved in vascular inflammation, have been previously reported in peripheral arterial obstructive disease (PAOD). We tested the hypothesis that intravenous prostaglandin E-1 (PGE(1)) treatment, which produces clinical benefits in this condition, might decrease such levels. Methods Ten subjects (age range 58 +/- 10 years, 6 male, 4 female) with characterized Fontaine stage IIa to IV PAOD (ankle/arm pressure index <0.96) were entered into a treatment protocol with twice daily intravenous infusions of PGE(1) (alprostadil) at 120 mug per day, repeated for 10 consecutive days. Preinfusion and postinfusion plasma samples were stored for blind enzyme immunoassays of soluble adhesion molecules and the fibrinolytic marker tissue plasminogen activator, type-1 plasminogen-activator inhibitor, and D-dimer. Results Estimates of severity of pain at rest, consumption of analgesics, magnitude of trophic lesions, remission to lower Fontaine stages, and favorable changes in the venoarteriolar reflex documented significant beneficial effects of the treatment. Significant (P < .01) pretreatment and posttreatment reductions of in all soluble markers explored were found. Particularly, sVCAM-1 exhibited a significant decrease after each infusion, which was sustained at the last day of treatment (from 854 +/- 214 ng/mL to 775 +/- 215 ng/mL across the first infusion, from 773 +/- 146 ng/mL to 680 +/- 110 ng/mL across the last infusion). Conclusion Thus a global decrease of vascular cell activation appears to occur as a result of PGE, administration and may contribute to the observed clinical benefits in PAOD.

关键词：前列地尔/投药和剂量前列地尔/药理学前列地尔/治疗应用动脉闭塞性疾病/血液动脉闭塞性疾病/诊断动脉闭塞性疾病/药物疗法运动试验/统计学和数值数据纤维蛋白溶解/药物作用输注静脉内胞间黏附分子1/血液胞间黏附分子1/药物作用疼痛测定外周血管疾病/血液外周血管疾病/诊断外周血管疾病/药物疗法治疗结果血管细胞黏附分子1/血液血管细胞黏附分子1/药物作用老年人女(雌)性人类男(雄)性中年人

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Increased postprandial lipemia in patients with normolipemic peripheral arterial disease

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AMERICAN HEART JOURNAL 2002年第4期143卷 733-738页

作者： Lupattelli, G Pasqualini, L Siepi, D Marchesi, S Pirro, M Vaudo, G Ciuffetti, G Mannarino, E Univ Perugia Dept Clin & Expt Med Internal Med Angiol & Atherosclerosis Unit I-06100 Perugia Italy

Methods We evaluated the postprandial lipid metabolism in patients with normolipemic peripheral arterial disease (PAD) after the administration of an oral fat load. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), HDL2 and HDL3 subfractions, triglycerides (TGs), lipoprotein(c), and LDL size were determined at baseline and for 8 hours after the meal. Results In patients with PAD, TGs increased significantly at the 4th, 6th, and 8th hours postprandially;in control subjects, TGs increased at the 4th and 6th hours. HDL decreased significantly at the 4th, 6th, and 8th hours in patients with PAD and at the 6th hour in control subjects. The magnitude of postprandial lipemia, expressed as "the area under the incremental curve for TGs," was higher in patients with PAD than in control subjects (770 +/- 476 vs 391 +/- 195 mg/dL at 8 hours, P < .05). Multiple-regression analysis showed that baseline TGs were positively related to the magnitude of postprandial lipemia (P = .01) and that LDL size was negatively related (P = .05). Conclusions This is the first documentation of postprandial behavior in patients with normolipemic PAD, suggesting the relevance of postprandial lipoprotein metabolism in the pathogenesis of peripheral atherosclerosis.

关键词：病例对照研究胆固醇 HDL/血液胆固醇 LDL/血液高血压/血液高血压/药物疗法脂类/血液外周血管疾病/血液饭后期间/生理学前瞻性研究回归分析时间因素甘油三酯类/血液老年人人类男(雄)性

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Intravenous prostaglandin E1 reduces monocyte chemoattractant protein-1 levels in peripheral arterial obstructive disease

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AMERICAN HEART JOURNAL 2003年第2期145卷 330-333页

作者： Matsui, K Ikeda, U Murakami, Y Yoshioka, T Shimada, K Jichi Med Sch Div Cardiovasc Med Minami Kawachi Tochigi 3290498 Japan

Objectives Blood monocytes are the precursors of the lipid-laden foam cells that are the hallmark of early atherosclerotic lesions, and monocyte chemoattractant protein-1 (MCP-1) plays important roles in their recruitment to the vessel wall. In this study, we measured serum levels of MCP-1 in patients with peripheral arterial obstructive disease (PAOD) and investigated whether intravenous prostaglandin E 1 (PGE1) treatment, which produces clinical benefits in PAOD, might decrease such levels. Methods Eight patients with PAOD at Fontaine stage 11 to IV were treated with a daily intravenous infusion of 10 mug of PGE1 for 7 consecutive days. Blood samples before and after 7-day PGE1 treatment were used for assays of MCP-1, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), von Willebrand factor (vWF), and endothelin-1 (ET-1). Results Serum MCP-1 levels in patients with PAOD were significantly higher than those in healthy control subjects (263.8 +/- 52.8 vs 136.5 +/- 15.0 pg/mL, P = .002). PGE1 administration for 7 days resulted in a significant decrease in the MCP-1 level, from 263.8 +/- 52.8 to 196.1 +/- 25.5 pg/mL (P = .02), whereas levels of IL-6, hs-CRP, and ET-1 and the activity of vWF were not affected. Conclusions Serum MCP-1 levels were elevated in patients with PAOD, indicating the involvement of activation of monocytes in the pathogenesis of this disorder. Parenteral administration of PGE1 appeared to decrease circulating MCP-1 levels, which might lead to the suppression of the development of atherosclerotic lesions in patients with PAOD.

关键词：前列地尔/投药和剂量前列地尔/治疗应用动脉闭塞性疾病/血液动脉闭塞性疾病/药物疗法生物学标记/血液 C反应蛋白质/分析病例对照研究趋化因子CCL2/血液内皮缩血管肽1/血液纤维蛋白溶解药/投药和剂量纤维蛋白溶解药/治疗应用注射静脉内白细胞介素6/血液间歇性跛行/血液间歇性跛行/药物疗法外周血管疾病/血液外周血管疾病/药物疗法血管舒张药/投药和剂量血管舒张药/治疗应用 vonWillebrand因子/分析成年人老年人女(雌)性人类男(雄)性中年人

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Net mass transfer of plasma cholesteryl esters and lipid transfer proteins in normolipidemic patients with peripheral vascular disease

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METABOLISM-CLINICAL AND EXPERIMENTAL 1999年第11期48卷 1361-1366页

作者： Rühling, K Lang, A Richard, F Van Tol, A Eisele, B Herzberg, V Till, U Univ Jena Ctr Vasc Biol & Med Erfurt D-99089 Erfurt Germany Hosp Erfurt Dept Med Erfurt Germany Dr Karl Thomae GmbH Dept Biol Res Biberach Germany Erasmus Univ Dept Biochem Cardiovasc Res Inst COEUR NL-3000 DR Rotterdam Netherlands

The role of plasma cholesteryl ester transfer and lipid transfer proteins in atherosclerosis is unclear. Recent data suggest both antiatherogenic and atherogenic properties for cholesteryl ester transfer protein (CETP). The overall effect of CETP on atherosclerosis may thus vary depending on individual lipid metabolism. To test whether lipid transfer parameters are of importance even in patients without major lipid risk factors for atherosclerosis, CETP mass and activity, net mass transfer of cholesteryl esters between endogenous lipoproteins (CET), and phospholipid transfer protein (PLTP) activity were determined in plasma from 18 normolipidemic male patients with peripheral vascular disease and 21 controls. Furthermore, lecithin: cholesterol acyltransferase (LCAT) activity was tested. The results show that CETP mass, CETP activity, and LCAT activity are not different between patients and controls. However, specific CETP activity (CETP activity/CETP mass) is lower in the patients (P < .02). On the contrary, higher CET is observed in patients' plasma (P < .001). Increased plasma PLTP activity (P = .052) is demonstrable in the patients. If the data of all subjects are combined, CET correlates positively with triglycerides ([TG], r = .45, P < .001) and with PLTP activity (r = .32, P < .05) but negatively with specific CETP activity (r = -.37 P < .05). CET and specific CETP activity remain significantly different in TG-matched patients and controls and are more strongly interrelated (r = -.71, P < .001), suggesting a higher and selective influence of lipid transfer inhibitor(s) on CET and CETP activity in the patients. CET allows the best discrimination between patients and controls in univariate and multivariate analysis. Eighty-eight percent of the subjects are correctly classified by CET as a single parameter. The results suggest that increased CET in the patients may reflect atherogenic alterations in TO metabolism and/or in lipid transfer protein activities despit

关键词：方差分析载体蛋白质类/血液病例对照研究胆固醇酯转运蛋白质类胆固醇酯类/血液糖蛋白类脂类/血液外周血管疾病/血液外周血管疾病/酶学磷脂酰胆碱类/血液磷脂类/血液甾醇O-酰基转移酶/血液老年人人类男(雄)性中年人

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Bilirubin and peripheral vascular disease

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BRITISH JOURNAL OF SURGERY 2000年第2期87卷 251-252页

作者： Krijgsman, B Mikhailides, DP Winder, AF Hamilton, G Royal Free Hosp Univ Dept Surg London NW3 2QG England Royal Free Hosp Dept Clin Biochem London NW3 2QG England

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Bilirubin and peripheral vascular disease

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BRITISH JOURNAL OF SURGERY 1999年第5期86卷 713-713页

作者： Kangas, E Teittinen, K Vilkko, P Utriainen, S So Carelia Cent Hosp Dept Surg SF-53130 Lappeenranta Finland So Carelia Cent Hosp Dept Internal Med SF-53130 Lappeenranta Finland

Comments on the article related to bilirubin and peripheral vascular disease. Impact of low bilirubin concentration on the solubilization of cholesterol; Relationship between bilirubin and ankle; Median concentration ... 详细信息

关键词：胆红素/血液生物学标记/血液外周血管疾病/血液前瞻性研究老年人老年人 80以上女(雌)性人类男(雄)性中年人

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