冠心病患者血浆PZ水平的检测及临床意义
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摘要
目的：观察冠心病患者血浆蛋白Z (protein Z, PZ)水平的变化与冠心病危险因素及冠状动脉粥样硬化严重程度(通过Gensini评分系统评分)的相关性,探讨其临床意义。
方法：采用酶联免疫吸附法测定经冠状动脉造影确诊的66例冠心病患者以及22例冠状动脉造影结果正常的对照者血浆中PZ的浓度。采用Gensini评分系统对冠心病患者冠状动脉血管病变程度进行定量评分并根据结果将其分为A (G≤30)、B (3070)三组,比较各组研究对象中PZ水平差异并分析PZ水平与冠心病危险因素和Gensini评分的关系。
结果：冠心病组血浆PZ水平显著低于对照组(715.65±287.13ng/ml比1049.19±266.32ng/ml, P<0.05)。CHD组中A组、B组和C组的血浆PZ水平分别为838.55±300.34ng/ml,664.44±281.29ng/ml和609.82±218.18ng/ml,呈逐渐下降的趋势,B、C组血浆PZ水平显著低于A组(P<0.05),B组与C组相比没有显著差异性(P>0.05)。相关分析发现冠心病组血浆PZ水平与Gensini评分呈显著负相关,(R=-0.292,P=0.018)。将冠心病组和对照组合并后,血浆PZ水平与hs-CRP亦呈显著的负相关(R=-0.262,P=0.020)。吸烟组血浆PZ水平明显低于不吸烟组(710.75±253.18ng/ml比885.24±356.75ng/ml, P<0.05)。PZ与血脂各组分如LDL, HDL, TC和TG之间无显著相关性。
结论：冠心病患者血浆PZ水平明显下降。血浆PZ水平与冠状动脉粥样硬化严重程度以及炎症指标如hs-CRP均呈显著负相关关系。吸烟可以使血浆PZ水平下降。这些提示了血浆PZ下降水平可能反映了冠状动脉粥样硬化的严重程度,吸烟、炎症反应可能在一定程度上影响PZ水平。
Objective:To investigate the alteration of plasma protein Z levels in patients with CHD and its relationships with risk factors of CHD and the severity of coronary atherosclerosis (defined by Gensini score system)
Methods:Plasma protein Z levels were measured by ELISA in 66 patients with coronary heart disease (CHD) which were confirmed by coronary angiography (CAG) and 22 controls with normal CAG findings. CHD group was divided into A (G≤30), B (30 70) groups according to the Gensini scores. The correlations of protein Z levels between traditional risk factors of CHD and Gensini scores were analyzed.
Results:The mean plasma protein Z level was lower in CHD group than in controls(715.65±287.13ng/ml vs 1049.19±266.32ng/ml, P<0.05). Mean plasma protein Z levels of A, B and C group were 838.55±300.34 ng/ml,664.44±281.29ng/ml and 609.82±218.18ng/ml respectively, which had a trend to be declining gradually. Mean plasma protein Z levels were significantly lower in group B and group C than in group A (P<0.05), while there was no significant difference between group B and group C(P>0.05). In CHD group, plasma protein Z levels was significant inversely correlated with Gensini scores (R=-0.292, P=0.018). Putting CHD group and control group together, we found that plasma protein Z levels was significant inversely correlated with hs-CRP levels (R=-0.262, P=0.02). Mean plasma protein Z level was lower in smoking subgroup than in no smoking subgroup (710.75±253.18ng/ml vs 885.24±356.75ng /ml, P<0.05). There was no significant relationship between plasma protein Z levels and lipid profiles such as LDL, HDL, TC and TG.
Conclusion:Mean plasma protein Z level was significantly decreased in CHD group, Plasma protein Z levels were inversely correlated with the severity of coronary atherosclerosis and hs-CRP. Smoking could induce the decrease of plasma protein Z levels. These results showed that protein Z levels may reflect the severity of coronary atherosclerosis, inflammation reaction and smoking could affect plasma protein Z levels in a certain extent.
方法：采用酶联免疫吸附法测定经冠状动脉造影确诊的66例冠心病患者以及22例冠状动脉造影结果正常的对照者血浆中PZ的浓度。采用Gensini评分系统对冠心病患者冠状动脉血管病变程度进行定量评分并根据结果将其分为A (G≤30)、B (30
结果：冠心病组血浆PZ水平显著低于对照组(715.65±287.13ng/ml比1049.19±266.32ng/ml, P<0.05)。CHD组中A组、B组和C组的血浆PZ水平分别为838.55±300.34ng/ml,664.44±281.29ng/ml和609.82±218.18ng/ml,呈逐渐下降的趋势,B、C组血浆PZ水平显著低于A组(P<0.05),B组与C组相比没有显著差异性(P>0.05)。相关分析发现冠心病组血浆PZ水平与Gensini评分呈显著负相关,(R=-0.292,P=0.018)。将冠心病组和对照组合并后,血浆PZ水平与hs-CRP亦呈显著的负相关(R=-0.262,P=0.020)。吸烟组血浆PZ水平明显低于不吸烟组(710.75±253.18ng/ml比885.24±356.75ng/ml, P<0.05)。PZ与血脂各组分如LDL, HDL, TC和TG之间无显著相关性。
结论：冠心病患者血浆PZ水平明显下降。血浆PZ水平与冠状动脉粥样硬化严重程度以及炎症指标如hs-CRP均呈显著负相关关系。吸烟可以使血浆PZ水平下降。这些提示了血浆PZ下降水平可能反映了冠状动脉粥样硬化的严重程度,吸烟、炎症反应可能在一定程度上影响PZ水平。
Objective:To investigate the alteration of plasma protein Z levels in patients with CHD and its relationships with risk factors of CHD and the severity of coronary atherosclerosis (defined by Gensini score system)
Methods:Plasma protein Z levels were measured by ELISA in 66 patients with coronary heart disease (CHD) which were confirmed by coronary angiography (CAG) and 22 controls with normal CAG findings. CHD group was divided into A (G≤30), B (30
Results:The mean plasma protein Z level was lower in CHD group than in controls(715.65±287.13ng/ml vs 1049.19±266.32ng/ml, P<0.05). Mean plasma protein Z levels of A, B and C group were 838.55±300.34 ng/ml,664.44±281.29ng/ml and 609.82±218.18ng/ml respectively, which had a trend to be declining gradually. Mean plasma protein Z levels were significantly lower in group B and group C than in group A (P<0.05), while there was no significant difference between group B and group C(P>0.05). In CHD group, plasma protein Z levels was significant inversely correlated with Gensini scores (R=-0.292, P=0.018). Putting CHD group and control group together, we found that plasma protein Z levels was significant inversely correlated with hs-CRP levels (R=-0.262, P=0.02). Mean plasma protein Z level was lower in smoking subgroup than in no smoking subgroup (710.75±253.18ng/ml vs 885.24±356.75ng /ml, P<0.05). There was no significant relationship between plasma protein Z levels and lipid profiles such as LDL, HDL, TC and TG.
Conclusion:Mean plasma protein Z level was significantly decreased in CHD group, Plasma protein Z levels were inversely correlated with the severity of coronary atherosclerosis and hs-CRP. Smoking could induce the decrease of plasma protein Z levels. These results showed that protein Z levels may reflect the severity of coronary atherosclerosis, inflammation reaction and smoking could affect plasma protein Z levels in a certain extent.
引文
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67. Dahlback B. Resistance to activated protein C caused by the factor VR506Q mutation is a common risk factor for venous thrombosis. Thromb Haemost 1997; 78:483-488.
68. Vasse M, Guegan-Massardier E, Borg JY, et al. Frequency of protein Z deficiency in patients with ischaemic stroke Lancet 2001; 357:933-934.
69. Martinelli I, Razzari C, Biguzzi E, et al. Low levels of protein Z and the risk of venous thromboembolism. J Thromb Haemost 2005; 3:2817-2819.
70. Kemkes-Matthes B, Nees M, Kuhnel G, et al. Protein Z influences the prothrombotic phenotype in Factor V Leiden patients. Thromb Res 2002; 106: 183-185.
71. Ayoub N, Esposito G, Barete S, et al. Protein Z deficiency in antiphospholipid-negative Sneddon's syndrome. Stroke 2004; 35:1329-1332.
72. Lopaciuk S, Bykowska K, Kwiecinski H, et al. Protein Z in young survivors of ischemic stroke. Thromb Haemost 2002; 88:536.
73. Kobelt K, Biasiutti FD, Mattle HP, et al. Protein Z in ischaemic stroke. Br J Haematol 2001; 114:169-173.
74. Marco P, Marin F, Garcia A, et al. Do protein Z levels influence the prothrombotic state in atrial fibrillation? Thromb Res 2002; 106:269-270.
75. Sofi F, Cesari F, Vigiani S, et al. Protein Z plasma levels in different phases of activity of coronary atherosclerosis. J Thromb Haemost 2005; 3:2254-2258.
76. Sofi F, Cesari F, Marcucci R, et al. Protein Z levels and prognosis in patients with acute coronary syndromes. Clin Chem Lab Med 2006; 44:1098-1102.
77. Cesari F, Fatini C, Sticchi E, et al. Protein Z gene polymorphisms (intron F 79 G>A;-13 A>G) are not associated with acute coronary syndromes. Thromb Haemost 2006; 96:98-99.
78. Morange PE, Juhan-Vague I; PRIME Study Group. Protein Z plasma levels are not associated with the risk of coronary heart disease:the PRIME Study. J Thromb Haemost 2004; 2:2050-2051.
79. Sofi F, Cesari F, Pratesi G, et al. Low protein Z levels in patients with peripheral arterial disease. Thromb Haemost 2007; 98:1114-1117.
80. Pardos-Gea J, Ordi-Ros J, Serrano S, et al. Protein Z levels and anti-protein Z antibodies in patients with arterial and venous thrombosis. Thromb Res 2007; doi:10.1016/j.thromres.2007.07.009
81. Koren-Michowitz M, Eting E, Rahimi-Levene N, et al. Protein Z levels and central retinal vein or artery occlusion. Eur J Haematol 2005; 75:401-405.
82. Ozturk MA, Ozbalkan Z, Onat AM, et al. Decreased protein Z concentrations complicating the hypercoagulable state of Behcet's disease. Clin Appl Thromb
Hemost 2003; 9:259-263.
83. Koutroubakis IE, Theodoropoulou A, Sfiridaki A, et al. Low plasma protein Z levels in patients with ischemic colitis. Dig Dis Sci 2003; 48:1673-1676.
84. McColl MD, Deans A, Maclean P, et al. Plasma protein Z deficiency is common in women with antiphospholipid antibodies. Br J Haematol 2003; 120:913-914.
85. Forastiero RR, Martinuzzo ME, Lu L, et al. Autoimmune antiphospholipid antibodies impair the inhibition of activated factor X by protein Z/protein Z-dependent protease inhibitor. J Thromb Haemost 2003; 1:1764-1770.
86. Gris JC, Amadio C, Mercier E, et al. Anti-protein Z antibodies in women with pathologic pregnancies. Blood 2003; 101:4850-4852.
87. Sailer T, Vormittag R, Koder S, et al. Clinical significance of anti-protein Z antibodies in patients with lupus anticoagulant. Thromb Res 2007; doi:10.1016/j.thromres.2007.07.014.
88. Gris JC, Quere I, Dechaud H, et al. High frequency of protein Z deficiency in patients with unexplained early fetal loss. Blood 2002; 99:2606-2608.
89. Gris JC, Mercier E, Quere I, et al. Low-molecularweight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood 2004; 103:3695-3699.
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54. Undar L, Karadogan I, Ozturk F. Plasma protein Z levels inversely correlate with plasma interleukin-6 levels in patients with acute leukemia and non-Hodgkin's lymphoma. Thromb Res 1999; 94:131-134.
55. Vasse M, Denoyelle C, Legrand E, et al. Weak regulation of protein Z biosynthesis by inflammatory cytokines. Thromb Haemost 2002; 87:350-351.
56. Cesari F, Gori AM, Fedi S, et al. Modifications of protein Z and interleukin-6 during the acute phase of coronary artery disease. Blood Coagul Fibrinolysis 2007; 18:85-86.
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64. Kemkes-Matthes B, Matthes KJ. Protein Z deficiency:a new cause of bleeding tendency. Thromb Res 1995; 79:49-55.
65. Gamba G, Bertolino G, Montani N, et al. Bleeding tendency of unknown origin and protein Z levels. Thromb Res 1998; 90:291-295.
66. Obach V, Munoz X, Sala N, et al. Intronic c.573+79G>A polymorphism of protein Z gene in haemorrhagic and ischaemic stroke. Thromb Haemost 2006;95: 1040-1041.
67. Dahlback B. Resistance to activated protein C caused by the factor VR506Q mutation is a common risk factor for venous thrombosis. Thromb Haemost 1997; 78:483-488.
68. Vasse M, Guegan-Massardier E, Borg JY, et al. Frequency of protein Z deficiency in patients with ischaemic stroke Lancet 2001; 357:933-934.
69. Martinelli I, Razzari C, Biguzzi E, et al. Low levels of protein Z and the risk of venous thromboembolism. J Thromb Haemost 2005; 3:2817-2819.
70. Kemkes-Matthes B, Nees M, Kuhnel G, et al. Protein Z influences the prothrombotic phenotype in Factor V Leiden patients. Thromb Res 2002; 106: 183-185.
71. Ayoub N, Esposito G, Barete S, et al. Protein Z deficiency in antiphospholipid-negative Sneddon's syndrome. Stroke 2004; 35:1329-1332.
72. Lopaciuk S, Bykowska K, Kwiecinski H, et al. Protein Z in young survivors of ischemic stroke. Thromb Haemost 2002; 88:536.
73. Kobelt K, Biasiutti FD, Mattle HP, et al. Protein Z in ischaemic stroke. Br J Haematol 2001; 114:169-173.
74. Marco P, Marin F, Garcia A, et al. Do protein Z levels influence the prothrombotic state in atrial fibrillation? Thromb Res 2002; 106:269-270.
75. Sofi F, Cesari F, Vigiani S, et al. Protein Z plasma levels in different phases of activity of coronary atherosclerosis. J Thromb Haemost 2005; 3:2254-2258.
76. Sofi F, Cesari F, Marcucci R, et al. Protein Z levels and prognosis in patients with acute coronary syndromes. Clin Chem Lab Med 2006; 44:1098-1102.
77. Cesari F, Fatini C, Sticchi E, et al. Protein Z gene polymorphisms (intron F 79 G>A;-13 A>G) are not associated with acute coronary syndromes. Thromb Haemost 2006; 96:98-99.
78. Morange PE, Juhan-Vague I; PRIME Study Group. Protein Z plasma levels are not associated with the risk of coronary heart disease:the PRIME Study. J Thromb Haemost 2004; 2:2050-2051.
79. Sofi F, Cesari F, Pratesi G, et al. Low protein Z levels in patients with peripheral arterial disease. Thromb Haemost 2007; 98:1114-1117.
80. Pardos-Gea J, Ordi-Ros J, Serrano S, et al. Protein Z levels and anti-protein Z antibodies in patients with arterial and venous thrombosis. Thromb Res 2007; doi:10.1016/j.thromres.2007.07.009
81. Koren-Michowitz M, Eting E, Rahimi-Levene N, et al. Protein Z levels and central retinal vein or artery occlusion. Eur J Haematol 2005; 75:401-405.
82. Ozturk MA, Ozbalkan Z, Onat AM, et al. Decreased protein Z concentrations complicating the hypercoagulable state of Behcet's disease. Clin Appl Thromb
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83. Koutroubakis IE, Theodoropoulou A, Sfiridaki A, et al. Low plasma protein Z levels in patients with ischemic colitis. Dig Dis Sci 2003; 48:1673-1676.
84. McColl MD, Deans A, Maclean P, et al. Plasma protein Z deficiency is common in women with antiphospholipid antibodies. Br J Haematol 2003; 120:913-914.
85. Forastiero RR, Martinuzzo ME, Lu L, et al. Autoimmune antiphospholipid antibodies impair the inhibition of activated factor X by protein Z/protein Z-dependent protease inhibitor. J Thromb Haemost 2003; 1:1764-1770.
86. Gris JC, Amadio C, Mercier E, et al. Anti-protein Z antibodies in women with pathologic pregnancies. Blood 2003; 101:4850-4852.
87. Sailer T, Vormittag R, Koder S, et al. Clinical significance of anti-protein Z antibodies in patients with lupus anticoagulant. Thromb Res 2007; doi:10.1016/j.thromres.2007.07.014.
88. Gris JC, Quere I, Dechaud H, et al. High frequency of protein Z deficiency in patients with unexplained early fetal loss. Blood 2002; 99:2606-2608.
89. Gris JC, Mercier E, Quere I, et al. Low-molecularweight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood 2004; 103:3695-3699.