急性冠状动脉综合征患者血浆同型半胱氨酸水平与左心室射血分数及心功能严重程度的相关性研究The relationship between homocysteine and left ventricular ejection fraction,severity of heart failure in acute coronary heart syndrome patients
莫合塔伯尔·莫敏,李建平,张岩,贾佳,霍勇
摘要(Abstract):
目的探讨急性冠状动脉综合征(ACS)患者血浆同型半胱氨酸(Hcy)水平与左心室收缩功能及临床心功能的相关性。方法纳入2005年至2013年就诊北京大学第一医院接受冠状动脉造影(CAG)的ACS患者548例,其中男394例,平均年龄(61.2±12.3)岁。检测患者入院时血浆Hcy、叶酸水平,行CAG收集冠状动脉病变数据,评估入院临床心功能,行超声心动图检查采集左心室射血分数(LVEF)指标,分析心脏收缩功能及临床心功能与血浆Hcy的相关性。结果多元线性回归分析显示,在校正混杂因素后,血浆Hcy与LVEF独立相关(β=-0.237,95%CI-0.375~-0.041,P=0.015);随着心功能分级的增加,血浆Hcy水平逐渐增加,NYHA/Killip分级Ⅲ/Ⅳ级Hcy显著高于Ⅱ级和Ⅰ级(P=0.046和P=0.021);亚组分析显示在女性组、非糖尿病组、正常肾功能组、非高血压组、非陈旧心肌梗死组及急性心肌梗死组中NYHA/Killip分级Ⅲ/Ⅳ级心力衰竭患者Hcy水平高于正常心功能患者,差异均有统计学意义(P<0.05);女性组在校正其他混杂因素后,Hcy是临床心力衰竭的独立危险因素(OR=1.188,P=0.006)。在全体人群及急性心肌梗死、不稳定型心绞痛、女性亚组中,随Hcy水平升高,中重度心力衰竭风险增加(OR分别为1.081、1.102、1.152、1.191,P<0.05)。结论 ACS患者血浆Hcy水平与LVEF负相关、与临床心功能严重程度相关;Hcy是女性ACS患者临床心力衰竭的危险因素;在全体人群及急性心肌梗死、不稳定型心绞痛、女性亚组中,随血浆Hcy水平升高中重度心力衰竭风险增加。
关键词(KeyWords): 同型半胱氨酸;急性冠状动脉综合征;左心室射血分数;心力衰竭
基金项目(Foundation): 北京大学医学部与密歇根大学医学院转化与临床医学联合研究所计划(MBU20110177);; “十二五”国家科技支撑计划(2011BAI11B06)
作者(Author): 莫合塔伯尔·莫敏,李建平,张岩,贾佳,霍勇
参考文献(References):
- [1]Yancy CW,Jessup M,Bozkurt B,et al.2013 ACCF/AHA guideline for the management of heart failure:a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.J Am Coll Cardiol,2013,62:e147-e239.
- [2]Weiss N,Keller C,Hoffmann U,et al.Endothelial dysfunction and atherothrombosis in mild hyperhomocysteinemia.Vasc Med,2002,7:227-239.
- [3]Coppola A,Davi G,De Stefano V,et al.Homocysteine,coagulation,platelet function,and thrombosis.Semin Thromb Hemos,2000,26:243-254.
- [4]Tsai JC,Wang H,Perrella MA,et al.Induction of cyclin A gene expression by homocysteine in vascular smooth muscle cells.J Clin Invest,1996,97:146-153.
- [5]Vizzardi E,Bonadei I,Zanini G,et al.Homocysteine and heart failure:an overview.Recent Pat Cardiovasc Drug Discov,2009,4:15-21.
- [6]May HT,Alharethi R,Anderson JL,et al.Homocysteine levels are associated with increased risk of congestive heart failure in patients with and without coronary artery disease.Cardiology,2007,107:178-184.
- [7]Vasan RS,Beiser A,D'Agostino RB,et al.Plasma homocysteine and risk for congestive heart failure in adults without prior myocardial infarction.JAMA,2003,289:1251-1257.
- [8]Norris RM.Progressive left ventricular dysfunction and remodeling after myocardial infarction.Circulation,1994,89:1905.
- [9]Sundstrm J,Sullivan L,Selhub J,et al.Relations of plasma homocysteine to left ventricular structure and function:the Framingham Heart Study.Eur Heart J,2004,25:523-530.
- [10]Lim U,Cassano PA.Homocysteine and blood pressure in the Third National Health and Nutrition Examination Survey,1988-1994.Am J Epidemiol,2002,156:1105-1113.
- [11]Dimitrova KR,De Groot K,Myers AK,et al.Estrogen and homocysteine.Cardiovasc Res,2002,53:577-588.
- [12]Nygrd O,Vollset SE,Refsum H,et al.Total plasma homocysteine and cardiovascular risk profile.The Hordaland Homocysteine Study.JAMA,1995,274:1526-1533.
- [13]Herrmann M,Kindermann I,Müller S,et al.Relationship of plasma homocysteine with the severity of chronic heart failure.Clin Chem,2005,51:1512-1515.
- [14]Herzlich BC,Lichstein E,Schulhoff N,et al.Relationship among homocyst(e)ine,vitamin B-12 and cardiac disease in the elderly:association between vitamin B-12 deficiency and decreased left ventricular ejection fraction.J Nutr,1996,126(4Suppl):1249s-1253s.
- [15]Agoston-Coldea L,Mocan T,Gatfosse M,et al.Plasma homocysteine and the severity of heart failure in patients with previous myocardial infarction.Cardiol J,2011,18:55-62.
- [16]Washio T,Nomoto K,Watanabe I,et al.Relationship between plasma homocysteine levels and congestive heart failure in patients with acute myocardial infarction.Homocysteine and congestive heart failure.Int Heart J,2011,52:224-228.
- [17]Ventura P,Panini R,Verlato C,et al.Hyperhomocysteinemia and related factors in 600 hospitalized elderly subjects.Metabolism,2001,50:1466-1471.
- [18]Vizzardi E,Nodari S,Fiorina C,et al.Raised homocysteine plasma concentration in patients with heart failure:clinical significance.Monaldi Arch Chest Dis,2007,68:96-102.
- [19]赵鹏,朱兴雷.急性心肌梗死与左室重构.国际内科学杂志,2007,34:17-20.
- [20]孟浩宇,张敏,陈彭生,等.经皮冠状动脉介入治疗与冠状动脉旁路移植术对无保护左主干病变患者的疗效和预后对比分析及Syntax积分的价值.中国介入心脏病学杂志,2013,21:205-211.
- [21]Meimoun P,M'Barek D,Dragomir C,et al.Incidence,associated factors,and follow-up of hospital heart failure complicating acute anterior myocardial infarction successfully treated by primary angioplasty.Ann Cardiol Angeiol,2013,62:293-300.
- [22]Al-Obaidi MK,Stubbs PJ,Collinson P,et al.Elevated homocysteine levels are associated with increased ischemic myocardial injury in acute coronary syndromes.J Am Coll Cardiol,2000,36:1217-1222.
- [23]Lentz SR.Homocysteine and vascular dysfunction.Life Sci,1997,61:1205-1215.
- [24]Moshal KS,Metreveli N,Frank I,et al.Mitochondrial MMP activation,dysfunction and arrhythmogenesis in hyperhomocysteinemia.Curr Vasc Pharmacol,2008,6:84-92
- [25]Tyagi N,Ovechkin AV,Lominadze D,et al.Mitochondrial mechanism of microvascular endothelial cells apoptosis in hyperhomocysteinemia.J Cell Biochem,2006,98:1150-1162.
- [26]Joseph J,Washington A,Joseph L,et al.Hyperhomocysteinemia leads to adverse cardiac remodeling in hypertensive rats.Am J Physiol Heart Circ Physiol,2002,283:H2567-H2574.
- [27]Kennedy RH,Owings R,Shekhawat N,et al.Acute negative inotropic effects of homocysteine are mediated via the endothelium.Am J Physiol Heart Circ Physiol,2004,287:H812-H817.
- [28]de Bree A,Verschuren WM,Blom HJ,et al.Association between B vitamin intake and plasma homocysteine concentration in the general Dutch population aged 20-65 y.Am J Clin Nutr,2001,73:1027-1033.
- [29]Witte KK,Nikitin NP,Parker AC,et al.The effect of micronutrient supplementation on quality-of-life and left ventricular function in elderly patients with chronic heart failure.Eur Heart J,2005,26:2238-2244.
- [30]Blacher J,Demuth K,Guerin AP,et al.Association between plasma homocysteine concentrations and cardiac hypertrophy in end-stage renal disease.Nephrol,1999,12:248-255.
- [31]Bnaa KH,Njlstad I,Ueland PM,et al.Homocysteine lowering and cardiovascular events after acute myocardial infarction.N Engl J Med,2006,354:1578-1588.
- [32]Lonn E,Yusuf S,Arnold MJ,et al.Homocysteine lowering with folic acid and B vitamins in vascular disease.N Engl J Med,2006,354:1567-1577.