脂蛋白(a)与冠心病患者临床稳定性及冠状动脉狭窄程度的关系
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摘要
目的探究血清脂蛋白(a)[Lp(a)]与冠状动脉粥样硬化性心脏病(CAD)及其冠状动脉狭窄程度的关系。方法回顾性收集2013年1月～2016年12月在南方医院行冠脉造影的患者531例,按照Lp(a)浓度是否大于30 mg/dL分为高Lp(a)组(HLPA, n=191)和低Lp(a)组(LLPA, n=340),根据冠脉造影结果判断是否罹患CAD;CAD患者根据临床稳定性分为稳定性心绞痛组(SAP组)和急性冠脉综合征组(ACS组),比较两者及其冠脉狭窄程度与Lp(a)的关系。结果高Lp(a)组和低Lp(a)组间在年龄、性别、体质量指数(BMI)、吸烟、高血压和糖尿病史无统计学差异(P>0.05),两组间有可比性。多因素Logisitic回归分析显示年龄、性别、低密度脂蛋白胆固醇(LDL-C)和Lp(a)是入组人群患CAD的独立危险因素。Lp(a)升高,罹患CAD风险增高(OR=2.443,95%CI:1.205～4.951,P=0.013)。且无论LDL-C水平高低,高Lp(a)组较低Lp(a)组患CAD的风险均更高(P=0.006和P=0.020)。在冠心病患者中,ACS组较SAP组Lp(a)水平更高(P<0.001);高Lp(a)和低Lp(a)两组间高Gensini评分的患者分别占17.3%和5.6%(P=0.026),其Gensini评分与Lp(a)呈线性关系(R=0.130, P=0.006)。结论 Lp(a)是CAD的独立危险因素,高Lp(a)是CAD的残余风险;Lp(a)升高与冠心病临床稳定性及冠状动脉狭窄程度相关。
Objective To analyze the correlation of lipoprotein(a) [Lp(a)] with the clinical stability and severity of coronary artery stenosis in patients with coronary artery disease(CAD).Methods A total of 531 patients undergoing coronary angiography in Nanfang Hospital between January,2013 and December,2016 were enrolled in this study.At the cutoff Lp(a)concentration of 300 mg/L,the patients were divided into high Lp(a) group(n=191) and low Lp(a) group(n=340).In each group,the patients with an established diagnosis of CAD based on coronary angiography findings were further divided into stable angina pectoris(SAP) group and acute coronary syndrome(ACS) group.The correlation between the severity of coronary artery stenosis and Lp(a) was evaluated.Results The patients in high and low Lp(a) groups showed no significant differences in age,gender,body mass index,smoking status,hypertension,or diabetes(P>0.05).Multivariate logistic regression analysis revealed that age,gender,and serum levels of low-density lipoprotein cholesterol(LDL-C) and Lp(a) were independent risk factors for CAD in these patients.A high Lp(a) level was associated with an increased risk of CAD(OR=2.443,95%CI:1.205-4.951,P=0.013).The patients with a high Lp(a) level were at a significantly higher risk of CAD than those with a low Lp(a) level irrespective of a low or high level of LDL-C(P=0.006 and 0.020).In the patients with CAD,the ACS group had a significantly higher Lp(a) level than the SAP group(P<0.001);the proportion of the patients with high Gensini scores was significantly greater in high Lp(a) group than in low Lp(a) group(17.3% vs 5.6%,P=0.026),and a linear relationship was found between Lp(a) level and Gensini score(R=0.130,P=0.006).Conclusion Serum level of Lp(a) is an independent risk factor for CAD,and an increased Lp(a) is the residual risk for CAD.In patients with CAD,a high Lp(a) level is associated with the clinical instability and severity of coronary artery stenosis.
Objective To analyze the correlation of lipoprotein(a) [Lp(a)] with the clinical stability and severity of coronary artery stenosis in patients with coronary artery disease(CAD).Methods A total of 531 patients undergoing coronary angiography in Nanfang Hospital between January,2013 and December,2016 were enrolled in this study.At the cutoff Lp(a)concentration of 300 mg/L,the patients were divided into high Lp(a) group(n=191) and low Lp(a) group(n=340).In each group,the patients with an established diagnosis of CAD based on coronary angiography findings were further divided into stable angina pectoris(SAP) group and acute coronary syndrome(ACS) group.The correlation between the severity of coronary artery stenosis and Lp(a) was evaluated.Results The patients in high and low Lp(a) groups showed no significant differences in age,gender,body mass index,smoking status,hypertension,or diabetes(P>0.05).Multivariate logistic regression analysis revealed that age,gender,and serum levels of low-density lipoprotein cholesterol(LDL-C) and Lp(a) were independent risk factors for CAD in these patients.A high Lp(a) level was associated with an increased risk of CAD(OR=2.443,95%CI:1.205-4.951,P=0.013).The patients with a high Lp(a) level were at a significantly higher risk of CAD than those with a low Lp(a) level irrespective of a low or high level of LDL-C(P=0.006 and 0.020).In the patients with CAD,the ACS group had a significantly higher Lp(a) level than the SAP group(P<0.001);the proportion of the patients with high Gensini scores was significantly greater in high Lp(a) group than in low Lp(a) group(17.3% vs 5.6%,P=0.026),and a linear relationship was found between Lp(a) level and Gensini score(R=0.130,P=0.006).Conclusion Serum level of Lp(a) is an independent risk factor for CAD,and an increased Lp(a) is the residual risk for CAD.In patients with CAD,a high Lp(a) level is associated with the clinical instability and severity of coronary artery stenosis.
引文
[1]戴闺柱.与血脂指南有关的若干脂质新理念[J].中华心血管病杂志,2015,43(11):930-33.
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[16]Rigamonti F,Carbone F,Montecucco F,et al.Serum lipoprotein(a)predicts acute coronary syndromes in patients with severe carotid stenosis[J].Eur J Clin Invest,2018,48(3):e12888.
[17]Erhart G,Lamina C,Lehtimaki TA,et al.Genetic factors explain a major fraction of the 50%lower lipoprotein(a)concentrations in finns[J].Arterioscler Thromb Vasc Biol,2018,38(5):1230-41.
[18]Mihaylova B,Emberson J,Blackwell L,et al.The effects of lowering LDL cholesterol with statin therapy in People at low risk of vascular disease:meta-analysis of individual data from 27randomised trials[J].Lancet,2012,380(9841):581-90.
[19]Laufs U,Weingaertner O.Pathological phenotypes of LDL particles[J].Eur Heart J,2018,39(27):2574-6.
[20]Weiss MC,Berger JS,Gianos E,et al.Lipoprotein(a)screening in patients with controlled traditional risk factors undergoing percutaneous coronary intervention[J].J Clin Lipidol,2017,11(5):1177-80.
[21]Sun D,Zhao X,Li S,et al.Lipoprotein(a)as a marker for predicting the presence and severity of coronary artery disease in untreated Chinese patients undergoing coronary angiography[J].Biomed Environ Sci,2018,31(4):253-60.
[22]Ellis KL,Boffa MB,Sahebkar AA,et al.The Renaissance of lipoprotein(a):Brave New World for preventive cardiology[J]?Prog Lipid Res,2017,68:57-82.
[23]Gencer B,Kronenberg F,Stroes ES,et al.Lipoprotein(a):the revenant[J].Eur Heart J,2017,38(20):1553-60.
[24]Gaudet D,Watts GF,Robinson JG,et al.Effect of alirocumab on lipoprotein(a)over≥1.5 years(from the phase 3 ODYSSEYprogram)[J].Am J Cardiol,2017,119(1):40-6.
[25]Verbeek R,Hoogeveen RM,Langsted AA,et al.Cardiovascular disease risk associated with elevated lipoprotein(a)attenuates at low low-density lipoprotein cholesterol levels in a primary prevention setting[J].Eur Heart J,2018,39(27):2589-96.
[26]Catapano AL,Graham I,De Backer G,et al.2016 ESC/EASguidelines for the management of dyslipidaemias[J].Eur Heart J,2016,37(39):2999-3058.
[2]Laschkolnig A,Kollerits B,Lamina CA,et al.Lipoprotein(a)concentrations,apolipoprotein(a)phenotypes,and peripheral arterial disease in three independent cohorts[J].Cardiovasc Res,2014,103(1):28-36.
[3]Gencer B and F Mach.Lipoprotein(a):the perpetual supporting actor[J].Eur Heart J,2018,39(27):2597-9.
[4]Nordestgaard BG,Chapman MJ,Ray K,et al.Lipoprotein(a)as a cardiovascular risk factor:current status[J].Eur Heart J,2010,31(23):2844-53.
[5]Varvel S,Mcconnell JP,Tsimikas S.Prevalence of elevated Lp(a)mass levels and patient thresholds in 532 359 patients in the United States[J].Arterioscler Thromb Vasc Biol,2016,36(11):2239-45.
[6]Waldeyer C,Makarova N,Zeller TA,et al.Lipoprotein(a)and the risk of cardiovascular disease in the European population:results from the BiomarCaRE consortium[J].Eur Heart J,2017,38(32):2490-8.
[7]Zhang HW,Zhao X,Guo YL,et al.Elevated lipoprotein(a)levels are associated with the presence and severity of coronary artery disease in patients with type 2 diabetes mellitus[J].Nutr Metab Cardiovasc Dis,2018,28(10):980-6.
[8]Zewinger S,Kleber ME,Tragante V,et al.Relations between lipoprotein(a)concentrations,LPA genetic variants,and the risk of mortality in patients with established coronary heart disease:a molecular and genetic association study[J].Lancet Diabetes Endocrinol,2017,5(7):534-43.
[9]Willeit P,Kiechl S,Kronenberg F,et al.Discrimination and net reclassification of cardiovascular risk with lipoprotein(a)[J].J Am Coll Cardiol,2014,64(9):851-60.
[10]中国成人血脂异常防治指南制订联合委员会.中国成人血脂异常防治指南[J].中华心血管病杂志,2016,31(10):937-50.
[11]Cannon CP,Brindis RG,Chaitman BR,et al.2013 ACCF/AHA key data elements and definitions for measuring the clinical management and outcomes of patients with acute coronary syndromes and coronary artery disease[J].Crit Pathw Cardiol,2013,12(2):65-105.
[12]Fox K,Garcia MA,Ardissino D,et al.Guidelines on the management of stable angina pectoris:executive summary:The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology[J].Eur Heart J,2006,27(11):1341-81.
[13]Gensini GG.A more meaningful scoring system for determining the severity of coronary heart disease[J].Am J Cardiol,1983,51(3):606.
[14]Puri R,Ballantyne CM,Hoogeveen RC,et al.Lipoprotein(a)and coronary atheroma progression rates during long-term highintensity statin therapy:Insights from Saturn[J].Atherosclerosis,2017,263:137-44.
[15]Simons LA,Simons J,Friedlander YA.LDL-cholesterol Predicts a First CHD Event in Senior Citizens,Especially So in Those With Elevated Lipoprotein(a):Dubbo Study of the Elderly[J].Heart Lung Circ,2018,27(3):386-9.
[16]Rigamonti F,Carbone F,Montecucco F,et al.Serum lipoprotein(a)predicts acute coronary syndromes in patients with severe carotid stenosis[J].Eur J Clin Invest,2018,48(3):e12888.
[17]Erhart G,Lamina C,Lehtimaki TA,et al.Genetic factors explain a major fraction of the 50%lower lipoprotein(a)concentrations in finns[J].Arterioscler Thromb Vasc Biol,2018,38(5):1230-41.
[18]Mihaylova B,Emberson J,Blackwell L,et al.The effects of lowering LDL cholesterol with statin therapy in People at low risk of vascular disease:meta-analysis of individual data from 27randomised trials[J].Lancet,2012,380(9841):581-90.
[19]Laufs U,Weingaertner O.Pathological phenotypes of LDL particles[J].Eur Heart J,2018,39(27):2574-6.
[20]Weiss MC,Berger JS,Gianos E,et al.Lipoprotein(a)screening in patients with controlled traditional risk factors undergoing percutaneous coronary intervention[J].J Clin Lipidol,2017,11(5):1177-80.
[21]Sun D,Zhao X,Li S,et al.Lipoprotein(a)as a marker for predicting the presence and severity of coronary artery disease in untreated Chinese patients undergoing coronary angiography[J].Biomed Environ Sci,2018,31(4):253-60.
[22]Ellis KL,Boffa MB,Sahebkar AA,et al.The Renaissance of lipoprotein(a):Brave New World for preventive cardiology[J]?Prog Lipid Res,2017,68:57-82.
[23]Gencer B,Kronenberg F,Stroes ES,et al.Lipoprotein(a):the revenant[J].Eur Heart J,2017,38(20):1553-60.
[24]Gaudet D,Watts GF,Robinson JG,et al.Effect of alirocumab on lipoprotein(a)over≥1.5 years(from the phase 3 ODYSSEYprogram)[J].Am J Cardiol,2017,119(1):40-6.
[25]Verbeek R,Hoogeveen RM,Langsted AA,et al.Cardiovascular disease risk associated with elevated lipoprotein(a)attenuates at low low-density lipoprotein cholesterol levels in a primary prevention setting[J].Eur Heart J,2018,39(27):2589-96.
[26]Catapano AL,Graham I,De Backer G,et al.2016 ESC/EASguidelines for the management of dyslipidaemias[J].Eur Heart J,2016,37(39):2999-3058.