目的 分析慢性肾脏病(chronic kidney disease，CKD) G3～5患者主要不良心血管事件(major adverse cardiovascular events，MACE)的危险因素，探讨血浆脂蛋白相关磷脂酶A2(lipoprotein-associated phospholipase A2，Lp-PLA2)对其MACE发生的预测价值。 方法 采用回顾性研究，选取2017年11月─2022年12月在东莞东华医院诊断CKD G3～5的患者，其中确诊MACE和未确诊MACE的患者各106例，比较2组间Lp-PLA2水平及各临床指标的差异，用Logistic回归分析MACE发生的危险因素，使用ROC曲线分析Lp-PLA2预测MACE事件的准确性。 结果 212例CKD G3～5患者中，MACE组Lp-PLA2高于非MACE组(t=8.909，P＜0.001)。Logistic回归分析显示除年龄及性别外，Lp-PLA2是该人群MACE发生的独立危险因素，优势比为1.026。亚组分析显示年长(OR=1.027，95% CI:1.009～1.045，P=0.003)、非年长(OR=1.025，95% CI:1.013～1.037，P＜0.001)、男性(OR=1.019，95% CI:1.009～1.029，P＜0.001)、女性(OR=1.052，95% CI:1.021～1.084，P=0.001)、糖尿病(OR=1.027，95% CI:1.012～1.043，P＜0.001)及非糖尿病(OR=1.025，95% CI:1.012～1.037，P＜0.001)患者Lp-PLA2是MACE发生的独立危险因素。ROC曲线分析显示Lp-PLA2预测MACE发生的截断值为189 ng/ml(灵敏度60.4%，特异度95.3%)。 结论 Lp-PLA2是CKD G3～5患者MACE发生的独立危险因素，其具有较高的预测MACE发生的临床价值。
Objective To assess the risk factors associated with major adverse cardiovascular events (MACE) in patients diagnosed with stages 3-5 chronic kidney disease (CKD), and to evaluate the predictive value of plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) for MACE within this specific patient population. Methods In this retrospective study, we enrolled a total of 212 patients diagnosed with CKD stages 3-5 at Dongguan Tungwah Hospital between November 2017 and December 2022. Among the two groups: 106 patients with confirmed MACE and an equal number of patients without MACE. We compared the differences in Lp-PLA2 levels and various clinical indicators between the two groups, employing logistic regression analysis to identify the risk factors associated with MACE. Additionally, we utilized ROC curve analysis to evaluate the predictive accuracy of Lp-PLA2 for MACE events. Results The Lp-PLA2 levels were significantly elevated in the MACE group compared to the non-MACE group (252.769±138.053 vs. 128.984±37.499，t=8.909，F=81.964，Z=-8.331， P＜0.001) among CKD stages 3-5 patients. Logistic regression analysis revealed that, besides age and sex, Lp-PLA2 independently contributed as a risk factor for MACE in CKD stages 3-5 patients with an odds ratio of 1.026. The analysis of age subgroups (elderly OR=1.027，95% CI:(1.009～1.045), P=0.003; non-elderly OR=1.025, 95% CI:(1.013～1.037), P＜0.001), gender subgroups [male OR=1.019, 95% CI: (1.009～1.029), P＜0.001; female OR=1.052, 95% CI:(1.021～1.084), P=0.001], and diabetes subgroup [diabetes OR=1.027, 95% CI: (1.012～1.043), P＜0.001; non-diabetes OR=1.025, 95% CI:(1.012～1.037), P＜0.001] revealed that Lp-PLA2 served as an independent risk factor for MACE. ROC curve analysis demonstrated that a cutoff value of 189 ng/ml for Lp-PLA2 predicted MACE with a sensitivity of 60.4% and specificity of 95.3%. Conclusions The Lp-PLA2 enzyme is an independent risk factor for MACE in CKD stages 3-5 patients, and it holds significant clinical value in predicting the occurrence of MACE in this patient population.
[1].参 考 文 献
[2]Francis A, Harhay M N, Ong A, et al.Chronic kidney disease and the global public health agenda: an international consensus[J].Nat Rev Nephrol, 2024, 20(7):473-485
[3]Wang L, Xu X, Zhang M, et al.Prevalence of Chronic Kidney Disease in China: Results From the Sixth China Chronic Disease and Risk Factor Surveillance[J].JAMA Intern Med, 2023, 183(4):298-310
[4]Ortiz A, Covic A, Fliser D, et al.Epidemiology,contributors to,and clinical trials of mortality risk in chronic kidney failure[J].Lancet, 2014, 383(9931):1831-1843
[5]Weiner D E, Tighiouart H, Stark P C, et al.Kidney disease as a risk factor for recurrent cardiovascular disease and mortality[J].Am J Kidney Dis, 2004, 44(2):198-206
[6]Moradi H, Pahl M V, Elahimehr R, et al.Impaired antioxidant activity of high-density lipoprotein in chronic kidney disease[J].Transl Res, 2009, 153(2):77-85
[7]Rolla R, De Mauri A, Valsesia A, et al.Lipoprotein profile,lipoprotein-associated phospholipase A2 and cardiovascular risk in hemodialysis patients[J].J Nephrol, 2015, 28(6):749-755
[8] Li J, Cao T, Wei Y, et al.A Review of Novel Cardiac Biomarkers in Acute or Chronic Cardiovascular Diseases: The Role of Soluble ST2 (sST2), Lipoprotein-Associated Phospholipase A2 (Lp-PLA2), Myeloperoxidase (MPO), and Procalcitonin (PCT)[J].[J].Dis Markers, 2021, 2021(6258865):-
[9].Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017[J][J].Lancet, 2020, 395(10225):709-733
[10]Bejan-Angoulvant T, Bergerot C, Juillard L, et al.Myocardial microvascular disease and major adverse cardiovascular events in patients with end-stage renal disease: rationale and design of the MICROCARD study[J].Nephrol Dial Transplant, 2012, 27(7):2886-2891
[11] Rossing P, Hansen T W, Kumler T.Cardiovascular and non-renal complications of chronic kidney disease: Managing risk[J][J].Diabetes Obes Metab, 2024, :-
[12]Cao Q, Bi Y, Alvarado F, et al.Five-Year Cumulative Cardiovascular Health and Clinical Events in Patients With Chronic Kidney Disease: The CRIC Study[J].J Am Heart Assoc, 2024, 13(10):e33001-
[13]Cozzolino M, Butti A, Chiarelli G, et al.Cardiovascular calcification and accelerated atherosclerosis in chronic kidney disease][J].Ital Heart J Suppl, 2005, 6(1):25-28
[14]Fakhry M, Sidhu M S, Bangalore S, et al.Accelerated and intensified calcific atherosclerosis and microvascular dysfunction in patients with chronic kidney disease[J].Rev Cardiovasc Med, 2020, 21(2):157-162
[15]Rogers M, Goettsch C, Aikawa E.Medial and intimal calcification in chronic kidney disease: stressing the contributions[J].J Am Heart Assoc, 2013, 2(5):e481-
[16]Bonnefont-Rousselot D.Lp-PLA2,a biomarker of vascular inflammation and vulnerability of atherosclerosis plaques][J].Ann Pharm Fr, 2016, 74(3):190-197
[17]Packard C J, O' Reilly D S, Caslake M J, et al.Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart diseaseWest of Scotland Coronary Prevention Study Group[J].N Engl J Med, 2000, 343(16):1148-1155
[18]Sabatine M S, Morrow D A, O' Donoghue M, et al.Prognostic utility of lipoprotein-associated phospholipase A2 for cardiovascular outcomes in patients with stable coronary artery disease[J].Arterioscler Thromb Vasc Biol, 2007, 27(11):2463-2469
[19]余航, 陈慧, 曹丽菲, 等.急性心肌梗死患者血清脂蛋白相关磷脂酶的表达及其与冠状动脉病变程度和预后的相关性[J].临床心血管病杂志, 2020, 36(5):433-437
[20]Oei H H, van der Meer I M, Hofman A, et al.Lipoprotein-associated phospholipase A2 activity is associated with risk of coronary heart disease and ischemic stroke: the Rotterdam Study[J].Circulation, 2005, 111(5):570-575
[21]Rolla R, De Mauri A, Valsesia A, et al.Lipoprotein profile,lipoprotein-associated phospholipase A2 and cardiovascular risk in hemodialysis patients[J].J Nephrol, 2015, 28(6):749-755
[22] Qu H, Zhang G, Pan J, et al.Evaluation of Lipoprotein-Associated Phospholipase A2 as a Prognostic Biomarker in Chronic Kidney Disease[J]. [J].Clin Lab, 2021, 67(8):-
[23]Wilensky R L, Shi Y, Mohler E R, et al.Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development[J].Nat Med, 2008, 14(10):1059-1066
[24]McCullough P A.Darapladib and atherosclerotic plaque: should lipoprotein-associated phospholipase A2 be a therapeutic target?[J].Curr Atheroscler Rep, 2009, 11(5):334-337
