血清PCSK9水平对老年非酒精性脂肪性肝病动脉粥样硬化程度及预后的判断价值

Predictive value of serum PCSK9 level for the degree of atherosclerosis in elderly patients with nonalcoholic fatty liver disease

目的探讨老年血清前蛋白转化酶枯草溶菌素9(PCSK9)水平对非酒精性脂肪性肝病(NAFLD)动脉粥样硬化程度及预后的判断价值。方法纳入2020年4月至2021年4月在唐山市中医医院、唐山市人工医院就诊的NAFLD患者254例,根据Gensini积分四分位法分为轻度组(0~24分)84例,中度组(25~53分)86例,重度组(≥54分)84例。根据NAFLD患者是否发生主要心脑血管事件(MACCE)分为MACCE组30例与无MACCE组224例。对比各组间的临床资料,Pearson分析Gensini积分与PCSK9的相关性,Cox分析发生MACCE风险的危险因素,ROC曲线分析PCSK9对老年NAFLD患者发生MACCE的预测价值。结果轻度组hs-CRP、PCSK9、TG、LDL-C、Lp(a)分别为5.79(4.17,7.81)mg/L、(329.17±50.26)ng/mL、(1.47±0.33)mmol/L、(2.69±0.52)mmol/L、(0.52±0.12)mg/L,中度组分别为6.22(4.61,7.58)mg/L、(416.33±55.92)ng/mL、(1.65±0.36)mmol/L、(2.87±0.35)mmol/L、(0.63±0.09)mg/L,重度组分别为7.85(6.21,9.11)mg/L、(498.55±61.28)ng/mL、(1.86±0.24)mmol/L、(3.95±0.48)mmol/L、(0.70±0.11)mg/L,依次升高;HDL-C在轻度组、中度组、重度组依次降低,分别为(1.46±0.25)mmol/L、(1.20±0.22)mmol/L、(1.06±0.27)mmol/L,差异均有统计学意义(P<0.05);PCSK9与Gensini呈正相关(r=0.657,P<0.01)。MACCE组的年龄为(72.1±5.5)岁、Gensini积分为(86.27±5.03)分、PCSK9为(489.71±63.05)ng/mL、LDL-C为(2.88±0.79)mmol/L,较无MACCE组的(68.6±3.4)岁、(61.09±4.52)分、(356.03±51.19)ng/mL、(2.52±0.77)mmol/L更高,差异有统计学意义(P<0.05)。多因素Cox风险回归分析结果显示,Gensini积分(HR=1.018,95%CI:1.006~1.029)、PCSK9(HR=1.147,95%CI:1.038~1.287)是发生MACCE的独立危险因素。PCSK9预测MACCE发生的AUC为0.724,灵敏度为68.25%,特异度为75.92%。结论血清PCSK9与老年NAFLD患者Gensini积分呈正相关,可作为患者发生MACCE的预测指标。

Objective To investigate the predictive value of serum proprotein convertase subtilisin 9(PCSK9)level in elderly patients with nonalcoholic fatty liver disease(NAFLD)in predicting the degree of atherosclerosis and prognosis.Methods From April 2020 to April 2021,254 NAFLD patients who were treated in Tangshan Traditional Chinese Medicine Hospital and Tangshan Artificial Hospital were divided into three groups according to the quartiles of Gensini score:Group 1(Gensini score≤24,n=84);Group 2(24<Gensini score≤53,n=86)and Group 3(Gensini score>53,n=84).According to whether NAFLD patients had major cardiovascular and cerebrovascular events(MACCE),they were divided into the MACCE group(n=30)and non-MACCE group(n=224).The clinical data among the groups were compared.The relationship between Gensini score and PCSK9 was analyzed by Pearson correlation analysis.The risk factors of MACCE risk were analyzed by Cox risk model,and the predictive value of PCSK9 on the occurrence of MACCE in elderly patients with NAFLD was analyzed by ROC curve.Results hs-CRP,PCSK9,TG,LDL-C,and Lp(a)increased in Group 1[5.79(4.17,7.81)mg/L,(329.17±50.26)ng/mL,(1.47±0.33)mmol/L,(2.69±0.52)mmol/L,(0.52±0.12)mg/L],Group 2[6.22(4.61,7.58)mg/L,(416.33±55.92)ng/mL,(1.65±0.36)mmol/L,(2.87±0.35)mmol/L,(0.63±0.09)mg/L],and Group 3[7.85(6.21,9.11)mg/L,(498.55±61.28)ng/mL,(1.86±0.24)mmol/L,(3.95±0.48)mmol/L,(0.70±0.11)mg/L]contrary to HDL-C[(1.46±0.25)mmol/L,(1.20±0.22)mmol/L,(1.06±0.27)mmol/L]].There were significant differences between the three groups(P<0.05);PCSK9 was positively correlated with Gensini score(r=0.657,P=0.000).The age,Gensini score,PCSK9 and LDL-C of the MACCE group[[(72.12±5.54)years,(86.27±5.03)points,(489.71±63.05)ng/mL,(2.88±0.79)mmol/L]were significantly higher than those of the non-MACCE group[(68.63±3.35)years,(61.09±4.52)points,(356.03±51.19)ng/mL,(2.52±0.77)mmol/L,all P<0.05].Multivariate Cox risk regression analysis showed that Gensini score and PCSK9 were independent risk factors for the risk of MACCE(P<0.05).The AUC of PCSK9 for predicting the occurrence of MACCE was 0.724,the sensitivity was 68.25%,and the specificity was 75.92%.Conclusion Serum PCSK9 is positively correlated with Gensini score in elderly patients with NAFLD,which could be used as a predictor of MACCE in patients.