Changes Of Lp(a) Levels And Its Correlation With Recurrent Vascular Events In Statin-treated Patients With Ischemic Stroke

Objectives: Statins either barely affect or increase lipoprotein(a)[Lp(a)] levels.This study aimed to explore the change of Lp(a)levels and its related factors as well as the relationship between Lp(a)and the recurrent vascular events in statin-treated patients with first acute ischemic stroke(AIS).Methods: Patients who were admitted to the Affiliated Hospital of Qingdao University with AIS from October 2018 to September 2020 were continuously screened according to the inclusion and exclusion criteria and included in a prospective cohort study.The following baseline data of the subjects were collected: age,gender,past histories(hypertension,diabetes mellitus,atrial fibrillation,coronary heart disease),smoking,drinking,laboratory tests(Lp(a),triglyceride,total cholesterol,low-density lipoprotein cholesterol [LDL-C],high-density lipoprotein cholesterol,fasting blood glucose,urea nitrogen,uric acid,creatinine,aspartate aminotransferase [AST],alanine aminotransferase,prothrombin time,activated partial thromboplastin time and D-Dimer),the National Institutes of Health Stroke Scale(NIHSS)score,the Trial of Org 10172 in Acute Stroke Treatment(TOSAT)classification and imaging examination.All eligible subjects were followed up.The blood lipid levels and endpoint events were recorded during the follow-up period.The end points of this study included AIS,transient ischemic attack(TIA),myocardial infarction(MI)and coronary revascularization.Compare the baseline and follow-up blood lipid levels of the subjects,and determine the relevant factors of the change of Lp(a)levels in stain-treated subjects through linear regression analysis.According to whether an endpoint event occurred during the follow-up period,the subjects were divided into an endpoint event group and a non-endpoint event group.Cumulative survival free of recurrent vascular events during follow-up were assessed using Kaplan–Meier survival analysis followed by the log rank test.Cox regression analysis were used to determine the associations between Lp(a)and recurrent vascular events.Results:1.In total,303 patients completed the follow-up.Their mean age was 64.26±11.38 years,211 cases(69.6%)were male and the median NIHSS score was 4 [interquartile range(IQR)1-6].Hypertension(221 cases,72.9%)and diabetes mellitus(114 cases,37.6%)were the most common vascular risk factors.2.The median baseline Lp(a)levels was 18.90 mg/d L(IQR 11.20-31.00 mg/d L)and the median follow-up Lp(a)levels was 19.00 mg/d L(IQR 10.95-34.2 mg/d L).The result of Spearman correlation analysis showed that there was a strong correlation between baseline and follow-up Lp(a)levels(Spearman correlation ρ: 0.824;P<0.001).During the followup period,Lp(a)levels increased in 153(50.5%)statin-treated patients and the mean percent change of Lp(a)levels was 14.48%(95% confidence interval [CI] 6.35%-22.61%).The result of multivariable linear regression analysis showed creatinine(β=0.152,95% CI0.125-0.791,P=0.007)and aspartate aminotransferase(AST)(β=0.160,95% CI 0.175-0.949,P=0.005)were positively associated with the percent change of Lp(a)levels.3.During a median follow-up of 26 months(IQR 18.0-33.0 months),66(21.8%)patients had a recurrent vascular event,including 61 AIS,1 TIA,2 MI and 2 coronary revascularizations.Kaplan-Meier survival curve showed that the rate of recurrent vascular events in patients with Lp(a)≥70 mg/d L was significantly higher than that in patients with Lp(a)<15 mg/d L(log rank P=0.037).Cox regression analysis showed that the on-statin Lp(a)levels ≥70 mg/d L(hazard ratio [HR] 2.539,95% CI 1.076-5.990,P=0.033)and the change of Lp(a)levels(HR per 10% increase in the change of Lp(a): 1.003,95% CI 1.000-1.005,P=0.033)were associated with the recurrent vascular events in statin-treated patients with first AIS after adjusting for confounding factors.4.The on-statin Lp(a)levels ≥70 mg/d L(HR 3.329,95%CI 1.106-10.015,P=0.032)and the change of Lp(a)levels(HR per 10% increase in the change of Lp(a): 1.029,95%CI1.002-1.057,P=0.034)were associated with the recurrent vascular events in AIS patients with large-artery atherosclerosis(LAA)after adjusting for age,gender and vascular risk factors.5.The on-statin Lp(a)levels ≥70 mg/d L increased the risk of recurrent vascular events in patients with LDL-C levels<1.8 mmol/L after adjusting for confounding factors(HR 3.612,95% CI 1.018-12.815,P=0.047).Conclusions:1.Creatinine and AST are associated with the change of Lp(a)levels in statin-treated patients with AIS.2.The on-statin Lp(a)level ≥70 mg/d L and the change of Lp(a)levels are associated with the recurrent vascular events in statin-treated patients with AIS.3.The correlation between Lp(a)level and recurrent vascular events may be more significant in AIS patients with LAA.4.Lp(a)is a determinant of residual vascular risk in AIS patients treated with statins.