| Part One The association between non-traditional lipid parameters and cerebral atherosclerotic stenosisBackground and objective: Cerebral atherosclerotic stenosis(CAS)is an important cause of the occurrence and recurrence of ischemic stroke,so early identification and active treatment of CAS can help prevent ischemic stroke.Dyslipidemia is an important risk factor for CAS and serum low-density lipoprotein cholesterol(LDL-C)level is the primary intervention target of current blood lipid management for CAS.However,studies have shown that despite aggressively lowering serum LDL-C levels,the risk of carotid atherosclerotic stenosis progression remains high,and the progression of carotid atherosclerotic stenosis is independently associated with the increased levels of serum triglyceride(TG).Thus,lipid parameters that are more sensitive to CAS than serum LDL-C levels are needed to guide the treatment of CAS.Previous studies have demonstrated that non-traditional lipid parameters are more associated with coronary atherosclerotic disease than serum LDL-C levels.However,the role of non-traditional lipid parameters in CAS remains unclear.Therefore,this part of our study aimed to investigate the association between non-traditional lipid parameters and CAS and to compare the predictive ability of non-traditional lipid parameters and serum LDL-C levels for CAS,hoping to find more sensitive lipid parameters to guide the treatment of CAS.Methods: This was a cross-sectional study based on the 2016-2017 "High-risk Stroke Population Screening and Intervention Program" in Dehui City,Jilin Province,using carotid ultrasound and transcranial Doppler ultrasound for cerebrovascular examinations in 4100 general residents aged ?40 years.According to the different involvement of intracranial and extracranial arteries,CAS was divided into isolated extracranial atherosclerotic stenosis(ECAS),isolated intracranial atherosclerotic stenosis(ICAS),and intracranial and extracranial atherosclerotic stenosis(ECAS+ICAS).Non-traditional lipid parameters were calculated according to serum total cholesterol(TC),TG,LDL-C,and high-density lipoprotein cholesterol(HDL-C)levels,including non-high-density lipoprotein cholesterol(non-HDL-C),TC/HDL-C,TG/HDL-C,and LDL-C/HDL-C.Multivariate logistic regression analyses and receiver operating characteristic(ROC)curves were used to assess the association between non-traditional lipid parameters and isolated ECAS and isolated ICAS.Results: This part of our study finally included 3624 subjects for analysis,of which 80(2.2%)had isolated ECAS,425(11.7%)had isolated ICAS,and 70(1.9%)had ECAS+ICAS.For isolated ECAS,when non-traditional lipid parameters were included as continuous variables,multivariate logistic regression analyses show that serum non-HDL-C(OR=1.256,95% CI: 1.066-1.480),TC/HDL-C(OR=1.260,95% CI: 1.112-1.427),and TG/HDL-C(OR=1.106,95% CI: 1.038-1.179)levels were positively associated with the risk of isolated ECAS,while serum LDL-C/HDL-C levels(OR=1.343,95% CI: 0.973-1.852)were not associated with the occurrence of isolated ECAS.When non-traditional lipid parameters were included as tertiles,multivariate logistic regression analyses show that serum non-HDL-C,TC/HDL-C,TG/HDL-C,and LDL-C/HDL-C levels were positively associated with the risk of isolated ECAS.ROC curves show that serum non-HDL-C(AUC=0.621,95% CI: 0.560-0.682),TC/HDL-C(AUC=0.639,95% CI: 0.573-0.704),TG/HDL-C(AUC= 0.622,95% CI: 0.564-0.680),and LDL-C/HDL-C(AUC=0.577,95% CI: 0.523-0.630)levels had predictive ability for isolated ECAS,and serum non-HDL-C and TC/HDL-C levels were better than serum LDL-C levels(AUC=0.547,95% CI: 0.489-0.605)in predicting isolated ECAS.For isolated ICAS,regardless of whether non-traditional lipid parameters were included as continuous variables or tertiles,multivariate logistic regression analyses show that serum non-HDL-C,TC/HDL-C,TG/HDL-C,and LDL-C/ HDL-C levels were not associated with the occurrence of isolated ICAS.ROC curves show that serum LDL-C/HDL-C levels(AUC=0.541,95% CI: 0.512-0.570)were able to predict isolated ICAS,while serum non-HDL-C(AUC=0.524,95% CI: 0.494-0.555),TC/HDL-C(AUC=0.526,95% CI: 0.496-0.556),and TG/HDL-C(AUC=0.487,95% CI: 0.457-0.516)levels had no predictive ability for isolated ICAS.However,the predictive ability of serum non-HDL-C,TC/HDL-C,TG/HDL-C,and LDL-C/HDL-C levels for isolated ICAS was not significantly different from that of serum LDL-C levels.Conclusions: Serum non-HDL-C,TC/HDL-C,TG/HDL-C,and LDL-C/HDL-C levels were positively associated with the risk of isolated ECAS,but were not associated with the occurrence of isolated ICAS.And compared with serum LDL-C levels,serum non-HDL-C and TC/HDL-C levels had a better predictive ability for the occurrence of isolated ECAS.Part Two The association between non-traditional lipid parameters and ischemic strokeBackground and objective: Dyslipidemia is an important risk factor for ischemic stroke and serum LDL-C level is the primary intervention target of current blood lipid management for the prevention of ischemic stroke.However,previous studies have shown that patients with ischemic stroke or transient ischemic attack,despite aggressively lowering serum LDL-C levels,still have a high residual risk of cardiovascular events,and this residual risk is associated with other blood lipid parameters.Therefore,lipid parameters that are more sensitive to the risk of ischemic stroke than serum LDL-C levels are needed to guide the prevention of ischemic stroke.Increasing numbers of studies have found that non-traditional lipid parameters are more associated with cardiovascular events than serum LDL-C levels.However,the association between non-traditional lipid parameters and ischemic stroke remains controversial.Thus,this part of our study aimed to investigate the association between non-traditional lipid parameters and ischemic stroke and to compare the predictive ability of non-traditional lipid parameters and serum LDL-C levels for ischemic stroke,hoping to find more sensitive lipid parameters to guide the prevention of ischemic stroke.Methods: This was a population-based cross-sectional study,and the participants of the 2016-2017 "High-risk Stroke Population Screening and Intervention Program" in Dehui City,Jilin Province were selected as the research objects.Non-traditional lipid parameters included non-HDL-C,TC/HDL-C,TG/HDL-C,and LDL-C/HDL-C.Ischemic stroke was diagnosed based on the medical documents or imaging data provided by participants.Multivariate logistic regression analyses and ROC curves were used to investigate the association between non-traditional lipid parameters and ischemic stroke.Results: A total of 4,025 subjects were included in this part of our study,of which 265(6.6%)had an ischemic stroke.ROC curves show that serum non-HDL-C(AUC=0.553,95% CI: 0.518-0.588),TC/HDL-C(AUC=0.571,95% CI: 0.537-0.605),and TG/HDL-C(AUC= 0.558,95% CI: 0.525-0.591)levels,but not serum LDL-C/HDL-C levels(AUC=0.533,95% CI: 0.500-0.566),had predictive ability for ischemic stroke,and serum TC/HDL-C levels were better than serum LDL-C levels(AUC=0.515,95% CI: 0.480-0.550)in predicting ischemic stroke.When non-traditional lipid parameters were included as tertiles,multivariate logistic regression analyses show that serum TC/HDL-C and TG/HDL-C levels were positively associated with the risk of ischemic stroke,while serum non-HDL-C and LDL-C/HDL-C levels were not associated with the occurrence of ischemic stroke.When non-traditional lipid parameters were divided into binary variables according to their optimum cut-off points for predicting ischemic stroke,multivariate logistic regression analyses show that serum non-HDL-C levels ?4.12(OR=1.393,95% CI: 1.059-1.833),TC/HDL-C levels ?4.14(OR=1.451,95% CI: 1.087-1.935),and TG/HDL-C levels ?1.13(OR=1.492,95% CI: 1.095-2.035)were independently associated with the occurrence of ischemic stroke,while serum LDL-C/HDL-C levels ? 1.46(OR=1.211,95% CI: 0.908-1.615)were not associated with the occurrence of ischemic stroke.Conclusions: Serum non-HDL-C,TC/HDL-C,and TG/HDL-C levels were positively associated with the risk of ischemic stroke,while serum LDL-C/HDL-C levels were not associated with the occurrence of ischemic stroke.And compared with serum LDL-C levels,serum TC/HDL-C levels had a better predictive ability for ischemic stroke.Part Three The association between non-traditional lipid parameters and hemorrhagic transformation and clinical outcome after thrombolysis in ischemic strokeBackground and objective: Although many studies have found that non-traditional blood lipid parameters were closely associated with the occurrence of ischemic stroke,the role of non-traditional blood lipid parameters in acute ischemic stroke is not clear.Understanding the role of non-traditional lipid parameters in acute ischemic stroke helps guide the management of blood lipids in the acute phase of ischemic stroke.Hence,this part of our study aimed to investigate the association between non-traditional lipid parameters and hemorrhagic transformation after thrombolysis and clinical outcome in patients with ischemic stroke.Methods: This part of our study consecutively included ischemic stroke patients who received intravenous thrombolysis with alteplase at the First Hospital of Jilin University from April 2015 to December 2018.Blood lipid levels were measured in a fasting state within 24 hours of admission.Non-traditional lipid parameters included non-HDL-C,TC/HDL-C,TG/HDL-C,and LDL-C/HDL-C.Hemorrhagic transformation after thrombolysis was defined as intraparenchymal or subarachnoid hemorrhage on brain CT/MRI 24 hours after thrombolysis.Clinical outcome was evaluated at 3 months of onset using the modified Rankin Scale(m RS)and m RS scores ?3 were defined as poor outcome.ROC curves and multivariate logistic regression analyses were used to investigate the association between non-traditional lipid parameters and hemorrhagic transformation after thrombolysis and poor outcome.Results: This part of our study included a total of 763 ischemic stroke patients treated with intravenous thrombolysis.Of which,78(10.2%)had hemorrhagic transformation after thrombolysis and 281(36.8%)had poor outcome.For hemorrhagic transformation after thrombolysis,ROC curves show that serum TC/HDL-C(AUC=0.580,95% CI: 0.513-0.646),TG/HDL-C(AUC=0.599,95% CI: 0.532-0.666),and LDL-C/HDL-C(AUC= 0.581,95% CI: 0.517-0.645)levels,but not serum non-HDL-C levels(AUC=0.527,95% CI: 0.461-0.593),were able to predict hemorrhagic transformation after thrombolysis.When non-traditional lipid parameters were divided into binary variables according to their optimum cut-off points for predicting hemorrhagic transformation after thrombolysis,multivariate logistic regression analyses show that serum TC/HDL-C levels <4.05(OR=1.727,95% CI: 1.008-2.960),TG/HDL-C levels <0.82(OR=2.064,95% CI: 1.241-3.432),and LDL-C/HDL-C levels <2.67(OR=1.935,95% CI: 1.070-3.501)were independently associated with the occurrence of hemorrhagic transformation after thrombolysis,while serum non-HDL-C levels <2.99(OR =0.990,95% CI: 0.583-1.680)were not associated with the occurrence of hemorrhagic transformation after thrombolysis in patients with ischemic stroke.For poor outcome,ROC curves show that serum TC/HDL-C(AUC=0.555,95% CI: 0.513-0.597),TG/HDL-C(AUC=0.567,95% CI: 0.524-0.609),and LDL-C/HDL-C(AUC= 0.553,95% CI: 0.511-0.595)levels,but not serum non-HDL-C levels(AUC=0.521,95% CI: 0.479-0.564),had predictive ability for poor outcome.When non-traditional lipid parameters were divided into binary variables according to their optimum cut-off points for predicting poor outcome,multivariate logistic regression analyses show that serum non-HDL-C levels <2.01(OR=2.340,95% CI: 1.150-4.764),TC/HDL-C levels <3.66(OR=1.423,95% CI: 1.025-1.977),TG/HDL-C levels <1.02(OR=1.539,95% CI: 1.102-2.151),and LDL-C/HDL-C levels <2.71(OR=1.608,95% CI: 1.133-2.283)were independently associated with the occurrence of poor outcome in ischemic stroke patients with intravenous thrombolysis.Conclusion:(1)Serum TC/HDL-C,TG/HDL-C,and LDL-C/HDL-C levels were negatively associated with the risk of hemorrhagic transformation after thrombolysis,while serum non-HDL-C levels were not associated with the occurrence of hemorrhagic transformation after thrombolysis in patients with ischemic stroke.(2)Serum non-HDL-C,TC/HDL-C,TG/HDL-C,and LDL-C/HDL-C levels were negatively associated with the risk of poor outcome in ischemic stroke patients with intravenous thrombolysis. |
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