Association Between Mean Arterial Pressure Fluctuation And Pulse Pressure Fluctuation With Poor Prognosis Of Ischemic Stroke

BackgroundCurrently,stroke remains the second leading cause of death and the leading cause of disability worldwide,which is the major global public health problem.Stroke also causes a huge disease burden in China.In 2019,there were about 3.94 million new stroke cases,which not only has a serious impact on the quality of life for patients and their families,but also causes a huge social and economic burden.Ischemic stroke accounts for more than 70%of new stroke cases.About 80%of patients with ischemic stroke are often accompanied by hypertension or elevated blood pressure,so the management of blood pressure in the acute stage of ischemic stroke is particularly important.Mean arterial pressure and pulse pressure are important arterial pressure indicators,which have been considered as risk markers for poor prognosis of ischemic stroke in past studies.Blood pressure fluctuation is an important indicator of ambulatory blood pressure and may be associated with poor prognosis after ischemic stroke.It is inferred that the mean arterial pressure fluctuation and pulse pressure fluctuation during hospitalization may affect the prognosis of ischemic stroke.Currently,there are few studies on the relationship between mean arterial pressure fluctuation and pulse pressure fluctuation and the prognosis of ischemic stroke during hospitalization,and they belong to small sample size studies,so large sample size prospective studies are needed for further verification.Based on the Chinese Acute Ischemic Stroke Blood pressure Lowering Test(C ATIS),this study used prospective cohort study methods to investigate the association between mean arterial pressure fluctuation and pulse pressure fluctuation during hospitalization and the clinical outcome at 3 months after ischemic stroke.ObjectiveTo investigate the independent effects of mean arterial pressure fluctuations and pulse pressure fluctuations during hospitalization on composite outcomes of death or severe disability,severe disability,death and vascular events at 3 months after stroke in patients with ischemic stroke,so as to provide a scientific basis for guiding the blood pressure management of patients with ischemic stroke during hospitalization and further predicting the poor prognosis for patients with ischemic stroke.Subjects and MethodsIn this study,ischemic stroke patients who completed blood pressure measurement during hospitalization and 3-month follow-up in the CATIS trial were selected.mean arterial pressure fluctuation during hospitalization was reflected by 2 parameters:Standard deviation of mean arterial pressure(MAP-SD)and difference between the maximum and minimum values of the mean arterial pressure(MAP-DMM).pulse pressure fluctuation during hospitalization was reflected by 2 parameters:Standard deviation of pulse pressure(PP-SD)and difference between the maximum and minimum values of the pulse pressure(PP-DMM).Demographic characteristics,ischemic stroke subtypes,and previous disease history were collected from all patients upon admission.Face-to-face follow-up was performed at 3 months after the onset of the disease.The modified Rankin Scale(mRS)score was completed,and death and vascular events were recorded.Study outcomes included the composite outcome of death or major disability(mRS Score 3-6),major disability,death and vascular events.Multivariate logistic regression model or COX proportional risk model were used to analyze the relationship between mean arterial pressure and pulse pressure fluctuation and study outcomes during hospitalization.Multifactor ordered logistic regression model was used to analyze the relationship between mean arterial pressure fluctuation and pulse pressure fluctuation during hospitalization and mRS scores at 3 months after ischemic stroke.Odds ratios(OR)or hazard ratios(HR)and 95%confidence intervals(CI)were calculated.Restricted cubic splines were used to assess the dose-response relationship between mean arterial pressure fluctuation and pulse pressure fluctuation and adverse ischemic stroke outcomes during hospitalization.Kaplan-Meier method was used to plot the cumulative outcome incidence curve of each group,and Log-rank test was used for comparison.We calculated the integrated discrimination improvement(IDI)and net reclassification index(NRI)to evaluate the value of adding mean arterial pressure fluctuation and pulse pressure fluctuation during hospitalization to the traditional model in predicting the outcome of ischemic stroke.In addition.we performed a subgroup analysis,dividing subjects into subgroups based on age(<65 vs≥65 years),smoking,alcohol consumption,history of hypertension,history of diabetes.dyslipidemia,time from onset to admission(<12 vs≥12 hours),and randomized antihypertensive intervention(antihypertensive vs control).The relationship between mean arterial pressure fluctuation and pulse pressure fluctuation during hospitalization and primary study outcomes(composite outcomes of death or severe disability)was analyzed separately.ResultRelationship between mean arterial pressure fluctuation during hospitalization with the prognosis of ischemic strokeAfter 3 months of follow-up,1000 patients experienced death or major disability(122 deaths and 878 major disabilities,respectively),and 182 experienced vascular events.The multivariable adjusted ORs or HR(95%CIs)associated with MAP-SD was 1.39(1.10-1.75)for primary outcome,1.24(1.08-1.57)for major disability and 1.96(1.12-3.41)for death,when comparing two extreme MAP-SD quartiles.The multivariable adjusted ORs or HRs(95%CIs)for the highest quartile vs lowest quartile of MAP-DMM was 1.43(1.13-1.80)for primary outcome,1.28(1.08-1.63)for major disability and 1.830(1.07-3.13)for death.Multivariable adjusted spline regression models showed a linear association of both MAPSD and MAP-DMM with composite outcome of death or major disability,major disability and death(Both Plinearity<0.05).The log-rank test showed that the cumulative death rate of the other three groups increased when the subjects in the lowest quartile MAP-SD were taken as the control group(Log-rank P=0.001).With the lowest quartile MAP-DMM as the control group,the cumulative incidence of death and the incidence of vascular events increased in the other three groups(log-rank P=0.024;Log-rank P=0.047),the differences were statistically significant.Adding MAP-SD to conventional risk factors improved the risk prediction for primary outcome,major disability and death at 3 months after ischemic stroke onset(All P<0.05),and adding MAP-DMM to conventional risk factors improved the risk prediction for primary outcome and major disability(All P<0.05).Relationship between pulse pressure fluctuation during hospitalization with the prognosis of ischemic strokeAfter 3 months of follow-up,1000 patients experienced death or major disability(122 deaths and 878 major disabilities,respectively),and 182 experienced vascular events.The multivariable adjusted HRs(95%CIs)associated with PP-SD was(1.37-4.42)for death and 1.86(1.01-3.42)for vascular events,when comparing two extreme PP-SD quartiles(Logrank P=0.024;Log-rank P<0.001).Multivariable adjusted spline regression models showed a linear association of PP-SD with death and vascular events(Both Plinearity<0.05).The multivariable adjusted HRs(95%CIs)for the highest quartile vs lowest quartile of PP-DMM was 1.81(1.02-3.21)for death(Log-rank P=0.024).Conclusions1.Large mean arterial pressure fluctuation during hospitalization was associated with a linear dose-response relationship with an increased risk of death or major disability,major disability and death at 3 months after ischemic stroke,and was an independent risk factor for death or major disability,major disability and death.After adding mean arterial pressure fluctuation to conventional risk factors,the risk prediction for 3-month death or major disability,major disability and death after ischemic stroke onset was improved in those patients.2.Large pulse pressure fluctuation during hospitalization was associated with an increased risk of death and vascular events at 3 months after ischemic stroke in a linear doseresponse relationship,and was independent risk factors for death and vascular events.