Impact Of Beta-blockers And Angiotensin-converting Enzyme Inhibitors/angiotensin Receptor Blockers On Systemic Immune Response And Outcomes In Patients With Acute Ischemic Stroke

ObjectiveChanges in the activation of sympathetic neurous system induced by ischemic stroke have a profound influence on systemic immune response in patients with acute ischemic stroke.Although previous studies have illustrated the antagonistic efficacy of beta-blockers and angiotensin-converting enzyme inhibitors(ACEIs)/angiotensin receptor blockers(ARBs)on the activation of sympathetic neurous system under stress conditions,no study has investigated the influence of pre-stroke use of beta-blockers or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on systemic immune response in patients with acute ischemic stroke.This study was designed to observe the impact of pre-stroke use of beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on systemic immune response and outcomes of patients with acute ischemic stroke.MethodThe medical records of 1211 patients with acute ischemic stroke were reviewed in the Fifth Affiliated Hospital of Zhengzhou University from January 1,2013 to October 31,2018.We retrospectively collected the clinical data of 69 patients with pre-stroke use of beta-blockers and 56 patients with pre-stroke use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers.We also consecutively selected 107 patients with acute ischemic stroke who meet the eligibility criteria as matched controls and 45 healthy peoples as healthy controls.The frequency of the circulating white blood cell subpopulations on day 1 after symptom onset was collected according to the medical records.National Institute of Health stroke scale(NIHSS)score was used to evaluate the neurologic deficits on admission.A modified Rankin scale(mRS)score of>3 on day 90 was used as a measure for the poor functional outcomes.The volume of infarct was calculated by ABC/2 method.We evaluate the impact of pre-stroke use of beta-blockers or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on the circulating white blood cell subpopulations and neurological functions of patients with ischemic stroke on day 90.Results1.The count of circulating neutrophil and NLR of patients.in the matched controls were significantly greater than that in the healthy controls.However,the frequency of lymphocytes in the peripheral blood and LMR were significantly lower than that in the healthy controls.2.Compared to matched controls,beta-blockers only significantly increased the absolute count of circulating lymphocytes and LMR;we did not find the differences in the frequency of immunocyte subpopulations between patients with pre-stroke use of ACEIs/ARBs and matched controls.3.The frequency of lymphocytes in the peripheral blood and LMR of ACS patients with pre-stroke use beta-blockers was significantly greater than that in the matched controls.LMR of PCS patients with pre-stroke use ACEIs/ARBs was significantly greater than that in the matched controls.However,no differences in the count of immunocyte subpopulations of ACS patients and PCS patients were found between patients with pre-stroke use of ACEIs/ARBs and matched controls.4.Patients with pre-use of beta-blockers and matched controls were dichotomized by modified Rankin Scale(mRS)as having a favorable outcome(mRS=0-3)or unfavorable outcome(mRS=4-6)on day 90 after ischemic stroke.The patients with favorable outcomes were significantly younger than patients with an unfavorable outcome.The infection rate while in hospital,NIHSS score and infarct volume of patients with favorable outcomes were significantly lower than that of patients with unfavorable outcomes.The higher NIHSS scores on admission and larger infarct volume on admission were independently associated with poor functional outcomes on day 90 after ischemic stroke onset.We did not find the influence of pre-stroke use of beta-blockers on functional outcomes on day 90 after ischemic stroke onset.Additionally,patients with pre-use of ACEIs/ARBs and matched controls were also dichotomized by modified Rankin Scale(mRS)as having a favorable outcome or unfavorable outcome on day 90 after ischemic stroke.The patients with favorable outcomes were also significantly younger than patients with unfavorable outcomes.The infection rate,NIHSS score and infarct volume of patients with favorable outcomes were also significantly lower than patients with unfavorable outcomes.The infection while in hospital,the higher NIHSS scores on admission and larger infarct volume were independently associated with poor functional outcomes on day 90 after ischemic stroke onset.Pre-stroke use of ACEIs/ARBs had no impact on functional outcomes on day 90 after ischemic stroke onset.Conclusion1.Obvious changes in the cellular immune system of patients with acute ischemic stroke when compared with healthy controls.2.Pre-stroke use of beta-blockers reversed lymphopenia and LMR caused by acute ischemic stroke.Pre-stroke use of ACEIs/ARBs did not influence the frequency of the subpopulations of circulating white blood cells in patients with acute ischemic stroke.3.Lesion location may have no influence on the frequency of peripheral immunocyte subpopulations in patients with pre-stroke use of beta-blockers or ACEIs/ARBs.4.The higher NIHSS scores and larger infarct volume were independently associated with poor functional outcomes on day 90 after ischemic stroke onset.Pre-stroke use of beta-blockers or ACEIs/ARBs had no impact on functional outcomes on day 90 after ischemic stroke.