Abstract TP115: The Increase In Plasma Angiotensinogen Is Associated With The Reduction Of Neurological Severity In Ischemic Stroke

Abstract

Background and Purpose: Activation of the renin-angiotensin system (RAS) is a crucial factor leading to the development of hypertension and atherosclerosis, thereby causing brain infarction. However, the significance of RAS in the acute phase of brain infarction has not been fully understood. Our goal was to elucidate the significance of RAS in the acute phase of ischemic stroke. Methods: We measured plasma angiotensinogen (AGTN), angiotensin-converting enzyme (ACE) and some associated biomarkers, and examined clinical information in 171 ischemic stroke patients at 5 time points (days 0, 3, 7, 14 and 90) after the onset and 171 age- and gender-matched healthy subjects. Results: plasma AGTN values were increased in all stroke subtypes with different profiles in the acute phase of brain infarction: they were continuously elevated in atherothrombotic brain infarction, while they fluctuated in cardioembolic and lacunar infarction. On the other hand, plasma ACE values remained decreased from the onset to the 90 day in all subtypes, suggesting that the final product Angiotensin II (Ang II) was increased in the plasma and suppressed the production of ACE in a feedback mechanism during the period. AGTN values were not significantly associated with blood pressure. Among the biomarkers we tested, AGTN was highly associated with adrenocorticotropic hormone (ACTH) (r = 0.62, p < 0.0001), but not with other pituitary hormones and inflammatory cytokines (IL-1b, IL-6 and TNFa). Neurological severity assessed by NIH Stroke Scale at day 0 was associated negatively with the AGTN values, while positively with ACE. Conclusions: Ang II production may be increased in the acute phase of brain infarction with decreased plasma ACE in all subtypes and different profiles of AGTN according to stroke subtypes. Increased production of AGTN leading to the increase in Ang II appears to be associated with the reduction of neurological severity in ischemic stroke.