Angiotensin 2 type 2 receptor activity and ischemic stroke severity

Background: Drugs that increase angiotensin 2 formation, including thiazides, calcium channel blockers, and angiotensin 2 type 1 (AT1) receptor blockers, may be more effective in stroke prevention than angiotensin 2 suppressive drugs such as angiotensin-converting enzyme inhibitors and β-blockers. Objective: To assess whether angiotensin 2 formation increasing drugs reduce incident stroke severity compared with angiotensin 2 formation suppressive drugs. Methods: Consecutive patients presenting within 24 hours of first-ever ischemic stroke over an 18-month period were studied. Subjects were only included if they were on only angiotensin 2 formation increasers, only angiotensin 2 formation suppressors, or no antihypertensive agents. NIH Stroke Scale (NIHSS) score at presentation was used as the index of stroke severity. Demographic data, risk factors, admission blood pressures, other medications, and stroke mechanisms were controlled for across the three groups using least absolute deviation linear regression. Results: One hundred seventy-five individuals met study criteria. Mean age was 67.4 years; 45% were women. Forty-nine patients were on angiotensin 2 formation suppressors and 16 on angiotensin 2 formation increasers. Age at admission, atrial fibrillation, previous antithrombotic use, cardioembolic and large-vessel atherosclerotic mechanisms, and mean systolic and diastolic blood pressure were significant univariate predictors of presenting median NIHSS score. On multivariate analysis, the adjusted median NIHSS score was lower in the angiotensin 2 increasers (median = 2.2; p = 0.005) and trended lower for angiotensin 2 suppressors (median = 4.4; p = 0.054) compared with the no-antihypertensive group (median = 6.0). There was no difference in stroke severity between angiotensin 2 increasers compared with angiotensin 2 suppressors (p = 0.123). Conclusions: Angiotensin 2 formation increasing agents did not reduce ischemic stroke severity more than angiotensin 2 formation suppressing agents. However, the prestroke use of antihypertensives was associated with reduced severity of incident ischemic strokes.

[1]  David C. Hess,et al.  Targets for Vascular Protection After Acute Ischemic Stroke , 2004, Stroke.

[2]  M. Müllner,et al.  Effect of pretreatment with statins on the severity of acute ischemic cerebrovascular events , 2004, Journal of the Neurological Sciences.

[3]  F. Messerli,et al.  Is the angiotensin ii type 2 receptor cerebroprotective? , 2004, Current hypertension reports.

[4]  F. Messerli,et al.  Cerebroprotection mediated by angiotensin II: a hypothesis supported by recent randomized clinical trials. , 2004, Journal of the American College of Cardiology.

[5]  K. Vemmos,et al.  Factors influencing acute blood pressure values in stroke subtypes , 2004, Journal of Human Hypertension.

[6]  J. Leonardi-Bee,et al.  Blood Pressure Reduction and Secondary Prevention of Stroke and Other Vascular Events: A Systematic Review , 2003, Stroke.

[7]  L. Vignolo,et al.  Volume Reduction in Cerebral Blood Flow in Patients with Alzheimer’s Disease: A Sonographic Study , 2003, Dementia and Geriatric Cognitive Disorders.

[8]  G. Donnan,et al.  Blood pressure reduction and ACE inhibition in secondary stroke prevention: mechanism uncertain. , 2003, Stroke.

[9]  R. Levine,et al.  Atrial Fibrillation Is Associated with Severe Acute Ischemic Stroke , 2003, Neuroepidemiology.

[10]  A. Tuttolomondo,et al.  Association between diabetes and stroke subtype on survival and functional outcome 3 months after stroke: data from the European BIOMED Stroke Project. , 2003, Stroke.

[11]  M. Sartori,et al.  Hypertension in acute ischemic stroke: a compensatory mechanism or an additional damaging factor? , 2003, Archives of internal medicine.

[12]  J. Broderick,et al.  Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial , 2002, Neurology.

[13]  H. Adams,et al.  Effect of Prior Aspirin Use on Stroke Severity in the Trial of Org 10172 in Acute Stroke Treatment (TOAST) , 2001, Stroke.

[14]  E. Schiffrin.  Effects of antihypertensive drugs on vascular remodeling: do they predict outcome in response to antihypertensive therapy? , 2001, Current opinion in nephrology and hypertension.

[15]  J. Alger,et al.  Impact on stroke subtype diagnosis of early diffusion-weighted magnetic resonance imaging and magnetic resonance angiography. , 2000, Stroke.

[16]  J. Marrugat,et al.  Timing for fever-related brain damage in acute ischemic stroke. , 1998, Stroke.

[17]  T. Olsen,et al.  The Copenhagen Stroke Study , 2007 .

[18]  G. Sette,et al.  Prediction of long-term outcome in the early hours following acute ischemic stroke , 1995 .

[19]  J. Lodder,et al.  Silent Brain Infarcts in 755 Consecutive Patients With a First‐Ever Supratentorial Ischemic Stroke: Relationship With Index‐Stroke Subtype, Vascular Risk Factors, and Mortality , 1994, Stroke.

[20]  J. Marler,et al.  Measurements of acute cerebral infarction: a clinical examination scale. , 1989, Stroke.

[21]  James N. Davis,et al.  Interrater reliability of the NIH stroke scale. , 1989, Archives of neurology.

[22]  C. Dickinson,et al.  Strokes and their relationship to hypertension. , 2003, Current opinion in nephrology and hypertension.

[23]  M. Safar,et al.  [New goals in hypertension management: target-organ protection beyond blood pressure lowering]. , 2003, Drugs.

[24]  P. Gorelick,et al.  Are cholesterol-lowering medications and antihypertensive agents preventing stroke in ways other than by controlling the risk factor? , 2003, Current atherosclerosis reports.

[25]  L. Hansson.  The Hypertension Optimal Treatment study and the importance of lowering blood pressure. , 1999, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[26]  P. Gorelick.  Stroke prevention: windows of opportunity and failed expectations? A discussion of modifiable cardiovascular risk factors and a prevention proposal. , 1997, Neuroepidemiology.

[27]  G. Sette,et al.  Prediction of long-term outcome in the early hours following acute ischemic stroke. Italian Acute Stroke Study Group. , 1995, Archives of neurology.