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 (AT(1)) receptor blockers, may be more effective in stroke prevention than angiotensin 2 suppressive drugs such as angiotensin-converting enzyme inhibitors and beta-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.