Angiotensin-converting Enzyme Inhibitor Use is Associated with Reduced Plasma Concentration of C-reactive Protein in Patients with First-ever Ischemic Stroke

Background And Purpose: High levels of C-reactive protein (CRP) are associated with an increased risk of future cardiovascular events in ischemic stroke. It has been hypothesized that the benefit of angiotensin-converting enzyme (ACE) inhibitors in patients at high vascular risk may also result from their anti-inflammatory action. Data evaluating this hypothesis are limited in ischemic stroke.

Methods: We conducted a prospective observational study in 507 patients with first-ever ischemic stroke to analyze the effect of ACE inhibitor treatment at the time of stroke onset on CRP levels within the first 24 hours and the relationship to outcome. Risk estimates were calculated according to Cox regression analysis controlled for blood pressure (BP) levels, clinical and neuroradiological confounding variables, and log-normalized CRP levels at entry.

Results: ACE inhibitor treatment was associated with lower (2.6-fold; P<0.0001) median CRP levels and with a reduced 2-year cardiovascular risk (hazard ratio, 0.39; 95% CI, 0.29 to 0.53; P<0.0001) compared with a different BP-lowering regimen. The relationship between ACE inhibitor status and log-normalized CRP levels remained significant (P<0.0001) after we controlled for important confounding variables and concomitant treatments. The reduced risk was also evident in multivariable analysis when ACE inhibitor treatment was controlled for BP, associated risk factors, neuroradiological findings, and concomitant treatments (hazard ratio, 0.43; 95% CI, 0.30 to 0.62; P<0.0001). This risk reduction was greatly attenuated and not more significant when log-normalized CRP levels were included (hazard ratio, 0.67; 95% CI, 0.43 to 1.04; P=0.0721) in the model.

Conclusions: Concomitant treatment with ACE inhibitor at the time of an acute stroke is associated with lower inflammatory response and better long-term outcomes, apparently apart from the effects on BP.