Late ventricular remodeling in non-reperfused acute myocardial infarction in humans is predicted by angiotensin II type 1 receptor density on blood platelets

Abstract

Background Ventricular remodeling after myocardial infarction (MI) is largely dependent on renin–angiotensin system activity, which is determined by angiotensin II concentration and angiotensin II type 1 receptor (AT 1R) density in target tissues. We have recently shown that AT 1R density in the acute phase of MI determines post-MI ventricular remodeling at discharge (8 days). The aim of this study was to test whether this correlation is retained in a longer follow-up (6 months), in the same group of patients. Methods In 48 patients with first acute MI who did not undergo reperfusion therapy, angiotensin AT 1R density on blood platelets (a presumable marker of cardiovascular AT 1R density) was assessed 13 ± 5 h after the onset of MI, using radioligand binding assay. Echocardiographic indices of left ventricular function and dimensions were used as measures of ventricular remodeling. Results 6 months after the infarction patients who at baseline had AT 1R density above median ( N = 17) as compared to those with AT 1R density below median ( N = 20) had higher left ventricular end-systolic volume index (LVESVI, 41.3 ± 2.7 vs. 33.2 ± 2.3) and lower ejection fraction (LVEF 48.1 ± 1.8 vs. 54.7 ± 2.0). Moreover LVESVI positively and LVEF negatively correlated with AT 1R density although the strength of these correlations was weaker than at discharge. Infarct size as reflected by a single troponin T measurement and post-MI therapy did not differ between high- and low-AT 1R groups: over 85% patients received ACE-inhibitor, β-blocker and statin. Conclusions High AT 1R density on blood platelets (a presumable marker of cardiovascular AT 1R density) drawn in the acute phase of MI predicts poorer left ventricular systolic function in 6-month follow up. This suggests that modern therapy offers suboptimal blockade of renin–angiotensin system activity in the setting of MI.