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

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(1)R) density in target tissues. We have recently shown that AT(1)R 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(1)R density on blood platelets (a presumable marker of cardiovascular AT(1)R 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(1)R density above median (N=17) as compared to those with AT(1)R 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(1)R 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(1)R groups: over 85% patients received ACE-inhibitor, beta-blocker and statin. CONCLUSIONS: High AT(1)R density on blood platelets (a presumable marker of cardiovascular AT(1)R 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.

Angiotensin II AT1 receptor density on blood platelets predicts early left ventricular remodelling in non-reperfused acute myocardial infarction in humans.

BACKGROUND: Renin-angiotensin-system activity, a principal factor determining ventricular remodelling after myocardial infarction (MI), is dependent on local angiotensin II concentration and angiotensin AT1 receptor (AT1R) density. The latter is regulated by systemic factors acting independently from angiotensin II concentration. OBJECTIVE: To test the hypothesis that AT1R density at the onset of MI determines post-MI ventricular remodelling. METHODS: In 48 patients with first acute MI who did not undergo reperfusion therapy, angiotensin AT1R density on blood platelets (reflecting cardiovascular AT1R density) was assessed 13+/-5 h after the onset of MI, using radioligand binding assay. Left ventricular end-systolic (LVESVI) and end-diastolic volume indices (LVEDVI) and ejection fraction (EF) were assessed by two-dimensional echocardiography as measures of ventricular remodelling. RESULTS: Predischarge LVESVI and LVEDVI positively and EF negatively correlated with AT1R density. Patients with AT1R density below median had significantly lower LVESVI (33.2+/-2.4 mL/m2), LVEDVI (70.0+/-2.8 mL/m2) and higher EF (52.8+/-2.3%) than patients with AT1R density above median (LVESVI = 44.9+/-2.6, LVEDVI = 81.3+/-3.9 mL/m2 and EF = 44.9+/-2.6%, all p<0.01). In multivariate analysis, only AT1R density and infarct size were independent predictors of early post-MI ventricular dilation. CONCLUSIONS: High density of AT1R at the onset of MI is a predictor of early left ventricular remodelling.