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

Abstract

Background: Renin -angiotensin-system activity, a principal factor determining ventricular remodelling after myocardial infarction (MI), is dependant on local angiotensin II concentration and angiotensin AT 1 receptor (AT 1 R) density. The latter is regulated by systemic factors acting independently from angiotensin II concentration. Objective: To test the hypothesis that AT 1 R 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 AT 1 R density on blood platelets (reflecting cardiovascular AT 1 R density) was assessed 13 T 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 AT 1 R density. Patients with AT 1 R density below median had significantly lower LVESVI (33.2 T 2.4 mL/m 2 ), LVEDVI (70.0 T 2.8 mL/m 2 ) and higher EF (52.8 T 2.3%) than patients with AT 1 R density above median (LVESVI = 44.9 T 2.6, LVEDVI = 81.3 T 3.9 mL/m 2 and EF = 44.9 T 2.6%, all p < 0.01). In multivariate analysis, only AT 1 R density and infarct size were independent predictors of early post-MI ventricular dilation. Conclusions: High density of AT 1 R at the onset of MI is a predictor of early left ventricular remodelling.

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

“…In the previous study we showed that high AT 1 R density on blood platelets drawn on average within 13 h from the onset of myocardial infarction was a strong and independent predictor of early remodeling (pre-discharge day 8 echocardiography) [7]. Now we extend these observations by showing that this effect is retained after 6 months.…”

“…Since LVESVI and EF are indices of systolic function, while LVEDVI is rather an index of dilation, this would suggest that AT 1 R density is a better predictor of post-MI function than post-MI dilation, although larger studies are needed to support this conclusion. Additionally correlation coefficients at 6 months were significantly poorer than 8 days after the infarction [7]. This indicates that AT 1 R density is a strong predictor of ventricular remodeling after myocardial infarction but strength of this effect decreases over time.…”

“…This was the same group of patients as reported previously [7]. Exclusion criteria were: age N 80 years, arterial hypertension, history of myocardial infarction, history of heart failure, ventricular hypertrophy on echocardiography or ECG, cardiomyopathy, significant valvular disease, unstable clinical condition, and treatment with ACE inhibitors, AT 1 R blockers, steroids or hypolipemic drugs within 6 months prior to enrollment.…”

“…We have recently shown that AT 1 R density on blood platelets, a presumable marker of systemic, including cardiovascular, AT 1 R density, is a predictor of early remodeling (ventricular dilation and systolic dysfunction) measured within 8 days in patients with first myocardial infarction [7]. In this paper we investigated whether these changes are retained in a prolonged follow-up in the same group of patients.…”

Left ventricular remodeling in the post-infarction heart: a review of cellular, molecular mechanisms, and therapeutic modalities

“…Angiotensin II receptor 2 (AT2R) is thought to cause opposite effects of AT1R. In post-myocardial infarction patients, a higher density of AT-1 receptor density, as detected on blood platelets, may confer a greater risk of undergoing ventricular remodeling for up to 6 months after an infarction [17,18].…”