Predictors of systemic endothelial recovery post-acute myocardial infarction: a 6 month follow-up of the FLARE-ACS study
G Zormpas, A Samaras, A Boulmpou, V Potoupni, N Chatzipapa, K Tsioni, N Fragakis, M Doumas, G Kassimis, V Vassilikos, C PapadopoulosAbstract
Background
Acute myocardial infarction (AMI) is a leading cause of global morbidity and mortality, closely correlated with high atherosclerosis burden and systemic endothelial dysfunction. While flow mediated dilation (FMD) is a validated prognostic marker for cardiovascular events, the drivers of endothelial recovery post-AMI still remain underexplored. It is currently unclear whether systemic endothelial repair is limited by the basic metabolic profile, coronary anatomical complexity, or intrinsic hemodynamic mechanisms.
Purpose
Our aim was to identify the independent clinical, metabolic, and hemodynamic predictors of the relative change in endothelial function, measured via brachial artery FMD, from the acute phase of AMI to a 6-month follow-up.
Methods
This sub-analysis of the prospective, single-center FLARE-ACS trial evaluated endothelial function via brachial artery FMD in patients with AMI during the acute phase (within 4 days) and at 6 months. The primary endpoint was the relative change in FMD% in diastole. Predictors identified through univariable regression (p<0.10) were entered into a multivariable model. This model adjusted for baseline hemodynamics (flow volume, baseline FMD), clinical status [presence of heart failure (HF)], metabolic markers [HbA1c, low-density lipoprotein cholesterol (LDL-C)] and coronary anatomical complexity [three-vessel disease (3VD)].
Results
The study analyzed 98 patients (60±11 years, 79% male). Most presented with STEMI (65.3%) or NSTEMI (33.7%), with 87.8% undergoing successful revascularization. Prevalent comorbidities were hypertension (44.9%), dyslipidemia (37.1%), and diabetes (17.3%), while 12.2% had prior coronary artery disease. Multivessel disease was common, including 27.6% with two-vessel and 6.1% with three-vessel involvement. Multivariate analysis showed that 6-month endothelial recovery was independently driven by baseline hemodynamics and clinical severity, whereas metabolic and anatomical variables lost significance. Relative FMD improvement was independently predicted by baseline branchial artery flow volume (β:0.330, p=0.013) and presence of HF (β:0.244, p=0.01), reflecting a lower baseline status and intensive medication-driven neurohormonal optimization. Notably, lower baseline FMD also predicted greater proportional recovery (β:-0.380, p<0.001). Conversely, HbA1c (p=0.188), LDL-C (p=0.175) and 3VD (p=0.249) did not retain independent predictive value for functional recovery (Table).
Conclusion
Following AMI, 6-month endothelial repair is driven by blood flow and shear stress rather than metabolic or anatomical factors. While metabolic risks cause initial vascular damage, they do not seem to limit the vessel’s ability to recover once hemodynamics stabilize. Our findings indicate that FMD serves as a marker of shear-induced repair, demonstrating that responding to physical flow stress is fundamental for endothelial recovery post-AMI.