Coincidence of Moderately Elevated N-Terminal Pro–B-Type Natriuretic Peptide, Endothelial Progenitor Cells Deficiency and Propensity to Exercise-Induced Myocardial Ischemia in Stable Angina

Aim: To assess endothelial progenitor cells (EPC) counts, a novel prognostic marker, in relation to classical adverse outcome predictors–N-terminal pro–B-type natriuretic peptide (NT-proBNP), impaired left ventricular (LV) relaxation and exercise-induced ischemia–in stable coronary artery disease (CAD) with preserved LV systolic function. Methods: We studied 30 non-diabetic men with one-vessel CAD, LV ejection fraction ≥ 60% and normal LV diastolic function (n = 16) or impaired LV relaxation (by ultrasound including tissue Doppler) (n = 14), and 14 non-CAD controls matched for risk profile and medication. CD34+/kinase-insert domain receptor (KDR)+ cells (CD34+/KDR+ cells), a leukocytes subpopulation enriched for EPC, were enumerated by flow cytometry. Results: CAD patients with abnormal LV relaxation exhibited significantly elevated NT-proBNP and decreased CD34+/KDR+ cells vs. CAD with regular diastolic function and non-CAD controls. An inverse NT-proBNP–CD34+/KDR+ cells relationship was precipitated by the clustering of high resting NT-proBNP and low CD34+/KDR+ cells in the subjects with a lower Duke treadmill score. Conclusions: Propensity to symptomatic exertional ischemia may underlie the coincidence of moderately elevated NT-proBNP and EPC deficiency in stable angina. Additionally, chronic subclinical ischemia can also be involved in these associations. These might result from BNP overexpression in the ischemic myocardium and a hypothetical exhaustion of the bone marrow capacity to mobilize EPC at multiple ischemic episodes, thus contributing to NT-proBNP prognostic effect irrespective of hemodynamic factors.