Background: Thrombosis formation and endothelial dysfunction are the pathogenesis of myocardial infarction. However, the relation between coronary endothelial dysfunction and platelet aggregability remains unclear. We investigated the relation between endothelium-dependent coronary blood flow volume (CBFV) and platelet aggregability in non-obstructive ischemic heart disease (IHD) patients who did not take any anti-platelet therapy.
Methods/Results: Consecutive 368 patients suspected angina with normal coronary arteries were initially enrolled. We performed coronary angiography and intracoronary acetylcholine-provocation test, and measured adenosine triphosphate-induced coronary flow reserve (CFR) to diagnose the presence of non-obstructive IHD by using Doppler FloWire at the proximal site of left anterior descending coronary artery before taking any vasodilators at the basal non-stress condition. Then, we excluded patients who take any anti-platelet agents from 62 patients with non-obstructive IHD. Finally, 25 non-obstructive IHD patients (mean age: 64.5±9.0, men:36%) were assessed the relation between CBFV change and platelet aggregability as P2Y12 reaction unit (PRU) by VerifyNow P2Y12 assay system. CBFV was measured by Doppler Flowire under 20γof intracoronary acetylcholine and calculated by the following formula; CBFV = 0.236хvascular diameter (m2) хmean peak flow velocity (cm/sec). CBFV change by intracoronary acetylcholine showed the significant negative correlation to PRU (r = 0.44, p = 0.03). There were no significant correlation between PRU and CFR. Multivariable linear regression analysis by the principle component analysis from age, sex, body mass index, diabetes, hypertension, dyslipidemia, smoking , platelet count, estimated glomerular filtration rate, Hemoglobin A1c, LDL-, HDL-cholesterol, triglyceride, C-reacitve protein, B-type natriuretic peptide, ejection fraction, medications indicated an incremental CBFV change was independently associated with PRU (β= 0.63, p<0.001).
Conclusions: In patients with non-obstructive IHD, CBFV change was significantly associated with PRU, indicating coronary endotherial dysfunction is an important pathogenesis for increased platelet aggregability.