Elevated plasma plasminogen activator inhibitor type-1 is an independent predictor of coronary microvascular dysfunction in hypertension.
BACKGROUND
Elevated plasma plasminogen activator inhibitor-1 (PAI-1) is related to cardiovascular events, but its role in subclinical coronary microvascular dysfunction remains unknown. Thus, in the present study it was investigated whether elevated plasma PAI-1 activity is associated with coronary microvascular dysfunction in hypertensive patients.


RESULTS
Thirty patients with untreated essential hypertension and 10 age-matched healthy controls were studied prospectively. Myocardial blood flow (MBF) was measured by using (15)O-water positron emission tomography. Clinical variables associated with atherosclerosis (low-density lipoprotein-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, homeostasis model assessment (HOMA-IR), and PAI-1 activity) were assessed to determine their involvement in coronary microvascular dysfunction. Adenosine triphosphate (ATP)-induced hyperemic MBF and coronary flow reserve (CFR) were significantly lower in hypertensive patients than in healthy controls (ATP-induced MBF: 2.77+/-0.82 vs 3.49+/-0.71 ml x g(-1) x min(-1); p<0.02 and CFR: 2.95 +/-1.06 vs 4.25+/-0.69; p<0.001). By univariate analysis, CFR was positively correlated with HDL-cholesterol (r=0.46, p<0.02), and inversely with HOMA-IR (r=-0.39, p<0.05) and PAI-1 activity (r=-0.61, p<0.001). By multivariate analysis, elevated PAI-1 activity remained a significant independent determinant of diminished CFR.


CONCLUSIONS
Elevated plasma PAI-1 activity was independently associated with coronary microvascular dysfunction, which suggests that plasma PAI-1 activity is an important clue linking hypofibrinolysis to the development of atherosclerosis.
Naya
Masanao
M
Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan. naya@med.hokudai.ac.jp
Tsukamoto
Takahiro
T
Inubushi
Masayuki
M
Morita
Koichi
K
Katoh
Chietsugu
C
Furumoto
Tomoo
T
Fujii
Satoshi
S
Tsutsui
Hiroyuki
H
Tamaki
Nagara
N
D000328:Adult; D050197:Atherosclerosis / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity; D016022:Case-Control Studies; D003326:Coronary Circulation; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000503:physiopathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies
D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1