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Elevated plasma plasminogen activator inhibitor type-1 is an independent predictor of coronary microvascular
Masanao Naya1, Takahiro Tsukamoto, Masayuki Inubushi
1Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan. naya@med.hokudai.ac.jp
Insights
Elevated plasminogen activator inhibitor-1 (PAI-1) activity is linked to coronary microvascular dysfunction in hypertensive patients. This finding suggests PAI-1 may play a role in atherosclerosis development.
Area of Science:
- Cardiovascular Research
- Hypertension Studies
- Atherosclerosis Research
Background:
- Elevated plasma plasminogen activator inhibitor-1 (PAI-1) is associated with cardiovascular events.
- The role of PAI-1 in subclinical coronary microvascular dysfunction is not well understood.
Purpose of the Study:
- To investigate the association between elevated plasma PAI-1 activity and coronary microvascular dysfunction in patients with hypertension.
Main Methods:
- Prospective study of 30 untreated hypertensive patients and 10 healthy controls.
- Myocardial blood flow (MBF) measured using (15)O-water positron emission tomography.
- Assessed clinical variables including PAI-1 activity, lipids, and HOMA-IR.
Main Results:
- Hypertensive patients showed significantly lower adenosine triphosphate (ATP)-induced hyperemic MBF and coronary flow reserve (CFR) compared to controls.
- Univariate analysis revealed CFR inversely correlated with homeostasis model assessment (HOMA-IR) and PAI-1 activity.
- Multivariate analysis identified elevated PAI-1 activity as an independent determinant of diminished CFR.
Conclusions:
- Elevated plasma PAI-1 activity is independently associated with coronary microvascular dysfunction.
- Plasma PAI-1 activity may serve as a key indicator linking hypofibrinolysis to atherosclerosis development.
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.
Methods And 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.
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