Diminished Endothelial Function and Hypofibrinolysis in High Risk Patients with Hypertension and High Plasma Levels of Inflammatory Markers: Need for Anti-Inflammatory Strategy

Abstract

39 Hypertension and diminished fibrinolysis are major determinants of progression of atherosclerosis, which is now regarded as an inflammatory disease. Flow-mediated dilation (FMD) of brachial artery reflects endothelial function and is a sensitive index of early atherosclerosis. FMD is reduced in patients with hypertension. Whether antihypertensive therapy alters FMD, fibrinolytic function or inflammation in high risk patients is not elucidated. To characterize the relationships among markers of fibrinolysis, inflammation and FMD, plasma levels of tissue-type plasminogen activator (t-PA), a sensitive index of endothelial damage, and tumor necrosis factor (TNF)-α, an established marker of inflammation, were determined by high-sensitive enzyme linked immunosorbent assays in normotensive (N, n = 20) and hypertensive (H, n = 17; calcium blocker n = 13, ACE inhibitor n = 4) patients. Both groups were hospitalized for evaluation of coronary heart disease. FMD was determined by high-resolution ultrasound. Blood pressure of treated H (134 ± 7(SD) / 78 ± 5 mmHg) was not significantly different from that of N (123 ± 3 / 75 ± 3 mmHg). However, FMD was significantly reduced in H (8.9 ± 1.3% compared to N (16.8 ± 1.8%, p < 0.005). Nitroglycerine induced endothelium independent vasodilation was not altered in H (15.3 ± 1.5%) as compared to N (17.6 ± 1.5%, p = NS). Plasma t-PA levels were increased in H (10.5 ± 1.3 ng/ml) compared to N (8.4 ± 1.1 ng/ml), indicating continued endothelial damage despite blood pressure reduction. Plasma TNF-α levels were also increased in H (1.7 ± 0.2 pg/ml) compared to N (1.3 ± 0.1 pg/ml), indicating persistent inflammation. These results suggest that (1) antihypertensive therapy alone is not sufficient to improve endothelial dysfunction in hypertensive patients with high plasma levels of inflammatory markers, and (2) additional therapy to target inflammation is necessary to improve endothelial function and to prevent progression of coronary atherosclerosis in high risk hypertensive patients with subclinical inflammations.