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Critical shear stress as a Novel hemorheologic biomarker for atherosclerosis.
연세대학교 의과대학 강남세브란스병원¹ 고려대학교 기계공학과²
이병권¹, 김종윤¹, 최의영¹, 민필기¹, 윤영원¹, 홍범기¹, 권혁문¹, 신세현²
Background: The hemodynamic force is important risk factor for atherosclerosis, but it cannot be easily measurable. However, the novel devices have been developed for measuring RBC aggregation and deformability. The reversible dynamics of red blood cells (RBCs) aggregation occurs during blood circulation where RBCs are exposed to high-to-low shear-flow conditions. RBCs are rarely aggregated in arterial system except in ischemia-induced lowered flow condition, but aggregated cells can easily be observed in venules. The threshold shear-rate was measured using an RBC aggregometer. By simultaneously measuring the blood viscosity, the disaggregative shear-stress was determined as a representative index of the mechanical forces acting on the RBCs. We studied the transient characteristics of RBC aggregation in a microfluidic rheometry. We defined a critical shear-stress (CSS) as either the minimum shear-stress required to disperse the aggregates, or the threshold shear required to aggregate RBCs under the shearing hydrodynamic force. The CSS was determined through a light scanning procedure. The objective of the present study is to investigate the role of CSS to clinical disease severity and to evaluate the correlation with fibrinogen, hs-CRP as usual biomarkers for atherosclerosis. Subjects and Methods: 712 Patients with presenting with symptoms of angina including acute MI were included. Blood samples for CSS were obtained via the femoral sheath into EDTA (1.5 mg/ml) just prior to angiography. The patients who had normal coronary angiogram, documented or inducible coronary artery spasm, acute or chronic inflammatory disease, or cancer were excluded. We have evaluated CSS value and other risk factors between stable angina (SA) and acute coronary syndrome (ACS). CSS measured within 6 hours after sampling by Rheoscan™ (Rheomeditec Co., Seoul, Korea). Results: The basic clinical characteristics were not significantly different between both groups. However, CSS was significantly higher in ACS (355.4±78.9 mPa) than in SA (212.5±68.2 mPa) (p<0.01). Interestingly, while CSS has no significant linear correlation with hs-CRP, but significant correlation with fibrinogen (r2 = 0.425, p<0.01), and ESR (r2 = 0.361, p<0.01) was well correlated with fibrinogen (r2 =0.451, p<0.01). Conclusion: CSS can be directly measured in the present, transient, microfluidic aggregometry. CSS might provide the useful information on the characteristics of RBC aggregation and hemorheological risk for cardiovascular diseases. The CSS can be a new aggregation index for which the dimension is the force per unit-area and a measurable novel biomarker for atherosclerosis.


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