the pathogenesis of acute coronary syndrome ( acs ) involves a complicated interaction between atherosclerotic plaque characteristics and coronary flow dynamics , including wall shear stress ( wss ) and intrinsic hemostatic / fibrinolytic dysfunction.1 ) a mechanical injury caused by increased wss of blood flow can be considered an inciting event for plaque rupture.2)3)4 ) it is known that whole - blood viscosity ( wbv ) can be increased due to elevated hemorheological parameters , including hematocrit , fibrinogen , immunoglobulin , and triglycerides.5)6)7)8 ) increased wbv may lead to high shear forces at the vascular endothelium , promoting the rupture of an occlusive plaque.9)10 ) it has also been reported that increased wbv at a low shear rate in patients with acs is associated with coronary plaque rupture.11 ) since wbv can be modified using drug therapy , as shown in hemodilution , low - density lipoprotein cholesterol ( ldl - c ) apheresis , and fibrinolysis,12)13 ) wbv may be a therapeutic target . beyond their lipid - lowering effects , statins also have a different potential mechanism , a rheological effect.14 ) however , there have been limited reports on the effect of statins on blood viscosity.15)16)17 ) moreover , there are no studies of statin effects on patients with acs in terms of wbv . therefore , the aim of this study was to investigate the effects of statins on wbv in patients with acs . we enrolled a total of 248 consecutive patients admitted to the emergency room of chonbuk national university hospital ( jeonju , korea ) for chest pain evaluation from april 2013 to march 2014 . among the recruited subjects , 59 non - acs patients were excluded , and the remaining 189 patients with acs were divided into two groups according to their previous statin medication use : patients who had used statins for more than 3 months before admission ( group i , n=51 ) and statin - nave patients ( group ii , n=138 ) ( fig . the present study was performed after approval from the ethics committee of chonbuk national university hospital . since most previous large randomized trials for evaluating the short - term effects of statins had been performed during the first 2 - 3 months of statin administration,18 ) group i in this study was defined as patients who had taken statins for more than 3 months before enrollment . the mean duration of statin administration before enrollment was 7.34.0 months , and the type of statin used by patients in group i varied ( atorvastatin : n=26 , 51.0% ; rosuvastatin : n=12 , 23.5% ; pitavastatin : n=6 , 11.8% ; simvastatin : n=4 , 7.8% ; or simvastatin / ezetimibe : n=3 , 5.9% ) . diagnostic angiography through the femoral artery was performed after premedication with aspirin ( 300 mg ) and clopidogrel ( 300 mg or 600 mg ) . if percutaneous coronary intervention ( pci ) was performed in patients with acs , additional unfractionated heparin was infused throughout the procedure to maintain an activated clotting time of 250 seconds or longer . we excluded patients with a history of recent thrombolysis in myocardial infarction , major bleeding , major surgery within one month , cardiogenic shock , uncontrolled severe hypertension , contraindication to antiplatelet agents ( such as aspirin or clopidogrel ) , previous history of myocardial infarction , multiple coronary stenosis ( diameter stenosis>50% ) requiring staged pci , severe valvular heart disease , concurrent infection , drug abuse , or severe hematological disease , including anemia ( hemoglobin<10.0 g / dl ) . all patients were administered standard medication , including rosuvastatin ( 16.24.9 mg ; 20 mg , 62.5% ; and 10 mg , 37.5% ) for one month after enrollment . clinical and laboratory characteristics were analyzed between groups at baseline and at the one - month follow - up . baseline blood samples for wbv were collected as soon as patients visited emergency room prior to drug or fluid administration to decrease the likelihood of a change in wbv by fluids . the time needed for blood sampling and wbv analysis was minimized in order to reduce errors caused by changes in blood properties . the viscosity (  ) of liquid is mathematically defined as the ratio of wss ( w ) to wall shear rate as described by the following equation . blood viscosities at shear rates of 1 s ( diastolic blood viscosity ; dbv ) and 300 s ( systolic blood viscosity ; sbv ) were measured with a scanning capillary tube viscometer ( bio - visco inc . , dbv represents the hemorheological state of blood corresponding to a very slow flow , as in microvessels , where the aggregated erythrocytes could result in increased flow resistance . sbv indicates the opposite state , which corresponds to high velocity and high wss , such as peak flow in epicardial coronary arteries.6 ) red blood cell ( rbc ) properties , including deformity and aggregation , were measured according to the most recent international society for clinical hemorheology guidelines by a microfluidic hemorheometer ( rheoscan - and300 ; rheo - meditech , seoul , korea).20 ) for continuous variables , comparisons between the two groups were made using the student 's t test . two sample t tests were performed to compare baseline and post - treatment statuses in group ii . the significant difference between two estimated correlation coefficients was tested based on a z score using fisher 's z transformation . all statistical processing was calculated using spss - pc 18.0 ( statistical package for the social sciences , spss - pc . there were no statistical differences in baseline clinical characteristics between the two groups except age ( group i vs. group ii : 64.59.6 years vs. 60.111.2 years , p=0.014 ) , hypertension ( 78.4% vs. 44.2% , p<0.001 ) , diabetes ( 41.2% vs. 22.5% , p=0.02 ) , previous history of ischemic heart disease ( 58.8% vs. 9.4% , p<0.001 ) , and use of anti - platelet agents , including aspirin ( 68.6% vs. 18.8% , p<0.001 ) and clopidogrel ( 29.4% vs. 3.6% , p<0.001 ) ( table 1 ) . baseline laboratory findings were not different between groups , except for ldl - c level ( 77.316.7 mg / dl vs. 108.632.3 mg / dl , p<0.001 ) ( tables 2 and 3 ) . in group ii , baseline wbv was higher than that in group i ( sbv : group i vs. group ii , 40.85.9 mp vs. 44.27.4 mp , p=0.003 ; dbv : 262.267.8 mp vs. 296.976.0 mp , p=0.002 ) . at the one - month follow - up , only dbv of group ii was significantly higher than that for group i ( sbv : group i vs. group ii , 40.60.5 mp vs. 42.02.0 mp , p=0.142 ; dbv : 250.382.7 mp vs. 281.452.6 mp , p=0.027 ) ( fig . 2 ) . the two - sample t - test revealed a significant change of the wbv in group ii ( sbv : 44.27.4 mp vs. 42.02.0 mp , p=0.012 ; dbv : 296.976.0 mp vs. 281.452.6 mp , p=0.044 ) ( table 4 ) . baseline hermatocrit , rbc aggregation , total protein , and albumin showed the highest linear associations with the baseline wbv in the correlation analysis ( fig . one month hematocrit , albumin , rbc aggregation , and alanine aminotransferase also showed the highest linear associations with the wbv in the correlation analysis ( fig . however , ldl - c level was not related to wbv at either baseline ( sbv : r2=0.074 , p=0.326 ; dbv : r2=0.073 , p=0.337 ) or the one - month follow - up ( sbv : r2=0.104 , p=0.265 ; dbv : r2=0.112 , p=0.232 ) . a comparison of the laboratory findings at admission to those after one month revealed that white blood cells ( wbc ) and aspartate aminotransferase ( ast ) were reduced in group i , while wbc , ast , ldl - c , and c - reactive protein were decreased in group ii ( table 2 ) . this study investigated the effects of rosuvastatin on the change in wbv both in previously statin administered and in statin - nave acs patients . our study was the first investigation to show the effectiveness of early intensive rosuvastatin administration in statin - nave acs patients in terms of blood viscosity . our results provide increased evidence to support the early use of rosuvastatin in patients with acs . based on previous studies of wbv changes in acs patients,11 ) a significant correlation between increased wbv and acs has been revealed . nevertheless , a new method or treatment for adjusting increased wbv has not been suggested . even though there have been attempts to reduce wbv using phlebotomy21 ) and other medications , no treatments have shown clinical impact to date . in addition , aspirin , an antiplatelet agent , also showed no significant effects on wbv.22 ) blood viscosity can be affected by various factors ( i.e. , measuring time and medication).23 ) in several clinical studies , the point at which wbv measurements were taken was not constant , and the effect of medication had not been fully considered . moreover , the change in wbv may be more variable in patients with acs , so it is very important to consider the hemorheological status of the patient and early blood sampling before administration of usual cardiovascular drugs ( such as anticoagulants or antiplatelet agents ) or fluids . in our previous study , the limitations were the timing and location of blood sampling ( coronary artery sampling after the administration of drugs  i.e. , antiplatelet agents , anticoagulants , and contrast media).11 ) in order to resolve this issue , early blood sampling in the emergency room and rapid analysis within 4 hours after blood sampling using automated equipment were applied in this study . baseline laboratory findings ( table 2 ) indicated that ldl - c level was significantly lower in group i compared to the statin - nave group ii patients . , the wbv reduction was noted in the statin - nave group ii . our previous study to determine the reference interval for wbv revealed that the reference intervals for wbv in healthy adults were 41.3 - 44.1 mp at shear rates of 300 s ( sbv ) and 253.3 - 260.9 mp at shear rates 1 s ( dbv).24 ) therefore , the wbv of group ii at admission was above the reference interval and it decreased significantly after one month . since plaque rupture in acs patients is closely related to wss and wbv,2 ) the decrement of wbv caused by statin can be another possible explanation for effectiveness of intensive statin administration , particularly in statin - nave acs patients . some studies showed a favorable influence of statins on the alteration of wbv,13)15)17)25 ) while other results suggest that statins were ineffective.16)26 ) however , there have been no studies on the effect of statin in patients with acs in terms of wbv . we hypothesize that intensive statin treatment ( i.e. , rosuvastatin ) can affect wbv , and we evaluated the alterations in wbv after rosuvastatin administration . interestingly , though there were correlations between traditional factors ( i.e. , hematocrit , protein , albumin ) and wbv,25 ) there were no statistical correlations between ldl - c level and wbv ( figs . 3 and 4 ) . these results imply statin has an effect on changing viscosity that was not caused by decreasing of ldl - c level . larger studies for red cell aggregation / deformability and other pleiotropic effects are needed to answer this question . first , only one type of statin was used in this study , and most patients were administered a moderate - dose . therefore , it is questionable whether different types of statins would show the same effects . second , there were differences in baseline age , diabetes , diagnosis of myocardial infarction , previous ischemic heart disease history and anti - platelet therapy ( i.e. , aspirin , clopidogrel ) between the two groups . our previous study for reference interval of wbv revealed age and sex differences even in healthy volunteers.27 ) considering the multiple risk factors in group i , wbv should have been higher in group i than in group ii . however , the wbv of group i was lower than that in group ii . we could not exclude the possible role of confounding variables , such as the relative short duration of rosuvastation administration ( one month ) in statin - nave group ii patients compared to group i patients ( 4-months ) or the effect of anti - platelet agents or acute phase reactions . third , there was no imaging or physiologic study to determine the relationship between coronary blood flow and wbv . previous statin medication was an important determinant for lowering wbv in acs patients . however , one month of medication with rosuvastatin decreased wbv in statin - nave patients with acs . previous statin medication was an important determinant for lowering wbv in acs patients . however , one month of medication with rosuvastatin decreased wbv in statin - nave patients with acs .
background and objectiveswall shear stress contributes to atherosclerosis progression and plaque rupture . 
 there are limited studies for statin as a major contributing factor on whole blood viscosity ( wbv ) in patients with acute coronary syndrome ( acs ) . 
 this study investigates the effect of statin on wbv in acs patients.subjects and methodswe prospectively enrolled 189 consecutive patients ( mean age , 61.310.9 years ; 132 males ; st - segment elevation myocardial infarction , n=52 ; non - st - segment elevation myocardial infarction , n=84 ; unstable angina n=53 ) . 
 patients were divided into two groups ( group i : previous use of statins for at least 3 months , n=51 ; group ii : statin - nave patients , n=138 ) . 
 blood viscosities at shear rates of 1 s-1 ( diastolic blood viscosity ; dbv ) and 300 s-1 ( systolic blood viscosity ; sbv ) were measured at baseline and one month after statin treatment . 
 rosuvastatin was administered to patients after enrollment ( mean daily dose , 16.24.9 mg).resultsbaseline wbv was significantly higher in group ii ( [ sbv : group i vs group ii , 40.85.9 mp vs. 44.27.4 mp , p=0.003 ] , [ dbv : 262.267.8 mp vs. 296.976.0 mp , p=0.002 ] ) . 
 wbv in group ii was significantly lower one month after statin treatment ( [ sbv : 42.04.7 mp , p=0.012 , dbv : 281.452.6 mp , p=0.044 ] ) . 
 however , low - density lipoprotein cholesterol level was not associated with wbv in both baseline ( sbv : r2=0.074 , p=0.326 ; dbv : r2=0.073 , p=0.337 ) and after one month follow up ( sbv : r2=0.104 , p=0.265 ; dbv : r2=0.112 , p=0.232).conclusionprevious statin medication is an important determinant in lowering wbv in patients with acs . 
 however , one month of rosuvastatin decreased wbv in statin - nave acs patients .