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154 No effect of wheat grain supplementation in diet on blood fibrinolysis in subjects with metabolic cardiovascular syndrome
POSTER PRESENTATIONS: Fibrinolysis in vascular disease I
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153 Lifestyle and other risk factors and fibrinolytic risk factors for ischaemic heart disease: The Caerphilly Study *RUMLEY A. *LOWE GDO. **SWEETNAM PM. and **YARNELL JWG *University Department of Medicine, Royal Infirmary. Glasgow. UK and **MRC Epidemiology Unit (South Wales), Penarth, UK We have reported that plasma fibrin D-dimer, tissue plasminogen activator (tPA) antigen, von Willebrand factor (vWF) antigen, fibrinogen, viscosity and blood white cell count (WCC) were predictors of ischaemic heart disease (IHD) in the Caerphilly Study of 2000 middle-aged men; but not plasma plasminogen activator inhibitor (PAl) activity. We now report a detailed analysis of the associations of these variables with lifestyle and other risk factors for IHD in this cohort. All variables increased with age, except WCC (no effect) and PAl (decrease). All variables increased with smoking (except vWF). Alcohol was associated with increased tPA and PAl; and decreased fibrinogen and WCC. Body mass index, lipids and blood pressure were associated with increased tPA, PAl, fibrinogen, viscosity and WCC. Social class was associated with decreased fibrinogen and viscosity. Leisure activity was
associated with decreased D-dimer, vWF, fibrinogen and viscosity. No variable was associated with lipoprotein (a) or homocysteine (except D-dimer and vWF for the latter). We conclude that fibrinolytic risk factors are associated with several major risk factors for IHD, including lifestyle, demographic and biochemical variables. These associations should be considered when interpreting the relationships between fibrinolytic markers and IHD.
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154 No effect of wheat grain supplementation in diet on blood fibrinolysis in subjects with metabolic cardiovascular syndrome *LAVRE S. **KEBER 1. and ***SUNDELL 1t3 *General Hospital SIovenj Gradec, SIovenia, **University Medical Centre, Department of Angiology, Ljubljana, SIovenia; ***Departments of Pathology and Nutritional Research. Umegt University, Ume& Sweden Background.The diet tberapyrepresentsthe mostimportantnonpharmacologictreatment strategy in metaboliccardiovascularsyndrome(MCVS),whichis characterized by cluster of severalmetabolicdisorders,arterial hypertension,visceralobesityand increasedthrombogenic potentialand is associated withincreasedrisk for accelerated atheroscleroticdisease. We examinedthe effectsof wheat grain supplementationin diet on fibrinolyticand metabolic variablesin subjectswith MCVS. Methods.Thirty-sevensubjectswithMCVS,26 malesand 11 females,aged27 to 65 years, mean47 years,withbody massindex (BMI)30.8 (s.d.:3.4) kg/m2wererandomlyassigned to two groups.Subjectsassignedto studygroupconsumed21 g of wheathuskfibergranules (Trifyba®)daily for 5 weeksin addition to their regulardiet. Subjectsassignedto the control groupmaintained their regulardiet only. Blood sampleswere collected between 08.00 and 09.30 in the morningon three occasions:at entry of the study, after 5 weeksof diet supplementationand at the end of 4 weekswash-outperiod. The serumlevel of lipids, glucoseand insulinand plasmafibrinolyticvariablesweredetermined. Oral glucosetolerancetest (OGTT)wasperformedat the entryand after5 weeksof treatmentperiod, indexof insulin resistance(IIR)was calculated as insulin/(22.5e t"gl~ose).
Results. Duringthe observationperiod of 9 weeksmeanBMI decreased from31.7 to 28.1 kg/m2 (p=0.02) in the study group and from 29.9 to 29.5 kg/m2(p=0.03) in the control group.No significantchangesin plasmatissueplasminogenactivatoractivity and antigen, plasminogenactivatorinhibitor- 1activityand antigen, fibrinogenlevel, factorVII activity and plasminogenactivity wereobservedin either groupduring treatmentperiod or washout period. In the study groupthe followingsignificantchangesoccurredafter treatment period: the meanfastingglucoselevel decreasedfrom4.9 m 4.6 mmoF1(p=0.03), the mean glucose level after 60 minutesof OGTr decreased from 9.2 to 7.9 mmol/1(p=0.03), the mean total cholesteroldecreased from6.5 to 5.6 mmol/l(p=0.001), the meanLDLcholesterol decreased from3.8 to 3.2 retool/1(p---'-~.002)and the meanHDLcholesteroldecreased from 1.1 to 1.0 mmol (p=0.03), while atherogealc index LDL/HDLcholesterol did not change significantly.Aftertreatment we also observedlowermedian fastinginsulinlevel (12.7 vs. 16.6 IU/ml,p=0.04) and lowermedian IIR (2.6 vs. 3.3, P=0.03) in studythan in control group.After4 weeksof wash-outperiodin the studygroupthe meanfastingglucose level, the mean total and LDL cholesterolvaluesreturnedto basal levels, the mean HDL cholesterol level remained unchanged while atherogenic index LDL/HDLcholesterol increased from 3,3 to 3,8 (p=O.01). No changes in metabolic parameterswere observed in controlgroupduring the observationperiod. in conclusion,our resultsshowedthat wheathusk supplementationin diet does not affect blood fibrinolysisin subjectswith MCVS but has favorableeffectson glucoseand lipid metabolism.
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155 Possible relation of intraplatelet PAl-1 to 4GI5G polymorphism in patients undergoing cardiopulmonary bypass surgery *WATALA C, *GOLANSKI J, **GOLANSKI R, ****P1ETRUCHA T, ***CHI~YI¢SKIK, and **IWASZKIEWICZ A *Laboratory of Haemostatic Disorders, *Department of Anaesthesiology and Intensive Care and ***Cardiology Clinic, Institute of Cardiology, ****Department of Biochemistry L Medical University of L6d~, Poland Cardiac surgery is believed to be associated with imbalance and disorders of coagulation and fibrinolysis. However, the detailed mechanisms underlying haemostatic dysfunctions in cardiopulmonary bypass surgery (CPB) patients remain unclear. In one of our previous study we suggested that the reduced platelet reactivity in response to agonistinduced platelet activation might reflect platelet increased consumption and/or rupture in CPB patients. To further explore the molecular mechanisms of haemostatic dysfunctions in the course of extracorporeal circulation we analysed the alterations in plasma PAl-1 levels at every time point of CPB, and determined the intraplatelet pool of PAl-l, which might be potentially released upon platelet activation. Plasma PAI-1 reached maximum at the time point of 3 days after CPB surgery and its
increase corresponded to the changes observed in the expression of platelet P-selectin, GPIb~ and platelet microparticles. We revealed that the amount of plasma PAI-1 correlated to both the activation of circulating platelets (as monitored by the expression of P-selectin, r=0.68) and platelet response to shear-stress induced activation ex vivo (r=0.89). Further, also the extent of platelet consumption under the condition of the ex vivo shear-stress induced platelet activation was related to overall plasma PAI-1 concentration (r=0.76). The amount of intraplatelet pool of PAI-1 was apparently related to the 4G/5G polymorphism in PAI-1 promoter, the extremely low and extremely high contents ofintraplatelet PAl-1 being recorded in 5G/5G and 4G/4G patients, respectively. In summary, it seems that the release of the intraplatelet PAI-1 is governed by platelet reactivity and hypersensitivity and its storage in platelet granules may correspond to the 4G/5G polymorphism in PAI-1 promoter. We conclude that this observation may be critical in the evaluation of thromboembolic risk in patients undergoing coronary artery surgery.
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153 Lifestyle and other risk factors and fibrinolytic risk factors for ischaemic heart disease: The Caerphilly Study *RUMLEY A. *LOWE GDO. **SWEETNAM PM. and **YARNELL JWG *University Department of Medicine, Royal Infirmary. Glasgow. UK and **MRC Epidemiology Unit (South Wales), Penarth, UK We have reported that plasma fibrin D-dimer, tissue plasminogen activator (tPA) antigen, von Willebrand factor (vWF) antigen, fibrinogen, viscosity and blood white cell count (WCC) were predictors of ischaemic heart disease (IHD) in the Caerphilly Study of 2000 middle-aged men; but not plasma plasminogen activator inhibitor (PAl) activity. We now report a detailed analysis of the associations of these variables with lifestyle and other risk factors for IHD in this cohort. All variables increased with age, except WCC (no effect) and PAl (decrease). All variables increased with smoking (except vWF). Alcohol was associated with increased tPA and PAl; and decreased fibrinogen and WCC. Body mass index, lipids and blood pressure were associated with increased tPA, PAl, fibrinogen, viscosity and WCC. Social class was associated with decreased fibrinogen and viscosity. Leisure activity was
associated with decreased D-dimer, vWF, fibrinogen and viscosity. No variable was associated with lipoprotein (a) or homocysteine (except D-dimer and vWF for the latter). We conclude that fibrinolytic risk factors are associated with several major risk factors for IHD, including lifestyle, demographic and biochemical variables. These associations should be considered when interpreting the relationships between fibrinolytic markers and IHD.
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154 No effect of wheat grain supplementation in diet on blood fibrinolysis in subjects with metabolic cardiovascular syndrome *LAVRE S. **KEBER 1. and ***SUNDELL 1t3 *General Hospital SIovenj Gradec, SIovenia, **University Medical Centre, Department of Angiology, Ljubljana, SIovenia; ***Departments of Pathology and Nutritional Research. Umegt University, Ume& Sweden Background.The diet tberapyrepresentsthe mostimportantnonpharmacologictreatment strategy in metaboliccardiovascularsyndrome(MCVS),whichis characterized by cluster of severalmetabolicdisorders,arterial hypertension,visceralobesityand increasedthrombogenic potentialand is associated withincreasedrisk for accelerated atheroscleroticdisease. We examinedthe effectsof wheat grain supplementationin diet on fibrinolyticand metabolic variablesin subjectswith MCVS. Methods.Thirty-sevensubjectswithMCVS,26 malesand 11 females,aged27 to 65 years, mean47 years,withbody massindex (BMI)30.8 (s.d.:3.4) kg/m2wererandomlyassigned to two groups.Subjectsassignedto studygroupconsumed21 g of wheathuskfibergranules (Trifyba®)daily for 5 weeksin addition to their regulardiet. Subjectsassignedto the control groupmaintained their regulardiet only. Blood sampleswere collected between 08.00 and 09.30 in the morningon three occasions:at entry of the study, after 5 weeksof diet supplementationand at the end of 4 weekswash-outperiod. The serumlevel of lipids, glucoseand insulinand plasmafibrinolyticvariablesweredetermined. Oral glucosetolerancetest (OGTT)wasperformedat the entryand after5 weeksof treatmentperiod, indexof insulin resistance(IIR)was calculated as insulin/(22.5e t"gl~ose).
Results. Duringthe observationperiod of 9 weeksmeanBMI decreased from31.7 to 28.1 kg/m2 (p=0.02) in the study group and from 29.9 to 29.5 kg/m2(p=0.03) in the control group.No significantchangesin plasmatissueplasminogenactivatoractivity and antigen, plasminogenactivatorinhibitor- 1activityand antigen, fibrinogenlevel, factorVII activity and plasminogenactivity wereobservedin either groupduring treatmentperiod or washout period. In the study groupthe followingsignificantchangesoccurredafter treatment period: the meanfastingglucoselevel decreasedfrom4.9 m 4.6 mmoF1(p=0.03), the mean glucose level after 60 minutesof OGTr decreased from 9.2 to 7.9 mmol/1(p=0.03), the mean total cholesteroldecreased from6.5 to 5.6 mmol/l(p=0.001), the meanLDLcholesterol decreased from3.8 to 3.2 retool/1(p---'-~.002)and the meanHDLcholesteroldecreased from 1.1 to 1.0 mmol (p=0.03), while atherogealc index LDL/HDLcholesterol did not change significantly.Aftertreatment we also observedlowermedian fastinginsulinlevel (12.7 vs. 16.6 IU/ml,p=0.04) and lowermedian IIR (2.6 vs. 3.3, P=0.03) in studythan in control group.After4 weeksof wash-outperiodin the studygroupthe meanfastingglucose level, the mean total and LDL cholesterolvaluesreturnedto basal levels, the mean HDL cholesterol level remained unchanged while atherogenic index LDL/HDLcholesterol increased from 3,3 to 3,8 (p=O.01). No changes in metabolic parameterswere observed in controlgroupduring the observationperiod. in conclusion,our resultsshowedthat wheathusk supplementationin diet does not affect blood fibrinolysisin subjectswith MCVS but has favorableeffectson glucoseand lipid metabolism.
I
155 Possible relation of intraplatelet PAl-1 to 4GI5G polymorphism in patients undergoing cardiopulmonary bypass surgery *WATALA C, *GOLANSKI J, **GOLANSKI R, ****P1ETRUCHA T, ***CHI~YI¢SKIK, and **IWASZKIEWICZ A *Laboratory of Haemostatic Disorders, *Department of Anaesthesiology and Intensive Care and ***Cardiology Clinic, Institute of Cardiology, ****Department of Biochemistry L Medical University of L6d~, Poland Cardiac surgery is believed to be associated with imbalance and disorders of coagulation and fibrinolysis. However, the detailed mechanisms underlying haemostatic dysfunctions in cardiopulmonary bypass surgery (CPB) patients remain unclear. In one of our previous study we suggested that the reduced platelet reactivity in response to agonistinduced platelet activation might reflect platelet increased consumption and/or rupture in CPB patients. To further explore the molecular mechanisms of haemostatic dysfunctions in the course of extracorporeal circulation we analysed the alterations in plasma PAl-1 levels at every time point of CPB, and determined the intraplatelet pool of PAl-l, which might be potentially released upon platelet activation. Plasma PAI-1 reached maximum at the time point of 3 days after CPB surgery and its
increase corresponded to the changes observed in the expression of platelet P-selectin, GPIb~ and platelet microparticles. We revealed that the amount of plasma PAI-1 correlated to both the activation of circulating platelets (as monitored by the expression of P-selectin, r=0.68) and platelet response to shear-stress induced activation ex vivo (r=0.89). Further, also the extent of platelet consumption under the condition of the ex vivo shear-stress induced platelet activation was related to overall plasma PAI-1 concentration (r=0.76). The amount of intraplatelet pool of PAI-1 was apparently related to the 4G/5G polymorphism in PAI-1 promoter, the extremely low and extremely high contents ofintraplatelet PAl-1 being recorded in 5G/5G and 4G/4G patients, respectively. In summary, it seems that the release of the intraplatelet PAI-1 is governed by platelet reactivity and hypersensitivity and its storage in platelet granules may correspond to the 4G/5G polymorphism in PAI-1 promoter. We conclude that this observation may be critical in the evaluation of thromboembolic risk in patients undergoing coronary artery surgery.