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1P-0014 The G(−30) A polymorphism in the promoter of the glucokinase gene is associated with angiographic coronary artery disease, type 2 diabetes mellitus and glucose metabolism
Monday September 29, 2003: Poster Session Coronary artery disease
22 1P-0014
The G(-30)A polymorphism in the promoter of the glucokinase gene is associated with angiographic coronary artery disease, type 2 diabetes mellitus and glucose metabolism
M. Nauck 1 , W. März 2 , M.M. Hoffmann 1 , D. Nagel 3 , B.O. Boehm 4 , B.R. Winkelmann 5 . 1 Clinical Chemistry, University Hospital Freiburg, Germany; 2 Clin Inst Med Chem Lab Diag, University Graz, Austria; 3 Clinical Chemistry, General Hospital, Ludwigshafen; 4 Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, Ulm; 5 Cooperation Unit Pharmacogenomics/Applied Genomics, Dep Int Med IV, University Heidelberg, Germany Type 2 diabetes substantially increases the risk of coronary artery disease (CAD). A G(-30A) polymorphism in the B cell-specific promoter of glucokinase has been implicated in reduced B cell function. The impact of this polymorphism on CAD has not been determined. The glucokinase G(-30A) variant was examined in 2567 patients with angiographically documented CAD and in 731 individuals in whom CAD had been ruled out by angiography. Assuming a dominant mode of inheritance, carriers of the A allele had odds ratios of 1.34 (95% confidence interval, CI: 1.12 - 1.60) and 1.20 (95% CI: 1.03 - 1.40) for CAD (stenoses > 20%) and type 2 diabetes, respectively. The association of the G(-30A) polymorphism with CAD was independent of cardiovascular risk factors including type 2 diabetes; the association with type 2 diabetes was robust against age, gender and body mass index. The A-allele was associated with higher glucose concentrations (fasting, p = 0.002, and 2 hours after oral glucose, p = 0.017) and glycated hemoglobin (HbA1c, p = 0.002). Further, presence of one A-allele was negatively related to B cell function, estimated by β% (p = 0.012) and by the ratios of proinsulin to insulin (p = 0.025) or proinsulin to C-peptide (p = 0.019). The (-30A) allele of the pancreatic promoter of glukokinase is independently associated the risk of both CAD and type 2 diabetes. Further, it appears to decerase β cell function. Assessment of this polymorphism may hence ameliorate cardiovascular risk stratification.
and >50% stenotic segments (r=0.30 and r=0.31, P<0.001) using Spearman’s rank test. Multivariate analysis revealed that the CRP level was the significant factor associated with CAD independent of conventional risk factors. Conclusions: Plasma CRP levels were found to be associated with the presence and extent of CAD in pts with stable CAD. However, Japanese pts with CAD are more likely to have lower CRP levels than other ethinics. 1P-0016
A. Gotsis, A. Labrou, A. Savvopoulou, P. Bozia, V. Karagiozaki, D. Theodoridis, L. Borghi, O. Koutsogiannis, A. Panagiotidou. General Hospital of Komotini, Komotini, Greece Objective: To study the implementation of lipid lowering therapy guidelines to patients with CAD after the diagnosis is made and to record the percentage of patients who are under treatment as well as those who have succeeded the target levels. Methods and Results: 404 patients with CAD were studied 341 M, 63 F aged 64±9 years old (231 had undergone a revascularization intervention) within 79±63 months after diagnosis was made. 143 patients (Group A) do not know whether they have normal serum lipid levels or not, 84 (Group B) state they have normal lipid levels and 175 (Group C) know they have hyperlipidaemia. Diet instructions were given in 132 of these patients while therapy was given in 150, but only 30% (Group C1) follow this therapy continuously and half of them started therapy during the first year, after the diagnosis was made. 61 of these patients (Group C2) are under observation to our outpatient clinics of hyperlipidaemias. Conclusions: Despite the bibliographic evidence and NCEP recommendations, the majority of CAD patients is not under therapy or does not follow the given therapy correctly. 70% of the patients either they have never been under therapy or discontinue their therapy, while from the rest, who are under continuous therapy, only 1/3 have succeeded the target levels. 1P-0017
1P-0015
Associations of plasma C-reactive protein (CRP) levels with the presence and extent of coronary artery disease (CAD) in Japanese patients with stable CAD
H. Taniguchi 1 , Y. Momiyama 1 , R. Ohmori 1 , R. Takahashi 1 , A. Yonemura 1 , T. Yamashita 2 , H. Nakamura 2 , F. Ohsuzu 1 . 1 National Defense Medical College, Tokorozawa, Saitama; 2 Mitsukoshi Health and Welfare Foundation, Japan Plasma CRP levels were shown to be powerful predictors for cardiac events in healthy people and patients (pts) with CAD, but associations of CRP levels with the extent of CAD remain controversial. It may be due to the inclusions of pts with ACS or those on statin. Moreover, we recently reported that the median CRP level in 3515 healthy Japanese was 0.2 mg/l, which was much lower than that reported in other ethnics. In Japanese, CRP levels may be low even in pts with CAD. To elucidate CRP levels in Japanese pts with CAD and associations of CRP with the extent of CAD, we measured plasma high-sensitivity CRP levels by nephelometry (Dade Behring) in 180 consecutive pts who had elective coronary angiography for suspected CAD. Pts with unstable angina within 1 month or MI within 6 months, those with a history of PCI or CABG, or those who had statin were excluded. The extents of CAD were evaluated as the numbers of >50% stenotic vessels and >25% and >50% stenotic segments. Results: Of the 180 pts, 109 had CAD (>50% stenosis). Compared with 71 pts without CAD, 109 with CAD had higher CRP levels (median value, 0.75 vs 0.50 mg/l, P<0.005), but CRP levels in our pts with CAD were lower than those reported in other ethnics with CAD (usually >1.5 mg/l). However, a stepwise increase in CRP levels was found depending on the number of >50% stenotic vessels: 0.63 mg/l in pts with 1VD, 0.80 in 2VD, and 0.86 in 3VD (P<0.02). Moreover, CRP levels were found to correlate with the numbers of >25%
Secondary prevention in patients with CAD. What about the implementation of guidelines?
Hypotriglyceridemic and non-lipid effects of atorvastatin and simvastatin therapy in coronary heart disease patients with combined hyperlipidemia and type 2 diabetes mellitus
E. Vasutina, V.A. Metelskaya, N.M. Akhmedzhanov, L.A. Ratnikova, R.G. Oganov. National Research Centre for Preventive Medicine, Russia Objective: To evaluate the effect of atorvastatin and simvastatin on lipid levels and major haemostasis parameters (fibrinogen, factor VII, ECLT) in CHD patients with combined (IIb) hyperlipidemia and type 2 diabetes mellitus. Methods: Study was randomized placebo-controlled in parallel groups. 40 men (age 61±1.1) were randomized into 3 groups:I-atorvastatin 10 mg (n=15), II-simvastatin 20mg (n=15), III-placebo (n=10). Total cholesterol (TC), LDL C, HDL C, triglycerides (TG) levels and haemostatic parameters have been determined at the beginning and after 3 mo of treatment. Results: In group I fibrinogen level decreased by 7% from 4.5±0.3 to 4.2±0.3 g/l; factor VII activity by 17.4% from 274±36.3 to 226±27.1%; ECLT did not change. The level of TC decreased by 29%, LDL C by 36%, TG by 32%, HDL C level increased by 18%. In group II fibrinogen level deceased by 21% from 4.2±0.4 to 3.3±0.3 g/l; factor VII activity by 25% from 276±22.21 to 206±20.8%; ECLT by 7% from 273±16.2 to 254±12.4 min. The levels of TC, LDL C, TG decreased by -29%,-39%,-33% respectively, HDL C elevated by 31%. In group III no significant changes were found. Conclusion: The both drugs therapy in equivalent doses have significant hypotriglyceridemic effect, significantly inceased HDL C level and in studied patients significantly improved haemostasis paraneters, reducing levels of fibrinogen and factor VII activity; simvastatin, in addition, resulted in some activation of fibrinolysis.
Abstract 1P-0016 – Table
Group A Group B Group C (on therapy) Group C (without therapy) Group C1 Group C2
TC (mg/dL)
LDL (mg/dL)
Non-HDL (mg/dL)
TG (mg/dL)
TG>200mg/dL
LDL<100mg/dL or Non-HDL<130mg/dL)
237±50 218±46 209±46 254±33 194±37 185±25
154±39 140±34 129±47 178±23 116±27 109±19
226±40 218±46 193±59 201±42 175±54 141±15
304±100 363±121 415±289 317±58 336±121 294±66
15.8% 11.25% 15.07% 40% 12.07% 8.20%
3% 13.75% 21.90% 0% 30.17% 34.43%
XIIIth International Symposium on Atherosclerosis, September 28–October 2, 2003, Kyoto, Japan
22 1P-0014
The G(-30)A polymorphism in the promoter of the glucokinase gene is associated with angiographic coronary artery disease, type 2 diabetes mellitus and glucose metabolism
M. Nauck 1 , W. März 2 , M.M. Hoffmann 1 , D. Nagel 3 , B.O. Boehm 4 , B.R. Winkelmann 5 . 1 Clinical Chemistry, University Hospital Freiburg, Germany; 2 Clin Inst Med Chem Lab Diag, University Graz, Austria; 3 Clinical Chemistry, General Hospital, Ludwigshafen; 4 Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, Ulm; 5 Cooperation Unit Pharmacogenomics/Applied Genomics, Dep Int Med IV, University Heidelberg, Germany Type 2 diabetes substantially increases the risk of coronary artery disease (CAD). A G(-30A) polymorphism in the B cell-specific promoter of glucokinase has been implicated in reduced B cell function. The impact of this polymorphism on CAD has not been determined. The glucokinase G(-30A) variant was examined in 2567 patients with angiographically documented CAD and in 731 individuals in whom CAD had been ruled out by angiography. Assuming a dominant mode of inheritance, carriers of the A allele had odds ratios of 1.34 (95% confidence interval, CI: 1.12 - 1.60) and 1.20 (95% CI: 1.03 - 1.40) for CAD (stenoses > 20%) and type 2 diabetes, respectively. The association of the G(-30A) polymorphism with CAD was independent of cardiovascular risk factors including type 2 diabetes; the association with type 2 diabetes was robust against age, gender and body mass index. The A-allele was associated with higher glucose concentrations (fasting, p = 0.002, and 2 hours after oral glucose, p = 0.017) and glycated hemoglobin (HbA1c, p = 0.002). Further, presence of one A-allele was negatively related to B cell function, estimated by β% (p = 0.012) and by the ratios of proinsulin to insulin (p = 0.025) or proinsulin to C-peptide (p = 0.019). The (-30A) allele of the pancreatic promoter of glukokinase is independently associated the risk of both CAD and type 2 diabetes. Further, it appears to decerase β cell function. Assessment of this polymorphism may hence ameliorate cardiovascular risk stratification.
and >50% stenotic segments (r=0.30 and r=0.31, P<0.001) using Spearman’s rank test. Multivariate analysis revealed that the CRP level was the significant factor associated with CAD independent of conventional risk factors. Conclusions: Plasma CRP levels were found to be associated with the presence and extent of CAD in pts with stable CAD. However, Japanese pts with CAD are more likely to have lower CRP levels than other ethinics. 1P-0016
A. Gotsis, A. Labrou, A. Savvopoulou, P. Bozia, V. Karagiozaki, D. Theodoridis, L. Borghi, O. Koutsogiannis, A. Panagiotidou. General Hospital of Komotini, Komotini, Greece Objective: To study the implementation of lipid lowering therapy guidelines to patients with CAD after the diagnosis is made and to record the percentage of patients who are under treatment as well as those who have succeeded the target levels. Methods and Results: 404 patients with CAD were studied 341 M, 63 F aged 64±9 years old (231 had undergone a revascularization intervention) within 79±63 months after diagnosis was made. 143 patients (Group A) do not know whether they have normal serum lipid levels or not, 84 (Group B) state they have normal lipid levels and 175 (Group C) know they have hyperlipidaemia. Diet instructions were given in 132 of these patients while therapy was given in 150, but only 30% (Group C1) follow this therapy continuously and half of them started therapy during the first year, after the diagnosis was made. 61 of these patients (Group C2) are under observation to our outpatient clinics of hyperlipidaemias. Conclusions: Despite the bibliographic evidence and NCEP recommendations, the majority of CAD patients is not under therapy or does not follow the given therapy correctly. 70% of the patients either they have never been under therapy or discontinue their therapy, while from the rest, who are under continuous therapy, only 1/3 have succeeded the target levels. 1P-0017
1P-0015
Associations of plasma C-reactive protein (CRP) levels with the presence and extent of coronary artery disease (CAD) in Japanese patients with stable CAD
H. Taniguchi 1 , Y. Momiyama 1 , R. Ohmori 1 , R. Takahashi 1 , A. Yonemura 1 , T. Yamashita 2 , H. Nakamura 2 , F. Ohsuzu 1 . 1 National Defense Medical College, Tokorozawa, Saitama; 2 Mitsukoshi Health and Welfare Foundation, Japan Plasma CRP levels were shown to be powerful predictors for cardiac events in healthy people and patients (pts) with CAD, but associations of CRP levels with the extent of CAD remain controversial. It may be due to the inclusions of pts with ACS or those on statin. Moreover, we recently reported that the median CRP level in 3515 healthy Japanese was 0.2 mg/l, which was much lower than that reported in other ethnics. In Japanese, CRP levels may be low even in pts with CAD. To elucidate CRP levels in Japanese pts with CAD and associations of CRP with the extent of CAD, we measured plasma high-sensitivity CRP levels by nephelometry (Dade Behring) in 180 consecutive pts who had elective coronary angiography for suspected CAD. Pts with unstable angina within 1 month or MI within 6 months, those with a history of PCI or CABG, or those who had statin were excluded. The extents of CAD were evaluated as the numbers of >50% stenotic vessels and >25% and >50% stenotic segments. Results: Of the 180 pts, 109 had CAD (>50% stenosis). Compared with 71 pts without CAD, 109 with CAD had higher CRP levels (median value, 0.75 vs 0.50 mg/l, P<0.005), but CRP levels in our pts with CAD were lower than those reported in other ethnics with CAD (usually >1.5 mg/l). However, a stepwise increase in CRP levels was found depending on the number of >50% stenotic vessels: 0.63 mg/l in pts with 1VD, 0.80 in 2VD, and 0.86 in 3VD (P<0.02). Moreover, CRP levels were found to correlate with the numbers of >25%
Secondary prevention in patients with CAD. What about the implementation of guidelines?
Hypotriglyceridemic and non-lipid effects of atorvastatin and simvastatin therapy in coronary heart disease patients with combined hyperlipidemia and type 2 diabetes mellitus
E. Vasutina, V.A. Metelskaya, N.M. Akhmedzhanov, L.A. Ratnikova, R.G. Oganov. National Research Centre for Preventive Medicine, Russia Objective: To evaluate the effect of atorvastatin and simvastatin on lipid levels and major haemostasis parameters (fibrinogen, factor VII, ECLT) in CHD patients with combined (IIb) hyperlipidemia and type 2 diabetes mellitus. Methods: Study was randomized placebo-controlled in parallel groups. 40 men (age 61±1.1) were randomized into 3 groups:I-atorvastatin 10 mg (n=15), II-simvastatin 20mg (n=15), III-placebo (n=10). Total cholesterol (TC), LDL C, HDL C, triglycerides (TG) levels and haemostatic parameters have been determined at the beginning and after 3 mo of treatment. Results: In group I fibrinogen level decreased by 7% from 4.5±0.3 to 4.2±0.3 g/l; factor VII activity by 17.4% from 274±36.3 to 226±27.1%; ECLT did not change. The level of TC decreased by 29%, LDL C by 36%, TG by 32%, HDL C level increased by 18%. In group II fibrinogen level deceased by 21% from 4.2±0.4 to 3.3±0.3 g/l; factor VII activity by 25% from 276±22.21 to 206±20.8%; ECLT by 7% from 273±16.2 to 254±12.4 min. The levels of TC, LDL C, TG decreased by -29%,-39%,-33% respectively, HDL C elevated by 31%. In group III no significant changes were found. Conclusion: The both drugs therapy in equivalent doses have significant hypotriglyceridemic effect, significantly inceased HDL C level and in studied patients significantly improved haemostasis paraneters, reducing levels of fibrinogen and factor VII activity; simvastatin, in addition, resulted in some activation of fibrinolysis.
Abstract 1P-0016 – Table
Group A Group B Group C (on therapy) Group C (without therapy) Group C1 Group C2
TC (mg/dL)
LDL (mg/dL)
Non-HDL (mg/dL)
TG (mg/dL)
TG>200mg/dL
LDL<100mg/dL or Non-HDL<130mg/dL)
237±50 218±46 209±46 254±33 194±37 185±25
154±39 140±34 129±47 178±23 116±27 109±19
226±40 218±46 193±59 201±42 175±54 141±15
304±100 363±121 415±289 317±58 336±121 294±66
15.8% 11.25% 15.07% 40% 12.07% 8.20%
3% 13.75% 21.90% 0% 30.17% 34.43%
XIIIth International Symposium on Atherosclerosis, September 28–October 2, 2003, Kyoto, Japan