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116 Anti-atherogenic effect of calcium antagonist plus statin combination: amlodipine and lovastatin
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Abstracts
115
113 of elderly referrals to a lipid clinic H. Nawawi, LB Day, D.P Mikhailidts, AI? WC&r Royal Free Hospital School of Medicine, London UK. Audit
terolemia. An “a priori” planned sub-group analysis of the A.D.E.P. hu Mawimo Milani, Michela Mademo’ and Aldo Longoni*. Cardiovascular and *Biometrics Departments, Sandoz PF, Milan, Italy. ln patients at high cardiovascular risk, concomitant hypercholestemlemia may reduce the protective effect of antiplatelet drugs such as aspirin or ticlopidine. It has been shown that hyperlipemic patients are at increased risk of stroke recurrence despite aspirin treatment (Bonrrtein 1994). Pi&amide is ao orally active a&platelet agent which inhibits thmmboxane (TX) A2 synthesis and antagonizes TX receptors. The ADEP (Atherosclerotic Disease Evolution by Pi&amide) trial had evaluated the effects on cardiovasular events of picotamide, in comparison to placebo, in 23 13 patients with peripheral occlusive vascular disease. In the shldy population as a whole, picotamide reduced cardiovascolar risk by 19% (P = 0.056; Logmnk test). We conducted, in an “a priori” planned hypothesis, a subgroup analysis to assessthe influence of concomitant hypercholesterolemia on the protective effect of picotsmide on cardiovascular events in claudicant patients. The efficacy of picotamide was therefore assessed in the ADEP subgroup of hypercholestemlemic patients in order to test if the drug was still effective in this higher risk group. Hypercholesterolemia was defmed as a sennn total cholesterol (TC) greater than 5.2 mmoliL, measured at baseline. In picotamide-treated group, hypercholesterolemic patients were 783, whereas 262 were the patients with a TC < 5.2 mmol/L. During the 18month of follow-up, there were 78 (9.9%) cardiovascular events (death, myocardial infarction, stroke, TIA, unstable angina, amputation) in the 783 hypercholestemlemic picotamide-treated patients as compared to 140 (13.1%) events in the 1066 placebo-treated subjects (Relative Risk Reduction: 27%, P = 0.03, Mantel-Haenszel Chi-Square test). In picotamide-treated patients, no statistical significant differences on cardiovascular event rate were observed among normo- and hyper-cholestemlemic patients (10.6% and 9.9%, respectively). In patients with peripheral occlusive vascular disease, picotamide effectively reduced cardiovascular events, irrespective to semm total cholesterol levels.
Current interest in routine health checks and in the burden of cardiovascular disease in old age has increased the proportion of elderly patients referred to specialist cardiovascular risk management clinics. Are these referrals justified? We have analysed patterns of referral and subsequent clinic findings for 67 male 84 female total 151 documented referrals at age 70+, range 7&92 years. Plasma lipid protIles at presentation (mean + Zsd) were: Males: cholesterol 7.0 * 3.4, triglycerides 5.1 * 4.6, HDL 1.3 * 0.7 mmol/l Females:cholesterol7.7 i 2.7,triglycerides 3.7 * 3.0, HDLl.5 & l.Ommolil Reason for referral was classified as: 12/151. * Routine health checks, ie no specific justification: 19051. * No cliical symptoms but other risk factors present: 119/151. * Presence of active cardiovascular disease: * None of above but clinical signs of lipaemia eg. xanthelasma: 11151. Clinic findings. other disorders with the potential to cause secondary lipaemia eg. diabetes, hypothyroid, were known at referral for 5 1, and at clinic were shown for a further 29, total SO/l51 patients. Overweight BMI > 25 affected 611151 (40%) of referrals. Undetected atheroma-related disease was found in 2 further patients, total 121/151 patients. Conclusions. Some referrals came from hospital clinics, mainly vascular surgery aod cardiology. Most came from family practitioners: our fmdiigs show that they have moderate but incomplete appreciation of secondary lipaemia, and the advantages of weight control supervised in family practices in the management of dyslipidaemia. Unexpectedly however the majority of referrals were justified on clinical grounds as secondary prevention in that patients had clinical atheroma-related disease. Also, the habit of routine health checks has not significantly increased the workload of elderly referrals to this clinic.
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116
The influence of Voglibose and Acarboae oo plasma lipids in NIDDM patients in the fasting aad postprandial state. M. Nauck. K M&z, I! Kleist, E. Stridde and H. F7eland. University of Freiburg, Germany; Takeda Euro R & D Centre, Fmnkfut, Germany
Anti-atherogenie effect of calcium antagonist plus statin combination: amlodipine and lovastatin A.N. Orekhov, M Term LA. Sobenin, E.M. Pivovarova Institute of Experimental Cardiology, Cardiology Research Center, Instihite for Atherosclerosis Research, Ltd., Moscow, Russia
Both, impairment of glucose and lipid metabolism are components of the insulin resistance syndrome. The aim of this study was to investigate whether the a-glucosidase inhibitors voglibose and acarbose influence plasma lipids in diabetics. 170 hospitalized NIDDM patients were mndomly allocated to six parallel groups and received 7 days treatment with either three times daily voglibose (0.5,1,2,5 mg), acarbose (100 mg) or placebo. Blood samples were taken before and 2,3 and 4 hours after a carbohydrate rich standard meal on day -1 and day 7 to aoalyse phospholipids (PL), triglycerides (TG), cholesterol (C) in the serum and in VLDL, LDL and HDL as well as apolipopmteins (ape) Al, All, B (total, VLDL, and LDL), Clll, E, and Lp(a). The effects of the treatments were analysed by one-factorial analysis of variance of the difference (day 7 minus day -1). 157 patients (mean age 54 years; 135 male) could be analysed. Fasting lipids. Voglibose decreased fasting TG (-8 % and -16% at 1 mg and 5 mg per day), VLDL-TG (-8 % and - 12%), VLDL-C and VL.DL-PL; none of these changes, however, was significantly different from placebo. Acarbose had no effect on fasting TG. Voglibose (5 mg) decreased apoE (- 13 %, p < 0.05) and apoCIIl (-7%. p = 0.170). There were no consistent cb.anges in LDL-C, apoB and Lp(a). Voglibose did not change fasting HDL-C, but acarbose lowered HDL-C fmm 0.95 to 0.90 mmovl (-6 %, p < 0.05). Postprandial lipids. On day -1, total TG increased in all groups by 12% on average 2 hours after the test meal. The 2 hours postprandial TG were dosedependently reduced by voglibose (from 2.1 to 1.6 nun&l at 5 fng, p = 0.02). Consistent changes were obtained with 5 mg Voglibose for VLDL-TG (- 16%, p < 0.05), VLDL-C (21%, p = 0.07), VLDL-PL (-22%, p < 0.05), apoE (-13%, p < 0.01) and apoCIH (-6 %, p < 0.05); there were only slight reductions in the acarbose group. We conclude that voglib-xe is more potent than acarbose in reducing fasting TGrich lipoproteins and the postprandial TG response.
In the t?ame of the Regression Gmwth Evaluation Statin Study (REGRESS) trial synergistic anti-athemgenic effect of lipid lowering therapy with pravastatin in combination with calcium antagonists has recently been shown. Such a combination retarded pmgression of stenosis and reduced the number of new lesions more effectively than statin alone. In present study, we tried to elucidate the mechanism of more pmnouoced effect of statincalcium antagonist combination on atherosclerotic lesion. For this purpose smooth muscle cells cultured from subendothelial intima of human aorta were incubated with whole blood serum or low density lipomtein (LDL) taken from patients cotreated with lovastatin and amlodipine. As a result of the treatment, serum added to cells cultured t?om athemsclerotic lesion reduced cell cholesterol. Such an anti-atherosclerotic effect of cotreatment with amlodipine-lovastatin has been revealed earlier and was more pronounced compared with the effect of the treatment with an&&pine or lovastatin alone. LDL isolated from athemgenic plasma stimulated cell cholesteml accumulation. Treatment with amlodipine alone sad amlodipine-lovastatin combination lowered this athemgenic effect of LDL. As compared with amlodipine alone, combination demonstrated considerably higher anti&erogenic effect at the LDL level. Amlodipine-lovastatin cotreatment increased sialic acid and decreased LDL susceptibility to oxidation more effectively than amlodipine alone. IO addition, the combination reduced LDL negative charge while amlodipine was impotent. These findings may serve as an explanation of more pronounced anti-a&m genie effect at the lipoprotein level of amlodipine-lovastatin cotreatment compared with amlodipine alone.
Abstracts
115
113 of elderly referrals to a lipid clinic H. Nawawi, LB Day, D.P Mikhailidts, AI? WC&r Royal Free Hospital School of Medicine, London UK. Audit
terolemia. An “a priori” planned sub-group analysis of the A.D.E.P. hu Mawimo Milani, Michela Mademo’ and Aldo Longoni*. Cardiovascular and *Biometrics Departments, Sandoz PF, Milan, Italy. ln patients at high cardiovascular risk, concomitant hypercholestemlemia may reduce the protective effect of antiplatelet drugs such as aspirin or ticlopidine. It has been shown that hyperlipemic patients are at increased risk of stroke recurrence despite aspirin treatment (Bonrrtein 1994). Pi&amide is ao orally active a&platelet agent which inhibits thmmboxane (TX) A2 synthesis and antagonizes TX receptors. The ADEP (Atherosclerotic Disease Evolution by Pi&amide) trial had evaluated the effects on cardiovasular events of picotamide, in comparison to placebo, in 23 13 patients with peripheral occlusive vascular disease. In the shldy population as a whole, picotamide reduced cardiovascolar risk by 19% (P = 0.056; Logmnk test). We conducted, in an “a priori” planned hypothesis, a subgroup analysis to assessthe influence of concomitant hypercholesterolemia on the protective effect of picotsmide on cardiovascular events in claudicant patients. The efficacy of picotamide was therefore assessed in the ADEP subgroup of hypercholestemlemic patients in order to test if the drug was still effective in this higher risk group. Hypercholesterolemia was defmed as a sennn total cholesterol (TC) greater than 5.2 mmoliL, measured at baseline. In picotamide-treated group, hypercholesterolemic patients were 783, whereas 262 were the patients with a TC < 5.2 mmol/L. During the 18month of follow-up, there were 78 (9.9%) cardiovascular events (death, myocardial infarction, stroke, TIA, unstable angina, amputation) in the 783 hypercholestemlemic picotamide-treated patients as compared to 140 (13.1%) events in the 1066 placebo-treated subjects (Relative Risk Reduction: 27%, P = 0.03, Mantel-Haenszel Chi-Square test). In picotamide-treated patients, no statistical significant differences on cardiovascular event rate were observed among normo- and hyper-cholestemlemic patients (10.6% and 9.9%, respectively). In patients with peripheral occlusive vascular disease, picotamide effectively reduced cardiovascular events, irrespective to semm total cholesterol levels.
Current interest in routine health checks and in the burden of cardiovascular disease in old age has increased the proportion of elderly patients referred to specialist cardiovascular risk management clinics. Are these referrals justified? We have analysed patterns of referral and subsequent clinic findings for 67 male 84 female total 151 documented referrals at age 70+, range 7&92 years. Plasma lipid protIles at presentation (mean + Zsd) were: Males: cholesterol 7.0 * 3.4, triglycerides 5.1 * 4.6, HDL 1.3 * 0.7 mmol/l Females:cholesterol7.7 i 2.7,triglycerides 3.7 * 3.0, HDLl.5 & l.Ommolil Reason for referral was classified as: 12/151. * Routine health checks, ie no specific justification: 19051. * No cliical symptoms but other risk factors present: 119/151. * Presence of active cardiovascular disease: * None of above but clinical signs of lipaemia eg. xanthelasma: 11151. Clinic findings. other disorders with the potential to cause secondary lipaemia eg. diabetes, hypothyroid, were known at referral for 5 1, and at clinic were shown for a further 29, total SO/l51 patients. Overweight BMI > 25 affected 611151 (40%) of referrals. Undetected atheroma-related disease was found in 2 further patients, total 121/151 patients. Conclusions. Some referrals came from hospital clinics, mainly vascular surgery aod cardiology. Most came from family practitioners: our fmdiigs show that they have moderate but incomplete appreciation of secondary lipaemia, and the advantages of weight control supervised in family practices in the management of dyslipidaemia. Unexpectedly however the majority of referrals were justified on clinical grounds as secondary prevention in that patients had clinical atheroma-related disease. Also, the habit of routine health checks has not significantly increased the workload of elderly referrals to this clinic.
114
116
The influence of Voglibose and Acarboae oo plasma lipids in NIDDM patients in the fasting aad postprandial state. M. Nauck. K M&z, I! Kleist, E. Stridde and H. F7eland. University of Freiburg, Germany; Takeda Euro R & D Centre, Fmnkfut, Germany
Anti-atherogenie effect of calcium antagonist plus statin combination: amlodipine and lovastatin A.N. Orekhov, M Term LA. Sobenin, E.M. Pivovarova Institute of Experimental Cardiology, Cardiology Research Center, Instihite for Atherosclerosis Research, Ltd., Moscow, Russia
Both, impairment of glucose and lipid metabolism are components of the insulin resistance syndrome. The aim of this study was to investigate whether the a-glucosidase inhibitors voglibose and acarbose influence plasma lipids in diabetics. 170 hospitalized NIDDM patients were mndomly allocated to six parallel groups and received 7 days treatment with either three times daily voglibose (0.5,1,2,5 mg), acarbose (100 mg) or placebo. Blood samples were taken before and 2,3 and 4 hours after a carbohydrate rich standard meal on day -1 and day 7 to aoalyse phospholipids (PL), triglycerides (TG), cholesterol (C) in the serum and in VLDL, LDL and HDL as well as apolipopmteins (ape) Al, All, B (total, VLDL, and LDL), Clll, E, and Lp(a). The effects of the treatments were analysed by one-factorial analysis of variance of the difference (day 7 minus day -1). 157 patients (mean age 54 years; 135 male) could be analysed. Fasting lipids. Voglibose decreased fasting TG (-8 % and -16% at 1 mg and 5 mg per day), VLDL-TG (-8 % and - 12%), VLDL-C and VL.DL-PL; none of these changes, however, was significantly different from placebo. Acarbose had no effect on fasting TG. Voglibose (5 mg) decreased apoE (- 13 %, p < 0.05) and apoCIIl (-7%. p = 0.170). There were no consistent cb.anges in LDL-C, apoB and Lp(a). Voglibose did not change fasting HDL-C, but acarbose lowered HDL-C fmm 0.95 to 0.90 mmovl (-6 %, p < 0.05). Postprandial lipids. On day -1, total TG increased in all groups by 12% on average 2 hours after the test meal. The 2 hours postprandial TG were dosedependently reduced by voglibose (from 2.1 to 1.6 nun&l at 5 fng, p = 0.02). Consistent changes were obtained with 5 mg Voglibose for VLDL-TG (- 16%, p < 0.05), VLDL-C (21%, p = 0.07), VLDL-PL (-22%, p < 0.05), apoE (-13%, p < 0.01) and apoCIH (-6 %, p < 0.05); there were only slight reductions in the acarbose group. We conclude that voglib-xe is more potent than acarbose in reducing fasting TGrich lipoproteins and the postprandial TG response.
In the t?ame of the Regression Gmwth Evaluation Statin Study (REGRESS) trial synergistic anti-athemgenic effect of lipid lowering therapy with pravastatin in combination with calcium antagonists has recently been shown. Such a combination retarded pmgression of stenosis and reduced the number of new lesions more effectively than statin alone. In present study, we tried to elucidate the mechanism of more pmnouoced effect of statincalcium antagonist combination on atherosclerotic lesion. For this purpose smooth muscle cells cultured from subendothelial intima of human aorta were incubated with whole blood serum or low density lipomtein (LDL) taken from patients cotreated with lovastatin and amlodipine. As a result of the treatment, serum added to cells cultured t?om athemsclerotic lesion reduced cell cholesterol. Such an anti-atherosclerotic effect of cotreatment with amlodipine-lovastatin has been revealed earlier and was more pronounced compared with the effect of the treatment with an&&pine or lovastatin alone. LDL isolated from athemgenic plasma stimulated cell cholesteml accumulation. Treatment with amlodipine alone sad amlodipine-lovastatin combination lowered this athemgenic effect of LDL. As compared with amlodipine alone, combination demonstrated considerably higher anti&erogenic effect at the LDL level. Amlodipine-lovastatin cotreatment increased sialic acid and decreased LDL susceptibility to oxidation more effectively than amlodipine alone. IO addition, the combination reduced LDL negative charge while amlodipine was impotent. These findings may serve as an explanation of more pronounced anti-a&m genie effect at the lipoprotein level of amlodipine-lovastatin cotreatment compared with amlodipine alone.