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Combined correction of CHD risk factors in metabolic syndrome
Posters 11. Lipid Lowering Drugs~Novel
98
provided greater reductions in total cholesterol (-42% vs -30%) (p < .001) and LDL cholesterol (-50% vs -37%) (13 < .01). Three patients treated with Atorvastatin (23%), but none receiving Simvastatin, met the NCEP LDL-C goal at the end of the study. No significant changes in fibrinogen and coagulative variables were observed from baseline. We conclude that in HFH patients Atorvastatin has greater cholesterol lowering efficacy than Simvastatin.
•
COMBINED CORRECTION OF CHD RISK FACTORS IN METABOLIC SYNDROME
N. Perova, M. Mamedov, A. Olferiev, I. Petrichenko, R. Oganov. National Research Center for Preventive Medicine, 10 Petroverigsky Lane, 101953, Moscow, Russia Metabolic syndrome is highly atherogenie since its components are independent risk factors of CHD metabolically integrated by insulin resistance. Purpose of the Study: Study the efficacy of complex correction of the metabolic syndrome components with imidazoline receptor agonist moxonidinc (Solvay Pharma)and hypolipidemic agent micronized fenofibrate (Laboratories Foumier). An open study was curried out in 20 patients (9 male, 11 female, 40-59 years) with 4 components of metabolic syndrome: mild-to-moderate hypertension, abdominal obesity, hyperlipidomia, and insulin resistance - glucose intolerance, hyperinsulinemia and/or fasting glucose/insulin ratio < 6. The study comprised of 3 treatment periods: 2 weeks of nonpharmacologic correction of hypertension and hyperlipidemia, 8 weeks of moxonidine monotherapy (0.2~).4 mg/daily), 8 weeks of combined therapy with moxonidinc at the same dosage and micronized fenofibrate (200 mg/daily). Following mono- and combined therapy systolic and diastolic blood pressure decreased by 12% and 11%, respectively, without alteration of heart rate. After combined therapy, the level of Tg decreased by 40%, apo B - by 25%, fibrinogen by 17%, HDL cholesterol increased by 14%. The levels of glucose, creatinin, uric acid, ALT, AST were unchanged. Fasting insulin decreased significantly from 20.8-4-2.3 to 15.9-1-1.8 mlU/ml after monotherapy and to 12.44-1.5 mlU/ml after combined therapy. The serum insulin becomes elevated after a glucose load comprising 134.7+23.7 mIU/ml in patients treated with combined therapy vs initial level 79.04-9.6 mlU/ml. The glucose/insulin ratio also increased from 5.14-0.5 initially to 6.5-4-0;6 and 10.44-1.9, respectively, after mono- and combined therapy. Conclusions: The combined treatment with moxonidine and micronized fenofibrate resulted in a reduction of insulin resistance and an improvement of atherogenic components of metabolic syndrome that altogether may diminish the total risk of CHD.
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PREVALENCE LONG-TERM THERAPY WITH 2TIBOLONE - ON• LIPIDOFTPROFILE H IN MENOPAUSAL E WOMEN
S. Kalogeropoulos, C. Petrogiannopoulos, A. Zaharof, G. Kalogeropoulos, D. Dandakis, G. Latsios, G. Hartzoulakis, P. Paziouros, C. Flevaris. 2nd
Dept. of Medicine, Hellenic Red Cross Hospital; Dept. of Gynecology, HERA Hospital, Athens, Greece Aim: To evaluate the efficacy of tibolone in lipids of women with menopause Material: The study included 84 rfienopausal women (mean age 49.6-1-3 years). All the women started therapy with tibolone for 4 years after their gynecologist's consultation. Consequently, a full clinical and laboratory follow-up was carried out annually. Results: 11/84 (13%) women stopped tibolone in the 2nd and 3rd year of therapy due to gynecological side effects. The following table shows the changes in lipids before and after 4 years therapy. Risk factors
before therapy
after 4 years
% change
Total eholeslerol (rag%) LDL.-eholesterol (mg%) HDL-eholesterol (mg%) Triglycerides (mg%) Lp(a) (rag%)
242-4-12 1565:8 625:4 1455:18 25-4-4
1985:16 1055:12 715:6 1385:14 225:6
-18 -32 -14.5 -4.8 -12
Conclusion: Long term therapy with tibolone on menopausal women with mild hypercholesterolemia appears to have a beneficial effect on lipid profile, by significantly reducing the levels of total and LDL cholesterol.
~-20-~ EFFECT OF COMBINED THERAPY WITH STATINS AND HYPOTENSIVE DRUGS OF DIFFERENT CLASS ON GLOBAL CORONARY RISK AND INSULIN RESISTANCE IN METABOLIC SYNDROME PATIENTS M. Mamedov, 0. Kosmatova, L. Khadipash, N. Perova, 17,. Oganov.
National Research Center for Preventive Medicine, 10 Petroverigsky Lane, 101953, Moscow, Russia Purpose of the Study: 1. To analyze the changes of global coronary risk in patients received combined therapy with statins and different classes of hypoteusive drugs. 2. To investigate the effects of 4 different types of combined therapy with lipid lowering and hypoteusive drugs on tissue insulin resistance. Methods: 203 patients (male and female) aged 45-65 with arterial hypertension diagnosed 5 years ago were selected. In all patients the components of metabolic syndrome were analyzed including: arterial hypertension-SBP 140-169 mm Hg and/or DBP 90-99 mm Hg; abdominal obesity - waist to hip ratio > 1.0 for men and >0.85 for woman if BMI > 25 KF/M2; hyperlipidemia - Tg level 200 mg/dl and/or total Ch 250 mg/dl; glucose intolerance - basal plasma glucose level up t o 120 mg/dl and 2 hours after 75 g glucose load, 140-200 mg/dl. After 2 weeks of diet 66 patients with metabolic syndrome were randomized on 4 parallel groups. I group patients (n = 16) received daily perindopril 4 mg and atorvastatin 10 rag, II group (n = 17) atenolol 50 mg and simvastatin 10 nag, III group (n = 17) amlodipin 5-10 mg and lovastatin 20 mg, IV group (n = 18) indapamid 2.5 mg and simvastatin 10 mg during 8 weeks. Insulin resistance was calculated as glucose to insulin ratio being less than 6 (fasting and/or 2 hours after glucose load). Global coronary risk was assessed using PROCAM STUDY model (taking into account LDL, Tg, and HDL levels, SBP, diagnosed NIDDM, smoking, patients and family history CHD). Summary of Results: The levels of SBP and DBP significantly decreased in I group (-10.6%, p < 0.01 and -8.4%, p < 0.05), II group (-18.4%, p < 0.001 and -15.4%, p < 0.01), in III group (-15.6% and -15.2%, p < 0.001) and in IV group (-14.1% and -12%, p < 0.01). The concentration of LDL CH in the I group (-42%, p < 0.001), II (-37%, p < 0.01), III (-19.2%, p < 0.01) and 1V group (-29.4%, p < 0.01) also decreased. There was no significant change in HDL level in the first two groups (2.2% and 13%), while in the III and IV groups HDL level increased (18.4% and 18.7%, p < 0.05). The level of Tg decreased by -18% p < 0.01 in I, -21% p < 0.01 in II, -16% p < 0.05 in III and -6.6% p < 0.05 in IV groups. Initially, global coronary risk was high in all groups: 1-31.5%, II-39.9%, I11-38.9% and IV-43.7%. After treatment global risk in all groups decreased significantly: -69.7%, -70.7%, -69.1% and -60.9%, respectively. However, as basal and 2 hours after loading glucose/insulin ratio didn't change significantly in all groups. Conclusions: The combined therapy of statins and hypotensive agents with different mechanisms of action markedly decreases the global coronary risk in metabolic syndrome patients. Significant decrease of LDL CH, Tg levels and blood pressure are not accompanied by changing of basal and postprandial glucose/insulin ratio. ~ - 2 - ~ CAN ATORVASTATIN REPLACE THE COMBINATION OF A FIBRIC ACID DERIVATIVE WITH A "STATIN" DRUG IN THE TREATMENT OF PATIENTS WITH TYPE IIb HYPERCHOLESTEROLEMIA? E. Wolfovitz, I. Avishar, J.G. Brook. Department Internal Medicine D, Rambam Medical Center and Rappaport Faculty of Medicine, Technion, Haifa 31096, lsrael The usual treatment of patients with type lib hyperlipoproteinemia comprises diet and a combination of a fibric acid derivative and a "statin". Atorvastatin has been claimed, unlike the other "statins", to be effective in reducing triglyceride as well as cholesterol levels. Thirty patients with type lib hyperlipoproteinemia receiving both a statin and fibric acid derivative were recruited from our lipid clinic. These patients were divided into 2 groups, one continuing with the regime of statin plus fibric acid derivative and the other commencing atorvastatin 20 rag/day. After 3 months, a crossover was implemented and the groups each received the alternative therapy. As expected, LDL cholesterol was reduced 30% more while the subjects were receiving atorvastatin. Triglyceride levels were 15% higher in the subjects on atorvastatin, but this was reduced when blood glucose levels were taken into consideration in the analysis. We conclude that atorvastatin is a valid substitute for combination therapy of fibric acid derivative and a statin drug in many patients.
72nd EAS Congress
98
provided greater reductions in total cholesterol (-42% vs -30%) (p < .001) and LDL cholesterol (-50% vs -37%) (13 < .01). Three patients treated with Atorvastatin (23%), but none receiving Simvastatin, met the NCEP LDL-C goal at the end of the study. No significant changes in fibrinogen and coagulative variables were observed from baseline. We conclude that in HFH patients Atorvastatin has greater cholesterol lowering efficacy than Simvastatin.
•
COMBINED CORRECTION OF CHD RISK FACTORS IN METABOLIC SYNDROME
N. Perova, M. Mamedov, A. Olferiev, I. Petrichenko, R. Oganov. National Research Center for Preventive Medicine, 10 Petroverigsky Lane, 101953, Moscow, Russia Metabolic syndrome is highly atherogenie since its components are independent risk factors of CHD metabolically integrated by insulin resistance. Purpose of the Study: Study the efficacy of complex correction of the metabolic syndrome components with imidazoline receptor agonist moxonidinc (Solvay Pharma)and hypolipidemic agent micronized fenofibrate (Laboratories Foumier). An open study was curried out in 20 patients (9 male, 11 female, 40-59 years) with 4 components of metabolic syndrome: mild-to-moderate hypertension, abdominal obesity, hyperlipidomia, and insulin resistance - glucose intolerance, hyperinsulinemia and/or fasting glucose/insulin ratio < 6. The study comprised of 3 treatment periods: 2 weeks of nonpharmacologic correction of hypertension and hyperlipidemia, 8 weeks of moxonidine monotherapy (0.2~).4 mg/daily), 8 weeks of combined therapy with moxonidinc at the same dosage and micronized fenofibrate (200 mg/daily). Following mono- and combined therapy systolic and diastolic blood pressure decreased by 12% and 11%, respectively, without alteration of heart rate. After combined therapy, the level of Tg decreased by 40%, apo B - by 25%, fibrinogen by 17%, HDL cholesterol increased by 14%. The levels of glucose, creatinin, uric acid, ALT, AST were unchanged. Fasting insulin decreased significantly from 20.8-4-2.3 to 15.9-1-1.8 mlU/ml after monotherapy and to 12.44-1.5 mlU/ml after combined therapy. The serum insulin becomes elevated after a glucose load comprising 134.7+23.7 mIU/ml in patients treated with combined therapy vs initial level 79.04-9.6 mlU/ml. The glucose/insulin ratio also increased from 5.14-0.5 initially to 6.5-4-0;6 and 10.44-1.9, respectively, after mono- and combined therapy. Conclusions: The combined treatment with moxonidine and micronized fenofibrate resulted in a reduction of insulin resistance and an improvement of atherogenic components of metabolic syndrome that altogether may diminish the total risk of CHD.
•
PREVALENCE LONG-TERM THERAPY WITH 2TIBOLONE - ON• LIPIDOFTPROFILE H IN MENOPAUSAL E WOMEN
S. Kalogeropoulos, C. Petrogiannopoulos, A. Zaharof, G. Kalogeropoulos, D. Dandakis, G. Latsios, G. Hartzoulakis, P. Paziouros, C. Flevaris. 2nd
Dept. of Medicine, Hellenic Red Cross Hospital; Dept. of Gynecology, HERA Hospital, Athens, Greece Aim: To evaluate the efficacy of tibolone in lipids of women with menopause Material: The study included 84 rfienopausal women (mean age 49.6-1-3 years). All the women started therapy with tibolone for 4 years after their gynecologist's consultation. Consequently, a full clinical and laboratory follow-up was carried out annually. Results: 11/84 (13%) women stopped tibolone in the 2nd and 3rd year of therapy due to gynecological side effects. The following table shows the changes in lipids before and after 4 years therapy. Risk factors
before therapy
after 4 years
% change
Total eholeslerol (rag%) LDL.-eholesterol (mg%) HDL-eholesterol (mg%) Triglycerides (mg%) Lp(a) (rag%)
242-4-12 1565:8 625:4 1455:18 25-4-4
1985:16 1055:12 715:6 1385:14 225:6
-18 -32 -14.5 -4.8 -12
Conclusion: Long term therapy with tibolone on menopausal women with mild hypercholesterolemia appears to have a beneficial effect on lipid profile, by significantly reducing the levels of total and LDL cholesterol.
~-20-~ EFFECT OF COMBINED THERAPY WITH STATINS AND HYPOTENSIVE DRUGS OF DIFFERENT CLASS ON GLOBAL CORONARY RISK AND INSULIN RESISTANCE IN METABOLIC SYNDROME PATIENTS M. Mamedov, 0. Kosmatova, L. Khadipash, N. Perova, 17,. Oganov.
National Research Center for Preventive Medicine, 10 Petroverigsky Lane, 101953, Moscow, Russia Purpose of the Study: 1. To analyze the changes of global coronary risk in patients received combined therapy with statins and different classes of hypoteusive drugs. 2. To investigate the effects of 4 different types of combined therapy with lipid lowering and hypoteusive drugs on tissue insulin resistance. Methods: 203 patients (male and female) aged 45-65 with arterial hypertension diagnosed 5 years ago were selected. In all patients the components of metabolic syndrome were analyzed including: arterial hypertension-SBP 140-169 mm Hg and/or DBP 90-99 mm Hg; abdominal obesity - waist to hip ratio > 1.0 for men and >0.85 for woman if BMI > 25 KF/M2; hyperlipidemia - Tg level 200 mg/dl and/or total Ch 250 mg/dl; glucose intolerance - basal plasma glucose level up t o 120 mg/dl and 2 hours after 75 g glucose load, 140-200 mg/dl. After 2 weeks of diet 66 patients with metabolic syndrome were randomized on 4 parallel groups. I group patients (n = 16) received daily perindopril 4 mg and atorvastatin 10 rag, II group (n = 17) atenolol 50 mg and simvastatin 10 nag, III group (n = 17) amlodipin 5-10 mg and lovastatin 20 mg, IV group (n = 18) indapamid 2.5 mg and simvastatin 10 mg during 8 weeks. Insulin resistance was calculated as glucose to insulin ratio being less than 6 (fasting and/or 2 hours after glucose load). Global coronary risk was assessed using PROCAM STUDY model (taking into account LDL, Tg, and HDL levels, SBP, diagnosed NIDDM, smoking, patients and family history CHD). Summary of Results: The levels of SBP and DBP significantly decreased in I group (-10.6%, p < 0.01 and -8.4%, p < 0.05), II group (-18.4%, p < 0.001 and -15.4%, p < 0.01), in III group (-15.6% and -15.2%, p < 0.001) and in IV group (-14.1% and -12%, p < 0.01). The concentration of LDL CH in the I group (-42%, p < 0.001), II (-37%, p < 0.01), III (-19.2%, p < 0.01) and 1V group (-29.4%, p < 0.01) also decreased. There was no significant change in HDL level in the first two groups (2.2% and 13%), while in the III and IV groups HDL level increased (18.4% and 18.7%, p < 0.05). The level of Tg decreased by -18% p < 0.01 in I, -21% p < 0.01 in II, -16% p < 0.05 in III and -6.6% p < 0.05 in IV groups. Initially, global coronary risk was high in all groups: 1-31.5%, II-39.9%, I11-38.9% and IV-43.7%. After treatment global risk in all groups decreased significantly: -69.7%, -70.7%, -69.1% and -60.9%, respectively. However, as basal and 2 hours after loading glucose/insulin ratio didn't change significantly in all groups. Conclusions: The combined therapy of statins and hypotensive agents with different mechanisms of action markedly decreases the global coronary risk in metabolic syndrome patients. Significant decrease of LDL CH, Tg levels and blood pressure are not accompanied by changing of basal and postprandial glucose/insulin ratio. ~ - 2 - ~ CAN ATORVASTATIN REPLACE THE COMBINATION OF A FIBRIC ACID DERIVATIVE WITH A "STATIN" DRUG IN THE TREATMENT OF PATIENTS WITH TYPE IIb HYPERCHOLESTEROLEMIA? E. Wolfovitz, I. Avishar, J.G. Brook. Department Internal Medicine D, Rambam Medical Center and Rappaport Faculty of Medicine, Technion, Haifa 31096, lsrael The usual treatment of patients with type lib hyperlipoproteinemia comprises diet and a combination of a fibric acid derivative and a "statin". Atorvastatin has been claimed, unlike the other "statins", to be effective in reducing triglyceride as well as cholesterol levels. Thirty patients with type lib hyperlipoproteinemia receiving both a statin and fibric acid derivative were recruited from our lipid clinic. These patients were divided into 2 groups, one continuing with the regime of statin plus fibric acid derivative and the other commencing atorvastatin 20 rag/day. After 3 months, a crossover was implemented and the groups each received the alternative therapy. As expected, LDL cholesterol was reduced 30% more while the subjects were receiving atorvastatin. Triglyceride levels were 15% higher in the subjects on atorvastatin, but this was reduced when blood glucose levels were taken into consideration in the analysis. We conclude that atorvastatin is a valid substitute for combination therapy of fibric acid derivative and a statin drug in many patients.
72nd EAS Congress