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MS67 INTERRELATION BETWEEN OBSTRUCTIVE SLEEP APNEA AND LIPID SPECTRUM AMONG CARDIOVASCULAR PATIENTS
78th EAS Congress
Atherosclerosis Supplements 11, no. 2 (2010) 109–222
MS63 PARADOXICAL DECREASE IN HIGH DENSITY LIPOPROTEIN CHOLESTEROL WITH FENOFIBRATE: A QUITE RARE PHENOMENON INDEED G. Mombelli1 , F. Pazzucconi1 , A. Bondioli1 , A. Zanaboni2 , S. Gaito2 , L. Calabresi3 , C.R. Sirtori1,3 . 1 University Center for Dyslipidemias, Niguarda Hospital, 2 Department of Computer Sciences, 3 Department of Pharmacological Sciences, University of Milan, Milan, Italy Some recent clinical reports have suggested that paradoxical decreases in high density lipoprotein cholesterol (HDL-C) levels after fenofibrate treatment may be quite common. These appear to occur mainly in patients with combined fibrate/statin therapy and possibly in those with low baseline HDL-C. Reports on HDL-C reductions after fenofibrate are possibly supported by the disappointing results in terms of HDL-C responses from the recent FIELD study. A survey on 581 patients treated for one year or longer was carried out in our Clinical Center. This indicated that paradoxical HDL-C reductions are a relatively uncommon phenomenon. Not more than 15.3% of the present series showed an HDL-C reduction, mostly of a modest degree. Further, reductions of HDL-C appear to occur mainly in individuals with significant HDL-C elevations (> 50 mg/dl), almost never in patients with low HDL-C. Otherwise, there seems to be no impact of a previous diagnosis of diabetes or hypertension on the HDL-C changes. From a very recent pharmacogenomic study on the apo A1/C3/A4/A5 gene cluster, genetic influences appear only to reduce the positive impact of fenofibrate on HDL-C, but do not indicate any risk of occurrence of HDL-C reductions. Also based on our very long experience with this drug, it appears that fenofibrate raises HDL-C levels in the vast majority of treated patient, with a particularly dramatic effect in individuals with low HDL-C and hypertriglyceridemia. MS64 CAPILLARY ISOTACHOPHORESIS AS AN OVERALL TOOL TO REVEAL ATHEROGENIC LIPOPROTEIN PHENOTYPE A. Dergunov1 , S. Visvikis-Siest2 , G. Siest2 . 1 Biochemistry, National Research Centre for Preventive Medicine, Moscow, Russia, 2 INSERM U525 − Equipe 4, EA 4003, Universite´ Henri Poincare´ − Faculte de Pharmacie, Nancy, France Object: Hypertriglyceridemia, diminished HDL content and the presence of small dense LDL are common features of atherogenic lipoprotein phenotype. Besides, the accumulation of nascent HDL with pre-beta electrophorertic mobility is suggested to reflect the deficiency of reverse cholesterol transport. Results and Conclusion: The original approach was developed to follow 11−12 individual lipoproteins by capillary isotachophoresis (CITP) of parallel plasma aliquots pre-stained with lipid-specific fluorescent probe or fluoresceinlabeled apoE. The slow HDL with pre-beta mobility (sHDL) and fast LDL with the increased negative charge (fLDL) were precisely localized in lipid and apolipoprotein CITP profiles. For 10 patients with e3/e3 genotype and plasma triglyceride content varying in a wide range, the fLDL content was positively associated with VLDL while negatively with HDL cholesterol, thus evidencing the fLDL accumulation in hypertriglyceridemia. Besides, apoE content in sHDL increased at the decrease of HDL cholesterol. The affinity parameters of apoE binding to individual lipoproteins were measured at plasma titration by apoC-III, followed by residual apoE detection. These parameters for sHDL and fLDL were associated positively, assuming the common metabolic pathway(s). This metabolomic-like approach is suggested to permit the overall, fast and quantitative determination of atherogenic lipoprotein phenotype. MS65 WOMEN’S HEALTH: ESTROGEN, PROGESTINS AND BLOOD PRESSURE R.-M. Korth. Research in General Medicine Fida, Lehrauftrag LMU, Munich, Germany Aim: A hypertensive risk was invented here with women during pregnancy, intolerance to glucose (IGTT:www.fidabus.com) or with hormone users or with non-pregnant women at metabolic risk beyond hormone use. Methods: Initial biomarkers were anonymously enrolled and oral glucose tolerance was tested (1h-50 g-oGTT Reflotron Roche, R.M. Korth, JMHG 2006). Results: First, pregnant women with reversible IGTT had values between 140– 169 mg/dl glucose (16% of 180, aged 31±5 years, 23±4 kg/m2 ) reporting healthy food and lifestyle. Normal blood pressure was observed (week 22±2: 104±13/64±11 mmHg; week 38±2: 110±8/73±5 mmHg, ±1S.D.). Pregnant women with persisting control-IGTT tended to gestation diabetes elsewhere (4% 170 mg/dl, 1-h-100 g glucose). Second, oral contraceptives were not correlated with raised blood pressure (p > 0.1) probably as weight and lipids were normal (n = 49, 22±4 kg/m2 , aged 27±7 years, 117±13/82±9 mmHg, LDL: 127±36, HDL: 66±14 mg/dl). Third, aging women with menopausal HRThormones (15 out of 46, aged 51±9 years, 25±5 kg/m2 ) were compared to those without HRT and led away from raised blood pressure (p > 0.35). Overall, non-pregnant women with IGTT and mixed hyperlipidemia showed hypertension (n = 14, aged 32±10 years, 26±6 kg/m2 , LDL: 167±65, HDL: 54±9, Trig: 254±73 mg/ml, 136±25/97±12 mmHg). Indeed, women with IGTT or mixed hyperlipidemia had significantly higher blood pressure than appropriate
123
controls (p < 0.003) and multivariate analysis provided evidence for direct risk of diastolic hypertension (p < 0.05). This model is suitable to adress hormonal compositions without hypertension as only participants with IGTThyperinsulinemia or mixed hyperlipidemia were at direct risk for diastolic hypertension. MS66 MODIFIED, EXTRACTED BARLEY BETA GLUCAN (BBG) EFFECTIVELY LOWERS LDL CHOLESTEROL DESPITE REDUCED VISCOSITY J. Keenan. Dept of Family Medicine, University of Minnesota, Minneapolis, MN, USA Many studies have shown that foods rich in viscous fibers can lower LDL- C. This study compared the effect on blood lipids of a food and beverage fortified with unmodified BBG (HMW), average molecular weight of 1000 kDa, to the effect of the same food and beverage fortified with modified BBG (LMW), average molecular weight 50–400 kDa in persons with moderate dyslipidemia. Subjects (N = 155) with LDL-C levels between 130 and 190 mg/dl after a 4 week run in period on a “heart-healthy” diet were randomized to 5 parallel treatment arms (5 g/d HMW, 5 g/d LMW, 3 g/d HMW, 3 g/d LMW or control). Over the six week treatment period subjects consumed one serving per day of a fortified cereal and one serving per day of a fortified beverage or control. Results: Change from baseline in LDL-C (5 g HMW = −22.5 mg/dl (−14.6%); 5 g LMW = −20.3 mg/dl (−13.1%); 3 g HMW = −14 mg/dl (−9%); 3 g LMW = −13.4 mg/dl (−9%). There was good compliance with all treatments with all subject groups consuming 94+% of servings and there were no drop outs or significant differences in side effects reported except for increased intestinal gas in the 5 g HMW compared to control. MS67 INTERRELATION BETWEEN OBSTRUCTIVE SLEEP APNEA AND LIPID SPECTRUM AMONG CARDIOVASCULAR PATIENTS N. Belinskaya1 , L. Yashina2 . 1 Sleep Medicine Center, 2 Polyclinic Therapy Department, Chelyabinsk State Medical University, Chelyabinsk, Russia Introduction: It has been proved in the research that people suffering from obstructive sleep apnea (OSA) are subject to high risk of atherosclerosis, hypertensive disease and death. Objectives: Research prevalence of OSA among cardiovascular patients. Research interrelation between obstructive sleep apnea and lipid spectrum among cardiovascular patients. Material and Methods: 242 patients with hypertensive disease and coronary heart disease with clinical signs of OSA have been examined. There were 172 men and 70 women, their age was from 32 to 65 years. Polysomnography, lipidogram, glucose and uric acid have been investigated. Results of research: Significant forms of OSA (apnea-hypopnea index is more than 15 per hour) have been revealed among 67 patients (27.6%), there were significantly more men (41.3%) than women (8.6%), p < 0.05. Hypercholesterolemia (LDL is more than 2.5 mmole/l) was discovered among 52% of the patients suffering from OSA against 18% without OSA. Reduced level of HDL-C was more often found among the patients with OSA − 69% against 38% (p < 0.05). Fasting hyperglycemia and impaired glucose tolerance was found among 12% with OSA and 11% without OSA; hyperuricemia − among 42% of the patients with OSA and 8% without OSA (p < 0.05). Conclusions: Thus, men with cardiovascular diseases are suffering definitely more often from OSA. Patients with SOAS more often have hyperuricemia, hypercholesterolemia and reduced level of HDL-C. MS68 ATHEROGENIC DISLIPIDEMIA IN METABOLIC SYNDROME: ROLE OF INSULIN RESISTANCE, NONESTERIFIED FATTY ACIDS AND ADIPOKINES D. Tanyanskiy1 , E. Firova1,2 , L. Shatilina2 , A. Denisenko1 . 1 Department of Biochemistry, 2 IEM Clinic, Institute of Experimental Medicine RAMS, St. Petersburg, Russia Objective: Metabolic syndrome (MS) is a result of complex interaction of different biochemical pathways. The aim was to evaluate the role of insulin resistance, nonesterified fatty acids (NEFA) and adipokines in pathogenesis of atherogenic dislipidemia in patients with metabolic syndrome. Methods: 113 patients (44 males and 69 females) with MS and 45 patients (24 males and 21 females) without MS were studied. Mean age was 57.4±9.2 years and it didn’t differed between groups. All patients had stable forms of coronary heart disease. We measured anthropometric and lipid parameters, concentration of plasma glucose. Insulin, leptin and adiponectin levels were determined by ELISA. Insulin sensitivity was estimated by index HOMA. Results: Patients with MS in comparison with control group had higher concentrations of triglycerides, NEFA, glucose, insulin, leptin and lower content of high-density lipoprotein cholesterol (HDL-C) and adiponectin. According to multiple linear regression analysis, plasma concentration of triglycerides was determined by body mass index (b = 0.40, p < 0.0001), contents of glucose (b = 0.22, p = 0.003) and NEFA (b = 0.23, p = 0.003), while concentration of HDL-C was determined only by NEFA content (b = −0.22, p = 0.01).
Atherosclerosis Supplements 11, no. 2 (2010) 109–222
MS63 PARADOXICAL DECREASE IN HIGH DENSITY LIPOPROTEIN CHOLESTEROL WITH FENOFIBRATE: A QUITE RARE PHENOMENON INDEED G. Mombelli1 , F. Pazzucconi1 , A. Bondioli1 , A. Zanaboni2 , S. Gaito2 , L. Calabresi3 , C.R. Sirtori1,3 . 1 University Center for Dyslipidemias, Niguarda Hospital, 2 Department of Computer Sciences, 3 Department of Pharmacological Sciences, University of Milan, Milan, Italy Some recent clinical reports have suggested that paradoxical decreases in high density lipoprotein cholesterol (HDL-C) levels after fenofibrate treatment may be quite common. These appear to occur mainly in patients with combined fibrate/statin therapy and possibly in those with low baseline HDL-C. Reports on HDL-C reductions after fenofibrate are possibly supported by the disappointing results in terms of HDL-C responses from the recent FIELD study. A survey on 581 patients treated for one year or longer was carried out in our Clinical Center. This indicated that paradoxical HDL-C reductions are a relatively uncommon phenomenon. Not more than 15.3% of the present series showed an HDL-C reduction, mostly of a modest degree. Further, reductions of HDL-C appear to occur mainly in individuals with significant HDL-C elevations (> 50 mg/dl), almost never in patients with low HDL-C. Otherwise, there seems to be no impact of a previous diagnosis of diabetes or hypertension on the HDL-C changes. From a very recent pharmacogenomic study on the apo A1/C3/A4/A5 gene cluster, genetic influences appear only to reduce the positive impact of fenofibrate on HDL-C, but do not indicate any risk of occurrence of HDL-C reductions. Also based on our very long experience with this drug, it appears that fenofibrate raises HDL-C levels in the vast majority of treated patient, with a particularly dramatic effect in individuals with low HDL-C and hypertriglyceridemia. MS64 CAPILLARY ISOTACHOPHORESIS AS AN OVERALL TOOL TO REVEAL ATHEROGENIC LIPOPROTEIN PHENOTYPE A. Dergunov1 , S. Visvikis-Siest2 , G. Siest2 . 1 Biochemistry, National Research Centre for Preventive Medicine, Moscow, Russia, 2 INSERM U525 − Equipe 4, EA 4003, Universite´ Henri Poincare´ − Faculte de Pharmacie, Nancy, France Object: Hypertriglyceridemia, diminished HDL content and the presence of small dense LDL are common features of atherogenic lipoprotein phenotype. Besides, the accumulation of nascent HDL with pre-beta electrophorertic mobility is suggested to reflect the deficiency of reverse cholesterol transport. Results and Conclusion: The original approach was developed to follow 11−12 individual lipoproteins by capillary isotachophoresis (CITP) of parallel plasma aliquots pre-stained with lipid-specific fluorescent probe or fluoresceinlabeled apoE. The slow HDL with pre-beta mobility (sHDL) and fast LDL with the increased negative charge (fLDL) were precisely localized in lipid and apolipoprotein CITP profiles. For 10 patients with e3/e3 genotype and plasma triglyceride content varying in a wide range, the fLDL content was positively associated with VLDL while negatively with HDL cholesterol, thus evidencing the fLDL accumulation in hypertriglyceridemia. Besides, apoE content in sHDL increased at the decrease of HDL cholesterol. The affinity parameters of apoE binding to individual lipoproteins were measured at plasma titration by apoC-III, followed by residual apoE detection. These parameters for sHDL and fLDL were associated positively, assuming the common metabolic pathway(s). This metabolomic-like approach is suggested to permit the overall, fast and quantitative determination of atherogenic lipoprotein phenotype. MS65 WOMEN’S HEALTH: ESTROGEN, PROGESTINS AND BLOOD PRESSURE R.-M. Korth. Research in General Medicine Fida, Lehrauftrag LMU, Munich, Germany Aim: A hypertensive risk was invented here with women during pregnancy, intolerance to glucose (IGTT:www.fidabus.com) or with hormone users or with non-pregnant women at metabolic risk beyond hormone use. Methods: Initial biomarkers were anonymously enrolled and oral glucose tolerance was tested (1h-50 g-oGTT Reflotron Roche, R.M. Korth, JMHG 2006). Results: First, pregnant women with reversible IGTT had values between 140– 169 mg/dl glucose (16% of 180, aged 31±5 years, 23±4 kg/m2 ) reporting healthy food and lifestyle. Normal blood pressure was observed (week 22±2: 104±13/64±11 mmHg; week 38±2: 110±8/73±5 mmHg, ±1S.D.). Pregnant women with persisting control-IGTT tended to gestation diabetes elsewhere (4% 170 mg/dl, 1-h-100 g glucose). Second, oral contraceptives were not correlated with raised blood pressure (p > 0.1) probably as weight and lipids were normal (n = 49, 22±4 kg/m2 , aged 27±7 years, 117±13/82±9 mmHg, LDL: 127±36, HDL: 66±14 mg/dl). Third, aging women with menopausal HRThormones (15 out of 46, aged 51±9 years, 25±5 kg/m2 ) were compared to those without HRT and led away from raised blood pressure (p > 0.35). Overall, non-pregnant women with IGTT and mixed hyperlipidemia showed hypertension (n = 14, aged 32±10 years, 26±6 kg/m2 , LDL: 167±65, HDL: 54±9, Trig: 254±73 mg/ml, 136±25/97±12 mmHg). Indeed, women with IGTT or mixed hyperlipidemia had significantly higher blood pressure than appropriate
123
controls (p < 0.003) and multivariate analysis provided evidence for direct risk of diastolic hypertension (p < 0.05). This model is suitable to adress hormonal compositions without hypertension as only participants with IGTThyperinsulinemia or mixed hyperlipidemia were at direct risk for diastolic hypertension. MS66 MODIFIED, EXTRACTED BARLEY BETA GLUCAN (BBG) EFFECTIVELY LOWERS LDL CHOLESTEROL DESPITE REDUCED VISCOSITY J. Keenan. Dept of Family Medicine, University of Minnesota, Minneapolis, MN, USA Many studies have shown that foods rich in viscous fibers can lower LDL- C. This study compared the effect on blood lipids of a food and beverage fortified with unmodified BBG (HMW), average molecular weight of 1000 kDa, to the effect of the same food and beverage fortified with modified BBG (LMW), average molecular weight 50–400 kDa in persons with moderate dyslipidemia. Subjects (N = 155) with LDL-C levels between 130 and 190 mg/dl after a 4 week run in period on a “heart-healthy” diet were randomized to 5 parallel treatment arms (5 g/d HMW, 5 g/d LMW, 3 g/d HMW, 3 g/d LMW or control). Over the six week treatment period subjects consumed one serving per day of a fortified cereal and one serving per day of a fortified beverage or control. Results: Change from baseline in LDL-C (5 g HMW = −22.5 mg/dl (−14.6%); 5 g LMW = −20.3 mg/dl (−13.1%); 3 g HMW = −14 mg/dl (−9%); 3 g LMW = −13.4 mg/dl (−9%). There was good compliance with all treatments with all subject groups consuming 94+% of servings and there were no drop outs or significant differences in side effects reported except for increased intestinal gas in the 5 g HMW compared to control. MS67 INTERRELATION BETWEEN OBSTRUCTIVE SLEEP APNEA AND LIPID SPECTRUM AMONG CARDIOVASCULAR PATIENTS N. Belinskaya1 , L. Yashina2 . 1 Sleep Medicine Center, 2 Polyclinic Therapy Department, Chelyabinsk State Medical University, Chelyabinsk, Russia Introduction: It has been proved in the research that people suffering from obstructive sleep apnea (OSA) are subject to high risk of atherosclerosis, hypertensive disease and death. Objectives: Research prevalence of OSA among cardiovascular patients. Research interrelation between obstructive sleep apnea and lipid spectrum among cardiovascular patients. Material and Methods: 242 patients with hypertensive disease and coronary heart disease with clinical signs of OSA have been examined. There were 172 men and 70 women, their age was from 32 to 65 years. Polysomnography, lipidogram, glucose and uric acid have been investigated. Results of research: Significant forms of OSA (apnea-hypopnea index is more than 15 per hour) have been revealed among 67 patients (27.6%), there were significantly more men (41.3%) than women (8.6%), p < 0.05. Hypercholesterolemia (LDL is more than 2.5 mmole/l) was discovered among 52% of the patients suffering from OSA against 18% without OSA. Reduced level of HDL-C was more often found among the patients with OSA − 69% against 38% (p < 0.05). Fasting hyperglycemia and impaired glucose tolerance was found among 12% with OSA and 11% without OSA; hyperuricemia − among 42% of the patients with OSA and 8% without OSA (p < 0.05). Conclusions: Thus, men with cardiovascular diseases are suffering definitely more often from OSA. Patients with SOAS more often have hyperuricemia, hypercholesterolemia and reduced level of HDL-C. MS68 ATHEROGENIC DISLIPIDEMIA IN METABOLIC SYNDROME: ROLE OF INSULIN RESISTANCE, NONESTERIFIED FATTY ACIDS AND ADIPOKINES D. Tanyanskiy1 , E. Firova1,2 , L. Shatilina2 , A. Denisenko1 . 1 Department of Biochemistry, 2 IEM Clinic, Institute of Experimental Medicine RAMS, St. Petersburg, Russia Objective: Metabolic syndrome (MS) is a result of complex interaction of different biochemical pathways. The aim was to evaluate the role of insulin resistance, nonesterified fatty acids (NEFA) and adipokines in pathogenesis of atherogenic dislipidemia in patients with metabolic syndrome. Methods: 113 patients (44 males and 69 females) with MS and 45 patients (24 males and 21 females) without MS were studied. Mean age was 57.4±9.2 years and it didn’t differed between groups. All patients had stable forms of coronary heart disease. We measured anthropometric and lipid parameters, concentration of plasma glucose. Insulin, leptin and adiponectin levels were determined by ELISA. Insulin sensitivity was estimated by index HOMA. Results: Patients with MS in comparison with control group had higher concentrations of triglycerides, NEFA, glucose, insulin, leptin and lower content of high-density lipoprotein cholesterol (HDL-C) and adiponectin. According to multiple linear regression analysis, plasma concentration of triglycerides was determined by body mass index (b = 0.40, p < 0.0001), contents of glucose (b = 0.22, p = 0.003) and NEFA (b = 0.23, p = 0.003), while concentration of HDL-C was determined only by NEFA content (b = −0.22, p = 0.01).