- Email: [email protected]
S36 Small dense LDL: cardiovascular impact and new therapeutic approaches
Abstracts There was also a wry high prevalence of subclinical cerebrovascular disease based on the MRI imaging of the brain in 3660 of the participants. Approximately l/3 of participants without a history of clinical stroke had MRI infarct-like lesions *3 mm. The MRI findings (such as infarcts, white matter grade, and ventricular size) were related to cognitive function tests and a decline in cognitive function over time.
of Symposia betes mellitus differ considerably. Incidence and prevalence of diabetes in Taiwan are approaching the US figures. Fibrinogen values in Taiwan are lower than those of many western countries. Prevalence of hypertension in Taiwan is close to that of US. But status on awareness, treatment, and control of hypertension is poorer in Taiwan than in US. Percentages of male smokers in mainland (83%) and in Taiwan (50%) are much greater than that in US. This comparison between Chinese in mainland and Taiwan and between Chinese and Caucasian can shed light on the etiology of cardiovascular diseases.
s34 CardiovascnIar disease (CVD) risk factor status in middle-age and health care costs in older age: the Chicago heart association detection project in industry @Xl.U study Kiang Liu, Martha L. Dauiglus, Lynn P. Lowe, Dnmel Garside, Phi/@ Greenland, Jeremiah Stander
S36 Small dense LDL: M. John Chapman,
cardiovascular Mmyse Guerin
impact and new therapeutic and Eric Rnrckm
approaches
Northwestern University Medical School, Chicago, IL, USA
INSERM Unit 321, HBpital de La Piti6, Paris, France
Objective: This study systematically examines relationships between CM risk factor status in middle-age-including cigarette smoking, high blood pressure, high serum cholesterol, high one-hour postload plasma ghwxe, body mass index, diabetes, and ECG abnormalities-and subsequent health care costs at age 65 years or older, utilizing data from the CHA Study. Methods: The sample consists of 7030 men and 6739 women in the CHA study aged 40-64 at baseline (1967-73) who in 1984-94 were or became eligible for Medicare (U.S. government health care financing for people 65 years of age or older). U.S. Health Care Finance Administration (RCFA) inpatient and outpatient charge data were. used to estimate and compare average annual casts for CVD, cancer, and total health are for people with different baseline levels of CVD risk factors. Results: Results indicate, for most risk factors, average annual utilization and inflation-adjusted costs increase with higher risk factor levels. For example, average annual age- and inflation-adjusted total Medicare costs for never smokers were 3868 USD/person for men and 2915 USD/person for women, while corresponding annual casts for those who in middle-age smoked more than 20 cigarettes per day were 6824 USA/man and 6750 IJSD/woman. For both men and women, average annual adjusted Medicare costs for those with no risk factors were only one half the costs for those with 3 + risk factors. Conclusion: These findings indicate that primary prevention of CVD risk factors early in life is important not only for reducing risks of premature morbidity, disability, and mortality but also for reducing future health care costs among survivors into older age. These results may he relevant for several Asian Pacific countries where the population is aging, and prevalence of cigarette smoking and hypertension is high.
Although it is well established that elevated circulating concentrations of low-density lipoproteins (LDL) represent a major risk factor for the premature development of coronary artery disease (CAD), similar plasma levels of LDL may confer dramatically different cardiovascular risk. This situation reflects the variable contribution of distinct subpopulations of LDL particles of elevated atherogenicity to the total LDL fraction. Abundant evidence has been provided to substantiate the abnormal quality of LDL particles in CAD patients, which are characterised by a predominance of small, dense LDL of elevated atherogenicity. The pharmacological modulation of the plasma concentrations and physicochemical properties of dense LDL are therefore of special interest, and represent a new therapeutic approach in the treatment of the atherogenic dyslipidemias. Hypolipidemic drugs vary significantly in their impact on the atherogenic, ape-Bcontaining lipoproteins (VLDL, IDL and LDL) and on apo-AI-containing, cardioprotective HDL. Earlier studies demonstrated that among the fibric acid-derivatives, fenofibrate induced marked reduction m VLDL-triglyceride and LDLcholesterol (up to 50% and 35% respectively), while significantly increasing HDL (up to 25%). To further understand the mechanisms responsible for the therapeutic bioaction of fenofibrate, we undertook clinical studies of its impact on the metabolism and profiles of both LDL and HDL particles in patients with combined hyperlipidemia. Our findings suggest that a key feature of such action, which involves reduction of up to 50% in dense LDL levels, is a marked reduction in the elevated CETP-mediated cholesteryl ester transfer from HDL to VLDL particles. Finally, subgroup analyses of data from the NLHLBI-II, STARS and CLAS regression studies indicated that the greatest arteriographic benefit occurred in CAD patients when levels of small, dense LDL were signilicantly reduced (Circulation, 1994, 90: 1056-1069). Atherogenic dense LDL are clearly therefore of major cardiovascular impact.
s35 Cardiovascular We-n-Ham Pan
disease
risk
in Chinese
living
in Taiwan
and in mainland
s37
Institute of Biomedical Sciences, Academia Sin&, Taipei, Taiwan
Modulation of the athemgenic lipoprotein phenotype C.E. Tan, ES. Tai, L.F. Chio, *A/Prof LX Chew
Comparing to many western countries, risk of coronary artery disease in Chinese is low. ‘Iltis is tme for Chinese not only in mainland but also in Taiwan. The risk of stroke is high in mainland and intermediate in Taiwan. But the risk of diabetes mellitus is high in Taiwan and low in China. These phenomena can be explained by the patterns of life-styles and CVD risk factors in hvo sides. Comparison is made with data collected in Nutrition and Health Surveillance in Taiwan 1993-1996, a study of the characteristics of 65 Chinese counties 1983, a study of the characteristics of 74 counties in China and 13 regions in Taiwan 1991, a survey of mortality in China 1989-1990, and long-term vital statistic data from Taiwan. Chinese in Taiwan consumes a diet with 34% calories from fat, 15.5% from protein, SOS% from carbohydrate, 5 grams of crude fiber, and moderate sodium (3750 mgl Even though the fat content of this diet is among the highest in oriental countries, the rising trend in CAD mortality is smafl due to a favorable dietary P/S ratio and a moderate mean serum cholesterol in last decade. However, the mean cholesterol levels of the various regions in Taiwan are beyond the upper tail of the cholesterol distribution of mainland counties. Diet in China is lower in fat (15%), higher in crude fiber (8 g), and higher in sodium (5740 mg). A dose response relation can be observed behveen CAD mortality and mean cholesterol values in various regions and counties in Taiwan and in mainland. Mean heights for men and women in middle age.art? the same for two sides. But Chinese in Taiwan are lo-11 Kg heavier than those in mainland. There is very little overlap in the range of plasma glucose concentrationP between two sides. Therefore, prevalence and mortality from dia-
Singapore General Hospital *Alexandra Hospital, Singapore
with
micronised
fenofibrate
The Atherogenic Lipoprotein Phenotype (ALP) is associated with an increased risk of coronary heart disease. KHD). It is also believed to be closely associated with the presence of the insulin resistance syndrome (IRS) and could be part of the same metabolic abnormality. Patients with non-insulin dependent diabetes melIitus (NIDDM) have increased risk of premature atherosclerosis because of glycation products and dyslipidaemia, in particular the dense, LDL cholesterol. We present the preliminary findings of a study involving young (aged 50 years and below), male, NIDDM patients without grossly elevated total or LDL cholesterol. A total of 15 patients have been studied to date and all exhibited the ALP with LDL-III greater than 100 mg/dl plasma. All were treated with micron&d Fenofibrate (Lipanthyl 200M@,) for a period of 6 months. Anthropometry, blood pressure, lipid profile, gh~cose, insulin and LDL subfractions were done before and after micron&d Fenofibrate. Results of the study are as follows. Pre-treatment profile. llw mean age of the patients was 42.5 Jo5.2 with body mass index of 26.5 it 6.4 kg/m2 and waist to hip ratio of 0.90 * 0.05. The lipid profile were as follows: total cholesterol (4.96 f 0.62 mmol/L), triglyceride (3.12 f 1.90 mmol/L), HDL (0.38 f 0.26 mmol/L) and LDL (2.65 f 1.0 mmol/Lf. LDL subfractions showed LDL-A: 10.2 + 9.76 mg/dl, LDL-II: 50.53 f 34.00 mg/dl and LDL-III: 156.2 zt 66.8 mg,‘dl.
of Symposia betes mellitus differ considerably. Incidence and prevalence of diabetes in Taiwan are approaching the US figures. Fibrinogen values in Taiwan are lower than those of many western countries. Prevalence of hypertension in Taiwan is close to that of US. But status on awareness, treatment, and control of hypertension is poorer in Taiwan than in US. Percentages of male smokers in mainland (83%) and in Taiwan (50%) are much greater than that in US. This comparison between Chinese in mainland and Taiwan and between Chinese and Caucasian can shed light on the etiology of cardiovascular diseases.
s34 CardiovascnIar disease (CVD) risk factor status in middle-age and health care costs in older age: the Chicago heart association detection project in industry @Xl.U study Kiang Liu, Martha L. Dauiglus, Lynn P. Lowe, Dnmel Garside, Phi/@ Greenland, Jeremiah Stander
S36 Small dense LDL: M. John Chapman,
cardiovascular Mmyse Guerin
impact and new therapeutic and Eric Rnrckm
approaches
Northwestern University Medical School, Chicago, IL, USA
INSERM Unit 321, HBpital de La Piti6, Paris, France
Objective: This study systematically examines relationships between CM risk factor status in middle-age-including cigarette smoking, high blood pressure, high serum cholesterol, high one-hour postload plasma ghwxe, body mass index, diabetes, and ECG abnormalities-and subsequent health care costs at age 65 years or older, utilizing data from the CHA Study. Methods: The sample consists of 7030 men and 6739 women in the CHA study aged 40-64 at baseline (1967-73) who in 1984-94 were or became eligible for Medicare (U.S. government health care financing for people 65 years of age or older). U.S. Health Care Finance Administration (RCFA) inpatient and outpatient charge data were. used to estimate and compare average annual casts for CVD, cancer, and total health are for people with different baseline levels of CVD risk factors. Results: Results indicate, for most risk factors, average annual utilization and inflation-adjusted costs increase with higher risk factor levels. For example, average annual age- and inflation-adjusted total Medicare costs for never smokers were 3868 USD/person for men and 2915 USD/person for women, while corresponding annual casts for those who in middle-age smoked more than 20 cigarettes per day were 6824 USA/man and 6750 IJSD/woman. For both men and women, average annual adjusted Medicare costs for those with no risk factors were only one half the costs for those with 3 + risk factors. Conclusion: These findings indicate that primary prevention of CVD risk factors early in life is important not only for reducing risks of premature morbidity, disability, and mortality but also for reducing future health care costs among survivors into older age. These results may he relevant for several Asian Pacific countries where the population is aging, and prevalence of cigarette smoking and hypertension is high.
Although it is well established that elevated circulating concentrations of low-density lipoproteins (LDL) represent a major risk factor for the premature development of coronary artery disease (CAD), similar plasma levels of LDL may confer dramatically different cardiovascular risk. This situation reflects the variable contribution of distinct subpopulations of LDL particles of elevated atherogenicity to the total LDL fraction. Abundant evidence has been provided to substantiate the abnormal quality of LDL particles in CAD patients, which are characterised by a predominance of small, dense LDL of elevated atherogenicity. The pharmacological modulation of the plasma concentrations and physicochemical properties of dense LDL are therefore of special interest, and represent a new therapeutic approach in the treatment of the atherogenic dyslipidemias. Hypolipidemic drugs vary significantly in their impact on the atherogenic, ape-Bcontaining lipoproteins (VLDL, IDL and LDL) and on apo-AI-containing, cardioprotective HDL. Earlier studies demonstrated that among the fibric acid-derivatives, fenofibrate induced marked reduction m VLDL-triglyceride and LDLcholesterol (up to 50% and 35% respectively), while significantly increasing HDL (up to 25%). To further understand the mechanisms responsible for the therapeutic bioaction of fenofibrate, we undertook clinical studies of its impact on the metabolism and profiles of both LDL and HDL particles in patients with combined hyperlipidemia. Our findings suggest that a key feature of such action, which involves reduction of up to 50% in dense LDL levels, is a marked reduction in the elevated CETP-mediated cholesteryl ester transfer from HDL to VLDL particles. Finally, subgroup analyses of data from the NLHLBI-II, STARS and CLAS regression studies indicated that the greatest arteriographic benefit occurred in CAD patients when levels of small, dense LDL were signilicantly reduced (Circulation, 1994, 90: 1056-1069). Atherogenic dense LDL are clearly therefore of major cardiovascular impact.
s35 Cardiovascular We-n-Ham Pan
disease
risk
in Chinese
living
in Taiwan
and in mainland
s37
Institute of Biomedical Sciences, Academia Sin&, Taipei, Taiwan
Modulation of the athemgenic lipoprotein phenotype C.E. Tan, ES. Tai, L.F. Chio, *A/Prof LX Chew
Comparing to many western countries, risk of coronary artery disease in Chinese is low. ‘Iltis is tme for Chinese not only in mainland but also in Taiwan. The risk of stroke is high in mainland and intermediate in Taiwan. But the risk of diabetes mellitus is high in Taiwan and low in China. These phenomena can be explained by the patterns of life-styles and CVD risk factors in hvo sides. Comparison is made with data collected in Nutrition and Health Surveillance in Taiwan 1993-1996, a study of the characteristics of 65 Chinese counties 1983, a study of the characteristics of 74 counties in China and 13 regions in Taiwan 1991, a survey of mortality in China 1989-1990, and long-term vital statistic data from Taiwan. Chinese in Taiwan consumes a diet with 34% calories from fat, 15.5% from protein, SOS% from carbohydrate, 5 grams of crude fiber, and moderate sodium (3750 mgl Even though the fat content of this diet is among the highest in oriental countries, the rising trend in CAD mortality is smafl due to a favorable dietary P/S ratio and a moderate mean serum cholesterol in last decade. However, the mean cholesterol levels of the various regions in Taiwan are beyond the upper tail of the cholesterol distribution of mainland counties. Diet in China is lower in fat (15%), higher in crude fiber (8 g), and higher in sodium (5740 mg). A dose response relation can be observed behveen CAD mortality and mean cholesterol values in various regions and counties in Taiwan and in mainland. Mean heights for men and women in middle age.art? the same for two sides. But Chinese in Taiwan are lo-11 Kg heavier than those in mainland. There is very little overlap in the range of plasma glucose concentrationP between two sides. Therefore, prevalence and mortality from dia-
Singapore General Hospital *Alexandra Hospital, Singapore
with
micronised
fenofibrate
The Atherogenic Lipoprotein Phenotype (ALP) is associated with an increased risk of coronary heart disease. KHD). It is also believed to be closely associated with the presence of the insulin resistance syndrome (IRS) and could be part of the same metabolic abnormality. Patients with non-insulin dependent diabetes melIitus (NIDDM) have increased risk of premature atherosclerosis because of glycation products and dyslipidaemia, in particular the dense, LDL cholesterol. We present the preliminary findings of a study involving young (aged 50 years and below), male, NIDDM patients without grossly elevated total or LDL cholesterol. A total of 15 patients have been studied to date and all exhibited the ALP with LDL-III greater than 100 mg/dl plasma. All were treated with micron&d Fenofibrate (Lipanthyl 200M@,) for a period of 6 months. Anthropometry, blood pressure, lipid profile, gh~cose, insulin and LDL subfractions were done before and after micron&d Fenofibrate. Results of the study are as follows. Pre-treatment profile. llw mean age of the patients was 42.5 Jo5.2 with body mass index of 26.5 it 6.4 kg/m2 and waist to hip ratio of 0.90 * 0.05. The lipid profile were as follows: total cholesterol (4.96 f 0.62 mmol/L), triglyceride (3.12 f 1.90 mmol/L), HDL (0.38 f 0.26 mmol/L) and LDL (2.65 f 1.0 mmol/Lf. LDL subfractions showed LDL-A: 10.2 + 9.76 mg/dl, LDL-II: 50.53 f 34.00 mg/dl and LDL-III: 156.2 zt 66.8 mg,‘dl.