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Deletion polymorphism of the angiotensin 1-converting enzyme gene in the elderly patients with coronary heart disease
Posters 4. Elderly
58
•4"•
J. Gussekloo 1 , T.J. Heeren 2, G.J. Blauw I , R.G.J. Westendorp1.
~4-~ STUDY OF CHANGES IN OXIDATIVE/ANTIOXIDATIVE STATUS OF LOW DENSITY LIPOPROTEINS IN MIDDLE AGED, ELDERLY AND LONG-LIVING MEN IN NOVOSIBIRSK
1Gerontology and Geriatrics, Department of General Internal Medicine, Leiden University Medical Center, Leiden; 2Department of Psychiatry, University Medical Center Utrechtand Department of Geriatric Psychiatry, HC Riimke Group, Zeist, The Netherlands
Institute of Internal Medicine, 630003, Novosibirsk, Vladimirooskyspusk 2a, Russia
FURTHER EVIDENCE FOR ATHEROSCLEROSIS UNDERLYING DEMENTIA IN THE OLDEST OLD
Objectives: Recent studies have shown that indicators of atherosclerosis are associated not only with vascular dementia but with Alzheimer's disease also. To further reveal whether atheroscierotic disease underlies dementia in the oldest old, we compared the causes of death in a cohort of very old subjects with and without dementia. Methods: Embedded in the population-based Leiden 85-plus Study we prospectively followed 196 cases of dementia (40 males, 156 females) at baseline (DSM-III diagnosis) for cause specific mortality over a 10-years period. As a control group we followed 111 males and 242 females without dementia as defined by a Mini-Mental State Examination score (MMSE) above 27 points. Age adjusted mortality risks were estimated in a Cox proportional-hazard model. Results: Mortality risk of atherosclerotic diseases in males with dementia was threefold increased (RR 2.9, 95% CI: 1.5 to 5.7) compared to males without dementia. Mortality risk of atherosclerotic diseases in females with dementia was twofold increased (RR 1.8, 95% CI: 1.3 to 2.6). Ten of the 40 males with dementia (25%) and 7 of the 111 males without dementia (6%) died from cerebrovascular disease, equal to a 9-fold increased mortality risk (RR 9.4, 95% CI: 3.2 to 28). The corresponding mortality risk in females was 1.5 (95% CI: 0.9 to 2.8). Conclusion: Mortality of atherosclerotic disease in males with dementia is threefold increased compared to males without dementia. The corresponding risk in females with dementia was twofold higher. The excess mortality of cerebrovascular diseases in males with dementia provides further evidence for atherosclerosis is underlying dementia in the oldest old, most clearly in males~
Yu. Ragino, V. Pentegova, E. Kashtanova, E. Berezovskaja, A. Shabalin.
The aim of the study was to evaluate the oxidative capacity of low density lipoproteins (LDL) and blood antioxidant status in elderly and long-living men comparing with middle aged men in Novosibirsk. Eighty men at the age of 38-105 were included into the study. The group of elderly included 25 men at the age of 61-90 (group-l). The group of long-living included 25 men at the age of 91-105 (group-2). The group of middle aged included 25 men at the age of 3840 (group-3). TCH, CHHDL and TG were measured using biochemical enzyme methods. The data of peroxidation lipid (POL) processes were studied in LDL as the most informative and modem. The initial level of POL products in LDL and oxidative capacity of LDL in vitro were evaluated. Blood concentrations of antioxidants (a- and ~,-tocopherol,I~-caroteneand retinol) were measured by high effective liquor chromatography. Results: In group-2 men the initial level of POL products in LDL and oxidative capacity of LDL in vitro were lowest (p < 0.01) in comparison with group-3 and group-1 men. In group-1 men the initial level of POL products in LDL and oxidative capacity of LDL in vitro were highest (p < 0.01) in comparison with group-3 and group-2 men. No differences in blood c~-tocopherol and "t-tocopherol concentrations between groups were revealed. But, 13-carotene and retinol levels in group-3 men were higher (p < 0.05) in comparison with group-1 men, but lower (p < 0.01) in comparison with group-2 men. Thus, elderly men have elevated oxidative capacity of LDL and reduced [3-carotene and retinol blood levels. On the contrary, longliving men in Novosibirsk have elevated resistance of LDL to oxidation in vitro which may be stipulated by elevated [3-carotene and retinol blood concentrations. ~4-~ DELETION POLYMORPHISM OF THE ANGIOTENSIN I-CONVERTING ENZYME GENE IN THE ELDERLY PATIENTS WITH CORONARY HEART DISEASE
~-~
THE AGING-RELATED CHANGES OF LIPID PROFILE: INDEPENDENT CONTRIBUTION OF BODY COMPOSITION AND INSULIN SENSITIVITY
L. Danti, G. Pasolim, M.E Merli, E Ablondi, G. Valenti. Chair of
Gerontology and Geriatrics, University of Parma, Parma, Italy Aging is associated with changes in lipoprotein profile, which could be due not to aging per-se, but to the concomitant changes in body composition and insulin sensitivity. This study was intended to assess in healthy, non-obese individuals, the relative and independent contribution of body composition and insulin sensitivity to the aging-related changes in lipid concentrations. To this aim, a sample of 240 healthy individuals (108 males and 132 females), with a wide age-range (18-100), selected on the basis of several exclusion criteria, including obesity and diabetes, was cross-examined. Body composition was assessed both by anthropometry and Bio-Impedance Analysis (BIA), with fat mass (FM%) estimated employing Segal's and Deurenberg's equations, respectively for subjects under and above 64 years. Insulin sensitivity was estimated as the homeostasis model assessment of insulin resistance (HOMA IR). Significant age-related differences were found in both sexes, for TC, TG, LDL-C and APOB, positively related to age. In females, an association with age was apparent also for Lp(a) (positive) and TC/ApoB ratio (negative). Multivariate stepwise regression analysis showed that, in males, the positive relation of TC, TG, LDL-C and TG with age was totally accounted for by the age-related increase in FM% and, for TG only, in HOMA IR. On the contrary, in females, age per se turned out as the strongest contributor to lipid variance. However, a slight association with TC, TG and ApoB was found for WHR, dependent of HOMA-IR. HOMA-IR accounted for most of TC/ApoB ratio variance (32%) in females, with 6% additional contribution by age. In conclusion, these data suggest that in healthy, non obese individuals, body composition (FM% in males and WHR in females) gives some contribution to the aging-related changes in lipid profile, especially in men. Insulin sensitivity, assessed by HOMA IR, is another independent contributor of lipid variability, especially in women. In this view, it is possible that adequate dietary and exercise interventions, could either prevent or reverse some of the detrimental changes in lipid profile due to aging.
B. Bergman-Markovi61, Z. Reiner2, M. Bergovec3, A. StavljenitRukavina4, D. Ivankovi65, J. Serti64, J. Vincelj3. 1Dept. of Family
Medicine, Zagreb School of Medicine; eDept, of lnternal Medicine, University Hospital Rebro; 3Dept. of Internal Medicine, Unioersity Hospital Dubrava; 41nstitate of Laboratory Medicine, UnioersityHospital Rebro; 5Dept. of Medical Statistics, Zagreb School of Medicine, Zagreb, Croatia Controversy exists whether deletion/deletion (D/D) genotipe of angiotensin 1-converting enzyme (ACE) gene polymorphism is associated with coronary heart disease (CHD) and atherosclerosis. There are only a few studies concerning this issue in the elderly and their results are also controversial. Therefore the predictive value of the ACE gene polymorphism for coronary heart disease was examined in 346 subjects older then 65 years (230 women and 116 men). The age range was 65-90 years. 90 subjects (60 women and 30 men) had CHD while 256 had no sign of CHD and were considered as a control group. Criteria for the inclusion into the group of CHD patients were: history of myocardial infarction, patients with angioplasty or coronary arterial bypass surgery, verified and treated angina pecturis and/or presence of Q wave in the ECG. Molecular analysis of the ACE genotype was performed by selective amplification of the polymorphic region in intron 16 of the gene (alu repetitive sequence) using polymerase chain reaction and gel electrophresis. Also, samples were re-amplified with insertion-specific primer pair which recognised the inserted sequence. Data were analysed by chi-square test as well as by discriminant analysis. The results obtained indicate that DD genotype has a predictive value for CHD in the elderly as proven by discriminant analysis (chi-square = 25.77; df = 16; p = 0.0620). However, using an univariate method no correlation between DD genotype of ACE gene polymorphism and CHD could be proved.
72nd EAS Congress
58
•4"•
J. Gussekloo 1 , T.J. Heeren 2, G.J. Blauw I , R.G.J. Westendorp1.
~4-~ STUDY OF CHANGES IN OXIDATIVE/ANTIOXIDATIVE STATUS OF LOW DENSITY LIPOPROTEINS IN MIDDLE AGED, ELDERLY AND LONG-LIVING MEN IN NOVOSIBIRSK
1Gerontology and Geriatrics, Department of General Internal Medicine, Leiden University Medical Center, Leiden; 2Department of Psychiatry, University Medical Center Utrechtand Department of Geriatric Psychiatry, HC Riimke Group, Zeist, The Netherlands
Institute of Internal Medicine, 630003, Novosibirsk, Vladimirooskyspusk 2a, Russia
FURTHER EVIDENCE FOR ATHEROSCLEROSIS UNDERLYING DEMENTIA IN THE OLDEST OLD
Objectives: Recent studies have shown that indicators of atherosclerosis are associated not only with vascular dementia but with Alzheimer's disease also. To further reveal whether atheroscierotic disease underlies dementia in the oldest old, we compared the causes of death in a cohort of very old subjects with and without dementia. Methods: Embedded in the population-based Leiden 85-plus Study we prospectively followed 196 cases of dementia (40 males, 156 females) at baseline (DSM-III diagnosis) for cause specific mortality over a 10-years period. As a control group we followed 111 males and 242 females without dementia as defined by a Mini-Mental State Examination score (MMSE) above 27 points. Age adjusted mortality risks were estimated in a Cox proportional-hazard model. Results: Mortality risk of atherosclerotic diseases in males with dementia was threefold increased (RR 2.9, 95% CI: 1.5 to 5.7) compared to males without dementia. Mortality risk of atherosclerotic diseases in females with dementia was twofold increased (RR 1.8, 95% CI: 1.3 to 2.6). Ten of the 40 males with dementia (25%) and 7 of the 111 males without dementia (6%) died from cerebrovascular disease, equal to a 9-fold increased mortality risk (RR 9.4, 95% CI: 3.2 to 28). The corresponding mortality risk in females was 1.5 (95% CI: 0.9 to 2.8). Conclusion: Mortality of atherosclerotic disease in males with dementia is threefold increased compared to males without dementia. The corresponding risk in females with dementia was twofold higher. The excess mortality of cerebrovascular diseases in males with dementia provides further evidence for atherosclerosis is underlying dementia in the oldest old, most clearly in males~
Yu. Ragino, V. Pentegova, E. Kashtanova, E. Berezovskaja, A. Shabalin.
The aim of the study was to evaluate the oxidative capacity of low density lipoproteins (LDL) and blood antioxidant status in elderly and long-living men comparing with middle aged men in Novosibirsk. Eighty men at the age of 38-105 were included into the study. The group of elderly included 25 men at the age of 61-90 (group-l). The group of long-living included 25 men at the age of 91-105 (group-2). The group of middle aged included 25 men at the age of 3840 (group-3). TCH, CHHDL and TG were measured using biochemical enzyme methods. The data of peroxidation lipid (POL) processes were studied in LDL as the most informative and modem. The initial level of POL products in LDL and oxidative capacity of LDL in vitro were evaluated. Blood concentrations of antioxidants (a- and ~,-tocopherol,I~-caroteneand retinol) were measured by high effective liquor chromatography. Results: In group-2 men the initial level of POL products in LDL and oxidative capacity of LDL in vitro were lowest (p < 0.01) in comparison with group-3 and group-1 men. In group-1 men the initial level of POL products in LDL and oxidative capacity of LDL in vitro were highest (p < 0.01) in comparison with group-3 and group-2 men. No differences in blood c~-tocopherol and "t-tocopherol concentrations between groups were revealed. But, 13-carotene and retinol levels in group-3 men were higher (p < 0.05) in comparison with group-1 men, but lower (p < 0.01) in comparison with group-2 men. Thus, elderly men have elevated oxidative capacity of LDL and reduced [3-carotene and retinol blood levels. On the contrary, longliving men in Novosibirsk have elevated resistance of LDL to oxidation in vitro which may be stipulated by elevated [3-carotene and retinol blood concentrations. ~4-~ DELETION POLYMORPHISM OF THE ANGIOTENSIN I-CONVERTING ENZYME GENE IN THE ELDERLY PATIENTS WITH CORONARY HEART DISEASE
~-~
THE AGING-RELATED CHANGES OF LIPID PROFILE: INDEPENDENT CONTRIBUTION OF BODY COMPOSITION AND INSULIN SENSITIVITY
L. Danti, G. Pasolim, M.E Merli, E Ablondi, G. Valenti. Chair of
Gerontology and Geriatrics, University of Parma, Parma, Italy Aging is associated with changes in lipoprotein profile, which could be due not to aging per-se, but to the concomitant changes in body composition and insulin sensitivity. This study was intended to assess in healthy, non-obese individuals, the relative and independent contribution of body composition and insulin sensitivity to the aging-related changes in lipid concentrations. To this aim, a sample of 240 healthy individuals (108 males and 132 females), with a wide age-range (18-100), selected on the basis of several exclusion criteria, including obesity and diabetes, was cross-examined. Body composition was assessed both by anthropometry and Bio-Impedance Analysis (BIA), with fat mass (FM%) estimated employing Segal's and Deurenberg's equations, respectively for subjects under and above 64 years. Insulin sensitivity was estimated as the homeostasis model assessment of insulin resistance (HOMA IR). Significant age-related differences were found in both sexes, for TC, TG, LDL-C and APOB, positively related to age. In females, an association with age was apparent also for Lp(a) (positive) and TC/ApoB ratio (negative). Multivariate stepwise regression analysis showed that, in males, the positive relation of TC, TG, LDL-C and TG with age was totally accounted for by the age-related increase in FM% and, for TG only, in HOMA IR. On the contrary, in females, age per se turned out as the strongest contributor to lipid variance. However, a slight association with TC, TG and ApoB was found for WHR, dependent of HOMA-IR. HOMA-IR accounted for most of TC/ApoB ratio variance (32%) in females, with 6% additional contribution by age. In conclusion, these data suggest that in healthy, non obese individuals, body composition (FM% in males and WHR in females) gives some contribution to the aging-related changes in lipid profile, especially in men. Insulin sensitivity, assessed by HOMA IR, is another independent contributor of lipid variability, especially in women. In this view, it is possible that adequate dietary and exercise interventions, could either prevent or reverse some of the detrimental changes in lipid profile due to aging.
B. Bergman-Markovi61, Z. Reiner2, M. Bergovec3, A. StavljenitRukavina4, D. Ivankovi65, J. Serti64, J. Vincelj3. 1Dept. of Family
Medicine, Zagreb School of Medicine; eDept, of lnternal Medicine, University Hospital Rebro; 3Dept. of Internal Medicine, Unioersity Hospital Dubrava; 41nstitate of Laboratory Medicine, UnioersityHospital Rebro; 5Dept. of Medical Statistics, Zagreb School of Medicine, Zagreb, Croatia Controversy exists whether deletion/deletion (D/D) genotipe of angiotensin 1-converting enzyme (ACE) gene polymorphism is associated with coronary heart disease (CHD) and atherosclerosis. There are only a few studies concerning this issue in the elderly and their results are also controversial. Therefore the predictive value of the ACE gene polymorphism for coronary heart disease was examined in 346 subjects older then 65 years (230 women and 116 men). The age range was 65-90 years. 90 subjects (60 women and 30 men) had CHD while 256 had no sign of CHD and were considered as a control group. Criteria for the inclusion into the group of CHD patients were: history of myocardial infarction, patients with angioplasty or coronary arterial bypass surgery, verified and treated angina pecturis and/or presence of Q wave in the ECG. Molecular analysis of the ACE genotype was performed by selective amplification of the polymorphic region in intron 16 of the gene (alu repetitive sequence) using polymerase chain reaction and gel electrophresis. Also, samples were re-amplified with insertion-specific primer pair which recognised the inserted sequence. Data were analysed by chi-square test as well as by discriminant analysis. The results obtained indicate that DD genotype has a predictive value for CHD in the elderly as proven by discriminant analysis (chi-square = 25.77; df = 16; p = 0.0620). However, using an univariate method no correlation between DD genotype of ACE gene polymorphism and CHD could be proved.
72nd EAS Congress