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Predictors of carotid atherosclerosis progression among women
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Oral session abstracts / Atherosclerosis 115 (Suppl.) (1995) $ 3 - $ 4 2 0 9 Nutrition
O53
054
APOLIPOPROTEIN B~.8 AND RETINYL ESTER RESPONSES TO MEALS OF VARYING MONOUNSATURATED FATTY ACID CONTENTS K.G. Jackson, J.M.E. Knapper, A. Zampelas, B.J. Gould, J.A. Lovegrove, J. Wright, C.M. Williams Nutritional Metabolism Research Group, University of Surrey, Guildford, UK
POSSIBLE PRESENCE OF INHIBITORS OF CYCLO-OXYGENASE ACTIVITY IN FOODS AND THEIR EFFECT ON PLATELET THROMBOXANE PRODUCTION IN MAN P.L.T.M.K. Janssen I J.W.N. Akkerman 2, P.C.H. Hollman 3, D.P. Venema3, W.A. van Staveren ~, M.B. Katan L ~Department of Human Nutrition, Wageningen, The Netherlands; 2Department of Haematology, Utrecht; 3State Institute for Quality Control of Agricultural Products, Wageningen
Measurements of postprandial retinyl ester (RE) concentrations following the consumption of test meals containing vitamin A have been used to evaluate postprandial responses of intestinally-derived lipids since the mid 1970s, but concern regarding the specificity of this method have provided impetus for the development of a reliable and rapid assay for apolipoprotein B-48 (apo B-48). We have raised a specific antibody to the C-terminal region of apo B~.8 and have applied this in the development of an ELISA method for the detection of apo B~18 in biological samples. RE concentrations were determined using normal phase chromatography. Triacylglycerol (TAG), RE and apo B-48 responses to the ingestion of test meals of varying monounsaturated fatty acid (MUFA) composition (12%, 17% and 24% dietary fat) were measured in the TAG-rich lipoprotein fraction of blood samples collected over 8 hours following the meal. Patterns of peak time responses to the 12% MUFA meal were similar for TAG, apo B-48 and RE (approximately 180 minutes in all cases), but for the 17% and 24% MUFA meals, responses of TAG and apo B-48 differed from that of RE, with RE peak response time delayed relative to TAG and apo B48, for the 17% and the 24% meals (420 minutes respectively) In conclusion, increasing the MUFA or decreasing the saturated fatty acid content of the test meals may have an effect on the incorporation of RE into the chylomicron core in the intestine. This study therefore underlines the limitations of the use of RE to characterise the metabolism of intestinally derived lipoproteins which may play an important role in the development of atherosclerosis.
Background: There is a growing interest in foods that affect cardiovascular risk through mechanisms other than cholesterol and blood pressure. Acetylsalicylic acid inhibits platelet thromboxane production and aggregation by irreversible acetylation of cyclo-oxygenase. It is effective in the prevention of cardiovascular disease. It has been suggested that a normal mixed Western diet provides 10-200 mg of natural salicylate and 3 mg acetylsalicylate daily. Objective: We identify foods that inhibit eyclo-oxygenase activity in man. Aspirin study: We first carried out a randomized placebocontrolled double-blind cross-over study in 10 healthy volunteers to see whether we could detect the effect of trace amounts of acetylsalicylic acid on platelet cyclo-oxygenase activity. Three mg acetylsalicylic acid daily caused a 39+8% decrease in maximally stimulated thromboxane production; mean within-subject variation over a 3-day period was 9%. Ginger study: Ginger extracts inhibit platelet aggregation and thromboxane production in vitro. We fed 18 volunteers 15 g of gingerroot, 40 g of stem ginger, and placebo for 2 weeks each in random order. Ginger did not influence platelet thromboxane production: the decrease in thromboxane production was 1 ±9% (mean_+sd) after consumption of gingerroot, and 1-t-8% after stem ginger. (Acetyl)salicylate in foods: We developed a highly specific and accurate hplc and fluorescence method, and measured levels of (acetyl)salicylate in Dutch foods. Total salicylate levels we found were 10-100 times lower than published by Swain (1985); we could not demonstrate any acetylsalicylate in foods. Our data suggest that foods contain less than 20 p.g acetylsalicylate per kg. Funding: Netherlands Heart Foundation (93084) and Foundation for Nutrition and Health Sciences, The Netherlands.
O10 A T H E R O S C L E R O S I S IN W O M E N 055
056
PREDICTORS OF CAROTID ATHEROSCLEROSIS PROGRESSION AMONG WOMEN R.P. Byington, H. Hoen, W. Applegate, C.D. Furberg, for the ACAPS Research Group Bowman Gray School of Medicine, Winston-Salem, NC, USA
A G E A T M E N O P A U S E AS A RISK F A C T O R FOR C A R D I O V A S CULAR MORTALITY Y.T. van der Schouw Y. van der GraaL J D . Banga Utrecht University and Academic Hospital, Utrecht, The Netherlands
Using data collected for the Asymptomatic Carotid Artery Progression Study (ACAPS), participant characteristics predictive of 3 year progression of atherosclerosis were identified for the 116 women (and 113 men) assigned to the placebo group. ACAPS was a 3 year, randomised, multicentered, factoriatly designed trial of lovastatin, warfarin, and their placebos in 919 high risk participants free of clinical vascular disease at baseline. The primary endpoint for the trial was the progression of carotid artery atherosclerosis measured by B-mode ultrasonography. Progression was defined as the 3 year change in the mean of 12 maximum intimal-medial thicknesses (IMTs) measured over 12 carotid walls (near and far walls in the bifurcation, common and internal carotid arteries on the left and right sides of the neck). Twenty-eight baseline demographic, medical, nutritional and risk factor characteristics were examined to determine their relationships with 1MT progression (adjusting for age and baseline mean-maximum IMT). Among the women, being on estrogen replacement therapy (ERT) was one of the strongest predictors of regression (-0.012 nun/year on ERT and 0.012 mm/year not on ERT, P=0.05). When the 87 women not on ERT were compared to the 113 men, the two groups had comparable 3 year progression rates (0.0072 mm /year for women compared to 0.0080 mm/year for men). The following characteristics were independently predictive of progression among women (P<_0.15): baseline IMT (-), vitamin E consumption (-), plasma triglyceride [TG] levels (-), and body mass index [BMll (+). There was statistical evidence of a gender interaction with TG and BMI, suggesting that women have unique characteristics that influence atherosclerosis.
To determine whether a reduced lifetime endogenous estrogen exposure as a result of an early menopause is associated with an increased cardiovascular disease risk, a cohort of 12,101 postmenopausal women was studied. Originally, these women were enroled to study the effect of screening for breast cancer (DOM-project). At baseline, they were 50-65 years (mean 57 years) and median followup time was 16 years (maximum 19 years). The authors tested the association between age at menopause and cardiovascular mortality with C o x ' proportional hazards analysis. Each year that natural or surgical menopause starts earlier increases the risk o f dying from cardiovascular diseases with 2% (age-adjusted hazard ratio (HR) 0.98, 95% CI 0.96-0.99). Adjustment for body mass index, body fat distribution, oral contraceptive use, parity and age at first delivery, smoking, hypertension, diabetes and previous cardiovascular disease did not alter this risk. An early menopause was a not a risk indicator for cardiovascular mortality in the subgroup of smoking women (HR 1.01, 95% CI 0.98-1.04) and a stronger risk indicator for women with diabetes (HR 0.95, 95% CI 0.91-0.99), although confidence intervals of these HRs showed overlap with those o f the opposing subgroup. The observed "dose-response" relationship supports the hypothesis that a reduced lifetime endogenous estrogen exposure determines partially the increased cardiovascular mortality. The effect of smoking seems to overrule the effect o f an early menopause.
Oral session abstracts / Atherosclerosis 115 (Suppl.) (1995) $ 3 - $ 4 2 0 9 Nutrition
O53
054
APOLIPOPROTEIN B~.8 AND RETINYL ESTER RESPONSES TO MEALS OF VARYING MONOUNSATURATED FATTY ACID CONTENTS K.G. Jackson, J.M.E. Knapper, A. Zampelas, B.J. Gould, J.A. Lovegrove, J. Wright, C.M. Williams Nutritional Metabolism Research Group, University of Surrey, Guildford, UK
POSSIBLE PRESENCE OF INHIBITORS OF CYCLO-OXYGENASE ACTIVITY IN FOODS AND THEIR EFFECT ON PLATELET THROMBOXANE PRODUCTION IN MAN P.L.T.M.K. Janssen I J.W.N. Akkerman 2, P.C.H. Hollman 3, D.P. Venema3, W.A. van Staveren ~, M.B. Katan L ~Department of Human Nutrition, Wageningen, The Netherlands; 2Department of Haematology, Utrecht; 3State Institute for Quality Control of Agricultural Products, Wageningen
Measurements of postprandial retinyl ester (RE) concentrations following the consumption of test meals containing vitamin A have been used to evaluate postprandial responses of intestinally-derived lipids since the mid 1970s, but concern regarding the specificity of this method have provided impetus for the development of a reliable and rapid assay for apolipoprotein B-48 (apo B-48). We have raised a specific antibody to the C-terminal region of apo B~.8 and have applied this in the development of an ELISA method for the detection of apo B~18 in biological samples. RE concentrations were determined using normal phase chromatography. Triacylglycerol (TAG), RE and apo B-48 responses to the ingestion of test meals of varying monounsaturated fatty acid (MUFA) composition (12%, 17% and 24% dietary fat) were measured in the TAG-rich lipoprotein fraction of blood samples collected over 8 hours following the meal. Patterns of peak time responses to the 12% MUFA meal were similar for TAG, apo B-48 and RE (approximately 180 minutes in all cases), but for the 17% and 24% MUFA meals, responses of TAG and apo B-48 differed from that of RE, with RE peak response time delayed relative to TAG and apo B48, for the 17% and the 24% meals (420 minutes respectively) In conclusion, increasing the MUFA or decreasing the saturated fatty acid content of the test meals may have an effect on the incorporation of RE into the chylomicron core in the intestine. This study therefore underlines the limitations of the use of RE to characterise the metabolism of intestinally derived lipoproteins which may play an important role in the development of atherosclerosis.
Background: There is a growing interest in foods that affect cardiovascular risk through mechanisms other than cholesterol and blood pressure. Acetylsalicylic acid inhibits platelet thromboxane production and aggregation by irreversible acetylation of cyclo-oxygenase. It is effective in the prevention of cardiovascular disease. It has been suggested that a normal mixed Western diet provides 10-200 mg of natural salicylate and 3 mg acetylsalicylate daily. Objective: We identify foods that inhibit eyclo-oxygenase activity in man. Aspirin study: We first carried out a randomized placebocontrolled double-blind cross-over study in 10 healthy volunteers to see whether we could detect the effect of trace amounts of acetylsalicylic acid on platelet cyclo-oxygenase activity. Three mg acetylsalicylic acid daily caused a 39+8% decrease in maximally stimulated thromboxane production; mean within-subject variation over a 3-day period was 9%. Ginger study: Ginger extracts inhibit platelet aggregation and thromboxane production in vitro. We fed 18 volunteers 15 g of gingerroot, 40 g of stem ginger, and placebo for 2 weeks each in random order. Ginger did not influence platelet thromboxane production: the decrease in thromboxane production was 1 ±9% (mean_+sd) after consumption of gingerroot, and 1-t-8% after stem ginger. (Acetyl)salicylate in foods: We developed a highly specific and accurate hplc and fluorescence method, and measured levels of (acetyl)salicylate in Dutch foods. Total salicylate levels we found were 10-100 times lower than published by Swain (1985); we could not demonstrate any acetylsalicylate in foods. Our data suggest that foods contain less than 20 p.g acetylsalicylate per kg. Funding: Netherlands Heart Foundation (93084) and Foundation for Nutrition and Health Sciences, The Netherlands.
O10 A T H E R O S C L E R O S I S IN W O M E N 055
056
PREDICTORS OF CAROTID ATHEROSCLEROSIS PROGRESSION AMONG WOMEN R.P. Byington, H. Hoen, W. Applegate, C.D. Furberg, for the ACAPS Research Group Bowman Gray School of Medicine, Winston-Salem, NC, USA
A G E A T M E N O P A U S E AS A RISK F A C T O R FOR C A R D I O V A S CULAR MORTALITY Y.T. van der Schouw Y. van der GraaL J D . Banga Utrecht University and Academic Hospital, Utrecht, The Netherlands
Using data collected for the Asymptomatic Carotid Artery Progression Study (ACAPS), participant characteristics predictive of 3 year progression of atherosclerosis were identified for the 116 women (and 113 men) assigned to the placebo group. ACAPS was a 3 year, randomised, multicentered, factoriatly designed trial of lovastatin, warfarin, and their placebos in 919 high risk participants free of clinical vascular disease at baseline. The primary endpoint for the trial was the progression of carotid artery atherosclerosis measured by B-mode ultrasonography. Progression was defined as the 3 year change in the mean of 12 maximum intimal-medial thicknesses (IMTs) measured over 12 carotid walls (near and far walls in the bifurcation, common and internal carotid arteries on the left and right sides of the neck). Twenty-eight baseline demographic, medical, nutritional and risk factor characteristics were examined to determine their relationships with 1MT progression (adjusting for age and baseline mean-maximum IMT). Among the women, being on estrogen replacement therapy (ERT) was one of the strongest predictors of regression (-0.012 nun/year on ERT and 0.012 mm/year not on ERT, P=0.05). When the 87 women not on ERT were compared to the 113 men, the two groups had comparable 3 year progression rates (0.0072 mm /year for women compared to 0.0080 mm/year for men). The following characteristics were independently predictive of progression among women (P<_0.15): baseline IMT (-), vitamin E consumption (-), plasma triglyceride [TG] levels (-), and body mass index [BMll (+). There was statistical evidence of a gender interaction with TG and BMI, suggesting that women have unique characteristics that influence atherosclerosis.
To determine whether a reduced lifetime endogenous estrogen exposure as a result of an early menopause is associated with an increased cardiovascular disease risk, a cohort of 12,101 postmenopausal women was studied. Originally, these women were enroled to study the effect of screening for breast cancer (DOM-project). At baseline, they were 50-65 years (mean 57 years) and median followup time was 16 years (maximum 19 years). The authors tested the association between age at menopause and cardiovascular mortality with C o x ' proportional hazards analysis. Each year that natural or surgical menopause starts earlier increases the risk o f dying from cardiovascular diseases with 2% (age-adjusted hazard ratio (HR) 0.98, 95% CI 0.96-0.99). Adjustment for body mass index, body fat distribution, oral contraceptive use, parity and age at first delivery, smoking, hypertension, diabetes and previous cardiovascular disease did not alter this risk. An early menopause was a not a risk indicator for cardiovascular mortality in the subgroup of smoking women (HR 1.01, 95% CI 0.98-1.04) and a stronger risk indicator for women with diabetes (HR 0.95, 95% CI 0.91-0.99), although confidence intervals of these HRs showed overlap with those o f the opposing subgroup. The observed "dose-response" relationship supports the hypothesis that a reduced lifetime endogenous estrogen exposure determines partially the increased cardiovascular mortality. The effect of smoking seems to overrule the effect o f an early menopause.