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Ultrasonic echolucent carotid plaques predict future strokes
Workshops Diabetes
Iw10.31 ASSOCIATION PRECLINICAL FREE-LIVING
OF BODY MASS INDEX WITH CAROTID ATHEROSCLEROSIS IN WOMEN FROM SOUTHERN ITALY
P.0. Rubba, M. De Michele, E. Celentano, A. Iammzzi, G. Covetti, R. Galasso, S. Panico. Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy An increased body mass index has long been considered a risk factor for cardiovascular disease. In the present study, we investigated the relationship between body mass index and subclinical atherosclerosis in a population of free-living women. Over 5000 women (n = 5062, age range 30-69 years) living in the area of Naples, Southern Italy, participated in the “Progetto Atena”, a populationbased study on the etiology of cardiovascular disease and cancer in the female population. A sample of 310 participants underwent high resolution B-mode ultrasound to assess intima-media thickness (IMT) of common carotid artery and carotid bitiucation. Women with atherosclerotic plaques (IMT > 1.2 mm) at the level of their common carotid artery had significantly higher age-adjusted values of body mass index (29 versus 27 Kg/m’, p < 0.01) compared with participants without plaques at this site, whereas no differences were found between the two groups in the bifurcation. The prevalence of common carotid atherosclerotic lesions increased gradually from the lowest to the highest quartile of body mass index. Body mass index in the upper quartile (BMI > 30 Kg/m*) was associated with an increased risk of common carotid plaques (odds ratio: 1.92, 95% CI: 1.1 l-3.33) compared to quartile l-3. This association was independent of other traditional cardiovascular risk factors (age, blood pressure, lipid abnormalities). The results of this population based study indicate a graded and independent association of body mass index with preclinical carotid atherosclerosis in clinically healthy women. Iw10.41
UL.TR4SONIC ECHOLUCENT PREDICT FUTURE STROKES
CAROTID
between HTG and endothelial dysfunction. Therefore, endotbelial function was studied in HTG patients with low and high hyperinsulinemia and compared to endothelial function of controls. Eleven patients with endogeneous HTG participated in the study. Data of these patients were dichotomized around the median of serum insulin levels, resulting in the formation of 2 groups: a HTG group with high hyperinsulinemia (HTG-HHI) and a HTG group with low hyperinsulinemia (HTG-LHI). Both groups were compared to a control group, consisting of 16 normolipidemic individuals. Cumulativedose infusions of serotonin and sodium nitroprusside were infused locally into the brachial artery to study endothelium-dependent and endotheliumindependent vasodilation, respectively. Results are expressed as median
(IQW. Age and body mass index were similar in all groups. Triglycerides levels were lower in the control group than in both HTG groups (both p < 0.01) and did not differ between both HTG groups. Insulin levels were higher in both HTG groups than in the control group both p < 0.05). No significant differences were observed in endothelial-dependent vasodilation between controls and the HTG-LHI group. In contrast, the response to serotonin was attenuated in the HTG-HHI group compared to controls (low and high dose by respectively -60 and -49%, both p < O.Ol), and tended to be lower than in the HTG-LHI group as well (-4l%, p = 0.068 and -3l%, p = 0.100 respectively). Endothelium-independent vasodilation did not significantly differ between the three groups (Tabel). Table: Swum triglycerides,
insulin and endotklium-dependent Controls
Serum triglycerides
(mmol/L)
(n=16)
wodilation HTG-LHI
(F6)
HTG-HHI
(n=S)
0.83 (0.65-1.23)
8.7 (5.8-9.2)
7.5 (6.6-12.9)
Serum insulin mun
11.0 (7.8-12.0)
20.0 (14.5-25.3)
43.0 (35.0-52.5)
Change in fore-arm blood flow upon semtonin 0.3 ng/kg/min (%)
67.6 (42.3-103.3)
47.3 (33.5-78.5)
26.8 (-l.O-Il.4)
Change in fore-am blood ilow upon serotonti 0.9 nglkgimin (%)
114.6 (90.1-147.6)
98.5 (64.8-141.4)
58.0 (40.0-77.6)
PLAQUES In conclusion, we suggest that endothelial dysfunction in HTG is determined by the degree of hyperinsulinemia and not by triglycerides concentrations per se.
M.L.M. B.G. Nordestgaard, T.V. Schroeder, S. Vorstrup, H. Sillesen. Dept. Vascular Surgery, Rigshospitalet, Denmark Echolucency of carotid plaques as a predictor of increased stroke incidence was examined in individuals with 250% carotid stenosis and compared with the incidence predicted by severity of stenosis. This prospective study over 4.4 years followed incidence of ipsilateral ischemic strokes in 246 patients with 250% relevant carotid artery stenosis. At inclusion, echogenicity of carotid plaques and degree of stenosis were evaluated using high-resolution B-mode ultrasound with computer-assisted image processing and Doppler ultrasound, respectively. We observed 44 ipsilateral ischemic strokes, an equivalent incidence to 53 per 1000 person-years. Relative risk of ipsilateral ischemic stroke for echolucent versus echorich plaques was 2.0 (95% CI:l.l-3.9), while for 80-99% versus 50-79% stenosis was 1.6 (0.9-2.9). Relative to patients with echorich 5&79% stenotic plaques, those with echorich 80-99% stenotic plaques, echolucent 50-79% stenotic plaques and echolucent 8& 99% stenotic plaques had relative risks of ipsilateml ischemic strokes of 1.1 (0.3-3.6), 1.7 (O&3.8), and 3.1 (1.3-7.4), respectively; equivalent absolute risk increases were l%, 8% and 17%. Relative risks in patients with previous focal neurological symptoms were 3.1 (0.7-14), 4.2 (1.2-15) and 7.9 (2.130), equivalent to absolute risk increases of 11%, 18% and 28%. Ultrasound B-mode measured echolucency of carotid plaques is associated with increased stroke incidence, particularly in symptomatic patients with S&99% stenosis. Measurement of echolucency together with degree of stenosis may improve selection of patients for carotid endarterectomy, increasing the effectiveness of this procedure.
Diabetes
jw11.11
HYPERINSULINEMIA CONTRIBUTES TO IMPAIRED ENDOTHELIUM-DEPENDENT VASODILATION IN CHRONIC HYPERTRIGLYCERIDEMIA
I.J.A.M. Jonkers’, A.H.M. Smelt’, F.H.A.F. de Man’, A. van der Laarse’, A.M. Kamper’ , G.J. Blauw’. ‘Leiden University Medical Center; Albinusdrzef 2, 2300 RC Leiden, The Netherlands Hyperinsulinemia is frequently (HTG) and may be responsible
43
present in chronic hypertriglyceridemia for the controversy regarding the relation
Iw11.21
HUMAN APOLIPOPROTEIN B-100 OLIGOSACCHARIDE STRUCTURE IS NOT ALTERED IN FAMILIAL HYPERCHOLESTEROLAEMIA OR NON INSULIN DEPENDENT DIABETES
B. Garner’#, D. Harvey’, M. Frischmann2, F. Nigon3, M.J. Chapman3, P.M. Rudd’ . ‘Oxford Glycobiology Institute, University of Oxford, Oxford OXI 3QU, UK; Institute for Medical Biology and Human Genetics, 6020 Innsbruck, Austria; ‘INSERM Unit 321. Hopital de la Pitie, 75651 Parts, France Plasma low density lipoprotein (LDL) concentration is strongly associated with atherosclerosis risk. Changes to the carbohydrate composition of LDL apolipoprotein (apo) BlOO have been suggested to be related to the atherogenic properties of LDL and to potentially serve as a marker for atherosclerosis risk. In the present study, a comprehensive analysis of apoBlO0 glycan composition was conducted using LDL derived from normolipidaemic, heterozygous and homozygous familial hypercholesterolaemic, and hypertriglyceridaemic non insulin dependent diabetic subjects as the apoBlO0 source. Using high performance liquid chromatography combined with exoglycosidase carbohydrate sequencing and matrix assisted laser desorption/ionisation mass spectrometry techniques to analyse fluorescently labelled oligosacchaxides, we have discovered several carbohydrates not previously found on human apoBlO0, including truncated complex biantennary N-glycans and hybrid N-glycans as well as several core type 1 and core type 2 0-glycans. The glycan content accounted for 6.3% of apoBlO0 mass and the oligosaccharide structures were found to be remarkably well conserved in all of the subjects studied. Similarly, the N-glycan composition of apoBlO0 derived from five different LDL subpopulations did not vary in either contrkl or hypercholesterolaemic subjects. Furthermore, we found no evidence for “desialylated” apoBlO0 glycans in any of the samples analysed. Analysis of the most abundant LDL ganglioside, a-N-acetylneuraminyllactosylceramide (GM3), revealed a relative deficiency of this glycolipid in small dense LDL subfractions as well as in the most buoyant subpopulation. Th.e use of indirect chemical methods to assess LDL carbohydrate and sialic acid levels should therefore take into account the potential contribution of the uneven distribution of GM3 throughout the LDL density subpopulations. These data
72nd EAS Congress
Iw10.31 ASSOCIATION PRECLINICAL FREE-LIVING
OF BODY MASS INDEX WITH CAROTID ATHEROSCLEROSIS IN WOMEN FROM SOUTHERN ITALY
P.0. Rubba, M. De Michele, E. Celentano, A. Iammzzi, G. Covetti, R. Galasso, S. Panico. Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy An increased body mass index has long been considered a risk factor for cardiovascular disease. In the present study, we investigated the relationship between body mass index and subclinical atherosclerosis in a population of free-living women. Over 5000 women (n = 5062, age range 30-69 years) living in the area of Naples, Southern Italy, participated in the “Progetto Atena”, a populationbased study on the etiology of cardiovascular disease and cancer in the female population. A sample of 310 participants underwent high resolution B-mode ultrasound to assess intima-media thickness (IMT) of common carotid artery and carotid bitiucation. Women with atherosclerotic plaques (IMT > 1.2 mm) at the level of their common carotid artery had significantly higher age-adjusted values of body mass index (29 versus 27 Kg/m’, p < 0.01) compared with participants without plaques at this site, whereas no differences were found between the two groups in the bifurcation. The prevalence of common carotid atherosclerotic lesions increased gradually from the lowest to the highest quartile of body mass index. Body mass index in the upper quartile (BMI > 30 Kg/m*) was associated with an increased risk of common carotid plaques (odds ratio: 1.92, 95% CI: 1.1 l-3.33) compared to quartile l-3. This association was independent of other traditional cardiovascular risk factors (age, blood pressure, lipid abnormalities). The results of this population based study indicate a graded and independent association of body mass index with preclinical carotid atherosclerosis in clinically healthy women. Iw10.41
UL.TR4SONIC ECHOLUCENT PREDICT FUTURE STROKES
CAROTID
between HTG and endothelial dysfunction. Therefore, endotbelial function was studied in HTG patients with low and high hyperinsulinemia and compared to endothelial function of controls. Eleven patients with endogeneous HTG participated in the study. Data of these patients were dichotomized around the median of serum insulin levels, resulting in the formation of 2 groups: a HTG group with high hyperinsulinemia (HTG-HHI) and a HTG group with low hyperinsulinemia (HTG-LHI). Both groups were compared to a control group, consisting of 16 normolipidemic individuals. Cumulativedose infusions of serotonin and sodium nitroprusside were infused locally into the brachial artery to study endothelium-dependent and endotheliumindependent vasodilation, respectively. Results are expressed as median
(IQW. Age and body mass index were similar in all groups. Triglycerides levels were lower in the control group than in both HTG groups (both p < 0.01) and did not differ between both HTG groups. Insulin levels were higher in both HTG groups than in the control group both p < 0.05). No significant differences were observed in endothelial-dependent vasodilation between controls and the HTG-LHI group. In contrast, the response to serotonin was attenuated in the HTG-HHI group compared to controls (low and high dose by respectively -60 and -49%, both p < O.Ol), and tended to be lower than in the HTG-LHI group as well (-4l%, p = 0.068 and -3l%, p = 0.100 respectively). Endothelium-independent vasodilation did not significantly differ between the three groups (Tabel). Table: Swum triglycerides,
insulin and endotklium-dependent Controls
Serum triglycerides
(mmol/L)
(n=16)
wodilation HTG-LHI
(F6)
HTG-HHI
(n=S)
0.83 (0.65-1.23)
8.7 (5.8-9.2)
7.5 (6.6-12.9)
Serum insulin mun
11.0 (7.8-12.0)
20.0 (14.5-25.3)
43.0 (35.0-52.5)
Change in fore-arm blood flow upon semtonin 0.3 ng/kg/min (%)
67.6 (42.3-103.3)
47.3 (33.5-78.5)
26.8 (-l.O-Il.4)
Change in fore-am blood ilow upon serotonti 0.9 nglkgimin (%)
114.6 (90.1-147.6)
98.5 (64.8-141.4)
58.0 (40.0-77.6)
PLAQUES In conclusion, we suggest that endothelial dysfunction in HTG is determined by the degree of hyperinsulinemia and not by triglycerides concentrations per se.
M.L.M. B.G. Nordestgaard, T.V. Schroeder, S. Vorstrup, H. Sillesen. Dept. Vascular Surgery, Rigshospitalet, Denmark Echolucency of carotid plaques as a predictor of increased stroke incidence was examined in individuals with 250% carotid stenosis and compared with the incidence predicted by severity of stenosis. This prospective study over 4.4 years followed incidence of ipsilateral ischemic strokes in 246 patients with 250% relevant carotid artery stenosis. At inclusion, echogenicity of carotid plaques and degree of stenosis were evaluated using high-resolution B-mode ultrasound with computer-assisted image processing and Doppler ultrasound, respectively. We observed 44 ipsilateral ischemic strokes, an equivalent incidence to 53 per 1000 person-years. Relative risk of ipsilateral ischemic stroke for echolucent versus echorich plaques was 2.0 (95% CI:l.l-3.9), while for 80-99% versus 50-79% stenosis was 1.6 (0.9-2.9). Relative to patients with echorich 5&79% stenotic plaques, those with echorich 80-99% stenotic plaques, echolucent 50-79% stenotic plaques and echolucent 8& 99% stenotic plaques had relative risks of ipsilateml ischemic strokes of 1.1 (0.3-3.6), 1.7 (O&3.8), and 3.1 (1.3-7.4), respectively; equivalent absolute risk increases were l%, 8% and 17%. Relative risks in patients with previous focal neurological symptoms were 3.1 (0.7-14), 4.2 (1.2-15) and 7.9 (2.130), equivalent to absolute risk increases of 11%, 18% and 28%. Ultrasound B-mode measured echolucency of carotid plaques is associated with increased stroke incidence, particularly in symptomatic patients with S&99% stenosis. Measurement of echolucency together with degree of stenosis may improve selection of patients for carotid endarterectomy, increasing the effectiveness of this procedure.
Diabetes
jw11.11
HYPERINSULINEMIA CONTRIBUTES TO IMPAIRED ENDOTHELIUM-DEPENDENT VASODILATION IN CHRONIC HYPERTRIGLYCERIDEMIA
I.J.A.M. Jonkers’, A.H.M. Smelt’, F.H.A.F. de Man’, A. van der Laarse’, A.M. Kamper’ , G.J. Blauw’. ‘Leiden University Medical Center; Albinusdrzef 2, 2300 RC Leiden, The Netherlands Hyperinsulinemia is frequently (HTG) and may be responsible
43
present in chronic hypertriglyceridemia for the controversy regarding the relation
Iw11.21
HUMAN APOLIPOPROTEIN B-100 OLIGOSACCHARIDE STRUCTURE IS NOT ALTERED IN FAMILIAL HYPERCHOLESTEROLAEMIA OR NON INSULIN DEPENDENT DIABETES
B. Garner’#, D. Harvey’, M. Frischmann2, F. Nigon3, M.J. Chapman3, P.M. Rudd’ . ‘Oxford Glycobiology Institute, University of Oxford, Oxford OXI 3QU, UK; Institute for Medical Biology and Human Genetics, 6020 Innsbruck, Austria; ‘INSERM Unit 321. Hopital de la Pitie, 75651 Parts, France Plasma low density lipoprotein (LDL) concentration is strongly associated with atherosclerosis risk. Changes to the carbohydrate composition of LDL apolipoprotein (apo) BlOO have been suggested to be related to the atherogenic properties of LDL and to potentially serve as a marker for atherosclerosis risk. In the present study, a comprehensive analysis of apoBlO0 glycan composition was conducted using LDL derived from normolipidaemic, heterozygous and homozygous familial hypercholesterolaemic, and hypertriglyceridaemic non insulin dependent diabetic subjects as the apoBlO0 source. Using high performance liquid chromatography combined with exoglycosidase carbohydrate sequencing and matrix assisted laser desorption/ionisation mass spectrometry techniques to analyse fluorescently labelled oligosacchaxides, we have discovered several carbohydrates not previously found on human apoBlO0, including truncated complex biantennary N-glycans and hybrid N-glycans as well as several core type 1 and core type 2 0-glycans. The glycan content accounted for 6.3% of apoBlO0 mass and the oligosaccharide structures were found to be remarkably well conserved in all of the subjects studied. Similarly, the N-glycan composition of apoBlO0 derived from five different LDL subpopulations did not vary in either contrkl or hypercholesterolaemic subjects. Furthermore, we found no evidence for “desialylated” apoBlO0 glycans in any of the samples analysed. Analysis of the most abundant LDL ganglioside, a-N-acetylneuraminyllactosylceramide (GM3), revealed a relative deficiency of this glycolipid in small dense LDL subfractions as well as in the most buoyant subpopulation. Th.e use of indirect chemical methods to assess LDL carbohydrate and sialic acid levels should therefore take into account the potential contribution of the uneven distribution of GM3 throughout the LDL density subpopulations. These data
72nd EAS Congress