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77 PREVALENCE OF CKD IN PATIENTS SUFFERING FROM DISLIPIDAEMIA
Abstracts, XXII National Congress of the Italian Society for the Study of Arteriosclerosis (SISA) media thickness of the common carotid artery and the possible interaction with polymorphisms of apolipoprotein E in 1541 healthy middle aged subjects form the general population enrolled in the PLIC study. Results: 670G carriers showed significantly increased plasma total cholesterol, LDL cholesterol, and Apo levels B while no significant differences were observed between carries of the I474V SNP. IMT was significantly increased in 670G carriers compared to wt carriers (0.640±0.102 vs 0.652±0.092 mm, p < 0.05). The role of the E670G SNP on the progression of IMT was evaluated in 475 subjects who performed two follow-up visits after two and seven years. The presence of the 670G allele was significantly associated with a greater progression of IMT compared to carriers of the 670E allele. Plasma total cholesterol, LDL cholesterol, apolipoprotein B, and IMT significantly increased from ApoE2;PCSK9 670EE carriers to ApoE4-PCSK9 670G carriers while no significant differences were observed when the presence of the ApoE alleles was combined with that of the PCSK9 I474V SNP. Conclusion: The E670G polymorphism of the PCSK9 gene is associated with increased IMT progression in the general population. When the presence of 670G allele is stratified according to the ApoE gene alleles, ApoE2;PCSK9 670EE carriers show a more favorable plasma lipid profile and decreased IMT compared ApoE4-PCSK9 670G carriers. 76 MR IMAGING OF ATHEROSCLEROTIC PLAQUES IN BRACHIOCEPHALIC ARTERIES OF APOLIPOPROTEIN E KNOCKOUT MICE C. Parolini1 , M. Marchesi1 , C. Cabella2 , L. Miragoli2 , L. Poggi2 , G. Valbusa2 , C.R. Sirtori1 , G. Chiesa1 . 1 Department of Pharmacological Sciences, Milan; 2 CRB Bracco Imaging, Colleretto G, Italy E-mail: [email protected] In view of the growing interest in the direct assessment of plaque size by non-invasive methods, magnetic resonance imaging (MRI) has emerged as a powerful tool in the evaluation of the efficacy of anti-atherosclerotic therapies. Genetically engineered mice are widely used as models of human atherosclerosis; particularly, apolipoprotein E knockout (apoEKO) mice develop severe atherosclerosis in all the arterial tree, in an anatomical and temporally predictable manner. Our interest was focused on the brachiocephalic artery where unstable lesions develop and may rupture after a few weeks of high fat feeding. The aim of the study was to identify, by MRI, plaques occurring at the brachiocephalic artery in view of studying the possibility of plaque stabilization by pharmacological treatments. Homozygous C57BL/6 male apoEKO mice, starting from 8 10 weeks of age have been maintained for 8 12 weeks on a high fat diet containing 21% fat from lard and 0.15% cholesterol. At the end of the dietary treatment, MR images were acquired before and until 2 hours post administration of the paramagnetic contrast agent B22956/1 at the dose of 0.1 mmol/kg (i.v.) in order to enhance the lesions. Animals were then sacrificed and, after perfusion with 10% formalin, brachiocephalic arteries were removed. Serial paraffin sections were stained with hematoxylin and eosin for comparison with MR images of plaques. Plaques were visible by MRI, particularly starting from 10 minutes until 2 hours after the injection of B22956/1. Histological results overlap with those obtained by MRI. In conclusion, these results confirm the feasibility of MRI visualization of plaques developing at the brachiocephalic artery in apoEKO mice and, therefore, this model will be used to study the efficacy of pharmacological treatments. 77 PREVALENCE OF CKD IN PATIENTS SUFFERING FROM DISLIPIDAEMIA M. Pasquale1 , A. Bruzzese2 , V. Bruzzese3 , F. Nasso1 , E. Stellitano1 . 1 U.O. Medicina, P.O. Taurianova, 2 Facolta’ di medicina Messina, 3 U.O. Emodialisi, P.O. Taurianova, Italy E-mail: [email protected] There aren’t certain data about the incidence of the CKD in the European Countries; in the USA, data are available since the 1990s years and the 13% in spite of applying criteria of inclusion very wide. About K/DOQI the chronic kidney disease is a renal damage characterized by: • presence of urinary deteriorations (microhematuria and/or proteinuria) • echographic renal deteriorations • structural damage histologically demonstrable • GRF < 60 ml/min with or without functional or structural deteriorations for a period of >3 months. About the classification of K/DOQI the CKD has to be distinguished in 5 stadia in relation to the GRF: CKD I stadium with GRF equal or higher than 90ml/min, CKD II with GRF included between 89 and 60 ml/min, CKD III stadium with GRF included between 59 and 30 ml/min, CKD IV stadium with GRF included between 29 and 15 ml/min, CKD V stadium with GRF < 15m/min. In all the stadia there are signs of renale damage. The distribution of prevalence of CKD in the various stadia about the classification K/DOQI in the American population is the following: stadium I = (3.2 million) 1.8%, stadium II between (5.6 million) 3.2%, stadium III = (13.6 million) 17.7%, stadium IV = (700,000) 0.35%, stadium V = (340,000) 0.17%. With the purpose to estimate the prevalence of the CKD in the patients suffering from dyslipidaemia belonging to our Lipid Center at the first checkup the GRF was calculated with the formula of Cockroft and Gault. The patients enlisted were 1,565, 683 male and 882 female, age included between 5 and 84 years old with the average age of 53.32. 879 (56.1%) patients were hypertensive, 400 (25.5%) diabetic, and among them, 304 (19.4%) suffering
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both from diabetes and from hypertension, 590 (37.6%) weren’t suffering from hypertension nor from diabetes. The GRF was calculated about 1,343 patients (85.8%), it wasn’t determinable in 222 patients, because they didn’t exhibite the dosage of the creatinine. The results are the following: GRF > 90 = 504 (37.4%), GRF between 89 and 60 ml/min = 546 (40.6%), GRF between 59 and 30 ml/min = 271 (20.1%), GRF between 29 and 15 ml/min = 20 (1.4%), GRF < 15 ml/min = 2 (0.14%). The patients who were studied by us are all suffering from dyslipidaemia and therefore, they have a higher risk than the general population for the development of renal failure and the prevalence of CKD aggred upon GRF < 60 ml/min is resulted as 21.64% and if we considered that the GRF was calculated only about 1,343 patients because 222 hadn’t execute the dosage of the creatinine, such percentage was certainly been higher, also because the half of patients was hypertensive and/or diabetic. For these reasons, we want to persuade the medical class to monitor creatinine clearance in their own patients, in particular in those at high risk, with the purpose of enabling all tricks suitable for the slackening of the progression towards the terminal CKD. 78 EFFECTS OF EXERCISE TRAINING ON CIRCULATING ENDOTHELIAL PROGENITOR CELLS IN PATIENTS WITH INTERMITTENT CLAUDICATION L. Pasqualini, M. Pirro, F. Bagaglia, D. Siepi, S. Gaggioli, B.P.R. Kouadio, L. Paoletti, R. Razzi, S. Innocente, M.R. Mannarino. Internal Medicine, Angiology and Arteriosclerosis Disease, University of Perugia, Italy E-mail: [email protected] Aim: Exercise training (ET) has been used to improve symptom-free exercise capacity and regional perfusion in patients with Intermittent Claudication (IC). EPCs are believed to replace injured endothelial cells, the amount of the injury being today evaluable by measurement of circulating endothelial microparticles (EMPs). EPCs also participate to neovascularization into ischemic areas. Aim of the study was to determine whether ET-induced tissue ischemia acutely influences the number of circulating EMPs and EPCs in patients with peripheral arterial disease (PAD). The effects of exercise training on pain-free walking distance, EMPs and EPCs has been also evaluated. Methods: The number of EMPs and that of CD34+/KDR+ EPCs was quantified by FACS analysis in 10 PAD patients with IC (Group A) before and 2, 24 and 48 hours after a standard treadmill test (2 m/h/12º/5 ) performed until lower limb pain appearance. Ten PAD patients with IC (Group B), underwent a 4 weeks daily ischemic ET and the number of EMPs and EPCs was measured at baseline and after the 4 weeks intervention. Results: In Group A exercise-induced ischemia until leg pain appearance was associated to 118% increase in circulating EMPs levels after 2 hours; the peak of EPCs was recorded 24 hours after standard treadmill test with a mean 52% increase. In Group B, the 4 weeks daily ischemic ET was associated with significant increased pain-free walking distance and 76% increase in the number of EPCs measured at rest (p < 0.05). Conclusions: Among PAD patients, exercise-induced limb ischemia is associated to a significant fast and reversible endothelial injury that is counterbalanced by a following attempt to regenerate the injured endothelium by circulating EPCs. The beneficial effects of daily exercise training on pain-free walking distance is paralleled by a concomitant increase in the number of circulating EPCs, thus suggesting a role of these progenitors on postnatal angiogenesis in patients with limb ischemia. 79 BRAIN DERIVED NEUROTROPHIC FACTOR (BDNF) LEVELS IN ELDERLY SUBJECTS WITH DIFFERENT FORMS OF COGNITIVE IMPAIRMENT AND WITH OR WITHOUT TYPE 2 DIABETES A. Passaro, E. Mari, E. Dalla Nora, C. Marcello, F. Di Vece, J.M. Sanz, C. Bosi, C. Bolognesi, M. Cavalieri, L. Testoni, R. Fellin. Dept. of Clinical and Experimental Medicine, Section of Int. Medicine, Gerontology and Geriatrics, University of Ferrara, Italy E-mail: [email protected] Background: Type 2 diabetes (T2D) is frequently associated with different degrees of cognitive impairment and diabetic subjects show an increased incidence of both vascular dementia (VaD) and Alzheimer’s disease (AD). Brain derived Neurotrophic Factor (BDNF), a member of neurotrophin family, is widely expressed in the nervous system and in other tissues. In vitro and animal studies demonstrate, beside the role of BDNF in nervous system development, a possible role of BDNF in energy balance, glucose metabolism and insulin resistance. Aim of this study was to evaluate the plasmatic levels of BDNF in elderly subjects with different forms of cognitive impairment: AD, VaD and subjects with cerebrovascular disease but not dementia (CDND). Moreover, we aimed to evaluate if subjects with T2D have different levels of circulating BDNF compared to non-diabetic subjects. Subjects and Methods: 129 subjects, attending our outpatients clinic for cognitive disorders, were consecutively enrolled for this study (75 female and 54 male, age 77±8 years). 37 patients were diabetic (DM age 76±9 yrs) and 92 not-diabetic (NDM; age 77±8 yrs). Subjects with secondary not-vascular dementia, congestive heart failure NYHA III/IV, history or presence of acute illness, neoplasia, severe renal or liver disease and COPD were excluded from the study. All subjects underwent a clinical evaluation and assessed with psychometric test and neuroimaging (TC scan). A blood sample was drawn for the determination of circulating BDNF with an ELISA kit (Promega Corporation).
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both from diabetes and from hypertension, 590 (37.6%) weren’t suffering from hypertension nor from diabetes. The GRF was calculated about 1,343 patients (85.8%), it wasn’t determinable in 222 patients, because they didn’t exhibite the dosage of the creatinine. The results are the following: GRF > 90 = 504 (37.4%), GRF between 89 and 60 ml/min = 546 (40.6%), GRF between 59 and 30 ml/min = 271 (20.1%), GRF between 29 and 15 ml/min = 20 (1.4%), GRF < 15 ml/min = 2 (0.14%). The patients who were studied by us are all suffering from dyslipidaemia and therefore, they have a higher risk than the general population for the development of renal failure and the prevalence of CKD aggred upon GRF < 60 ml/min is resulted as 21.64% and if we considered that the GRF was calculated only about 1,343 patients because 222 hadn’t execute the dosage of the creatinine, such percentage was certainly been higher, also because the half of patients was hypertensive and/or diabetic. For these reasons, we want to persuade the medical class to monitor creatinine clearance in their own patients, in particular in those at high risk, with the purpose of enabling all tricks suitable for the slackening of the progression towards the terminal CKD. 78 EFFECTS OF EXERCISE TRAINING ON CIRCULATING ENDOTHELIAL PROGENITOR CELLS IN PATIENTS WITH INTERMITTENT CLAUDICATION L. Pasqualini, M. Pirro, F. Bagaglia, D. Siepi, S. Gaggioli, B.P.R. Kouadio, L. Paoletti, R. Razzi, S. Innocente, M.R. Mannarino. Internal Medicine, Angiology and Arteriosclerosis Disease, University of Perugia, Italy E-mail: [email protected] Aim: Exercise training (ET) has been used to improve symptom-free exercise capacity and regional perfusion in patients with Intermittent Claudication (IC). EPCs are believed to replace injured endothelial cells, the amount of the injury being today evaluable by measurement of circulating endothelial microparticles (EMPs). EPCs also participate to neovascularization into ischemic areas. Aim of the study was to determine whether ET-induced tissue ischemia acutely influences the number of circulating EMPs and EPCs in patients with peripheral arterial disease (PAD). The effects of exercise training on pain-free walking distance, EMPs and EPCs has been also evaluated. Methods: The number of EMPs and that of CD34+/KDR+ EPCs was quantified by FACS analysis in 10 PAD patients with IC (Group A) before and 2, 24 and 48 hours after a standard treadmill test (2 m/h/12º/5 ) performed until lower limb pain appearance. Ten PAD patients with IC (Group B), underwent a 4 weeks daily ischemic ET and the number of EMPs and EPCs was measured at baseline and after the 4 weeks intervention. Results: In Group A exercise-induced ischemia until leg pain appearance was associated to 118% increase in circulating EMPs levels after 2 hours; the peak of EPCs was recorded 24 hours after standard treadmill test with a mean 52% increase. In Group B, the 4 weeks daily ischemic ET was associated with significant increased pain-free walking distance and 76% increase in the number of EPCs measured at rest (p < 0.05). Conclusions: Among PAD patients, exercise-induced limb ischemia is associated to a significant fast and reversible endothelial injury that is counterbalanced by a following attempt to regenerate the injured endothelium by circulating EPCs. The beneficial effects of daily exercise training on pain-free walking distance is paralleled by a concomitant increase in the number of circulating EPCs, thus suggesting a role of these progenitors on postnatal angiogenesis in patients with limb ischemia. 79 BRAIN DERIVED NEUROTROPHIC FACTOR (BDNF) LEVELS IN ELDERLY SUBJECTS WITH DIFFERENT FORMS OF COGNITIVE IMPAIRMENT AND WITH OR WITHOUT TYPE 2 DIABETES A. Passaro, E. Mari, E. Dalla Nora, C. Marcello, F. Di Vece, J.M. Sanz, C. Bosi, C. Bolognesi, M. Cavalieri, L. Testoni, R. Fellin. Dept. of Clinical and Experimental Medicine, Section of Int. Medicine, Gerontology and Geriatrics, University of Ferrara, Italy E-mail: [email protected] Background: Type 2 diabetes (T2D) is frequently associated with different degrees of cognitive impairment and diabetic subjects show an increased incidence of both vascular dementia (VaD) and Alzheimer’s disease (AD). Brain derived Neurotrophic Factor (BDNF), a member of neurotrophin family, is widely expressed in the nervous system and in other tissues. In vitro and animal studies demonstrate, beside the role of BDNF in nervous system development, a possible role of BDNF in energy balance, glucose metabolism and insulin resistance. Aim of this study was to evaluate the plasmatic levels of BDNF in elderly subjects with different forms of cognitive impairment: AD, VaD and subjects with cerebrovascular disease but not dementia (CDND). Moreover, we aimed to evaluate if subjects with T2D have different levels of circulating BDNF compared to non-diabetic subjects. Subjects and Methods: 129 subjects, attending our outpatients clinic for cognitive disorders, were consecutively enrolled for this study (75 female and 54 male, age 77±8 years). 37 patients were diabetic (DM age 76±9 yrs) and 92 not-diabetic (NDM; age 77±8 yrs). Subjects with secondary not-vascular dementia, congestive heart failure NYHA III/IV, history or presence of acute illness, neoplasia, severe renal or liver disease and COPD were excluded from the study. All subjects underwent a clinical evaluation and assessed with psychometric test and neuroimaging (TC scan). A blood sample was drawn for the determination of circulating BDNF with an ELISA kit (Promega Corporation).