- Email: [email protected]
[126] ARE ESTIMATED GLOMERULAR FILTRATION RATE AND PROTEINURIA ASSOCIATED WITH CARDIOVASCULAR MORTALITY? RESULTS FROM THE PROGETTO VENETO ANZIANI (Pro.V.A.) STUDY
Abstracts, XXIII National Congress of the Italian Society for the Study of Atherosclerosis (SISA) 124 PREVALENCE OF THE METABOLIC SYNDROME IN TYPE 2 DIABETIC PATIENTS A. Torri1 , P. Marenco1 , O. Disoteo2 , G. Pizzi2 , A. Branchi1 . 1 Dep Intern Med, Fond IRCCS Osp. Maggiore,Milan, 2 Diabetes Unit, Garbagnate M, Diabetology Niguarda H., Italy E-mail: [email protected] In patients with type 2 diabetes, metabolic syndrome (MetS) increases the risk for future cardiovascular disease beyond that due to diabetes itself. A major problem is the definition of MetS. The most widely used are the the definition of the National Cholesterol Education Program Adult Treatment Panel III (ATPIII) and the more recent one of the International Diabetes Federation (IDF). In the present study, we have compared the 2 definitions in a series of 2,042 type 2 diabetic patients to verify the impact of the different criteria on the allocation of patients into groups with and without the MetS. According to ATPIII 68% of male and 80% of females patients could be classified as MetS, the percentage of patients with MetS was significantly greater when the syndrome was diagnosed with the IDF criteria (77% in males and 94% in females). Concordance between the 2 definitions of MetS reached 80% in males (in 63% of cases both definitions were positive for MetS and in 17% of cases were negative) and 91% in females (83% positive and 8% negative for MetS with both definitions). As expected, misclassification was mainly due to a greater proportion of patients defined as affected by MetS according to IDF but not according to ATPIII criteria (14% of males and 7% of females) and was accounted for by the lower cut point for definition of central obesity in IDF than in ATPIII. Of interest are the few patients who were classified into the MetS group according to the ATPIII, but not to the IDF criteria (6% males and 2% females). In all cases, the patients had a cluster of risk factors (hypertension, low HDL cholesterol, hypertriglyceridemia in various combinations) without central obesity. Central obesity is the hallmark of the MetS according to IDF; in its absence, the criteria for diagnosis of MetS are not fulfilled though the other components are present. In these conditions, the IDF definition may underestimate the real cardiovascular risk in type 2 diabetic patients. 125 WORK-PLACE MEDICINE, AN OPPORTUNITY TO TREAT THE METABOLIC SYNDROME AND PREVENT CARDIOVASCULAR DISEASES R. Volpe1 , J. Pille2 , R. Gavita1 . 1 Italian National Council Research (CNR), Rome; 2 Food and Agriculture Organization (FAO) of the United Nations, Rome, Italy E-mail: [email protected] From 2003 to 2009 the Medical Service of FAO, in collaboration with CNR, has offered a “Coronary Heart Disease (CHD) Prevention Programme” to its multinational staff working in Rome. The study targeted males (M) >45 years of age and females (F) 50 years of age (<50 if in premature menopause). The programme consisted in screening of major risk factors, calculation of individual CHD risk profile over the next 10 years, identification of subjects at risk (>10% of CHD risk in 10 years and, from 2005, also with metabolic syndrome (MS) (NCEP classification), and their inclusion in a 2nd level programme. 632 staff members took part in the study (359 M, 273 F). The prevalence of the MS was 22% in M (n. 79) versus 9% in F (n. 25, p < 0.05). Of the 104 subjects with MS that have been invited to participate at the 2nd level of the programme, 61 (59%) have adhered (intervention group), while 43 (41%) did not participated (control group). Life-style intervention has been based on promoting a healthier diet and on achieving a healthy body-weight (4 different lists of recommended foods to treat risk factors typical of MS have been developed) and on practising a physical activity. The pharmacological treatment has been required in 37 subjects (61%). The intervention resulted in a good control of the major risk factors of MS: at long-term follow-up (4 years), the prevalence of MS has been reduced of 70% (p < 0.001) and the calculated risk from 14.7 dropped to 8.2 ( 44%, p < 0.001). On the contrary, in the control group, the calculated risk has been increased from 7.4 to 11.5 (+36%, p < 0.001). Our results suggest that workplace-medicine, characterized by a close collaboration between doctor and patients, can be an important opportunity to prevent CVD. 126 ARE ESTIMATED GLOMERULAR FILTRATION RATE AND PROTEINURIA ASSOCIATED WITH CARDIOVASCULAR MORTALITY? RESULTS FROM THE PROGETTO VENETO ANZIANI (Pro.V.A.) STUDY S. Zanoni1 , S. Zambon1 , M.L. Casagrande1 , D. Petricca1 , R. Marin1 , M. Noale2 , M.C. Corti1 , G. Baggio1 , G. Crepaldi2 , E. Manzato1,2 . 1 Dept of Medical and Surgical Sciences, Univ of Padova; 2 CNR, Sez Invecchiamento, Padova, Italy E-mail: [email protected] Background: Impaired kidney function and proteinuria are known independent predictors of total and cardiovascular mortality, but only few studies addressed their prognostic significance in older people. Aim: To explore the association of estimated glomerular filtration rate (eGFR) and proteinuria with cardiovascular mortality in a general Italian elderly population.
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Research Design and Methods: Proteinuria, detected by spot urinary excretion, eGFR using 4-variable MDRD Study equation, and cardiovascular mortality were evaluated in 3063 subjects aged 65 years and older of the Pro.V.A. Study during a mean follow-up time of 4.4 years. Results: Of the baseline cohort, 956 subjects (263 men, and 693 women) had a eGFR <60 ml/min/1.73 m2 , and in 852 subjects (411 out of 1230 men, and 441 out of 1833 women) proteinuria was detected by spot urinary excretion (not weighted data). Subjects with eGFR <60 ml/min/1.73 m2 presented a higher prevalence of proteinuria in comparison with those with eGFR >60 ml/min/1.73 m2 (33.8% vs 25.1%, p < 0.0001). After adjustment for age, sex, education level, socio-economic status, smoking, physical activity, BMI, LDL and HDL cholesterol, proteinuria, uric acid levels, hypertension and diabetes, eGFR <60 ml/min/1.73 m2 was associated with increased cardiovascular mortality among all subjects (HR = 1.68, 95% CI 1.02 2.78, p = 0.0422), among women (HR = 1.73, 95% CI 0.92 3.27, p = 0.0906), and among men (HR = 2.13, 95% CI 0.84 5.42, p = 0.1137). On the other hand, in the same model proteinuria was significantly associated with increased cardiovascular mortality in all subjects (HR = 2.07, 95% CI 1.31 3.27, p = 0.0020), among women (HR = 3.38, 95% CI 1.81 6.31, p = 0.0001), but not among men (HR = 1.33, 95% CI 0.64 2.77, p = 0.4505). Conclusions: Our findings demonstrate that cardiovascular mortality is predicted independently by both low eGFR and proteinuria in a general Italian elderly population. The MDRD equation and a simple urine dipstick to test proteinuria can be used to evaluate the mortality risk associated to an impaired kidney function in older people. 127 CYCLOSPORINE A MODULATES THE MACROPHAGE REVERSE CHOLESTEROL TRANSPORT IN VIVO I. Zanotti1 , G. Stomeo1 , F. Zimetti1 , F. Pot` ı2 , F. Bernini1 . 1 Dip. di Scienze a di Parma, Farmacol., Biol. e Chim. Applicate, 2 Dip. Clin. Med, Universit` Italy E-mail: [email protected] Introduction: Increased susceptibility to cardiovascular disease is a major concern for the use of immunosuppressive agents in organ transplanted patients. The process of reverse cholesterol transport (RCT) exerts an antiatherosclerotic activity by driving the release of cholesterol from peripheral cells to the liver for the ultimate elimination into the feces. In this work we investigated whether the immunosuppressive drug cyclosporine A (CsA) may influence RCT in vivo. Methods: this process was measured in C57BL/6J mice treated for 7 days with CsA 50 mg/kg/day or vehicle and i.p. injected with 3H-cholesterol-loaded macrophages, in order to trace the cholesterol mobilization along the RCT pathway from macrophages to plasma, liver and feces. Although the release of cholesterol from these cells represents only a tiny fraction of overall cholesterol efflux from all organs and tissues, this macrophage RCT is the most relevant with regard to atherosclerosis. Results: CsA did not affect plasma levels of total cholesterol, HDL-cholesterol or triglycerides, but significantly increased the amount of radioactive cholesterol in plasma (% cpm/cpm injected±s.d: 2.1%±1.2 vs 1.2%±1.0; p < 0.05). Whereas no difference was detected in the 3H-cholesterol content in the liver (4.2%±1.0 vs 4.4%±0.6 for vehicle and CsA-treated mice respectively), less radioactivity was found in the feces of CsA-treated animals compared to control (0.36%±0.05 vs 0.63%±0.12). This result indicates an impairment of the last step of RCT. Conclusion: CsA treatment in mice induced a significant reduction of fecal sterol excretion, resulting in the accumulation of cholesterol in the plasma compartment and the impairment of the overall process. This observation may provide a potential mechanism for the high incidence of atherosclerotic coronary artery disease following organ transplantation. 128 CHOLESTEROL FLUX BETWEEN CELLS AND HUMAN SERUM F. Zimetti1 , E. Favari1 , M.P. Adorni1 , M. Moya2 , G.H. Rothblat2 , F. Bernini1 . 1 Dept. Pharmacological and Biological Sciences and Applied Chemistries, University of Parma, Italy; 2 Children’s Hospital of Philadelphia, Philadelphia PA, USA E-mail: [email protected] The net movement of cholesterol in and out of cells determine progression or regression of atherosclerosis. We have addressed two questions related to the movement of free cholesterol (FC) between cells and lipoproteins: 1) Does the cell type influence fractional efflux of cholesterol? 2) How does cholesterol content of cells influence the flux of cholesterol mass between cells and human serum? To address the first question we compared % efflux from cholesterol-enriched J774 cells to Fu5AH rat hepatoma cells. The main efflux mechanisms from the Fu5AH cells are the passive diffusion (PD) and SRBI. When exposed to whole sera there are correlations (r2 = 0.58, p < 0.0001) between fractional efflux to HDL-C, but no association of efflux to prebetaHDL. The major efflux pathway from cholesterol-enriched J774 is via ABCA1, with contributions by ABCG1 and PD. In this case there are significant associations between efflux to human sera and the concentrations of apoA-I (r2 = 0.32, p = 0.006) and prebeta-HDL (r2 = 0.23, p = 0.02). To address the second question we measured changes in cholesterol mass using cholesterolnormal and -enriched macrophages exposed for 8h to human serum, apoB depleted serum, isolated HDL3 or apoA-I. Incubating cholesterol-enriched cells for 8h resulted in the net reduction of cell cholesterol mass (net efflux). If
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Research Design and Methods: Proteinuria, detected by spot urinary excretion, eGFR using 4-variable MDRD Study equation, and cardiovascular mortality were evaluated in 3063 subjects aged 65 years and older of the Pro.V.A. Study during a mean follow-up time of 4.4 years. Results: Of the baseline cohort, 956 subjects (263 men, and 693 women) had a eGFR <60 ml/min/1.73 m2 , and in 852 subjects (411 out of 1230 men, and 441 out of 1833 women) proteinuria was detected by spot urinary excretion (not weighted data). Subjects with eGFR <60 ml/min/1.73 m2 presented a higher prevalence of proteinuria in comparison with those with eGFR >60 ml/min/1.73 m2 (33.8% vs 25.1%, p < 0.0001). After adjustment for age, sex, education level, socio-economic status, smoking, physical activity, BMI, LDL and HDL cholesterol, proteinuria, uric acid levels, hypertension and diabetes, eGFR <60 ml/min/1.73 m2 was associated with increased cardiovascular mortality among all subjects (HR = 1.68, 95% CI 1.02 2.78, p = 0.0422), among women (HR = 1.73, 95% CI 0.92 3.27, p = 0.0906), and among men (HR = 2.13, 95% CI 0.84 5.42, p = 0.1137). On the other hand, in the same model proteinuria was significantly associated with increased cardiovascular mortality in all subjects (HR = 2.07, 95% CI 1.31 3.27, p = 0.0020), among women (HR = 3.38, 95% CI 1.81 6.31, p = 0.0001), but not among men (HR = 1.33, 95% CI 0.64 2.77, p = 0.4505). Conclusions: Our findings demonstrate that cardiovascular mortality is predicted independently by both low eGFR and proteinuria in a general Italian elderly population. The MDRD equation and a simple urine dipstick to test proteinuria can be used to evaluate the mortality risk associated to an impaired kidney function in older people. 127 CYCLOSPORINE A MODULATES THE MACROPHAGE REVERSE CHOLESTEROL TRANSPORT IN VIVO I. Zanotti1 , G. Stomeo1 , F. Zimetti1 , F. Pot` ı2 , F. Bernini1 . 1 Dip. di Scienze a di Parma, Farmacol., Biol. e Chim. Applicate, 2 Dip. Clin. Med, Universit` Italy E-mail: [email protected] Introduction: Increased susceptibility to cardiovascular disease is a major concern for the use of immunosuppressive agents in organ transplanted patients. The process of reverse cholesterol transport (RCT) exerts an antiatherosclerotic activity by driving the release of cholesterol from peripheral cells to the liver for the ultimate elimination into the feces. In this work we investigated whether the immunosuppressive drug cyclosporine A (CsA) may influence RCT in vivo. Methods: this process was measured in C57BL/6J mice treated for 7 days with CsA 50 mg/kg/day or vehicle and i.p. injected with 3H-cholesterol-loaded macrophages, in order to trace the cholesterol mobilization along the RCT pathway from macrophages to plasma, liver and feces. Although the release of cholesterol from these cells represents only a tiny fraction of overall cholesterol efflux from all organs and tissues, this macrophage RCT is the most relevant with regard to atherosclerosis. Results: CsA did not affect plasma levels of total cholesterol, HDL-cholesterol or triglycerides, but significantly increased the amount of radioactive cholesterol in plasma (% cpm/cpm injected±s.d: 2.1%±1.2 vs 1.2%±1.0; p < 0.05). Whereas no difference was detected in the 3H-cholesterol content in the liver (4.2%±1.0 vs 4.4%±0.6 for vehicle and CsA-treated mice respectively), less radioactivity was found in the feces of CsA-treated animals compared to control (0.36%±0.05 vs 0.63%±0.12). This result indicates an impairment of the last step of RCT. Conclusion: CsA treatment in mice induced a significant reduction of fecal sterol excretion, resulting in the accumulation of cholesterol in the plasma compartment and the impairment of the overall process. This observation may provide a potential mechanism for the high incidence of atherosclerotic coronary artery disease following organ transplantation. 128 CHOLESTEROL FLUX BETWEEN CELLS AND HUMAN SERUM F. Zimetti1 , E. Favari1 , M.P. Adorni1 , M. Moya2 , G.H. Rothblat2 , F. Bernini1 . 1 Dept. Pharmacological and Biological Sciences and Applied Chemistries, University of Parma, Italy; 2 Children’s Hospital of Philadelphia, Philadelphia PA, USA E-mail: [email protected] The net movement of cholesterol in and out of cells determine progression or regression of atherosclerosis. We have addressed two questions related to the movement of free cholesterol (FC) between cells and lipoproteins: 1) Does the cell type influence fractional efflux of cholesterol? 2) How does cholesterol content of cells influence the flux of cholesterol mass between cells and human serum? To address the first question we compared % efflux from cholesterol-enriched J774 cells to Fu5AH rat hepatoma cells. The main efflux mechanisms from the Fu5AH cells are the passive diffusion (PD) and SRBI. When exposed to whole sera there are correlations (r2 = 0.58, p < 0.0001) between fractional efflux to HDL-C, but no association of efflux to prebetaHDL. The major efflux pathway from cholesterol-enriched J774 is via ABCA1, with contributions by ABCG1 and PD. In this case there are significant associations between efflux to human sera and the concentrations of apoA-I (r2 = 0.32, p = 0.006) and prebeta-HDL (r2 = 0.23, p = 0.02). To address the second question we measured changes in cholesterol mass using cholesterolnormal and -enriched macrophages exposed for 8h to human serum, apoB depleted serum, isolated HDL3 or apoA-I. Incubating cholesterol-enriched cells for 8h resulted in the net reduction of cell cholesterol mass (net efflux). If