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PubblicatoFloriano Donato Modificato 10 anni fa
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Adult Treatment Panel III (ATP III) Guidelines May 2001 Ipercolesterolemie famigliari Ipercolesterolemie e rischio cardio vascolare globale
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Chilomicroni (apo B-48, C, E) MACROFAGO VLDL Apo B-100 Apo C, E IDL LDL Apo B-100 HDL3 Apo AI-II HDL2 TG Fatty Acids COL trasporto inverso Site of Synthesis of Lipoproteins
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CM VLDL IDL LDL HDL Lipoprotein Nomenclature and Composition Major apoB apoB apoB apoB apoA-I Protein Major TGTG CE CE CE Lipid CM= chylomicronTG=triglyceride VLDL= very low density lipoproteinCE= cholesteryl ester IDL= intermediate density lipoprotein LDL= low density lipoprotein HDL= high density lipoprotein Apo = apolipoprotein
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Iperlipoproteinemie secondo Fredrikson Classificazione fenotipica VChilomicroni, VLDLTG & Col IVVLDLTG & Col IIIIDL, VLDL, ChilomicroniCol & TG (1/1) IIbLDL & VLDLCol & TG IIaLDLCol IChilomicroniTG
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Iperlipoproteinemie genetiche Ipercol FamIV o V2-3/1000AD? IperlipidemiaIIb o IV3-5/1000AD? Familiare Combinata FHIIa o IIb1/500ADdef recettore LDL FDAIIa1/500ADApo B100 def PoligenicaIIa??? DisßIII?ARApo E2E2 IperchiloI o Vrara +ARDeficit LPL/Apo C-II Iper Col > Iper TG Iper TG > Iper Col
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Diagnosi iperlipoproteinemie genetiche - Criteri clinici - Famigliarità per ipercolesterolemia (parenti di I grado) Famigliarità per CVD < 55 anni (parenti di I grado) Xantomi tendinei LDL cut off ?? LDL 190 - 220 mg/dl ?? Apo B cut off
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Adult Treatment Panel III (ATP III) Guidelines May 2001 National Cholesterol Education Program
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ATP I & ATP II MAJOR GOAL OF THERAPY LDL-CHOLESTEROL MAJOR TARGETS OF THERAPY FH Het & Hom FDA apo B-100 PH
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T2DM/T1DM Ipotiroidismo Cushing IRC Sindrome Nefrosica Colestasi Obesità Iperlipemia iatrogena Alcohol High-CARBO Diet Estrogeni Ticlopidina Diuretici ß-block Glucocorticoidi Iperlipoproteinemie secondarie
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New Features of ATP III Multiple metabolic risk factors (metabolic syndrome) Focus on Multiple Risk Factors Diabetes: CHD risk equivalent Framingham projections of 10-year CHD risk
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Diabete e CVD rischio relativo 1 2 3 0 no DM no IMA no DM IMA DM no IMA DM IMA Mukamal KJ et al Diabetes Care 24; 1422, 2001 rischio relativo di mortalità CVD
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NEFA Il paradigma dellaumentato flusso dei NEFA Perseghin G. et al. Curr Opin Lipidol, 2005 Dieta Sedentarietà Geni
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Eccesso di grasso viscerale e dislipidemia Pouliot MC et al. Diabetes 1992;41:826-34 310 248 186 124 62 0 60 45 30 mg/dL Trigliceridi Magri Colesterolo HDL Grasso viscerale (soggetti obesi) BassoAlto Magri Grasso viscerale (soggetti obesi) BassoAlto
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Leccesso di grasso viscerale promuove un fenotipo aterogeno Elevati trigliceridi, basso C-HDL e elevate particelle piccole e dense di C-LDL C-LDL normale LDL d ense TG C-HDL TG C-HDL Magri grasso viscerale Rischio CHD Despres JP. Ann Med 2001;33:534-41
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Fattori di Rischio Cardiovascolare
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Rischio Cardiovascolare Globale
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UKPDS BMJ 316; 823, 1998 Diabete e CVD PRIORITA
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pazienti con eventi vascolari (%) 0 20 10 Placebo SIMVA HPS Lancet 360; 7, 2002 Terapia farmacologica EFFICACIA delle STATINE
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Modulazione dellintervento
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LDL Cholesterol Goals and Cutpoints for Therapeutic Lifestyle Changes (TLC) and Drug Therapy in Different Risk Categories 190 (160–189: LDL- lowering drug optional) 160 <1600–1 Risk Factor 10-year risk 10–20%: 130 10-year risk <10%: 160 130 <130 2+ Risk Factors (10-year risk 20%) 130 (100–129: drug optional) 100 <100 CHD or CHD Risk Equivalents (10-year risk >20%) LDL Level at Which to Consider Drug Therapy (mg/dL) LDL Level at Which to Initiate Therapeutic Lifestyle Changes (TLC) (mg/dL) LDL Goal (mg/dL)Risk Category
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Terapia farmacologica EFFICACIA delle STATINE Colesterolo totale20-40% LDL-C30-50% Trigliceridi5-20% HDL-C5% Terapia farmacologica EFFETTI PLEIOTROPICI delle STATINE Infiammazione Funzione endoteliale Stabilità di placca
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Drug Therapy HMG CoA Reductase Inhibitors (Statins) Major side effects –Myopathy (CK) –Increased liver enzymes (AST, ALT) Contraindications –Absolute: liver disease –Relative: use with certain drugs Fibrati (assoluta controindicazione ad associazione con gemfibrozil, mentre la più tollerata è con fenofibrato), immunosoppressori (CyA), ketoconazolo –Citocromo P450 (macrolidi, chinolonici)
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Terapia farmacologica quale statina? The Curves Study atorva simva lova prava fluva Jones P et al Am J Cardiol 81: 582, 1998 rosuva
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PravaSimvaFluvaAtorva/Rosuva Emivita CYP 450 Int Warfarin Int Digitale Lipofilia 2h3h3h15h noyesyesyes yesyesnoyes noyesyesyes noyes no yes Drugs Features
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Drug Therapy Bile Acid Sequestrants Major actions –Reduce LDL-C 15–30% –Raise HDL-C 3–5% –May increase TG Side effects –GI distress/constipation –Decreased absorption of other drugs Contraindications –Dysbetalipoproteinemia –Raised TG (especially >400 mg/dL)
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Bile Acid Sequestrants DrugDose Cholestyramine4–16 g
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Bile Acid Sequestrants (continued) Demonstrated Therapeutic Benefits Reduce major coronary events Reduce CHD mortality
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Drug Therapy Fibric Acids Major actions –Lower LDL-C 5–20% (with normal TG) –May raise LDL-C (with high TG) –Lower TG 20–50% –Raise HDL-C 10–20% Side effects: dyspepsia, gallstones, myopathy Contraindications: Severe renal or hepatic disease
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Fibric Acids DrugDose Gemfibrozil600 mg Fenofibrate145/200 mg Bezafibrate400 mg
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Simvastatina + Ezetimibe
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Age-standardized mortality from cardiovascular disease, i.e. ischaemic heart disease and cerebrovascular disease combined, in European regions (men; age group 45-74 years; year 2000) J Muller-Nordhorn, et al. Eur Heart J 2008;29:Epub online
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