IMPLEMENTATIE ESC GUIDELINES 2013 LIPIDEN IN PRAKTIJK Casuistiek Dr. Celen Hendrik Cardiologie Heilig Hart Ziekenhuis Leuven 6/3/2013
IMPLEMENTATIE ESC GUIDELINES LIPIDEN 2010 IN PRAKTIJK Risicofactoren, Lipoproteïnes en Atherogenese Werkingsmechanisme van hyolipimiërende farmaca Richtlijnen Casuistiek
Viscerale obesitas en lipoproteïnes
Lower Cholesterol Levels Associated CHD Incidence per 1000 150 125 100 75 50 25 Castelli WP. Am J Med. 1984;76:4-12. 0 204 205-23 4 The Framingham Heart Study 235-26 265-29 4 4 Serum Cholesterol (mg/100 ml) 295
Atherogene balans
Atherogenic and anti-atherogenic lipoproteins From the liver Back to the liver Reverse cholesterol transport TG C apob TG C apob C apob C apob C apo A-I VLDL IDL large buoyant LDL small dense LDL HDL Atherogenic Anti-atherogenic
Lipoprotein (a) Homocysteine IL-6 TC LDLC sicam-1 SAA Apo B TC:HDLC hs-crp hs-crp + TC:HDLC 0 1.0 2.0 4.0 6.0 Relative Risk of Future Cardiovascular Events Ridker et al, N Engl J Med 2000;342:836-843 Risk Factors for Future Cardiovascular Events: Women s Health Study
LDL Cholesterol Hoeksteen van de lipidentherapie Associatie met pathogenese atherosclerose en cardiale eindpunten 10% stijging resulteert in 20% stijging in CVrisico 1 bevat vooral cholesterolester en veel lipoproteine B opname door hepatocyten en non hepatisch weefsel dense smalle LDL cholesterolpartikels 1. Wood D et al. Atherosclerosis. 1998;140:199-270. 2. National Centre for Health Statistics. National Health and Nutrition Examination Survey (III), 1994. 3. Jacobson TA, et al. Arch Intern Med. 2000;160:1361-1369.
LDL-C Lowering With Statins: Reduced CHD Events 25 Secondary Prevention Primary Prevention 4S-PL 20 4S-Rx LIPID-PL Events (%) 15 10 CARE-Rx LIPID-Rx CARE-PL WOSCOPS-Rx WOSCOPS-PL 5 AFCAPS-Rx AFCAPS-PL 0 50 70 90 110 130 150 170 190 210 LDL Cholesterol (mg/dl) Adapted from Illingworth DR. Med Clin North Am. 2000;84:23-42.
HDL Cholesterol Laag HDL cholesterol onafhankelijke predictor voor CHD 1 Hoe lager het HDL-cholesterol, hoe hoger risico CHD 2 Laag HDL is gedefinieerd als < 40 mg/dl 1 HDL cholesterol is laag als triglyceridengehalte hoog is 1. NCEP, Adult Treatment Panel III. JAMA. 2001;285:2486-2497. 2. Wood D, et al. Atherosclerosis. 1998;140:199-270.
Low HDL Cholesterol Levels Increase CHD Risk Even When TC Is Normal: Framingham Heart Study 14-y incidence rates for CHD (%) 14 12 10 8 6 4 2 0 12.50 11.91 11.24 10.7 6.56 4.67 4.15 11.91 9.05 6.6 5.53 4.85 <40 40-49 50-59 60 HDL cholesterol (mg/dl) 3.77 260 230-259 200-229 TC <200 (mg/dl) 2.78 2.06 3.83 Risk of CHD by HDL cholesterol and TC levels; subjects aged 48-83 y. Castelli WP et al. JAMA. 1986;256:2835-2838.
Cholesterol Homeostasis ATHEROGENIC DYSLIPIDEMIA ATHEROGENIC DYSLIPIDEMIA : PLAQUE PROGRESSION Type 2 Diabetes Mixed Hyperlipidemia Metabolic Syndrome Hypercholesterolemia Renal Disease FH Anti-atherogenic HDL ApoAI Atherogenic ApoB100- containing LPs VLDL VLDL Remnants IDL LDL; Dense LDL Plaque Cholesterol content Apo.B LPs HDL Apo AI Influx Cholesterol Efflux Plaque = Inflammation Fragilisation = Cholesterolrich plaque Cardiovascular Events LDL-C : HDL-C > 3:1
ATHEROSCLEROTIC PLAQUE STABILISATION Apo.B LPs HDL Apo AI Influx Cholesterol Efflux Cholesterolrich plaque Plaque Cholesterol content Plaque = stability = Cardiovascular Events
Een deel van het residuele risico : De atherogene triade Meer atherogeen! Klein en dense LDL Athertogene Lipiden Triade HDL-C TG rijk aan Lp Non-HDL-C (maar apob) Frequen geobserveerd : type 2 diabetes (T2D) patiënten met MetS patiënten met nierinsufficiëntie ziekten van het auto-immuunstelsel With the courtesy of Prof. Michel Farnier, Dijon.
De dosering van LDL-C is misleidend LDL-C: 114 mg/dl Triglyceriden: 150 mg/dl LDL-C: 114 mg/dl Triglyceriden: 198 mg/dl Apo B: 0,9 g/l Apo B: 1,3 g/l 1 apo B per LDL-partikel Presented by M. Langlois Lipid Club Dec 2011
Non-HDL-C Het bepalen van non-hdl-c (TC - HDL-C) bevat alle atherogene lipoproteïnes : VLDL, IDL, LDL
Dyslipidaemie hypercholesterolaemie : LDL receptorgenmutatie? hypercholesterolaemie met laag HDL Gemengde dyslipidaemie :apo B overproductie? hypertriglyceridaemie : LPL deficientie metabool syndroom geïsoleerd laag HDLfamiliaal hypoalfalipoporteïnaemie normaal lipidenprofiel en CVD?
IMPLEMENTATIE ESC GUIDELINES LIPIDEN Casuistiek Risicofactoren, Lipoproteïnes en Atherogenese Werkingsmechanisme van hyolipimiërende farmaca Richtlijnen Casuistiek
Statin Liver Endogenous Cholesterol Synthesis LDL-Receptors VLDL-LDL-Cholesterol HDL Atherogenic VLDL, IDL,LDL ApoB LPs HDL Plaque Cholesterol Content HDL = Influx Cholesterol Efflux Atherogenic VLDL, IDL, LDL = Atheroma Plaque Stability Cardiovascular Events Sposito, Chapman ATVB 2002; 22 : 1524-34
Two sources of Cholesterol VLDL IDL LDL Synthesis 800mg/day BILIARY CHOLESTEROL (1000 mg/day) Absorption (700mg/day) INTESTINE DIETARY CHOLESTEROL (300-700 mg/day) Excretion
IMPLEMENTATIE ESC GUIDELINES LIPIDEN Casuistiek Risicofactoren, Lipoproteïnes en Atherogenese Werkingsmechanisme van hyolipimiërende farmaca Richtlijnen Casuistiek
De ESC-richtlijnen voor de behandeling van dyslipidemie definiëren 4 risiconiveaus Reiner & al. ESC/EAS Guidelines for the management of dyslipidaemias 2011 Adapted O. Descamps Louvain Médical 2012
Aanbevelingen voor dyslipidemieën (ESC 2011) 4 risico niveaus 3 LDL niveaus < 115 < 100 < 70 Non-HDL Reiner &AL. ESC/EAS Guidelines for the management of dyslipidaemias 2011 Adapted O. Descamps Louvain Médical 2012
Aanbevelingen ADA Aanbevolen waarden voor metabool syndroom/diabetes en lipidenafwijkingen Patiënten met zeer hoog risico +++ In secundaire preventie of diabetes + CV risicofactoren (RF) Patiënten met hoog risico ++ In primaire preventie, zonder diabetes maar > 2 RF of diabetes zonder RF LDL (mg/dl) Non- HDL (mg/dl) Apo B (mg/dl) <70 < 100 < 80 < 100 < 130 < 90 Brunzell, Diabetes Care 2008 FR = Facteurs de risque
EVOLUTIE RICHTLIJNEN
Populatie afhankelijk
SCORE : HDL
HDL (mg/dl) man vrouw 30 X 1.8 X 1.3 HDL 38 X 1.5 X 1.1 46 X 1.2 X 1 54 X 1 X 0.9 62 X 0.8 X 0.8 70 X 0.7 X 0.7
Factoren die het risico verhogen Familiaal vroegtijdig CV ziekten (man < 55j, vrouw < 60j) Risico x 1.7 vrouw x 2.0 man
<48j, relatief risico
In the overall population, the primary endpoint of major CV events was reduced by 8% (NS) 100 20 Proportion with event (%) 80 60 40 20 10 0.92 (95% CI 0.79-1.08), p=0.32 0 Placebo Fenofibrate 0 1 2 3 4 5 6 7 8 No. At Risk Fenofibrate Placebo 0 0 1 2 3 4 5 6 7 8 2765 2753 2644 2634 2565 2528 2485 2442 1981 1979 Major CV events defined as CV death, nonfatal MI and nonfatal stroke Years 1160 1161 412 395 249 245 137 131 ACCORD Study Group. N Engl J Med. 2010; 362(17):1563-74.
Lipanthyl significantly reduced CV events in the elevated TG + low HDL-C subgroup by 31% 18 In patients with TG 204 mg/dl and HDL-C 34 mg/dl Proportion with event (%) 16 14 12 10 8 6 4 17.32% -31% p=0.03 12.37% Number needed to treat (NNT) for 5 years to prevent one CV event 20 2 0 Simvastatin Simvastatin + Lipanthyl The primary endpoint of major CV events (CV death, nonfatal MI and nonfatal stroke) was not reduced significantly in the overall population (HR=0.92, 95% CI 0.79-1.08, p=0.32) ACCORD Study Group. N Engl J Med. 2010; 362(17):1563-74. Elam MB et al. AHA 2010. Presentation 19724.
SCORE endiabetes? 5X VROUWEN 3X MANNEN UKPDS RISC ENGINE
Clinical Trials and Recent Patterns in the Use of Statins National Ambulatory Medical Care Survey LRC- CPPT 4S NCEP WOSCOP CARE Am Heart J 2001; 141(6):957-963
Chapter 1 : Generic + ZOCOR Prescribed freely without any control ( ~ cheap products ) IndicaAon : PaAents with Hypercholesterolemia Products : Zocor, Simva Generic, Prava Generic, Pravasine, atorva Generic, Totalip Chapter 2 : Original StaAns Prescribed in B with a posteriori control Reimbursement: PaAents not at goal aker 3 months on cheap staans Products : AtorvastaAn 10,20,40,80 mg and RosuvastaAn 10,20,40 mg Chapter 4 : EZETROL & INEGY Prescribed in Bf with a priori control through the medical advisor General PracAAoner needs a posiave advice of the Specialist IndicaAon : PaAents at goal aker 3 months aker staan therapy Products : Ezetrol and Inegy 10/20, 10/40, 10/80 mg