Hyperlipidaemiák Szollár Lajos Klinikai kórélettan Szeptember 28.

Metabolic pathways for endogenous and exogenous lipids

The path of normal lipid metabolism

Reverse cholesterol transport Reverse Cholesterol Transport Peripheral tissues Cell membrane VLDL, IDL, LDL LDL receptor LCAT CETP FC CE CE TG HDL HDL3 TG CE Free cholesterol Triglycerides Cholesteryl esters CETP Cholesteryl ester transfer protein LCAT Lecithin cholesterol acyltransferase SRB1 FC ABCA1 Liver

HDL metabolism and reverse cholesterol transport

Regulation of cholesterol biosynthesis

LDL receptor structure- function relationship

A Utah pedigree with familial hypercholestolaemia

Prevalence of tendon xanthomas and full circumference corneal arcus in 354 Utah patients

Factors altering the course of cardiovascular disease

NCEP ATP III Guidelines (2004 proposed modifications) Grundy SM et al. Circulation 2004;110: Patients with High risk: CHD or CHD risk equivalents (10-year risk >20%) Initiate TLC* if LDL-C  100 mg/dL † Drug therapy considered if LDL-C  100 mg/dL (<100 mg/dL: drug optional) LDL-C goal <160 mg/dL † <130 mg/dL † (optional goal: <100 mg/dL † ) <100 mg/dL † (optional goal: <70 mg/dL † ) † 70 mg/dL = 1.8 mmol/L; 100 mg/dL = 2.6 mmol/L; 130 mg/dL = 3.4 mmol/L; 160 mg/dL = 4.1 mmol/L; 190 mg/dL = 5 mmol/L: * TLC: therapeutic lifestyle changes Moderately high risk: >2 risk factors (10-year risk 10-20%) Moderate risk: >2 risk factors (10-year risk <10%) Lower risk: 0-1 risk factors <130 mg/dL †  130 mg/dL †  160 mg/dL †  130 mg/dL ( mg/dL: drug optional)  160 mg/dL †  190 mg/dL † ( mg/dL: drug optional)

NCEP ATP III: LDL-C Goals (2004 proposed modifications) *Therapeutic option in very high-risk patients and in patients with high TG, non-HDL-C<100 mg/dL; ** Therapeutic option; 70 mg/dL =1.8 mmol/L; 100 mg/dL = 2.6 mmol/L; 130 mg/dL = 3.4 mmol/L; 160 mg/dL = 4.1 mmol/L High Risk CHD or CHD risk equivalents (10-yr risk >20%) LDL-C level Lower Risk < 2 risk factors Moderately High Risk ≥ 2 risk factors (10-yr risk 10-20%) Target 160 mg/dL Target 130 mg/dL 70 - Target 100 mg/dL or optional 70 mg/dL* Moderate Risk ≥ 2 risk factors (10-yr risk <10%) Target 130 mg/dL or optional 100 mg/dL** Grundy SM et al. Circulation 2004;110:

LDL-koleszterin- szint egy nyugat-európai népességben:, fiziológiás tartomány és terápiás célok. Fiziológiás tartomány Célértékek LDL-cholesterin mmol/L Népesség frekvencia Adapted from: O. Faergeman, S. M. Grundy. Dyslipidaemia. Elsevier. 2003

Impact of Recent Clinical Trials: Revised CAD Risk Categories

Estimate total CVD risk of fatal CVD event in 10 years using SCORE chart Total CVD risk <5% TC 5 mmol/L (190 mg/dL) Total CVD risk 5% TC 5 mmol/L (190 mg/dL) Measure fasting lipids, give lifestyle advice, with repeat lipids after 3 months Lifestyle advice Aim: TC<5 mmol/L (190 mg/dL) LDL-C <3.0 mmol/L (115 mg/dL) Follow-up at 5-year intervals TC <5 mmol/L (190 mg/dL) and LDL-C <3.0 mmol/L (115 mg/dL) Maintain lifestyle advice with annual follow-up. If total risk remains 5%, consider drugs to lower TC to <4.5 mmol/L (175 mg/dL) and LDL-C to <2.5 mmol/L (100 mg/dL) TC 5 mmol/L (190 mg/dL) or LDL-C 3 mmol/L (115 mg/dL) Maintain lifestyle advice and start drug therapy De Backer G et al. Eur Heart J 2003;24:1601– European Guidelines: Guide to lipid management in asymptomatic subjects

3rd European Guidelines Goals - Risk factors:  Prophylactic drug therapy should be considered in particular groups. These parameters have been summarized as a mnemonic for the practitioner as the "European heart health telephone number":  140 mm Hg SBP  90 mm Hg DBP  5 mmol/L (150 mg/dL) total cholesterol  3 mmol/L (115 mg/dL) LDL cholesterol  0 NO SMOKING

Risk estimation is based on age, sex, smoking habits, systolic blood pressure (SBP), and either total cholesterol or cholesterol/HDL ratio. [7] Using the SCORE model, risk charts can be provided for all European countries. Total risk can be calculated from SCORE charts The low-risk chart is for countries such as Belgium. France, Greece, Italy, Luxembourg, Portugal, Spain, and Switzerland. Relative risk is calculated by comparing an individual's risk category with that of a nonsmoking person of the same age and gender with blood pressure </= 140/90 mm Hg and total cholesterol < 5 mmol/L (< 190 mg/dL).

Risk estimation is based on age, sex, smoking habits, systolic blood pressure (SBP), and either total cholesterol or cholesterol/HDL ratio. [7] Using the SCORE model, risk charts can be provided for all European countries. Total risk can be calculated from SCORE charts. The high-risk chart is for use in all other European countries. Relative risk is calculated by comparing an individual's risk category with that of a nonsmoking person of the same age and gender with blood pressure </= 140/90 mm Hg and total cholesterol < 5 mmol/L (< 190 mg/dL).

II. Magyar Terápiás Konszenzus Ajánlás a kardiovaszkuláris betegségek megelőzéséről és preventív kezeléséről Háziorvos Továbbképzô Szemle 2006; 11: 131–138