Dislipidemia definete existena unei tulburri n coninutul lipidelor din snge - fie a coninutului total, fie a spectrului substanelor lipidice (modificarea raporturilor unor fraciuni lipidice).

Lipidele sanguineTrigliceridele Acizii graiFosfolipideleColesterolul

Lipoproteineleparticule globulare, cu mas molecular mare, care transport lipidele nepolare (trigliceride i colesteril esteri) prin plasm

Structura lipoproteinelor

Clasificarea lipoproteinelorn funcie de densitate:chilomicroniVLDLLDLIDLHDL

MotilitateMotilitate electroforetic

PROPRIETILE LIPOPROTEINELOR PLASMATICEClasa deLipide OrigineDensitateMotilitateApo lipoproteineprincipaleg/mlelectroforetic

ChilomicroniiTrigliceride Intestin1,006Ramn la origineAI, AII, exogeneA IV, B 48 VLDLTrigliceride Ficat1,006pre-B 100endogeneC (E)LDLColesterilCatabo 1,019B 100esterilismulVLDLIDLColesterilCatabo1,019-1,063Uor pre-E, BesterilismulVLDLHDLColesterilFicat,1,063-1,210AI, AIIesteriintestin C (D,E)

ALTE LIPOPROTEINELipoproteina (a)FR independent pentru ateroscleroz, particula LDL-like cu apo B100 i apo (a)

lipoproteinele remnante

LDL oxidate

Metabolismul lipoproteinelorSistemul de transport exogenSistemul de transport endogenSistemul de retransport al colesterolului de la periferie spre ficat

Metabolismul lipoproteinelor

Ateroscleroza este o maladie InflamatorieRoss R. N Engl J Med 1999;340:115-126.EndotheliumVessel LumenIntimaFoam CellMonocyteCytokinesGrowth FactorsMetalloproteinasesCell Proliferation Matrix DegradationMacrophage

LIPOPROTEINELE I INFLAMAIAHDLLDLChylomicrons, VLDL, and their catabolic remnants> 30 nm2022 nmPotentially proinflammatory915 nmPotentially anti- inflammatory

LDLLDLLDLEndotheliumVessel LumenMonocyteMacrophageAdhesion MoleculesFoam CellIntimaModified LDLCytokinesCell Proliferation Matrix DegradationGrowth Factors MetalloproteinasesRoss R. N Engl J Med 1999;340:115-126.MCP-1

LDLLDLCockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:1987-1994.EndotheliumVessel LumenMonocyteModified LDLMacrophageMCP-1Adhesion MoleculesCytokinesHDLIntimaHDL Inhibit Oxidation of LDLHDL Inhibit Adhesion Molecule ExpressionFoam CellHDL Promote Cholesterol Efflux

Development of Atherosclerotic PlaquesNormalFatty streakFoam cellsLipid-rich plaqueLipid coreFibrous capThrombus

LumenulCalot FibroasMiezLipidicMiezLipidicCalot FibroasLumenulPlaca vulnerabilPlaca Stabil Calot fibroas groas Smooth muscle cells: more extracellular matrix Plac srac n lipide Calot fibroas subire Infiltrate celulare cu activitate proteolitic Plac bogat n lipideLibby P. Circulation. 1995;91:2844-2850.Plcile aterosclerotice

Thrombosis Influences the Severity of a Cardiovascular EventNonocclusive thrombusOcclusive thrombusUnstable anginaNonQ-wave MIQ-wave MISudden death

Minor plaque disruptionHigh flowLow thrombotic tendency

Major plaque disruptionLow flow or vasospasmThrombotic tendencyKullo IJ, et al. Ann Intern Med. 1998;129:1050-1060.Factors favoring thrombosis:Factors limiting thrombosis:

Plasma Chol and CV Mortal.

Hiperlipidemia reprezint majorarea coninutului substanelor lipidice n snge.Hipercolesterolemia reprezint majorarea nivelului colesterolului sangvin. Hipertrigliceridemia reprezint majorarea coninutului n snge de trigliceride. Hiperlipidemia mixt (combinat) definete majorarea concomitent a coninutului de colesterol i de trigliceride n snge.

Etiopatogenia dislipidemiilorFactori genetici (monogenici sau poligenici)Factori dobndii (exces alimentar, abuz de alcool, fumat, boli asociate, etc)

Principalele mecanisme patogenetice ale hiperlipoproteinemiei creterea sintezei sau produciei lipoproteice; diminuarea catabolismului lipoproteic; combinarea mai multor factori i mecanisme de producere

Clasificarea hiperlipoproteinemiilor dup Fredrickson

Tiplp crescutnivelul plasmaticnivelul plasmatical colesterolului al TG

IChilomicroniinormal sau crescut crescutIIaLDLcrescutnormal

IIbLDL i VLDLcrescutcrescut

IIIIDLcrescutcrescut

IVVLDLnormal sau crescut uorcrescutVVLDL i crescut uorcrescutChilomicronii

Hipercolesterolemiile (IIa) Hipertrigliceridemile (I, IV, V)Hiperlipidemiile mixte (IIb, III)Clasificarea hiperlipoproteinemiilor

Clasificarea hiperlipoproteinemiilorPrimareSecundare

Clasificarea NCEP, ATP III 2001

mg/dl

mmol/l

LDL-

< 100

< 2,6 Optimal

colesterolul

100-129

2,6-3,4Aproape optimal

130-159

0,0263,4-4,1Limita superioar

160-189

4,1-4,9nalt

190

4,9

Foarte nalt

Colesterolul

total

< 200

< 5,2Dezirabil

200-239

0,026

5,2-6,2Limita superioar

240

6,2nalt

HDL-

colesterolul

< 40

0,026

1,0Sczut

60

1,6nalt

Trigliceridele

< 150

< 1,5Normal

150-199

0,01

1,5-1,99Limita superioar

200-499

2,0-4,99nalt

500

5,0Foarte nalt

HIPERCOLESTEROLEMIIForma monogenic (hipercolesterolemia familial)Forma poligenic (hipercolesterolemia comun)

HIPERCOLESTEROLEMIA FAMILIALeste o maladie genetic cu transmiterea autosom-dominant, care cauzeaz alterarea funciei receptorilor LDL

HIPERCOLESTEROLEMIA FAMILIALForma heterozigot1:500Forma homozigot1:1000000

Apariia prematur i accelerat a ATS coronariene i a CPI pn la 40 de aniXantoame tendinoaseArc corneanXantelasme HIPERCOLESTEROLEMIA FAMILIAL(forma heterozigot)

Ateroscleroz cu rspndire larg CPI se dezvolt n adolescen sau n copilrieStenoz aortic supravalvular Riscul de moarte subit este foarte nalt, ce poate fi o prima manifestare a boliiXantoamele tendinoase apar n copilrie i au aspectul florid Xantoamele cutanate galbene-portocalie n fosa poplitea i antecubitalHIPERCOLESTEROLEMIA FAMILIAL(forma homozigot)

se caracterizeaz prin creterea valorilor colesterolului, ce reflect interaciunea complex dintre multiple gene (inclusiv cele de codificare a apo E i B) i factorii de mediu mai ales alimentariHIPERCOLESTEROLEMIA POLIGENIC

Reprezint cauza cea mai frecvent de cretere a colesterolemiei (1:250) Mai puin studiat dect hipercolesterolemie familial, care se ntlnete mult mai rar Nu exist nici un semn caracteristic pentru hipercolesterolemie poligenic (xantelasme sau arc cornean)HIPERCOLESTEROLEMIA POLIGENIC

HIPERTRIGLICERIDEMIIHipertrigliceridemii majore exogene (I i V)

Hipertrigliceridemii endogene (IV)

Hipertrigliceridemii majore exogene (I i V)dureri abdominale, tulburri de tranzit, anorexie i vome (pancrearit acut)Xantoame eruptive Lipaemia retinalisHepatomegalieSplenomegalie

Hipertrigliceridemii endogene (IV)

Rareori sunt prezente manifestrile HTG majore (Xantoame eruptive, xantelasme,arcul cornean, pancreatit acut) semnele necaracteristice (astenie postprandial, cefalee, dispepsie)

HIPERLIPIDEMII MIXTEHiperlipidemia combinat (IIb)

Disbetalipoproteinemia (III)

Dislipidemiile, care n-au intrat n clasificare Modificrile concentraiei HDL-colesteroluluiHiperalfalipoproteinemiileHipoalfalipoproteinemiileHipoalfalipoproteinemia familial Maladia Tangier (analfalipoproteinemie) Deficiena LCAT (Fish eye disease)Hipoalfalipoproteinemia familial izolatApoproteina A-I Milano Sindromul X metabolicCreterea concentraiei de Lp(a)Hiperlipidemie familial combinat

Sindromul X metabolicse caracterizeaz prin prezena intoleranei la glucoza sau DZ tip 2 i / sau rezistenei la insulin asociat cu cel puin 3 condiii:

Sindromul X metabolic

- circumferina abdominal > 102 cm la brbai i > 88 cm la femei;- TG 1,7 mmol/l ( 150 mg/dl);- HDL-col < 1,0 mmol/l (< 40 mg/dl) la brbai i < 1,3 mmol/l (< 50 mg/dl) la femei;- creterea TA 130/85 mm Hg;- glucoza 6,1 mmol/l (110 mg/dl)

Hiperlipoproteinemiile secundareexcesele alimentareabuzul de alcooldiabetul zaharathipotiroidiasindromul nefrotic IRCcolestaza unele medicamente (corticosteroizi, -blocantele neselective, diuretice tiazidice etc)

Diagnosticulantecedentele familiale;anamneza;examenul clinic;diagnosticul lipidologic;excluderea formelor secundare

Lipidograma la persoanele sntoaseLipideUniti SIUniti convenionale

Colesterolul total5 mmol/l190 mg/dlLDL-col3 mmol/l115 mg/dlHDL-col (B)1 mmol/l40 mg/dl (F) 1,2 mmol/l46 mg/dlTrigliceridele1,7 mmol/l 150 mg/dl

European guidelines on cardiovascular disease prevention in clinical practice, EHJ 2003, (24 )1601-1610.

n caz de cretere a concentraiei TG mai sus de 4 mmol/l plasma devine tulbure, iar pentru HTG sever este caracteristic lactescena plasmei

Dislipidemia aterogenelevarea trigliceridelor ( 150 mg/dl)apariia particulelor mici LDL reducerea HDL-colesterolului (< 40 mg/dl)

Explorrile lipidologice-dozarea apoproteinelor B i A I;-electroforeza plasmei;-dozarea activitii enzimatice (lipoproteinlipazei);-studiile genetice-ultracentrifugare

Managementul clinic al hiperlipoproteinemiilor

1. Determinarea spectrului lipidic; 2. Identificarea prezenei ATS, ce confirm riscul nalt pentru CPI sau echivalentele CPI;3. Identificarea altor FR majori prezeni;4. Stabilirea nivelului-int al LDL-colesterolului (dup stratificarea riscului); 5. Determinarea strategiei terapeutice

NCEP ATP III valorile int pentru LDL - C Categorie de riscLDL intNivel LDL la care se iniiaz farmacoterapiaCPI sau echivalent 20% opional)risc la 10 ani 10%-20%: 2 factori de risc

TRATAMENT NEFARMACOLOGICModificarea stilului de viaa include:- scderea grsimelor saturate (< 7% din caloriile) i colesterolului (< 200 mg pe zi);- creterea stenolilor/sterolilor vegetale (2 g/zi) i creterea fibrelor (10-25 g/zi);scderea n greutate; - creterea activitii fizice

TRATAMENT FARMACOLOGICStatineleRezineleFibraiiAcidul nicotinic

StatineleLDL receptormediated hepatic uptake of LDL and VLDL remnantsSerum VLDL remnantsSerum LDL-CCholesterol synthesisLDL receptor (BE receptor) synthesisIntracellular CholesterolApo BApo EApo BSystemic CirculationHepatocyteReduce hepatic cholesterol synthesis, lowering intracellular cholesterol, which stimulates upregulation of LDL receptor and increases the uptake of non-HDL particles from the systemic circulation.Serum IDLVLDL

STATINELEInhibitorii HMG-CoA reductazei: lovastatin, pravastatin, simvastatin, atorvastatin, fluvastatin

LDL 18%-55% HDL 5%-15%TG 7%-30%

STATINELEIndicaii: - hipercolesterolemie pur (IIa)- dislipidemie mixt (IIb) Reacii adverse:- miopatie- ALAT, ASAT

STATINELEProprieti pleiotrope cu o influena major asupra aterosclerozei: - efectul vasodilator - antioxidant - antiinflamator - imunomodulator - antitrombotic - antiproliferativ - placa stabilizator

Rezinele LDL-C LDL Receptors VLDL and LDL removal Cholesterol 7- hydroxylase Conversion of cholesterol to BA BA Secretion BA ExcretionTerminal IleumBile AcidEnterohepatic RecirculationReabsorption of bile acids

REZINELESechestranii acizilor biliari:colesteramin, colestipol

LDL 15%-30% HDL 3%-5%TG nu influeneaz sau cresc moderat

REZINELEIndicaii: - hipercolesterolemie pur (IIa)- dislipidemie mixt (IIb) Reacii adverse:- tulburri GI- absorbiei medicamentelor

FibraiiLiverBBTGCMR/IDLC-IICM/VLDLLPLA-ICECEFCFCLCATA-IABC1MacrophageMature HDLNascent HDLLDLRHLFIBRATESFIBRATESIntestine

FIBRAIIgemfibrozil, fenofibrat, clofibrat

LDL 5%-20% HDL 15%-35%TG 20%-50%

FIBRAIIIndicaii: - hipertrigliceridemii (IV, V)- dislipidemie mixt n asociere cu statine Reacii adverse:- dispepsie- litiaz biliar- miopatie

Acidul NicotinicLiverCirculationHDLSerum VLDL results in reduced lipolysis to LDL Serum LDLVLDLDecreases hepatic production of VLDL and of apo BVLDL secretionApo BHepatocyteSystemic CirculationMobilization of FFATG synthesisVLDL

ACIDUL NICOTINICLDL 5%-25% HDL 10%-20%TG 20%-50%

ACIDUL NICOTINICIndicaii: - hipercolesterolemie pur (IIa)- dislipidemie aterogen Reacii adverse:- hiperglicemie- hiperuricemie- tulburri GI

ProfilaxiePrimar

Secundar

ABORDAREA PRACTIC A DISLIPIDEMIILOR(caz clinic)Catedra medicin intern N 1 USMF "N.Testemianu"Victor Botnaru Alexandru Corlteanu

Pacientul n vrst de 62 aniIstoricul familial nesemnificativStil de via: Fumtor 1 pachet/ziAlcool ocazional Alimentaie neraionalCaz clinic

Examenul clinic:xantelasmeleTA 125/80 mm Hg Medicaia: Quinapril 20 mg/zi

Caz clinic

Examenul paraclinicColesterolul total7,3 mmol/l280 mg/dlTrigliceride1,7 mmol/l170 mg/dlHDL-colesterol0,9 mmol/l 34 mg/dlCaz clinic

LDL-colesterol5,6 mmol/l212 mg/dl Glicemia4,5 mmol/l

1.Estimai riscul de infarct miocardic sau moarte coronar la 10 ani 2. Strategia terapeuticCaz clinic

Scorul total : 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25risculla10 ani: 1 1 1 1 1 1 2 2 3 4 5 6 8 10 12 16 20 25 30 1 1 1 1 1 2 2 3 4 5 6 8 11 14 17 22 27 30Scorul Framingham Estimarea riscului de infarct miocardic sau moarte coronarla 10 ani pentru brbai / femei Vrsta20-34 = -9/-735-39 = -4/-340-44 = 0/045-49 = 3/350-54 = 6/655-59 = 8/860-64 = 10/1065-69 = 11/1270-74 = 12/1475-79 = 13/16TA sistolic, mm Hgtratamentul: Fr Cu 120 = 0/0 0/0120-129 = 0/1 1/3130-139 = 1/2 2/4140-159 = 1/3 2/5 160 = 2/4 3/6 HDL-Col

60 = -1/-150-59 = 0/040-49 = 1/1 40 = 2/2 Fumtor

(v 50-59 ani) Nu = 0/0 Da = 3/4

(v 6069 ani) Nu = 0/0 Da = 1/2

(v 7079 ani) Nu = 0/0 Da = 1/1Col total (v 6069 ani) 160 = 0/0160-199 = 1/1200-239 = 1/2 240-279 = 2/3 280 = 3/4NCEP ATP III. Circulation. 2002;106:3143-3421.

Scorul total echivaleaz 17 puncteVrsta 62 ani10 pColesterolul total280 mg/dl 3 pFumtor 1 pHDL-colesterol 34 mg/dl 2 pTA sistolic (mm Hg)125 1 p17 puncte

Caz clinicRiscul pacientului pentru IMA sau moarte coronar la 10 ani este 30 %

CATEGORIILE DE RISC I OBIECTIVELE TERAPEUTICE LDL-COLESTEROL Categoria de riscRiscul de CPI nObiectivul urmtorii 10 aniLDL-colesterol

Risc crescut > 20%< 100 mg/dl (CPI sau echiva-(< 2,6 mmol/l)lente de CPI)Risc mediu 10-20% < 130 mg/dl (peste 2 factori < 10% (< 3,4 mmol/l)majori de risc)Risc sczut < 10%< 160 mg/dl (0-1 factori (< 4,1 mmol/l) majori de risc)NCEP, Adult Treatment Panel III. JAMA. 2001;285:2486-2497.

NIVELELE DE INTERVENIE CONFORM CATEGORIEI DE RISC

Categorie ObiectivNivelul LDLNivelul LDL de riscLDLpentru modi-pentru iniierea ficarea stilului tratamentului de viaamedicamentos Risc crescut< 100 mg/dl100 mg/dl130 mg/dl (CPI sau echi-(< 2,6 mmol/l)(2,6 mmol/l)( 3,4 mmol/l) valente de CPI) Risc mediu < 130 mg/dl 130 mg/dlrisc la 10 ani 10-20% ( 2 fac-(< 3,4 mmol/l)( 3,4 mmol/l)130 mg/dl tori majori ( 3,4 mmol/l)de risc)risc la 10 ani < 10% 160 mg/dl ( 4,1 mmol/l) Risc sczut< 160 mg/dl 160 mg/dl 190 mg/dl (0-1 factori (< 4,1 mmol/l)( 4,1 mmol/l)( 4,9 mmol/l) majori de risc)NCEP, Adult Treatment Panel III. JAMA. 2001;285:2486-2497.

Strategia terapeutic

Modificarea stilului de via

Iniierea tratamentului hipolipemiant

Modificarea stilului de via

Stoparea fumatuluiDieta hipolipidicScderea ponderalIntensificarea activitii fizice

Tratamentul medicamentosAtorvastatin 10 mg / ziCaz clinic

Profilul lipidic

Colesterolul total7,3 mmol/lTrigliceride1,7 mmol/lHDL-colesterol0,9 mmol/lLDL-colesterol5,6 mmol/lCaz clinic Atorvastatin (10 mg) 5,3 mmol/l 1,5 mmol/l 0,98 mmol/l 3,6 mmol/l

********************During the initiation of atherosclerosis, LDL cholesterol accumulates in the subendothelial extracellular space within the arterial wall. Local vascular cells mildly oxidize LDL to a form known as minimally modified LDL, which is able to stimulate recruitment of monocytes and eventual deposition of macrophages.1 These further oxidize LDL to a form that can be scavenged and internalized, resulting in so-called foam cells.1 Such cells form the earliest visible lesion of atherosclerosis, the fatty streak.2The aggregation of LDL-rich foam cells, derived from macrophages and T lymphocytes within the intima, progresses to development of an atherosclerotic plaque.2 This results from the death and rupture of the lipid-laden foam cells in the fatty streak. A crucial component of the maturing atherosclerotic plaque is the formation of a fibrous cap that separates the highly thrombogenic lipid-rich core from circulating platelets and other coagulation factors.3 Stable atherosclerotic plaques are characterized by the necrotic lipid core covered by a thicker, almost protective vascular smooth muscle cell-rich fibrous cap.3 Such a cap can be better strengthened and maintained by reducing LDL cholesterol.3

References Diaz MN, Frei B, Vita JA, Keaney JF. Antioxidants and atherosclerotic heart disease. New Engl J Med. 1997;337(6):408-416. Ross R. The pathogenesis of atherosclerosis: A perspective for the 1990s. Nature. 1993;362:801-809. Weissberg PL. Atherosclerosis involves more than just lipids: Plaque dynamics. Eur Heart J. 1999;1(suppl T):T13-T18.********Once a plaque has ruptured, the severity of the cardiovascular event is influenced by the extent of thrombosis. An occlusive thrombus results in a Q-wave MI or sudden death.1 A nonocclusive thrombus may be silent, present as unstable angina, or cause a nonQ-wave MI.1 The extent of the rupture, the rate of blood flow in the area, the presence or absence of vasospasm, and the tendency of the blood to clot are all important in determining whether the thrombus is occlusive or nonocclusive.1 Oxidized LDL, incidentally, has been shown to induce endothelial cells to express high levels of tissue factor, which is primarily responsible for initiating thrombogenesis. In addition, oxidized LDL has been linked to a variety of reactions, which inhibit further vasodilation once a clot has started to form. Thus LDL may have a role not only in plaque formation but in the actual pathogenesis of acute coronary thrombosis itself.2

References Kullo IJ, Edwards WD, Schwartz RS. Vulnerable plaque: Pathobiology and clinical implications. Ann Intern Med. 1998;129:1050-1060. Berliner J, Navab M, Fogelman AM, et al. Atherosclerosis: Basic mechanisms: Oxidation, inflammation, and genetics. Am Heart J. 1995;91(9):2488-2496.

****The metabolic syndromeThis slide emphasizes the need to identify patients with metabolic syndrome and the characteristic "abdominal profile" of those who have it. Note that abdominal obesity is measured at the top of the iliac crest and not the umbilicus. A tape measure should be in every examining room to facilitate this measurement. Although abdominal obesity as determined by waist circumference is not as accurate as results obtained from a CT scan, it is easy, cheap, and available.

Reference:National Institutes of Health. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in AdultsThe Evidence Report. Obes Res 1998;6 (suppl 2):51S-209S.****The metabolic syndromeThis slide emphasizes the need to identify patients with metabolic syndrome and the characteristic "abdominal profile" of those who have it. Note that abdominal obesity is measured at the top of the iliac crest and not the umbilicus. A tape measure should be in every examining room to facilitate this measurement. Although abdominal obesity as determined by waist circumference is not as accurate as results obtained from a CT scan, it is easy, cheap, and available.

Reference:National Institutes of Health. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in AdultsThe Evidence Report. Obes Res 1998;6 (suppl 2):51S-209S.****Statins: mechanism of actionAs inhibitors of hepatic HMG-CoA reductase, the enzyme catalyzing the rate-limiting step in hepatic cholesterol synthesis, statins decrease synthesis of cholesterol by the liver, which results in two important effects: the up-regulation of LDL receptors by hepatocytes and consequent increased removal of apolipoprotein (apo) E and Bcontaining lipoproteins from the circulation, and a reduction in the synthesis and secretion of lipoproteins from the liver. The net effect of statin therapy is to lower plasma concentrations of cholesterol-carrying lipoproteins, the most prominent of which is LDL. Importantly, however, statins also increase the removal and reduce the secretion of remnant particles, i.e., very low density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL). This means that in patients who have an elevation of both LDL-C and triglycerides (indicating increased levels of triglyceride-rich VLDL and IDL remnants as well as LDL), a statin is one of the therapies of choice because of its ability to effectively lower LDL-C and nonhigh-density lipoprotein cholesterol (non-HDL-C) levels.****Bile acid resins: mechanism of actionBile acid resins bind bile acids in the intestine, which reduces the enterohepatic recirculation of bile acids. This promotes the upregulation of 7- hydroxylase and the conversion of more cholesterol in the hepatocyte into bile acids. This decreases the cholesterol content in the hepatocyte, which enhances LDL-receptor expression, which in turn increases the removal of LDL and VLDL remnant particles from the circulation. The liver also increases its synthesis of cholesterol, which partially negates the LDL-Clowering efficacy of the bile acid resin. In some persons, especially in patients who have an elevated triglyceride level, resins increase hepatic VLDL production and thereby raise serum triglyceride levels.********Nicotinic acid: mechanism of actionThe last of our LDL-Clowering drugs is nicotinic acid, or niacin. Niacin appears to exert its effects by inhibiting lipoprotein synthesis and decreasing the production of VLDL particles by the liver. It inhibits the peripheral mobilization of free fatty acids, thus reducing hepatic synthesis of triglycerides and the secretion of VLDL. It also reduces apo B. The net result is a reduction in VLDL particles secreted by the liver and thus less substrate to make LDL particles. It increases the production of apo A-I and thereby HDL through mechanisms that are not clear. Case Study: Elderly ManTeaching / Discussion Point(s)Case illustrates a patient with only two risk factors and no CHD or CHD risk equivalents.Following NCEP ATP III, if 2+ risk factors are present without CHD or CHD risk equivalent, 10-year CHD risk should be assessed.Without calculating the patients risk, treatment may not have been aggressive enough. The patients 10-year risk of 25% places him into the highest risk category and therefore his LDL goal should be in fact 100 mg/dL.

Case Study: Elderly ManTeaching / Discussion Point(s)Case illustrates a patient with only two risk factors and no CHD or CHD risk equivalents.Following NCEP ATP III, if 2+ risk factors are present without CHD or CHD risk equivalent, 10-year CHD risk should be assessed.Without calculating the patients risk, treatment may not have been aggressive enough. The patients 10-year risk of 25% places him into the highest risk category and therefore his LDL goal should be in fact 100 mg/dL.

Case Study: Elderly ManTeaching / Discussion Point(s)Case illustrates a patient with only two risk factors and no CHD or CHD risk equivalents.Following NCEP ATP III, if 2+ risk factors are present without CHD or CHD risk equivalent, 10-year CHD risk should be assessed.Without calculating the patients risk, treatment may not have been aggressive enough. The patients 10-year risk of 25% places him into the highest risk category and therefore his LDL goal should be in fact 100 mg/dL.

Case Study: Elderly ManTeaching / Discussion Point(s)Case illustrates a patient with only two risk factors and no CHD or CHD risk equivalents.Following NCEP ATP III, if 2+ risk factors are present without CHD or CHD risk equivalent, 10-year CHD risk should be assessed.Without calculating the patients risk, treatment may not have been aggressive enough. The patients 10-year risk of 25% places him into the highest risk category and therefore his LDL goal should be in fact 100 mg/dL.

3.09Case Study: Elderly ManTeaching / Discussion Point(s)Case illustrates a patient with only two risk factors and no CHD or CHD risk equivalents.Following NCEP ATP III, if 2+ risk factors are present without CHD or CHD risk equivalent, 10-year CHD risk should be assessed.Without calculating the patients risk, treatment may not have been aggressive enough. The patients 10-year risk of 25% places him into the highest risk category and therefore his LDL goal should be in fact 100 mg/dL.

Case Study: Elderly ManTeaching / Discussion Point(s)Case illustrates a patient with only two risk factors and no CHD or CHD risk equivalents.Following NCEP ATP III, if 2+ risk factors are present without CHD or CHD risk equivalent, 10-year CHD risk should be assessed.Without calculating the patients risk, treatment may not have been aggressive enough. The patients 10-year risk of 25% places him into the highest risk category and therefore his LDL goal should be in fact 100 mg/dL.