dyslipidenmia

DYSLIPIDEMIA DAN DYSLIPIDEMIA DAN RISIKO PJKRISIKO PJK

BY: WINANGUNBY: WINANGUN..

PENDAHULUANPENDAHULUAN

DYSLIPIDEMIADYSLIPIDEMIA MASALAH KESEHATAN, MASALAH KESEHATAN, PENYAKIT DEGENERATIF PENYAKIT DEGENERATIF ↑↑, GERIATRI, ↑↑, GERIATRI, ATEROSKLEROSIS, PJK, STROKE. ATEROSKLEROSIS, PJK, STROKE. 80%80% F F DAN >> KEMATIAN PADA DM.75%DAN >> KEMATIAN PADA DM.75%

LIPIDLIPID PENTING PENTING UNTUKUNTUK: MEMBENTUK DAN : MEMBENTUK DAN FUNGSI SEL, SUMBER ENERGI, PELINDUNG FUNGSI SEL, SUMBER ENERGI, PELINDUNG TUBUH, SYNTESE HORMON STEROID, TUBUH, SYNTESE HORMON STEROID, PERKURSOR PROSTAGLANDIN,PERKURSOR PROSTAGLANDIN,

LIPID TAK LARUT AIR LIPID TAK LARUT AIR IKAT IKAT APOPROTEINAPOPROTEIN LIPOPROTEIN LARUT AIRLIPOPROTEIN LARUT AIR SIRKULASI SIRKULASI

LIPOROTEINLIPOROTEIN ADA 5: KILOMIKRON, VLDL. IDL, ADA 5: KILOMIKRON, VLDL. IDL, HDL DAN HDL DAN LDL YANG PALING JAHATLDL YANG PALING JAHAT..

PENGERTIANPENGERTIAN

DYSLIPIDEMIADYSLIPIDEMIA: KELAINAN METABOLISME : KELAINAN METABOLISME LEMAK TUBUH DITANDAI LEMAK TUBUH DITANDAI ↑↑ ATAU ↓ FRAKSI ↑↑ ATAU ↓ FRAKSI LIPID DL PLASMA. ↑KOLESTEROL TOTAL, TG LIPID DL PLASMA. ↑KOLESTEROL TOTAL, TG DAN LDL SERTA ↓↓ HDL.DAN LDL SERTA ↓↓ HDL.

KOMPONEN PENTING KOMPONEN PENTING ATEROSKLEROSISATEROSKLEROSIS DIKENAL DIKENAL TRIAD LIPIDTRIAD LIPID..

KECENDRUNGAN ↑↑ KASUS DYSLIPIDEMIAKECENDRUNGAN ↑↑ KASUS DYSLIPIDEMIA GG VASKULER , ATEROSKLEROSISGG VASKULER , ATEROSKLEROSIS PJK , PJK , STROKE STROKE PERLU PERLU PENCEGAHAN & TH/PENCEGAHAN & TH/ MENYELURUH.MENYELURUH.

KOLESTEROLKOLESTEROLdalam jumlah tepat bermanfaat, Jika berlebih berbahaya

MANFAAT KOLESTEROLSumber energiPembentukan dinding selPembentukan hormon

BAHAYA KOLESTEROL BERLEBIHDapat melekat pada dinding pembuluh darahsehingga terjadi Aterosklerosisyang dapat mengakibatkan PJK/Stroke

DislipidemiaDislipidemia

Kelainan metabolisme lipid (lemak) yang ditandai dengan

peningkatan maupun penurunan

komponen lemak dalam darah

DISLIPIDEMIADISLIPIDEMIADitandai dengan :

Kolesterol TotalKolesterol Total

TrigliseridaTrigliserida

Kolesterol-LDLKolesterol-LDL

Kolesterol-HDLKolesterol-HDL

Agar dapat diangkut ke sel yang memerlukan, kolesterol

berikatan dengan proteinmembentuk Lipoprotein

Kolesterol tidak dapat larut dalam air (darah)

Kolesterol dari makanan

Diolah dalam saluran cerna

Diserap masuk aliran darah

Didistribusikan ke sel-selYang memerlukan

Contoh Lipoprotein :Kilomikron

HDL (High Density Lipoprotein)LDL (Low Density Lipoprotein)

Lipid MetabolismLipid Metabolism

Cholesterol synthesisCholesterol synthesis

Lipoproteins:Lipoproteins:

VLDLVLDL

LDLLDL

HDLHDL

ChylomicronsChylomicrons

ApolipoproteinsApolipoproteins

LDL receptorLDL receptor

KLASIFIKASIKLASIFIKASI

A.KAUSA:A.KAUSA: 1. DYSLP. 1. DYSLP. PRIMERPRIMER >> FAKTOR GENETIK >> FAKTOR GENETIK 2. DYSLP. 2. DYSLP. SKUNDERSKUNDER: E/ PENYAKIT TT: : E/ PENYAKIT TT:

HYPOTYROID, DM, NS, SH, CRF DLL DAN HYPOTYROID, DM, NS, SH, CRF DLL DAN OBAT2AN: DIURETIK, OBAT2AN: DIURETIK, ββ BLOKER, ESTROGEN BLOKER, ESTROGEN

B. KLINISB. KLINIS:: 1.HYPERKOLESTEROLEMIA, 1.HYPERKOLESTEROLEMIA, ( HYPERKOLEST( HYPERKOLEST)) 2.HYPERTRIGLISERIDEMIA2.HYPERTRIGLISERIDEMIA,( HYPER TG),( HYPER TG) 3.CAMPURAN3.CAMPURAN

Fredrickson ClassificationFredrickson ClassificationType Elevated

particlesAssociated clinical disorders

Serum TC

Serum TG

I Chylomicrons Lipoprotein lipase deficiency, apolipoprotein C-II deficiency

↔ ↑↑

IIa LDL Familial hypercholesterolemia, polygenic hypercholeterolemia, nephrosis, hypothyroidism, familial combined hyperlipidemia

↑↑ ↔

IIb LDL, VLDL Familial combined hyperlipidemia

↑↑ ↑

Fredrickson ClassificationFredrickson ClassificationType Elevated

particlesAssociated clinical disorders

Serum TC

Serum TG

III IDL Dysbetalipoproteinemia ↑ ↑

IV VLDL Familial hypertriglyceridemia, familial combined hyperlipidemia, sporadic hypertriglyceridemia, diabetes

↔↑ ↑↑

V Chylomicrons, VLDL

Diabetes ↑ ↑↑

Secondary Causes of Lipoprotein Secondary Causes of Lipoprotein AbnormalitiesAbnormalities

KRETERIA DIAGNOSTIKKRETERIA DIAGNOSTIK

PATOKAN NILAI KOLESTEROL DIKAITKAN DG PATOKAN NILAI KOLESTEROL DIKAITKAN DG RISIKO PJK RISIKO PJK ≈ ≈ Penelitian jangka panjangPenelitian jangka panjang

a. KADAR MASIH a. KADAR MASIH AMAN << 200 mg/dlAMAN << 200 mg/dl b. KADAR BORDRLINE HIGH: 200-239 mg/dlb. KADAR BORDRLINE HIGH: 200-239 mg/dl c. KADAR TINGGI c. KADAR TINGGI BERBAHAYA >> 240 mg/dlBERBAHAYA >> 240 mg/dl.. KESETARAANKESETARAAN KOLESTEROL TOTAL DG LDL. KOLESTEROL TOTAL DG LDL. KOL: 240 mg/dl KOL: 240 mg/dl LDL 160 mg /dl LDL 160 mg /dl KOL: 200 mg/dl KOL: 200 mg/dl LDL 130 mg/dlLDL 130 mg/dl KOL: 155 mg/dl KOL: 155 mg/dl LDL 100 mg/dl LDL 100 mg/dl

HUBUNGAN PROFIL LIPIDHUBUNGAN PROFIL LIPID DG RISIKO PJK DG RISIKO PJK

KADAR KADAR KOLESKOLES

DESIRE DESIRE ABLEABLE

BORDER BORDER LINELINE

HIGHHIGH

TOTALTOTAL << 200<< 200 200-239200-239 >> 240>> 240

KO KO LDLLDL

PJK (-)PJK (-)

PJK (+)PJK (+)

<< 130<< 130

<< 100<< 100

130-159130-159

--

>> 160>> 160

--

HDLHDL >> 45>> 45 35-4535-45 << 35<< 35

TRIGLITRIGLI

PJK (-)PJK (-) << 200<< 200 200-299200-299 >> 400>> 400

PJK (+)PJK (+) << 150<< 150 -- --

Fredrickson Classification of HyperlipidemiasFredrickson Classification of Hyperlipidemias

Type Predominant lipoprotein

Predominant lipid

Xanthoma CHD risk

Pancreatitis

I Chylomicrons Triglycerides >1000

Eruptive - +

IIa LDL Cholesterol >300

Tendon;

Xanthelasma+ -

IIb VLDL + LDL TG and CH <1000 >300

+ -

III Remnants TG and CH Palmar and tuberous

+ -

IV VLDL CH + -

V Chylomicrons + VLDL

TG and CH >1000 >300

Eruptive - +

Classification of Lipid LevelsClassification of Lipid LevelsTotal cholesterol mg/dl LDL cholesterol mg/dl

< 200 Desirable < 100 Optimal

200-239 Border line high 100-129Near optima/Above optimal

≥ 240 High

130-159 Borderline high

160-189 High

≥ 190 Very high

NCEP ATP III Classification of Blood Lipids

Diagnosis

Classification of Lipid LevelsClassification of Lipid LevelsTriglycerides mg/dl HDL cholesterol mg/dl

< 150 Normal

< 40 Low

150-199 Border line high

200-400 High

≥ 60 High

≥ 500 Very high

NCEP ATP III Classification of Blood Lipids

Diagnosis

Overview of Cholesterol Overview of Cholesterol Metabolism: Absorption ynthesisMetabolism: Absorption ynthesis

LDL Oxidation and AtherosclerosisLDL Oxidation and Atherosclerosis

Mechanism of Atherogenic Mechanism of Atherogenic DyslipidemiaDyslipidemia

Insulin resistance increased NEFA and glucose flux to liver

Insulin resistance and decreased apo-B degradation

Insulin resistance and decreased LPL

IR impairs LDLR

Increased VLDL

FCHL

DM II

Metabolic syndrome

Pathogenesis of AtherosclerosisPathogenesis of Atherosclerosis

Rationale for Treating Dyslipidemia

FoamCells

FattyStreak

IntermediateLesion Atheroma

FibrousPlaque

ComplicatedLesion/Rupture

Endothelial Dysfunction

Smooth muscleand collagen

From first decadeFrom first decade From third decadeFrom third decade From fourth decadeFrom fourth decade

Growth mainly by lipid accumulationThrombosis,hematoma

Adapted from Stary HC et al. Circulation 1995;92:1355-1374.

Atherosclerosis Timeline

Faktor-faktor Risiko PJK

Tidak Dapat dimodifikasi :

• Usia• Jenis Kelamin• Riwayat Keluarga• Ras

Faktor-faktor Risiko PJK

Dapat dimodifikasi :Dapat dimodifikasi :

• Lipid/lemak dan Lipoprotein• Diabetes Melitus• Hipertensi• Kebiasaan Merokok• Obesitas (kegemukan)

KilomikronKilomikron

Low Density Lipoprotein (LDL)Low Density Lipoprotein (LDL)

Mengangkut lemak dari saluran cerna menuju hatiMengangkut lemak dari saluran cerna menuju hati

Mengangkut kolesterol ke sel-sel tubuhMengangkut kolesterol ke sel-sel tubuhyang memerlukanyang memerlukan

Mengangkut kolesterol dari sel tubuhMengangkut kolesterol dari sel tubuhmenuju hatimenuju hati

High Density Lipoprotein (HDL)High Density Lipoprotein (HDL)

LDL – teroksidasiLDL – teroksidasipaling berbahayapaling berbahaya

LDL – densitas kecilLDL – densitas kecillebih berbahayalebih berbahaya

LDL – kolesterolLDL – kolesterolberbahayaberbahaya

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BERBAHAYABERBAHAYA karena merupakan cikal bakal terjadinya proses Aterosklerosis

KOLESTEROL

Faktor Risiko PJK yang paling

Mendasar

Cikal bakal PJK dan Stroke

KOLESTEROL PENTING

Fungsinya antara lain :

• Prekursor hormon steroid (aldosterone)• Prekursor hormon seks (estrogen)• Komponen membran sel

BAHAYA BILA BERLEBIHAN !!!!BAHAYA BILA BERLEBIHAN !!!!

?

Dapat melekat pada dinding pembuluh darahsehingga terjadi Aterosklerosisyang dapat mengakibatkan PJK/Stroke

Agar dapat diangkut ke sel

yang memerlukan, kolesterol

berikatan dengan protein

membentuk Lipoprotein

Kolesterol tidak dapat larut dalam air (darah)

Kolesterol dari makanan

Diolah dalam saluran cerna

Diserap masuk aliran darah

Didistribusikan ke sel-selYang memerlukan

Contoh Lipoprotein :Kilomikron

HDL (High Density Lipoprotein)LDL (Low Density Lipoprotein)

fosfolipid

Kolesterol bebas

apolipoprotein

STRUKTUR DASAR LIPOPROTEIN

Kilomikron

Low Density Lipoprotein (LDL)

Mengangkut lemak menuju hati

Mengangkut kolesterol ke sel-sel tubuhyang memerlukan

Mengangkut kolesterol menuju hati

High Density Lipoprotein (HDL)

LipoproteinLipoprotein

Very Low Density Lipoprotein (VLDL)Intermediate Density Lipoprotein (IDL)

Cholesterol MetabolismCholesterol Metabolism

ImportanceImportance– Vital component of all Vital component of all

cell structurecell structure– Source of energySource of energy

DangersDangers– Abnormal metabolism Abnormal metabolism

results in vascular results in vascular diseasedisease

Lipid PhysiologyLipid Physiology

ApoE mediated

Goodman and Gilman’s Pharmacological Basis of Therapeutics, 10th ed. 2001

Kolesterol LDLFaktor risiko terkuat kolesteroljahat

Kolesterol HDLPembersih Kolesterol kolesterolbaik

Apoprotein A-1Komponen utama HDLPembersih lemak

Apoprotein BKomponen utama LDL

LDL – teroksidasipaling berbahaya

LDL – densitas kecillebih berbahaya

LDL – kolesterolberbahaya

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LDL KOLESTEROL

KEUNGGULANKEUNGGULAN1. Lebih Akurat

0% 10% 20% 30% 40% 50%

Tri

gly

ceri

de

leve

ls

< 200 mg/dL (2.26 mmol/L): 15%

201-300 mg/dL (2.27-3.39 mmol/L): 23%

301-400 mg/dL (3.40-4.52 mmol/L): 41%

n = 4797

Percentage of patients with misclassified LDL valuesPercentage of patients with misclassified LDL values

KOLESTEROL–LDL (Direk)KOLESTEROL–LDL (Direk)

Kemungkinan kesalahan perhitungandengan memakai rumus Friedewald dapat dihindari (LDL = TC-HDL-TG/5)

Kadar LDL tetap dapat diperoleh walau-pun kadar trigliserida > 400 mg/dl

2. Pemeriksaan dapat dilakukan dalam kondisi tidak puasa dan hal ini bermanfaat bagi :

* Pasien pediatrik (anak-anak)* Pasien geriatrik (orang tua)

* Pasien yang sedang dalam pengobatan* Pasien Diabetes Melitus

3. Dapat digunakan untuk menentukan Small Dense LDL

Yaitu dengan menghitung rasio :Kolesterol LDL direk/Apo B

Jika rasio Kolesterol LDL direk/Apo B < 1,2 menunjukkan adanyaSmall dense LDL atau LDL kecil padat

Small-dense LDLSmall-dense LDL

(LDL kecil-padat)(LDL kecil-padat)

Diperkirakan dariDiperkirakan dari

LDL-Kolesterol/Apo B < 1,2LDL-Kolesterol/Apo B < 1,2

LDL kecil padat (SMALL DENSE LDL)LEBIH BERBAHAYA

KARENA :• Mudah terperangkap dan masuk ke dalam lapisan dinding pembuluh darah (Intima) karena ukurannya lebih kecil• Mudah teroksidasi menjadi Oxidized-LDL

OXIDIZED – LDL LDL YANG PALING BERBAHAYA

KARENA :

Menyebabkan Plak Ateroma tidak stabil

Plak mudah Koyak

Terbentuk Trombus/Embolus

Aliran darah tersumbat

SERANGAN JANTUNG/STROKE

Oksidasi LDL

LDL LDL teroksidasi Antioksidan

Status Antioksidan TotalStatus Antioksidan Total

Proses oksidasi LDL secara normal dihambat oleh sistem antioksidan di dalam tubuh

Cukup tidaknya sistem antioksidan tubuh seseorang dapat dilihat dariPemeriksaan Status Antioksidan Total

MENGAPA BERBAHAYA(dianggap sebagai Faktor Risiko) ?

HIPERTRIGLISERIDEMIA

Hati mensintesis VLDL dalam jumlah banyak

Hipertrigliseridemia

VLDL diuraikan menjadi Small Dense LDL

• Berkaitan dengan peningkatan LDLkecil - padat

Peningkatan LDL-kecil padat akanmeningkatkan risiko PJK sebanyak3 kali

Hipertrigliseridemia

Lipoprotein (a)

Seperti halnya LDL, Lp(a) mempunyaikandungan kolesterol yang tinggiMerupakan faktor risiko ‘independen’yang sangat penting untuk PJK danStroke

Apo BApo BLp(a)Lp(a)

Small-DenseSmall-Dense LDL : Kolest LDL/Apo LDL : Kolest LDL/Apo BBOx-LDL : Status Antioksidan TotalOx-LDL : Status Antioksidan Total

• CholesterolTriglycerideLDL-CholesterolHDL-Cholesterol

SAMPAI DIMANA RISIKOSAMPAI DIMANA RISIKOANDA TERHADAP PJK ?ANDA TERHADAP PJK ?

Lakukan pemeriksaan laboratorium

hs-CRP is the Clinical Assay ofchoice for CVD Risk Prediction

Nilai prediktif yang lebih baik

Stratifikasi risiko

Penanda prognostik yang lebih dini

PENGELOLAANPENGELOLAAN

MELIPUTI PENCEGAHAN DAN PENGOBATANMELIPUTI PENCEGAHAN DAN PENGOBATAN A. PENCEGAHANA. PENCEGAHAN:: 1.POLA 1.POLA MAKAN SEHATMAKAN SEHAT SEIMBANG BANYAK SEIMBANG BANYAK MAKAN SAYUR DAN BUAHMAKAN SAYUR DAN BUAH BATASI KONSUMSI DIET TINGGI LEMAKBATASI KONSUMSI DIET TINGGI LEMAK 2. 2. OLAHRAGAOLAHRAGA CUKUP, RUTIN, TERATUR. CUKUP, RUTIN, TERATUR. 3. PERTAHANKAN 3. PERTAHANKAN BERAT BADANBERAT BADAN IDEAL. IDEAL. 4.TIDAK MEROKOK4.TIDAK MEROKOK..

B. PENGOBATANB. PENGOBATAN 1. TH/ NON FARMAKOLOGIK1. TH/ NON FARMAKOLOGIK:: a.PENYULUHANa.PENYULUHAN b.PERENCANAAN MAKAN / DIET,b.PERENCANAAN MAKAN / DIET, c. LATIHAN JASMANI / OLAH RAGA TERATUR,c. LATIHAN JASMANI / OLAH RAGA TERATUR, d. PENGENDALIAN GULA DARAH PD DMd. PENGENDALIAN GULA DARAH PD DM 2. TH/ FARMAKOLOGIK2. TH/ FARMAKOLOGIK / OBAT HYPOLIPIDEMIK / OBAT HYPOLIPIDEMIK a. PENGIKAT RESIN: KOLESTIPOL, KOLESTIRAMINa. PENGIKAT RESIN: KOLESTIPOL, KOLESTIRAMIN b. ASAM NIKOTINAT: ACIPIMOX, ASAM NIKOTINATb. ASAM NIKOTINAT: ACIPIMOX, ASAM NIKOTINAT c. GOLONGAN FIBRAT: GEMPIBROSIL, FENOFIBRATc. GOLONGAN FIBRAT: GEMPIBROSIL, FENOFIBRAT d. GOLONGAN STATIN: SIMVASTATIN,LOVASTATIN, d. GOLONGAN STATIN: SIMVASTATIN,LOVASTATIN, ATORVASTATINATORVASTATIN,, FLUVASTATIN. DLL. FLUVASTATIN. DLL.

AHA/ACC guidelinesfor patients with CHD*,2

<100 mg/dL:Goal for allpatients with CHD†,2

<70 mg/dL:A reasonable goal for all patientswith CHD†,2

ATP IIIUpdate 20041

<100 mg/dL:Patients withCHD or CHD riskequivalents(10-year risk >20%)1

<70 mg/dL:Therapeuticoption for veryhigh-risk patients1

Intensive LDL-C Goals for High-Intensive LDL-C Goals for High-Risk PatientsRisk Patients

<100 mg/dL

<70 mg/dL

*And other forms of atherosclerotic disease.2

† Factors that place a patient at very high risk: established cardiovascular disesase (CVD) plus:multiple major risk factors (especially diabetes); severe and poorly controlled risk factors (eg, cigarette smoking); metabolic syndrome (triglycerides [TG] ≥200 mg/dL + non–HDL-C ≥130 mg/dL with HDL-C <40 mg/dL); and acute coronary syndromes.1

1. Grundy SM et al. Circulation. 2004;110:227–239.2. Smith SC Jr et al. Circulation, 2006; 113:2363–2372.

2006Update

Recommended LDL-C treatment goals

• If it is not possible to attain LDL-C <70 mg/dL because of a high baseline LDL-C, it generally is possible to achieve LDL-C reductions of >50% with more intensive LDL-C─lowering therapy, including drug combinations.

Rationale for Treating Rationale for Treating DyslipidemiaDyslipidemia

Pathogenesis of atherosclerosisPathogenesis of atherosclerosis

Epidemiological studiesEpidemiological studies

Clinical trialsClinical trials

LDL cholesterol as a primary target of LDL cholesterol as a primary target of therapytherapy

Dual Inhibition of Cholesterol Dual Inhibition of Cholesterol Synthesis and AbsorptionSynthesis and Absorption

Bileacids

Synthesis

Atherogeniclipoproteins

Smallintestine

Excretion in feces

Bile

Absorption

Liver

Diet

Statin

CholesterolNPC1L1

Ezetimibe

Clinical TrialsClinical TrialsTrial Intervention Initial LDL Change

in LDLCHD event reduction

CHD & CHD risk equivalent

4S Simvastatin 188-117 ↓ 35% ↓ 34%

LIPID Pravastatin 150-112 ↓ 25% ↓ 24%

CARE Pravastatin 139-98 ↓ 32% ↓ 24%

Post-CABG Lovastatin/Resin

136-98 ↓ 39% ↓ 24%




Acute coronary syndrome patients

MIRACL Atorvastatin 124-72 ↓ 42% ↓ 26%

AVERT Atorvastatin 145-77 ↓ 42% ↓ 36%




Patients without evidence of CHD

LRC-CPPT Resin 205-175 ↓ 15% ↓ 19%

WOSCOPS Pravastatin 192-142 ↓ 26% ↓ 31%

Tex/AFCAPS

Lovastatin 150-115 ↓ 25% ↓ 40%

ASCOT Atorvastatin 132-85 ↓ 31% ↓ 50%


Mechanism ofMechanism ofIntestinal-Acting AgentsIntestinal-Acting Agents

Many High-Risk Patients Were Not Tested and Many Who Many High-Risk Patients Were Not Tested and Many Who Were Tested and Treated Did Not Achieve Were Tested and Treated Did Not Achieve

LDL-C LDL-C 100 mg/dL100 mg/dL11

Of those who did not achieve LDL-C <100 mg/dL at 6 months and continued treatment, 51.9% (n=122) attained LDL-C <100 mg/dL within the Of those who did not achieve LDL-C <100 mg/dL at 6 months and continued treatment, 51.9% (n=122) attained LDL-C <100 mg/dL within the entire follow-up period (average 25 months).entire follow-up period (average 25 months).11

In 1999, ATP II recommended an LDL-C goal of ≤100 mg/dL for patients with CHD.In 1999, ATP II recommended an LDL-C goal of ≤100 mg/dL for patients with CHD. 22

1. Data available on request from Merck & Co., Inc., Professional Services-DAP, WP1-27, PO Box 4, West Point, PA 19486-0004. Please specify information package 20507201(1)-MSP.

2. The Expert Panel. Summary of the Second Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA. 1993; 269; 3015–3023.

In a retrospective subgroup analysis of patients with CHD (N=3,320), only 42.7% received lipid testing (n=1,418) within 6 months of diagnosis. Of the 1,418 CHD patients who were tested, 70% had an LDL-C ≥100 mg/dL.

45.9%(n=651)

48.2%(n=314)

25.5%(n=71)

74.5%(n=208)

51.8%(n=337)

DID NOT achieveLDL-C <100 mg/dL

achievedLDL-C <100 mg/dL

DID NOT achieveLDL-C <100 mg/dL

achievedLDL-C <100 mg/dL

Of those CHD patients tested,

were treated

At 6 months At 12 months

Treatment defined as 1 or more prescription fills within a 6-month period (mean days supply = 150) for CHD patients.

279 patients had at least1 prescription filled after 6 months

All CHD patients who were treated had LDL-C ≥100 mg/dL

Increased Atherogenicity of Small Increased Atherogenicity of Small Dense LDLDense LDL

Direct AssociationDirect Association– Longer residence time in Longer residence time in

plasma than normal sized LDL plasma than normal sized LDL due to decreased recognition by due to decreased recognition by receptors in liverreceptors in liver

– Enhanced interaction with Enhanced interaction with scavenger receptor promoting scavenger receptor promoting foam cell formationfoam cell formation

– More susceptible to oxidation More susceptible to oxidation due to decreased antioxidants due to decreased antioxidants in the corein the core

– Enter and attach more easily to Enter and attach more easily to arterial wall arterial wall

– Endothelial cell dysfunctionEndothelial cell dysfunction

Indirect AssociationIndirect Association– Inverse relationship with HDLInverse relationship with HDL– Marker for atherogenic TG Marker for atherogenic TG

remnant accumulationremnant accumulation– Insulin resistanceInsulin resistance

Evolution of NHLBI Supported Evolution of NHLBI Supported GuidelinesGuidelines

Angiographic trials (FATS, POSCH, SCOR, STARS, Ornish, MARS)Meta-analyses(Holme, Rossouw)

NCEP ATP I1988

NCEP ATP II1993

NCEP ATP III2001

HPSPROVE-ITASCOT-LLAPROSPERALLHAT-LLT

Updated NCEP ATP III2004

FraminghamMRFITLRC-CPPTCoronary Drug ProjectHelsinki HeartCLAS

4SWOSCOPSCARELIPIDAFCAPS/ TexCAPS

TNTIDEAL

AHA/ACC Update2006

More Intensive Treatment Recommendations

NHLBI = National Heart, Lung, and Blood Institute.NCEP ATP = National Cholesterol Education Panel Adult Treatment Panel.AHA = American Heart Association.ACC = American College of Cardiology.

dyslipidenmia

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