DYSLIPIDEMIA DAN

RISIKO PJK

BY: WINANGUN.
 PENDAHULUAN
DYSLIPIDEMIA MASALAH KESEHATAN,
PENYAKIT DEGENERATIF , GERIATRI,
ATEROSKLEROSIS, PJK, STROKE. 80% F
DAN >> KEMATIAN PADA DM.75%
LIPID PENTING UNTUK: MEMBENTUK DAN
FUNGSI SEL, SUMBER ENERGI, PELINDUNG
TUBUH, SYNTESE HORMON STEROID,
PERKURSOR PROSTAGLANDIN,
LIPID TAK LARUT AIR IKAT APOPROTEIN
LIPOPROTEIN LARUT AIR SIRKULASI
LIPOROTEIN ADA 5: KILOMIKRON, VLDL. IDL,
HDL DAN LDL YANG PALING JAHAT.
 PENGERTIAN
DYSLIPIDEMIA: KELAINAN METABOLISME
LEMAK TUBUH DITANDAI ATAU FRAKSI
LIPID DL PLASMA. KOLESTEROL TOTAL, TG
DAN LDL SERTA HDL.
KOMPONEN PENTING ATEROSKLEROSIS
DIKENAL TRIAD LIPID.
KECENDRUNGAN KASUS DYSLIPIDEMIA
GG VASKULER , ATEROSKLEROSIS PJK ,
STROKE PERLU PENCEGAHAN & TH/
MENYELURUH.
KOLESTEROL
dalam jumlah tepat bermanfaat, Jika berlebih berbahaya

MANFAAT KOLESTEROL
Sumber energi
Pembentukan dinding sel
Pembentukan hormon

BAHAYA KOLESTEROL BERLEBIH

Dapat melekat pada dinding pembuluh darah
sehingga terjadi Aterosklerosis
yang dapat mengakibatkan PJK/Stroke
 Dislipidemia

Kelainan metabolisme lipid

(lemak) yang ditandai dengan
peningkatan maupun penurunan
komponen lemak dalam darah
DISLIPIDEMIA
Ditandai dengan :

Kolesterol Total

Trigliserida

Kolesterol-LDL

Kolesterol-HDL
 Kolesterol dari makanan Kolesterol tidak dapat larut
dalam air (darah)
Agar dapat diangkut ke sel
Diolah dalam saluran cerna
yang memerlukan, kolesterol
berikatan dengan protein
membentuk Lipoprotein
Diserap masuk aliran darah

Didistribusikan ke sel-sel
Yang memerlukan
Contoh Lipoprotein :
Kilomikron
HDL (High Density Lipoprotein)
LDL (Low Density Lipoprotein)
 Lipid Metabolism
Cholesterol synthesis
Lipoproteins:
VLDL

LDL

HDL

Chylomicrons
Apolipoproteins
 KLASIFIKASI
A.KAUSA:
1. DYSLP. PRIMER >> FAKTOR GENETIK
2. DYSLP. SKUNDER: E/ PENYAKIT TT:
HYPOTYROID, DM, NS, SH, CRF DLL DAN
OBAT2AN: DIURETIK, BLOKER, ESTROGEN
B. KLINIS:
1.HYPERKOLESTEROLEMIA, ( HYPERKOLEST)
2.HYPERTRIGLISERIDEMIA,( HYPER TG)
3.CAMPURAN
 Fredrickson Classification
Type Elevated Associated clinical Serum Serum
particles disorders TC 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 Classification
Type Elevated Associated clinical Serum Serum
particles disorders TC TG

III IDL Dysbetalipoproteinemia

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

V Chylomicrons, Diabetes
VLDL
 Secondary Causes of Lipoprotein
Abnormalities
Hypothyroidism; Obstructive liver
Hypercholesterolemia disease; Nephrotic syndrome; Drugs:
progestogens, cyclosporine, thiazides

Obesity, DM, Pregnancy, CRF, Alcohol,

Stress, Sepsis, Acute hepatitis, SLE,
Hypertriglyceridemia
Drugs: estrogen, -blockers, steroids,
acid resins, thiazides

Type-2 DM, Rheumatoid arthritis,

Low HDL Malnutrition, Obesity, Cigarette
smoking, Beta blockers
 KRETERIA DIAGNOSTIK
PATOKAN NILAI KOLESTEROL DIKAITKAN DG
RISIKO PJK Penelitian jangka panjang
a. KADAR MASIH AMAN << 200 mg/dl
b. KADAR BORDRLINE HIGH: 200-239 mg/dl
c. KADAR TINGGI BERBAHAYA >> 240 mg/dl.
KESETARAAN KOLESTEROL TOTAL DG LDL.
KOL: 240 mg/dl LDL 160 mg /dl
KOL: 200 mg/dl LDL 130 mg/dl
KOL: 155 mg/dl LDL 100 mg/dl
HUBUNGAN PROFIL LIPID
DG RISIKO PJK
KADAR DESIRE BORDER HIGH
KOLES ABLE LINE
TOTAL << 200 200-239 >> 240
KO LDL
PJK (-) << 130 130-159 >> 160
PJK (+) << 100 - -
HDL >> 45 35-45 << 35
TRIGLI
PJK (-) << 200 200-299 >> 400
Fredrickson Classification of Hyperlipidemias

Type Predominant Predominant Xanthoma CHD Pancreatitis

lipoprotein lipid risk
I Chylomicrons Triglycerides Eruptive - +
>1000
IIa LDL Cholesterol Tendon; + -
>300 Xanthelasma
IIb VLDL + LDL TG and CH + -
<1000 >300
III Remnants TG and CH Palmar and + -
tuberous
IV VLDL CH + -

V Chylomicrons TG and CH Eruptive - +

+ VLDL >1000 >300
Diagnosis

Classification of Lipid Levels

Total cholesterol mg/dl LDL cholesterol mg/dl
< 200 Desirable < 100 Optimal

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

130-159 Borderline high

240 High 160-189 High

190 Very high

NCEP ATP III Classification of Blood Lipids

Diagnosis

Classification of Lipid Levels

Triglycerides 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

 Overview of Cholesterol
Metabolism: Absorption ynthesis
LDL Oxidation and Atherosclerosis
 Mechanism of Atherogenic
Dyslipidemia
Insulin resistance
Increased
increased NEFA and VLDL
glucose flux to liver

IR impairs
LDLR
Insulin resistance
Insulin
and decreased FCHL
resistance
apo-B and DM II
degradation decreased
LPL Metabolic
syndrome
Rationale for Treating Dyslipidemia

Pathogenesis of Atherosclerosis
Atherosclerosis Timeline
Foam Fatty Intermediate Fibrous Complicated
Cells Streak Lesion Atheroma Plaque Lesion/Rupture

Endothelial Dysfunction
From first decade From third decade From fourth decade
Smooth muscle Thrombosis,
Growth mainly by lipid accumulation and collagen hematoma

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

Faktor-faktor Risiko PJK

Tidak Dapat dimodifikasi :

Usia
Jenis Kelamin
Riwayat Keluarga
Ras
Faktor-faktor Risiko PJK

Dapat dimodifikasi :
Lipid/lemak dan Lipoprotein
Diabetes Melitus
Hipertensi
Kebiasaan Merokok
Obesitas (kegemukan)
Kilomikron
Mengangkut lemak dari saluran cerna menuju hati

Low Density Lipoprotein (LDL)

Mengangkut kolesterol ke sel-sel tubuh
yang memerlukan

High Density Lipoprotein (HDL)

Mengangkut kolesterol dari sel tubuh
menuju hati
BERBAHAYA karena merupakan cikal bakal
terjadinya proses Aterosklerosis

LDL teroksidasi 1
paling berbahaya
LDL densitas kecil 2
lebih berbahaya

LDL kolesterol 3
berbahaya
 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 !!!!
Dapat melekat pada dinding pembuluh darah
sehingga terjadi Aterosklerosis
yang dapat mengakibatkan PJK/Stroke
 Kolesterol dari makanan Kolesterol tidak dapat larut
dalam air (darah)

Agar dapat diangkut ke sel

Diolah dalam saluran cerna yang memerlukan,
kolesterol
berikatan dengan protein
membentuk Lipoprotein
Diserap masuk aliran darah
Contoh Lipoprotein :
Kilomikron
HDL (High Density Lipoprotein)
Didistribusikan ke sel-sel LDL (Low Density Lipoprotein)
Yang memerlukan
STRUKTUR DASAR LIPOPROTEIN

fosfolipid

Kolesterol
bebas
apolipoprotein
 Lipoprotein
Kilomikron Mengangkut lemak menuju hati

Very Low Density Lipoprotein (VLDL)

Intermediate Density Lipoprotein (IDL)
Low Density Lipoprotein (LDL)
Mengangkut kolesterol ke sel-sel tubuh
yang memerlukan
High Density Lipoprotein (HDL)
Mengangkut kolesterol menuju hati
Cholesterol Metabolism
Importance
Vital component of all
cell structure
Source of energy
Dangers
Abnormal metabolism
results in vascular
disease
Lipid Physiology

ApoE mediated

Goodman and Gilmans Pharmacological Basis of Therapeutics, 10th ed. 2001

Kolesterol LDL
Faktor risiko terkuat kolesterol
jahat

Kolesterol HDL
Pembersih Kolesterol kolesterol
baik
Apoprotein A-1
Komponen utama HDL
Pembersih lemak

Apoprotein B
Komponen utama LDL
LDL KOLESTEROL

LDL teroksidasi 1
paling berbahaya
LDL densitas kecil 2
lebih berbahaya
LDL kolesterol
berbahaya 3
KOLESTEROLLDL (Direk)
KEUNGGULAN
n = 4797

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

Triglyceride levels
1. Lebih Akurat
Kemungkinan kesalahan perhitungan 201-300 mg/dL (2.27-3.39 mmol/L): 23%

dengan memakai rumus Friedewald

dapat dihindari (LDL = TC-HDL-TG/5) 301-400 mg/dL (3.40-4.52 mmol/L): 41%

Kadar LDL tetap dapat diperoleh walau-

pun kadar trigliserida > 400 mg/dl 0% 10% 20% 30% 40% 50%
Percentage of patients with misclassified LDL values

2. Pemeriksaan dapat dilakukan dalam kondisi tidak puasa

dan hal ini bermanfaat bagi :
* Pasien pediatrik (anak-anak) * Pasien yang sedang dalam pengobatan
* Pasien geriatrik (orang tua) * 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 adanya
Small dense LDL atau LDL kecil padat
Small-dense LDL
(LDL kecil-padat)

Diperkirakan dari
LDL-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 Total

Proses oksidasi LDL secara normal

dihambat oleh sistem antioksidan di
dalam tubuh

Cukup tidaknya sistem antioksidan

tubuh seseorang dapat dilihat dari
Pemeriksaan Status Antioksidan Total
HIPERTRIGLISERIDEMIA

MENGAPA BERBAHAYA
(dianggap sebagai Faktor Risiko) ?

Hipertrigliseridemia

Hati mensintesis VLDL dalam jumlah banyak

VLDL diuraikan menjadi Small Dense LDL

Hipertrigliseridemia

Berkaitan dengan peningkatan LDL

kecil - padat

Peningkatan LDL-kecil padat akan

meningkatkan risiko PJK sebanyak
3 kali
 Lipoprotein (a)

Seperti halnya LDL, Lp(a) mempunyai

kandungan kolesterol yang tinggi
Merupakan faktor risiko independen
yang sangat penting untuk PJK dan
Stroke
SAMPAI DIMANA RISIKO
ANDA TERHADAP PJK ?
Lakukan pemeriksaan laboratorium
Apo B
Lp(a)
Small-Dense LDL : Kolest LDL/Apo
B
Ox-LDL : Status Antioksidan Total
Cholesterol
Triglyceride
LDL-Cholesterol
HDL-Cholesterol
hs-CRP is the Clinical Assay of
choice for CVD Risk Prediction

Nilai prediktif yang lebih baik

Stratifikasi risiko
Penanda prognostik yang lebih dini
 PENGELOLAAN
MELIPUTI PENCEGAHAN DAN PENGOBATAN
A. PENCEGAHAN:
1.POLA MAKAN SEHAT SEIMBANG BANYAK
MAKAN SAYUR DAN BUAH
BATASI KONSUMSI DIET TINGGI LEMAK
2. OLAHRAGA CUKUP, RUTIN, TERATUR.
3. PERTAHANKAN BERAT BADAN IDEAL.
4.TIDAK MEROKOK.
 B. PENGOBATAN
1. TH/ NON FARMAKOLOGIK:
a.PENYULUHAN
b.PERENCANAAN MAKAN / DIET,
c. LATIHAN JASMANI / OLAH RAGA TERATUR,
d. PENGENDALIAN GULA DARAH PD DM
2. TH/ FARMAKOLOGIK / OBAT HYPOLIPIDEMIK
a. PENGIKAT RESIN: KOLESTIPOL, KOLESTIRAMIN
b. ASAM NIKOTINAT: ACIPIMOX, ASAM NIKOTINAT
c. GOLONGAN FIBRAT: GEMPIBROSIL, FENOFIBRAT
d. GOLONGAN STATIN: SIMVASTATIN,LOVASTATIN,
ATORVASTATIN, FLUVASTATIN. DLL.
 Intensive LDL-C Goals for High-
Risk Patients
Recommended LDL-C treatment goals
ATP III AHA/ACC guidelines 2006
Update 20041 for patients with CHD*,2 Update

<100 mg/dL: <100 mg/dL:

Patients with Goal for all
CHD or CHD risk <100 mg/dL patients with CHD,2
equivalents
(10-year risk >20%)1 <70 mg/dL:
A reasonable
<70 mg/dL: goal for all patients
Therapeutic with CHD,2
option for very
high-risk patients1 <70 mg/dL

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-Clowering therapy, including
* And other forms of atherosclerotic disease.2 drug combinations.
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 + nonHDL-C 130 mg/dL with HDL-C <40 mg/dL); and acute coronary
syndromes.1
1. Grundy SM et al. Circulation. 2004;110:227239.
2. Smith SC Jr et al. Circulation, 2006; 113:23632372.
 Rationale for Treating
Dyslipidemia
Pathogenesis of atherosclerosis
Epidemiological studies
Clinical trials
LDL cholesterol as a primary target of
therapy
 Dual Inhibition of Cholesterol
Synthesis and Absorption
Diet

Liver
Bile
Bile acids Statin

Small NPC1L1 Cholesterol Synthesis

intestine
Absorption

Ezetimibe

Excretion in Atherogenic
feces lipoproteins
Rationale for Treating Dyslipidemia

Clinical Trials
Trial Intervention Initial LDL Change CHD event
in LDL 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/Resi 136-98 39% 24%

n
Rationale for Treating Dyslipidemia

Clinical Trials
Trial Intervention Initial LDL Change CHD event
in LDL reduction

Acute coronary syndrome patients

MIRACL Atorvastatin 124-72 42% 26%

AVERT Atorvastatin 145-77 42% 36%

Rationale for Treating Dyslipidemia

Clinical Trials
Trial Intervention Initial LDL Change CHD event
in LDL reduction

Patients without evidence of CHD

LRC-CPPT Resin 205-175 15% 19%

WOSCOPS Pravastatin 192-142 26% 31%

Tex/AFCAP Lovastatin 150-115 25% 40%

S
ASCOT Atorvastatin 132-85 31% 50%
 Mechanism of
Intestinal-Acting Agents
 Many High-Risk Patients Were Not Tested and Many Who
Were Tested and Treated Did Not Achieve
LDL-C 100 mg/dL1
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.

At 6 months At 12 months

74.5% DID NOT achieve

(n=208) LDL-C <100 mg/dL

51.8% DID NOT achieve 279 patients had at least

Of those CHD patients tested, (n=337) LDL-C <100 mg/dL 1 prescription filled after 6 months

45.9% 25.5% achieved

(n=651) (n=71) LDL-C <100 mg/dL

were treated 48.2% achieved

(n=314) LDL-C <100 mg/dL
All CHD patients who were treated
had LDL-C 100 mg/dL

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

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).1
In 1999, ATP II recommended an LDL-C goal of 100 mg/dL for patients with CHD.2

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; 30153023.
 Increased Atherogenicity of Small
Dense LDL
Direct Association Indirect Association
Longer residence time in Inverse relationship with HDL
plasma than normal sized LDL Marker for atherogenic TG
due to decreased recognition by remnant accumulation
receptors in liver Insulin resistance
Enhanced interaction with
scavenger receptor promoting
foam cell formation
More susceptible to oxidation
due to decreased antioxidants
in the core
Enter and attach more easily to
arterial wall
Endothelial cell dysfunction
 Evolution of NHLBI Supported
Guidelines Updated AHA/ACC
NCEP ATP I NCEP ATP II NCEP ATP III NCEP ATP III Update
1988 1993 2001 2004 2006

More Intensive Treatment Recommendations

Framingham Angiographic trials 4S HPS TNT

MRFIT (FATS, POSCH, WOSCOPS PROVE-IT IDEAL
LRC-CPPT SCOR, STARS, CARE ASCOT-LLA
Coronary Ornish, MARS) LIPID PROSPER
Drug Project Meta-analyses AFCAPS/ ALLHAT-LLT
Helsinki Heart (Holme, Rossouw) TexCAPS
CLAS

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.