1

Hyperlipidemia
Dyslipidemias
Hiperlipoproteinemia

Dr. Nanang Miftah F , SpPD-KEMD

:
Divisi Endokrin, Metabolik dan Diabetes
FK UNLAM – RS Ulin
The Fact of Lipid
Komposisi Lipid
 Sintesis Kolesterol

Acetyl- Acetoacetyl- HMG-

CoA CoA CoA

HMG-CoA
reductase
Hepatocy
te Mevalonat
e

Cholester
ol

Adapted from Dietschy JM Am J Clin Nutr 1997;65:1581S-

1589S.
Lipid Metabolism

5
LIPOPROTEIN METABOLISM
 7

Lipid Transport

TG EC

Apoprotein boat

Apo A I and A II for HDL Apo B100 for LDL, Lp(a)

Apo B100+C+E – VLDL, IDL Apo B48+C+A+E – Chy. microns
 8

Lipoproteins

HDL LDL

C C
T TG
G
A I, A II B 100

VLDL Chilomicron

TG TG
C
B 100 + E +C B 48+E+C
Jenis Lipoprotein, apoprotein dan 9

kandungan lipid
10
 11

Ukuran dan Densitas Lipoprotein

Chylomicrons VLDL IDL

<< 1.006 < 1.006 < 1.019

LDL Small LDL HDL

< 1.063 < 1.085 < 1.210

Atherogenisitas meningkat seiring dengan meningkatnya densitas partikel Lipoprotein

Small LDL adalah Fraksi Lipoprotein yang paling atherognik
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Atherogenic Particles
Apolipoprotein B
Measurement Non-HDL-C
s

Small
VLDL VLDLR IDL LDL Dense LDL

TG-rich lipoproteins
 Lipids and Lipoproteins

Cholesterol Triglycerides (rich lipoproteins)

HDL LDL Lp(a) IDL VLDL Chylomicrons

(remnants)

Anti atherogenic Atherogenic Lipoproteins

INCREASED PLASMA LEVELS OF TG-RICH LIPOPROTEINS:

Visceral obesity, Type 2 diabetes, FCHL, Chronic kidney disease, Polycystic Ovary
Syndrome
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Pembagian Lemak Dalam Darah

LIPID Dalam Darah

TOTAL CHOLESTEROL TRIGLYCERIDES

GOOD CHOLESTEROL BAD CHOLESTEROL

HDL 1 and HDL 2 LDL, ( IDL, VLDL, Lp(a))
 Dislipidemia
• Dislipidemia adalah kelainan metabolisme lipid
yang ditandai dengan peningkatan maupun
penurunan fraksi lipid dalam plasma
• Ditandai dengan :
– LDL ↑
– TG ↑
– Total cholesterol ↑
– HDL ↓
• Hyperlipidemia ?
– Peningkatan kadar lemak dalam darah
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Klasifikasi Dislipidemia

Primary 5%
Familial & genetic

Secondary 95%
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Dislipidemia Primer
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Dislipidemia Sekunder
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Tanda Yang Mengarahkan Kecurigaan Dislipidemia

Tuberous xanthoma. Flat-

Xanthelasma.
topped, yellow, firm tumor
Multiple, longitudinal, creamy-orange,
slightly elevated papules on eyelids .
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Tanda Yang Mengarahkan Kecurigaan Dislipidemia

Tendinous xanthomas. Large sub-

cutaneous tumors adherent to the Achilles
tendons.
Papular eruptive xanthomas. Multiple,
discrete, red-to-yellow confluent papules
Dislipidemia Dan Atherosclerosis 21
ATHEROSCLEROSIS PROGRESS SILENTLY FOR MANY YEARS

Plaque
Endothelial Cholesterol Oxidation & instability
dysfunction flux Inflammation EVENTS
and thrombus

Plaque rupture
Adhesion Macrophage Oxidize
Monocyte LDL-C molecule d
Foam cell LDL-C
CRP

Smooth muscle
cells

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

Libby P. Circulation. 2001;104:365-372; Ross R. N Engl J Med. 1999;340:115-126.

 Manifestasi Klinis Dislipidemia 23

• Seringkali tidak khas

• Kesemutan
• Rasa berat di leher.
• Gejala yang dikaitkan
dengan penyakit
penyerta :
– Nyeri dada
– Kelemahan pada anggota
gerak
– Sakit sakit di otot dan
sendi
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Penapisan Pasien Dislipidemia

§ Diabetes
§ Hipertensi
§ Riwayat keluarga dengan PJK dini
§ Riwayat keluarga dengan hiperlipidemia
§ Penyakit ginjal kronik
§ Penyakit inflamasi kronik
§ Lingkar pinggang > 90 cm untuk laki-laki ; > 80 cm untuk wanita
§ Disfungsi ereksi
§ Adanya aterosklerosis atau abdominal aneurisma
§ Manifestasi klinis dari hiperlipidemia
§ Obesitas (IMT > 27 kg/m2) --> Untuk orang Asia IMT ≥ 25 kg/m2
§ Laki-laki usia ≥ 40 tahun atau wanita dengan usia ≥ 50 tahun atau sudah menopause
§ Perokok aktif
 RISK FACTORS 25

2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary
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Pengukuran Faktor Resiko Dislipidemia dan
Gangguan Kardiovaskuler
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Pengelolaan Dislipidemia
A. Non Farmakologi
• Diet
• Olah Raga
• Stop Merokok
B. Farmakologi
1. HMG co A Reductase Inhibitors
2. Fibric Acid derivatives
3. Nicotinic Acid
4. Ezetimibe
5. Bile Acid binding Resins (BAR)
¢
HMG: Hydroxy Methyl Glutaryl
 28

Anjuran Diit Pada Pasien Dislipidemia

Nutrient Recommended Intake

• Saturated fat < 7% of calories
• PUFA fat Up to 10% of calories
• MUFA fat Up to 20% of calories
• Total fat 25–35% of calories
• Carbohydrate 50–60% of calories
• Fiber 20–30 grams per day
• Protein Approx. 15% of calories
• Cholesterol Less than 200 mg/day
TARGET TERAPI 29

Lipid Management Algorithm, Endocr Pract. 2020;26(No. 10) 

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Treatment of ↑ LDLc
High LDLc

Therapeutic Lifestyle Change

Drug Therapy

Therapy of Choice: Statin

Add on drug - EZETIMIBE ,PCSK9 INHIBITOR, BAR

LDL LOWERING DRUG 31
 PRIMARY PREVENTION

2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary
 ESC 2019 Dyslipidemia Guideline1
New LDL- C target for very high risk (<55 mg/dL)

Mach F, et al. European Heart Journal. 2019; 00: 1-78.

High-intensity statin is recommended (class IA) to prescribed up to the highest tolerated dose to reach
the goals
 Atherosclerotic Cardiovascular Disease Risk
Categories, Characteristics, Lipid Targets, and
Therapy

Endocrine Practice  2022 28923-1049DOI: (10.1016/j.eprac.2022.08.002)

Drug-Effectiveness for Low-Density Lipoprotein
CholesteroleLowering Therapy

Endocrine Practice  2022 28923-1049DOI: (10.1016/j.eprac.2022.08.002)

 36
Statins – Mechanism of Action

VL
Cholesterol DL
V
synthesis Apo B
LDL receptor L LDL receptor–mediated
D hepatic uptake of LDL
HMGCoA (B–E receptor) Apo E
LR and VLDL remnants
Intracellular synthesis Apo B Serum LDL-C
L
Cholesterol D Serum VLDL remnants
L
Serum IDL

Hepatocyte Systemic Circulation

1. Reduce hepatic cholesterol synthesis (HMG CoA),
2. lowering intracellular cholesterol,
3. Upregulation of LDL receptor and
4. ↑ the uptake of non-HDL from circulation.
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Time course of Statin effects
Vulnerable
LDL-C Inflammation plaques
lowered* reduced stabilized

Endothelial Ischemic Cardiac events

function episodes reduced*
restored reduced

Days Years
* Time course established
STATIN MECHANISM OF ACTION
 39
HMG CoA Reductase
Inhibitors (Statins)

Statin Dose Range

Lovastatin 20–80 mg
Pravastatin 20–40 mg
Fluvastatin 20–80 mg
Simvastatin 20–80 mg
Atorvastatin 10–80 mg
Rosuvastatin 5–20 mg
Cerivastatin 0.4–0.8 mg
High, Moderate, and Low Intensity Statin Therapy

Donald M. Lloyd-Jones DM, Morris PB, et al. JACC 2016;68:92-125

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Efek Samping Pemberian Statin
⮚ Efek Samping Utama
⮚ Headache, Myalgia, Fatigue, GI intolerance
⮚ Peningkatan Enzim Liver
⮚ 0.5 to 2.5% , Sangat Tergantung besarnya dosis Statin
⮚ Myopathy --> 0.2 - 0.4%
⮚ Rhabdomyolysis
⮚ Upaya mengurangi kejadian Rhabdomyolisis :
⮚ Hati hati menggunakan statin pada pasien dengan
gangguan fungsi ginjal
⮚ Digunakan mulai dengan dosis efektif terendah
⮚ Hati hati bila melakukan kombinasi statins dengan fibrates
⮚ Statin dihentikan bila ada tanda tanda myopathy
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Ezetimibe: Lipid Absorbtion Blocker

Lymph Enterocyte Intestinal

Lumen
Ezetimibe
Cholesterol

ACAT
X
NPC1L1

Cholesteryl
Ester ABCG5/G8
 TREATMENT GUIDELINE 43

Precision and Future Medicine 2020; 4(4): 133-140

AACE GUIDELINE : LDL TX 44
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Treatment of ↓ HDLc
Low HDLc

Therapeutic Lifestyle Change

Drug Therapy
Therapy of Choice :
Niacin
Add on drug - Finofibrate
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Penyebab HDL Rendah

⮚ Smoking
⮚ Obesity (visceral fat), Physical inactivity
⮚ Very high Carbohydrate diet
⮚ Type II Diabetes
⮚ Hyper-triglyceridemia
⮚ Drugs like beta-blockers, androgenic steroids
and androgenic progestins
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Treatment of ↑ TG
High TG

Therapeutic Lifestyle Change

Drug Therapy
Therapy of Choice :
Fibrate
Add on drug – Statin, Niacin
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Triglycerides

TG Level Classification Treatment

< 150 mg% Normal TG No Rx.

150 to 200 mg% Borderline high Diet alone

201 to 500 mg% High Diet + drugs

> 500 mg% Very high Diet + Intensive Rx

NCEP 2002 Guidelines by expert panel on TG

 Fenofibrate

Mode of Action
❖ Enhances the activity of lipoprotein lipase
❖ Reduces hepatic fatty acid synthesis
❖ Inhibits HMG co-enzyme A reductase activity
❖ Reduces the CETP activity
❖ Increases the LCAT activity
❖ Increases the production of Apo AI and Apo A II
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Fibric Acid Derivatives

• Major actions
– Lower TG 20–50%,↓VLDL synthesis
– Raise HDL-C 10–20%
– ↓ LDL (TG is N), ↑ LDL (TG is ↑)
– Increase the SDL particle size (less athero)
• Side effects
Dyspepsia, gallstones, myopathy, Abn. LFT
• Contraindications
Severe renal or hepatic / biliary disease
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Fibric Acid Derivatives

Drug Dose
• Clofibrate 1000 mg BID
• Bezafibrate 200 mg BID
• Gemfibrozil 600 mg BID
• Fenofibrate 200 mg OD
• Fenofibrate micronized 160 mg OD
 Figure 2

Endocrine Practice  2022 28923-1049DOI: (10.1016/j.eprac.2022.08.002)

 53

Treatment of ↑ LDL + ↑ TG
Combined

Therapeutic Lifestyle Change

Drug Therapy

Therapy of Choice : Statin + Fibrate

Add on drug – Niacin, BAR

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Statin + Fibrate – Precautions

⮚ Use statin alone for non-HDL-C goals

⮚ Use fish oils or niacin rather than fibrates
⮚ Keep the doses of the statin and fibrate low
⮚ Dose the fibrate in the AM and the statin in the PM
⮚ Avoid (or cautiously use) combo in renal impairment
⮚ Teach the patient to recognize muscle symptoms
⮚ Discontinue therapy if muscle symptoms are present
and CK is >10 times the upper limit of normal
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Summary : The Three Canons

TE

↓H
RA

DL
FIB

-NIA
G-

DYSLIPIDEMIA

CIN
↑T

↑ LDL - STATIN
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Summary of Drug choice
Lipid abnormality type First choice Additional Remarks

↑ LDL Statin Ezetimibe Myopathy ↑

↑ TG Fibrate Niacin ↓ CHO intake

↓ HDL Niacin Fibrate Exercise

↑ LDL + ↑ TG Statin + Fibrate Niacin Myo risk ↑ ↑

↑ LDL + ↓ HDL Statin + Niacin Fibrate Exercise

↑ TG + ↓ HDL Fibrate + Niacin Statin Exercise
↑ LDL + ↑ TG + ↓ HDL Statin + Fibrate E, N, BA, FO Myo risk ↑ ↑ ↑
SUMMARY : LIPID LOWERING DRUGS PROFILE57
Thank You