LIPID MANAGEMENT

Why,when and how ?

Divisi Endokrin, Metabolik, dan Diabetes

Department of Internal Medicine
Brawijaya University
Malang
2017
Pokok bahasan
Apa yang dimaksud dengan lipid dan
dislipidemia ?
Mengapa dislipidemia harus diobati ?
Apakah ada bukti bahwa pengobatan
dislipidemia bermanfaat ?
Kapan pengobatan harus dimulai ?
Berapa sasaran lipid yang harus dicapai ?
Bagaimana melakukan penatalaksanaan
dislipidemia yang rasional ?
DISLIPIDEMIA
merupakan kelainan metabolisme lipid yang ditandai
dengan peningkatan maupun penurunan fraksi lipid
dalam plasma

mempunyai peran yang penting pada timbulnya

penyakit kardio- vaskuler (atherosklerosis)

kelainan utama adalah:

peningkatan kolesterol total
peningkatan trigliserida
peningkatan LDL-kolesterol
penurunan HDL-kolesterol
 LIPID
Molekul organik yang tidak larut dalam air
Sebagian besar terdiri dari hidro karbon
Dibagi menjadi :
Lipid sederhana : asam lemak
Lipid kompleks : Ester asam lemak
(gabungan antara asam lemak dengan
alkohol; monoacylglycerol atau
triacylglycerol )
FUNGSI LIPID

Sebagai sumber dan cadangan energi

Membentuk tekstur tubuh
Fungsi pelindung mekanik
Bahan untuk sintesis hormon
Bahan untuk sintesis dinding sel
Bahan untuk sintesis prostaglandin dll
SUMBER LIPID

Diet / makanan ( eksogen )

Sintesis oleh tubuh ( endogen )
TRANSPORTASI LIPID

Jalur eksogen ( mengangkut lipid yang

berasal dari diet )
Jalur endogen ( mengangkut lipid yang
berasal dari sintesis oleh hati )
Lipid diangkut oleh Lipoprotein
 LIPOPROTEIN

Kompleks lipid dengan protein

Terdiri dari :
Fosfolipid
Apolipoprotein
Kholesterol bebas
Kholesterol ester
Trigliserida
 LIPOPROTEIN
Untuk transportasi Lipid ( Trigliserida
dan kholesterol )
Bentuk bentuk Lipoprotein :
Chylomicrons
Very Low Density Lipoprotein ( VLDL )
Intermediate Density Lipoprotein ( IDL )
Low Density Lipoprotein ( LDL )
High Density Lipoprotein ( HDL )
 Lipoprotein Classes and Inflammation

Chylomicrons, LDL HDL

VLDL, and
their catabolic
remnants
> 30 nm 2022 nm 915 nm
Potentially anti-
Potentially proinflammatory
inflammatory
Doi H et al. Circulation 2000;102:670-676; Colome C et al. Atherosclerosis 2000;
149:295-302; Cockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:1987-
1994.
 LIPOPROTEIN METABOLISM
Exogenous Endogenous
Dietary Bile
lipids acids
+
Cholesterol

Peripheral
tissues

Chylomicron
Chylomicron remnant

Capillaries Capillaries
LDLR
ApoB
ApoE
FFA FFA
ApoCs
Muscle Adipose Muscle Adipose
Reverse cholesterol
transport process by which cholesterol is removed from the tissues and
returned to the liver.

LCAT (Lecithin-cholesterol acyltransferase)

CETP (Cholesterylester transfer protein)
PROTEIN
LDL receptor
LDL receptor-related protein (LRP)
Scavenger receptor B1 (SR-B1)
Lipoprotein lipase (LPL)
Lecithin-cholesterol acyltransferase
(LCAT)
Cholesteryl ester transfer protein
(CETP)
ATP binding cassette A1
FUNCTIONS
Clearance of apo B100 and apo Econtaining
lipoproteins, activity increased by statin drugs,
deficiency causes familial hypercholesterolemia
Clearance of apo Econtaining lipoproteins
HDL receptor
Rate limiting for triglyceride metabolism,
deficiency causes chylomicronemia syndrome
Esterifies cholesterol in HDL to increase HDL
cholesterol levels, deficiency decreases HDL
levels
Exchanges cholesteryl ester in HDL for
triglyceride in apo Bcontaining lipoproteins,
deficiency increases HDL levels
Transfers cholesterol in tissues to nascent HDL
particles, deficiency causes Tangier disease
 The density and size-distribution of the major classes of
lipoprotein

0.95
VLDL

1.006
IDL
Density, g/mL

1.02 Chylomicron
remnants
LDL
Chylomicron
1.06

1.10 HDL
1.20
5 10 20 40 60 80 1000
Diameter, mm
 Dietary Regulation of
Lipoprotein Synthesis
Chylomicron Synthesis VLDL Synthesis (Liver)

Chylomicron VLDL (+)

High CARB FA/TG
Insulin

(+)
Acetyl CoA
Dietary Fat

Intestinal Epithelium
(+)
Glucose
DYSLIPIDEMIA ??

Total cholesterol
LDL cholesterol
Trigliserida
( Small dense LDL )
( Non HDL cholesterol )
HDL cholesterol
Apa akibat dari dislipidemia ?
Atherosclerosis: A Progressive Disease
Plaque rupture

Adhesion Macrophage
Oxidized
Monocyte LDL-C molecule
LDL-C
Foam cell
CRP

Smooth muscle
cells

Endothelial Plaque instability

Inflammation Oxidation
dysfunction and thrombus

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

Atherosclerosis
 Macrophages and Foam Cells Express Growth
Factors and Proteinases

Monocyte Vessel Lumen

LDL

Adhesion Endothelium
MCP-1
Molecules LDL
Intima
Modified
Cytokines LDL Growth Factors
Metalloproteinases

Cell Proliferation
Macrophage
Foam Cell Matrix Degradation
Ross R. N Engl J Med 1999;340:115-126.
Apakah ada bukti bahwa lipid
berbahaya dan dapat
menyebabkan adanya penyakit
kardiovaskuler ?
METABOLIC
SYNDROME
Pertanyaan !!
Kapan pengobatan harus dimulai ?
Berapa sasaran cholesterol yang
harus dicapai ?
Bagaimana melakukan pengobatan
dislipidemia ?
Jenis obat apa yang sesuai ?
 Primary Prevention With
LDL-Lowering Therapy

Public Health Approach

Reduced intakes of saturated

fat and cholesterol
Increased physical activity
Weight control
 Therapeutic Lifestyle Changes in
LDL-Lowering Therapy
Major Features
TLC Diet
Reduced intake of cholesterol-raising nutrients
(same as previous Step II Diet)
Saturated fats <7% of total calories
Dietary cholesterol <200 mg per day
LDL-lowering therapeutic options
Plant stanols/sterols (2 g per day)
Viscous (soluble) fiber (1025 g per day)
Weight reduction
Increased physical activity
 Therapeutic Lifestyle Changes
Nutrient Composition of TLC Diet

Nutrient Recommended Intake

Saturated fat Less than 7% of total calories
Polyunsaturated fat Up to 10% of total calories
Monounsaturated fat Up to 20% of total calories
Total fat 2535% of total calories
Carbohydrate 5060% of total calories
Fiber 2030 grams per day
Protein Approximately 15% of total calories
Cholesterol Less than 200 mg/day
Total calories (energy) Balance energy intake and
expenditure to maintain desirable body weight/
prevent weight gain
Terapi farmakologi
 HMG CoA Reductase
Inhibitors (Statins)

Statin Dose Range

Lovastatin 2080 mg
Pravastatin 2040 mg
Simvastatin 2080 mg
Fluvastatin 2080 mg
Atorvastatin 1080 mg
Cerivastatin 0.40.8 mg
 Bile Acid Sequestrants
Drug Dose Range
Cholestyramine 416 g
Colestipol 520 g
Colesevelam 2.63.8 g

Demonstrated Therapeutic Benefits

Reduce major coronary events

Reduce CHD mortality
Fibric Acids

Major actions
Lower LDL-C 520% (with normal TG)
May raise LDL-C (with high TG)
Lower TG 2050%
Raise HDL-C 1020%
Side effects: dyspepsia, gallstones, myopathy
Contraindications: Severe renal or hepatic disease
 Fibric Acids
Drug Dose

Gemfibrozil 600 mg BID

Fenofibrate 200 mg QD
Clofibrate 1000 mg BID

Demonstrated Therapeutic Benefits

Reduce progression of coronary lesions

Reduce major coronary events
 Drug Therapy for Primary Prevention

First Step
Initiate LDL-lowering drug therapy
(after 3 months of lifestyle therapies)
Usual drug options
Statins
Bile acid sequestrant or nicotinic acid
Continue therapeutic lifestyle changes
Return visit in about 6 weeks
Second Step

Intensify LDL-lowering therapy (if LDL goal not achieved)

Therapeutic options
Higher dose of statin
Statin + bile acid sequestrant
Statin + nicotinic acid
Return visit in about 6 weeks

Third Step

If LDL goal not achieved, intensify drug therapy or refer to

a lipid specialist
Treat other lipid risk factors (if present)
High triglycerides (200 mg/dL)
Low HDL cholesterol (<40 mg/dL)
Monitor response and adherence to therapy
(Q 46 months)
 Non-HDL Cholesterol

Non-HDL chol = Total chol HDL chol

Non-HDL chol goal = 30 + LDL-chol goal
As secondary target if tryglicerides are 200
mg/dl
LDL-C Goal Non-HDL-C
Risk Category (mg/dL) Goal (mg/dL)
CHD and CHD Risk Equivalent
<100 <130
(10-year risk for CHD >20%
Multiple (2+) Risk Factors and
<130 <160
10-year risk <20%

01 Risk Factor <160 <190

 Low HDL Cholesterol
Management of Low HDL Cholesterol

LDL cholesterol is primary target of therapy

Weight reduction and increased physical
activity (if the metabolic syndrome is
present)
Non-HDL cholesterol is secondary target of
therapy (if triglycerides 200 mg/dL)
Consider nicotinic acid or fibrates
(for patients with CHD or CHD risk
equivalents)
 Diabetic Dyslipidemia

Lipoprotein pattern: atherogenic

dyslipidemia
(high TG, low HDL, small LDL particles)
LDL-cholesterol goal: <100 mg/dL
Baseline LDL-cholesterol 130 mg/dL
Most patients require LDL-lowering drugs
Baseline LDL-cholesterol 100129 mg/dL
Consider therapeutic options
Baseline triglycerides: 200 mg/dL
Non-HDL cholesterol: secondary target of
therapy
Kategori resiko

CHD or risk equivalent

Diabetes mellitus
PVD
10 year risk for CHD 20 %
2 or more risk factors
0 1 risk factor
 LDL Cholesterol Goals and Cutpoints for Therapeutic Lifestyle
Changes (TLC)
and Drug Therapy in Different Risk Categories

LDL Level at
LDL Level at
Which to Initiate
Which
Therapeutic
to Consider
LDL Goal Lifestyle
Drug Therapy
Risk Category (mg/dL) Changes (TLC)
(mg/dL)
(mg/dL)
CHD or CHD Risk
130
Equivalents
<100 100 (100129: drug
(10-year risk
optional)
>20%)
10-year risk 10
2+ Risk Factors 20%: 130
(10-year risk <130 130
20%) 10-year risk
<10%: 160
190
(160189: LDL-
01 Risk Factor <160 160
lowering drug
optional)