HIPERLIPIDEMIA

HIPERLIPIDEMIA

Dra. Fita Rahmawati, Sp.FRS, Apt
Dra. Fita Rahmawati, Sp.FRS, Apt
 DEFINISI
PENINGKATAN SATU ATAU LEBIH DARI
KOLESTEROL, PHOSPHOLIPID ATAU
TRIGLISERIDA

Tiga jenis lipoprotein utama dalam serum:

LDLs (low density lipoproteins)
Bentuk antara VLDL dan LDLs (IDL) dlm
pengukuran termasuk dalam LDL
HDLs (high-density lipoproteins)
jumlahnya menurun pada penderita gemuk,
perokok, DM , pengguna kontrasepsi
VLDLs (very low-density lipoproteins)
 PENELITIAN
Hypercholesterolemia, peningkatan LDL dan
HDL rendah peningkatan resiko mortalitas
dan morbiditas CHD dan cerebrovascular
(terutama LDL)
PANCREATITIS
Patients with triglycerides >1,000 are at
increased risk of pancreatitis.
Px type 2 DM bersama dg faktor resiko lain
(hypertensi, tinggi LDL-C, rendah HDL-C,
obesitas) meningkatkan resiko cardiac events.
PENURUNAN KOLESTEROL MENURUNKAN
PENYAKIT KORONER 20 % DENGAN RESIKO
KEMATIAN AKIBAT PENYAKIT KORONER 11 %
Clinical predictors of increased risk for
Atherosclerotic Cardiovascular Disease ASCVD
(in addition to elevated LDL cholesterol) include:

Age (males > 45 years, females > 55 years or

menopause < age 40?)
Family history of premature coronary artery disease;
definite myocardial infarction (MI) or sudden death
before age 55 in father or other male first-degree
relative, or before age 65 in mother or other female
first-degree relative
Current cigarette smoker
Hypertension (systolic blood pressure > 140 mmHg or
diastolic blood pressure > 90 mmHg confirmed on more
than one occasion, or current therapy with
antihypertensive medications)
Diabetes mellitus (DM)
High-density lipoprotein (HDL)-cholesterol < 40 mg/dL
 PENYEBAB
HIPERLIPIDEMIA
1. PRIMER (MONOGENIK) KETURUNAN
2. SEKUNDER/POLIGENIK/MULTIFAKTORIAL
PENYAKIT LAIN
Hypothyroidism, chronic renal failure, and
the nephrotic syndrome are well known to cause
elevated LDL-C.
Px with hypercholesterolemia might include
measurement of serum thyroid-stimulating
hormone (TSH), BUN/creatinine, and a dipstick
urinalysis, to exclude these relatively common
conditions
DIET : ALKOHOL , MEROKOK
OBAT-OBATAN : TIAZID, ESTROGEN

 Efek obat pada serum lipid

Gol. obat Kolesterol Trigliserid HDL
Tiazid 5 10 % 30 50 % 10 20 G/L
B-bloker Tetap 15 50 % 5 15 %
Prazozin 09% 0 16 % 0 17 %
Estrogen 5% 40 60 %
Cyklospori 15 20 % Tetap Tetap
Captopril Tetap Tetap
Methyldopa 5 10 % 0 25 % Tetap
 Patients with the following results of
lipid measurements will require
therapy for a lipid disorder:
LDL > 130 mg/dL
HDL < 40 mg/dL
TG > 400 mg/dL
 KLASIFIKASI HIPERLIPIDEMIA

Lipoprotein Lipoprotein Lipid Changes

phenotype Abnormality
I Kilomikron Pe Trigliserida

IIA Low density Pe Kolesterol

IIB Low & Very low Pe Triglisedida

Pe Kolesterol
III Remnant Pe Triglisedida
(IDL/LDL1) Pe Kolesterol
IV Very low density Pe Triglisedida

V Kilomokron & Pe Triglisedida

Very low density Pe Kolesterol
 KLASIFIKASI HIPERLIPIDEMIA
Most severe forms of hypercholesterolemia are
the result of genetic disorders.

JENIS-JENIS HIPERLIPOPROTEINEMIA GENETIK

HIPERTRIGLISERIDA

FAMILIAL HIPERTRIGLISERIDA
( TG = 250 750, VLDL TYPE IV ) .
FAMILIAL LPL DEFICIENCY
( TG = 750, VLDL , CHILOMIKRON , TYPE I,V ) .
FAMILIAL APO CII
( TG = >750, VLDL , CHILOMIKRON , TYPE I,V )
 JENIS-JENIS HIPERLIPOPROTEINEMIA GENETIK
HIPERKOLESTEROLEMIA

1.FAMILIAL HIPERKOLESTEROLEMIA HETEROZYGOT ( TC = 275

500, LDL TYPE II A) DAN HOMOZYGOTE (TC = > 500, LDL
TYPE II A)
2.FAMILIAL DEFECTIVE APO B 100 HETEROZYGOT ( TC = 275
500, LDL TYPE II A)
3.POLYGENIC HIPERKOLESTEROLEMIA
( TC = 275 500, LDL TYPE II A)

JENIS-JENIS HIPERLIPOPROTEINEMIA GENETIK

HIPERTRIGLISERIDA & HIPERKOLESTEROLEMIA

1.KOMBINASI HIPERLIPIDEMIA
( TG = 250 -750, TC = 250 500, VLDL & LDL , TYPE IIB ) .
2. DYSBETALIPOPROTEINEMIA
( TG = 250 -750, TC = 250 500, VLDL & IDL , LDL
NORMAL, TYPE III ) .

 GOAL OF THERAPY

Based upon the risk factors, 10-years

CHD estimate, and the presence and
absence of CHD in the patient. NCEP
recommends the LDL treatment goal
The long term goal is to prevent
cardiac event and premature death
 Penatalaksanaan
Hiperlipidemia
Primary prevention
Increase LDL, but no history of CHD. Drug
therapy is cost effective in high risk
patients (e.g. strong history family or
coexistent diabetes) when non drug
therapy fail
Secondary prevention
Increase LDL, and history of CHD. Drug
therapy definitely indicated when non drug
therapy fail
 Penatalaksanaan
Hiperlipidemia
Initial therapy : therapeutic lifestyle changes
- Diet : restricted intake of total & saturated fat and
cholesterol, increase in polysaturated fat
- Smoking
- Regular exercise -- increase of HDL
- Antioxidant vitamin (A,C,E), long term may slow
atherogenesis
Many experts also recommend attention to the
following additional lifestyle modifications:
Limitation of alcohol intake to 1-2 drinks per day
Reduced calorie diet to promote weight loss, if
overweight
Stress management
A minimum of three to six months of intensive diet and
exercise is recommended before medications are initiated for
primary prevention.
 Penatalaksanaan
Hiperlipidemia
Other intervention
1. Remove or reduce dose of possible drugs
affecting plasma lipid
2.Treat other possible causes of dyslipidemia eg;
Hypothyroidism. Thyroid supplements (l-
thyroxine) may normalize LDL level
Metabolic syndrome (combined obesity,
hypertension, diabetes --- optimize insulin
therapy to enhance lipoprotein lipase activity in
hypertrigliceridemia)
Nephrotic syndrome
Obstructive liver disease
 Pengobatan
Hiperlipidemia
Treatment should be based on LDL-C and CHD risk. CHD risk
factors are age, family history, current smoker, hypertension,
diabetes, and HDL-C < 40 mg/dL.
Known CHD
Baseline LDL-C [mg/dL] > 100: Diet/exercise; consider drug
Baseline LDL-C [mg/dL] > 130: Diet/exercise + drug
Diabetes (without known CHD)
Baseline LDL-C [mg/dL] > 100: Diet/exercise; consider drug
Baseline LDL-C [mg/dL] > 130: Diet/exercise + drug
No known CHD but > 2 risk factors
Baseline LDL-C [mg/dL] > 100: No treatment
Baseline LDL-C [mg/dL] > 130: Diet/exercise
Baseline LDL-C [mg/dL] > 160: Diet/exercise + drug
 Pengobatan
Hiperlipidemia
No known CHD but < 2 risk factors
Baseline LDL-C [mg/dL] > 100 - < 160 : No treatment
Baseline LDL-C [mg/dL] > 160: Diet/exercise
Baseline LDL-C [mg/dL] > 190: Diet/exercise + drug
LDL-Cholesterol Goals in the Treatment of Dyslipidemia Based on Risk
for ASCVD
Known CHD: <120 mg/dL*
Diabetes (without known CHD): <120 mg/dL*
No known CHD, but > 2 risk factors: <130 mg/dL
No known CHD, but < 2 risk factors: <160 mg/dL
*NCEP III recommends an LDL-C goal of < 100 mg/dL in patients
with known CHD and CHD equivalents (i.e., type 2 diabetes mellitus)
 Jenis obat hiperlipidemia
Statin atau HMG Co-ARI
(hydroxymethylglutaryl coenzyme-A
reductase inhibitor) : Simvastatin,
Pravastatin
BAR (Bile acid resins) : Cholestyramin ,
Colestipol
Fibric acids : Clofibrate, Gemfibrozil
Fish oil
Probucol
Nicotinic acid (niacin)
 Pengobatan
Hiperlipidemia
Statin drug of choice px hypercholesterolemia
Sebagai monotherapy --- paling poten menurunkan
LDL. Bekerja dengan mencegah konversi HMG-
CoA menjadi asam mevalonat
Higest patient acceptance
Rosuvastatin paling poten diantara gol statin
Cost of drug and laboratory monitoring is high

Px yg tidak berespon dg monotherapy statin,

diberikan kombinasi terapi dan dimonitor resiko
ESO & interaksi obat
 Niasin least expensive drug
Has the most desirable lipid-lowering
potential (decrease LDL, TG, increase
HDL)
Acute reactions (itching, flushing) and the
risk of hepatotoxicity at high dose
Relative contraindicated in diabetes
Bile acid resin (not absorb) free of
systemic side effect
Compliance is limited by taste and
inconvenience of preparation
May increase triglyceride (avoid in
hypertrygliceride)
 Ezetimibe (cholesterol absorption blocker)
better tolerated than bile acid resin with
good LDL-lowering properties.
Effective in combination with statin.

Fibrates (gemfibrozil or fenofibrate)

primarily are indicated for lowering TG or
raising HDL, reserve for mixed
hyperlipidemia. Not recommended for LDL
lowering only
 Fish Oil
The effect on LDL varied
Effect of HDL variable
Little value unless unless combined with a
proper diet containing several fish meals
per week
Most useful in hypertriglyceridemia and
who cannot achieve adequate control with
(niacin and a fibrate)
CHD risk reduction due to antiarrhytmic
effect
 Pengobatan
Hiperlipidemia
Treatment of Hypertriglyceridemia (TG >1000 mg/dL)
Statin, niasin and fibrate
First Choice:
Hypertriglyceridemia and normal cholesterol : Fibrates
Niacin most effective and least expensive, but most
side effect
Hypertriglyceridemia and elevated LDL-C : statin
Statin are better tolerated than niasin
Remarks: Fibrates are contraindicated in severe
renal disease. Niacin is contraindicated in
hepatic disease and relatively
contraindicated in DM, gout, and history
of complicated/active peptic ulcer disease
(PUD).
 Pengobatan
Hiperlipidemia
Lipid Disorder: Elevated LDL-C
Initial monotherapy: Statins
Efficacy: LDL -22 to -60%
Considerations: Caution using statins in hepatic
disease
Alternate monotherapy: Niacin
Efficacy: LDL -13 to -21%
Considerations: Niacin is contraindicated in hepatic
disease and relatively contraindicated in DM, gout,
and history of complicated/active PUD;
Alternate monotherapy: Bile acid resin (resin)
Efficacy: LDL -10 to -20%
Considerations: Resins may increase TG
 Pengobatan
Hiperlipidemia
Lipid Disorder: Elevated LDL-C and Elevated TG
Initial monotherapy: Niacin
Efficacy: LDL -13 to -21%; TG -10 to -24%
or
Initial monotherapy: Statin
Efficacy: LDL -22 to -60%; TG -06 to -37%
Alternate monotherapy: Fibrates
Efficacy: LDL +10 to -35%; TG -32 to -53%
Considerations: For high TG, use fibrates or niacin;
for high LDL, use statins
 Pengobatan
Hiperlipidemia
Lipid Disorder: Elevated LDL and Decreased HDL
Initial monotherapy: Niacin
Efficacy: LDL -13 to -21%; HDL +10 to +24%
or
Initial monotherapy: Statin
Efficacy: LDL -22 to -60%; HDL +2 to +12%
or
Initial monotherapy: Fibrates
Efficacy: LDL +10 to -35%; HDL +2 to +34%
Considerations: No preferences in terms of efficacy
 Pengobatan
Hiperlipidemia
Lipid Disorder: TG 400-1000 mg/dL
Consider gemfibrozil if HDL-C < 40 mg/dL
For high TG, use direct LDL-C measurement or
non-HDL-C as lipid disorder to guide therapy
For CHD/ASCVD Patients
For patients with known CHD/ASCVD who have
HDL < 40 mg/dL pharmacotherapy with
gemfibrozil is recommended:
LDL-C < 130 mg/dL and HDL-C < 40 mg/dL
Efficacy: LDL +10 to 35%; HDL +2 to 34%
Considerations: Outcome data for
secondary prevention only
 LIPOPROTEIN PHENOTYPE AND
RECOMMENDED DRUG
TREATMENT

Lipoprotein Drug of choice Combination therapy

type
I Not indicated -
II A Statin Niacin or BAR
Resin Statin or Niacin
Niiacin Statin or BAR
ERT/HRT
II B Statin BAR, fibric acid , niacin
Fibric acid Statin, niacin or BAR
Niacin Statin atau fibric acid
 LIPOPROTEIN PHENOTYPE AND
RECOMMENDED DRUG
TREATMENT

Lipoprotein Drug of Combination therapy

type choice
III Fibric acid Statin or niacin
Niacin Statin or fibric acid
IV Fibric acid Niacin
Niacin Fibric acid
V Fibric acid Niacin
Niacin Fish oil
 Patient compliance
Reasons for medication noncompliance :
Medication side effects: Particularly an issue for
niacin and resins, statins may cause myalgias and
nonspecific gastrointestinal symptoms.
Incomplete patient education: Patients may not
understand benefit of medication or need for
long-term therapy.
Cost: Patients may not be able to afford
medications.
Reasons for diet and exercise noncompliance :
Incomplete patient effort and self-motivation:
Some patients are unable or unwilling to comply
with strict dietary changes, and a regular
exercise regimen.
 Patient compliance
Reasons for diet and exercise noncompliance :
- Suboptimal social support: Family and lifestyle may
not be conducive to strict dietary changes. Patients
may not have access to exercise facilities or safe
environment
Incomplete patient education: Some patients may
not have received adequate information because of
missed visits or inadequate time for counseling.
Cost: Patients may perceive that dietary
interventions increase costs, though this is
generally not the case. Patients unable to walk may
not have access to other exercise options
(swimming, stationary bike/machines, etc.).
 Monitoring terapi

1. SERUM LIPID
Repeat Lipid Evaluation at Least Annually
2. TANDA-TANDA TOKSISITAS OBAT:
FUNGSI HATI (ASAM NIKOTINAT,
CLOFIBRATE, GEMVIBROSIL, SIMVASTATIN,
PRAVASTATIN)
GULA DARAH ( ASAM NIKOTINAT,
GEMFIBROSIL)
KREATININ KINASE (SIMVASTATIN,
PRAVASTATIN, CLOFIBRATE)
SERUM KREATININ DAN UREA
(SIMVASTATIN, PRAVASTATIN)
TRIMAKASIH