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DYSLIPIDEMIA AND

LIPOPROTEIN Dya Andryan MD

DISORDER
LIPOPROTEIN
Lipoproteins are large macromolecular complexes that transport
hydrophobic lipids (primarily triglycerides cholesterol, and fat-
soluble vitamins) through body fluids (plasma, interstitial fluid, and
lymph) to and from tissues
Lipoproteins play an essential role in
the absorption of dietary cholesterol, long-chain fatty acids, and fatsoluble
vitamins;
the transport of triglycerides, cholesterol, and fat-soluble vitamins from the liver
to peripheral tissues;
and the transport of cholesterol from peripheral tissues to the liver
CLASS OF LIPOPROTEIN
chylomicrons,
very low density lipoproteins (VLDLs),
Intermediatedensity lipoproteins (IDLs),
low-density lipoproteins (LDLs),
and high-density lipoproteins (HDLs).
APOLIPOPROTEIN
The proteins associated with lipoproteins, called apolipoproteins
Apolipoproteins activate enzymes important in lipoprotein
metabolism and act as ligands for cell surface receptors
LIPOPRO
TEIN
PATHWAY
REVERSE CHOLESTEROL
TRANSPORT

*Faciltated by HDL
FAMILIAL LIPOPROTEIN
DISORDER
elevations of chylomicrons (type I),
beta lipoproteins (LDL) (type II),
type III hyperlipoproteinemia,
VLDL or prebeta lipoproteins (type IV),
elevations of both chylomicrons and VLDL (type V).
TYPE 1-FAMILIAL
CHYLOMICRONEMIA
SYNDROME
Elevated Chylomycrons, sometimes with high TG
type I hyperlipoproteinemia exists in several forms:
Lipoprotein lipase deficiency (type Ia), due to a deficiency oflipoprotein lipase
(LPL) or alteredapolipoprotein C2, Familial apoprotein CII deficiency (type Ib),[7]
[8]a condition caused by a lack of lipoprotein lipase activator. [9]:533

Chylomicronemia due to circulating inhibitor of lipoprotein lipase (type Ic)[10]

Clinical Manifestation : Eruptive Xanthoma and Pancreatitis


Molecular damage : Lipoprotein lipase and Apolipoprotein C2
TYPE 2A FAMILIAL
HYPERCHOLESTEROLEMIA
The Most Common Dyslipidemia, ditandai dengan elevated LDL
Clinical Manifest : Tendon Xanthoma, Coronary Atherosclerosis at
young age
Molecular damage :PCSK9, ARH, ABCG5 and ABCG8, APO B 100,
LDL Receptor
TYPE 2B FAMILIAL
COMBINED HYPERLIPIDEMIA
Marked by Elevated LDL and VLDL
Clinical manifestation : Atherosclerosis, CAD, PAD
Molecular defect : Unknown
TYPE 3 HIGH
CHYLOMYCRONS AND IDL
(BROAD BETA
DISEASE)/DYSBETALIPOPROT
EINEMIA
Elevated Chylomycron and VLDL Remnants
Clinical Manifestation : Palmar Xanthomas, CAD and PAD
Molecular defects : ApoE
TYPE 4 & 5, FAMILIAL
HYPERTRIGLYCERIDEMIA
Known for elevated TG + VLDL (4), and Chylomicrons, TG, and
VLDL
Autosomal dominant
Appr. 1% world population
Clinical Manifestation : Eruptive xanthoma, Pancreatitis, CAD, PAD
Molecular defect : ApoA - V
Metabolic Diabetes
Lipodystrophy
Glycogen storage disorders
Renal Chronic renal failure
Glomerulonephritis
Hepatic Cirrhosis
Hormonal Estrogens
Progesterones
ACQUIRED Growth hormone
HYPERLIPIDE

Thyroid disorders (hypothyroidism)
Corticosteroids
MIAS Lifestyle Physical inactivity
Obesity
Diet rich in fats, saturated fats
Alcohol intake
Medications Retinoic acid derivatives
Glucocorticoids
Exogenous estrogens
Thiazide diuretics
Beta-adrenergic blockers (selective)
Testosterone
Immunosuppressive medications
(cyclosporine)
Antiviral medications (human
immunodeficiency virus protease
TOTAL CARDIOVASCULAR
RISK ESTIMATION
1) Those with
known CVD
type 2 diabetes or type 1 diabetes with
Microalbuminuria
very high levels of individual risk factors
chronic kidney disease (CKD)

are automatically at VERY HIGH or HIGH TOTAL CARDIOVASCULAR


RISK and need active management of all risk factors.
(2) For all other people, the use of a risk estimation system such as
SCORE is recommended to estimate total CV risk because many people
have several risk factors which, in combination, may result in
unexpectedly high levels of total CV risk.
SCORE CHART
(HI RISK
COUNTRY)
MANAGEMENT BASED ON
TOTAL CV RISK SCORE
LIPID PROFILING
HDL-C
LDL-C target treatment
TC
TG
TARGET LDL
LIFESTYLE INTERVENTION
ETIOLOGY HIGH TG
DYSLIPIDEMIA IN DM
In IDDM, and presence of microalbuminuria, LDL C lowering with
statin as first choice
In NIDDM, with CVD or CKD, target goal LDL < 70 mg/dl,
In NIDDM without CKD or CVD, LDL target < 100 mg/dl
DYSLIPIDEMIA IN PAD
High risk condition
Statin best for reduce progression carotid and aortic atherosclerosis
and aneurysm
DRUG FOR
DYSLIPIDEMIA
STATIN
Statins reduce synthesis of cholesterol in the liver by competitively
inhibiting HMG-CoA reductase activity.
The reduction in intracellular cholesterol concentration induces
low-density lipoprotein receptor (LDLR) expression on the
hepatocyte cell surface, which results in increased extraction of
LDL-C from the blood and a decreased concentration of circulating
LDL-C and other apo B-containing lipoproteins including TG-rich
particles
Side Effect : Myopathy, Myolisis
Contraindication : Liver disease
BILE ACID SEQUESTRANTS
MOA : binding the bile acids, the drugs prevent the entry of bile
acid into the blood and thereby remove a large portion of the bile
acids from the enterohepatic circulation.
The liver, depleted of bile, synthesizes more from hepatic stores of
cholesterol. The decrease in bile acid returned to the liver leads to
up-regulation of key enzymes responsible for bile acid synthesis
from cholesterol clearing LDL-C from the circulation
Side effect : GI problem
CHOLESTEROL ABSORBTION
INHIBITORS
MOA : inhibits intestinal uptake of dietary and biliary cholesterol
without affecting the absorption of fat-soluble nutrients.
FIBRATES
Agonist peroxisome proliferator-activated receptor-a (PPAR-a),
acting via transcription factors regulating various steps in lipid and
lipoprotein metabolism
have good efficacy in lowering fasting TG levels as well as post-
prandial TG and triglyceride-rich lipoprotein (TRL)
NICOTINIC ACID
decrease fatty acid influx to the liver and the secretion of VLDL by
the liver;
this effect appears to be mediated in part by the effects on
hormone-sensitive lipase in the adipose tissue.
N-3 FATTY ACID
3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic
acid (DHA)] are components of fish oil and the Mediterranean diet,
MOA : The underlying mechanism is poorly understood, although it
may be related, at least in part, to their ability to interact with
PPARs and to a decreased secretion of apo B

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