DISLIPIDEMIA

DYSLIPIDEMIA
Dyslipidemia:
• A disorder of lipoprotein metabolism, including
lipoprotein overproduction or deficiency.

• Elevation of the total cholesterol, the "bad"

low density lipoprotein (LDL) cholesterol and
the triglyceride concentrations,
• And a decrease in the “good" high-density
lipoprotein (HDL) cholesterol concentration in
the blood.
 OUTLINE
EPIDEMIOLOGY ASCVD

EVIDENCE BASED LOW LDL REDUCED RISK ASCVD

SCRENING AND RISK ASCVD

PRIMARY PREVENTION

SECONDARY PREVENTION

ATP III VS ATP IV

CONCLUSION
 ASCVD GLOBAL REPORT
Basic health Survey 2013 in Indonesia  CAD
• Prevalence of CAD 1.5% (14-54 YO)
• Total death CAD in Indonesia 12.9%
• 7th position in non communicable disease
• CAD is number one cause of death, while CVA is in 5th position

Dyslipidemia is a primary, major risk factor for ASCVD and may

even be a prerequisite for ASCVD, occurring before other major
risk factors come into play.

Epidemiologic data also suggest that hypercholesterolemia and

perhaps coronary atherosclerosis itself are risk factors for
ischemic cerebrovascular accident (CVA)
DEATH IN EUROPE
 9

Emerging Risk Factors

Lipoprotein (a)
Homocysteine
Prothrombotic factors
Proinflammatory factors
Impaired fasting glucose
Subclinical atherosclerosis
Proteinuria
Autoimmune disease
HIV
CKD
 LDL Particles Cause Atherosclerosis

Low Density Lipoprotein

particles (LDL) are the causal
agents in atherosclerosis.1

The more LDL particles a person has, the higher

the risk for plaque buildup that causes heart
attacks, regardless of how much cholesterol those
particles carry.
1 Fredrickson et al. NEJM 1967; 276: 148
 Key Lipid and Lipoprotein Labs

Primary (Tier I) Secondary (Tier II)

 TC  LDL-P
 Apo B
 LDL  Apo A1
 HDL  Apo C II & III
 TG  CRP
 Lp(a)
 nonHDL  oxyLDL
 LpPla2
 Apo E isoforms
 Lipoprotein ratios
 hs-cTnI
 Genotypes
 Others
Primary Dyslipidemia
 Common Secondary Causes of Dyslipidemia
Conditions
Affected lipids
• Hypothyroidism
• Nephrosis
↑ Total • Dysgammaglobulinemia (systemic lupus erythematosus, multiple myeloma)
cholesterol and • Progestin or anabolic steroid treatment
• Cholostatic diseases of the liver due to abnormal lipoproteins, as in primary
LDL-C
biliary cirrhosis
• Protease inhibitors for treatment of HIV infection
• Chronic renal failure
• T2DM
• Obesity
• Excessive alcohol intake
• Hypothyroidism
↑ Triglycerides
• Antihypertensive medications (thiazide diuretics and b-adrenergic blocking
and VLDL-C agents)
• Corticosteroid therapy (or severe stress that increases endogenous
corticosteroids)
• Orally administered estrogens, oral contraceptives, pregnancy
• Protease inhibitors for treatment of HIV infection
• Pemeriksaan laboratorium untuk trigliserida membutuhkan
puasa selama 12 jam.
• Penghitungan K-LDLyang menggunakan Friedewald formula
membutuhkan data trigliserida, sehingga harus puasa 12
jam.
• Pemeriksaan total kolesterol, K-HDL dapat dilakukan dalam
keadaan tidak puasa.
Anderson T, et al., Canadian Journal of Cardiology, DOI: http://dx.doi.org/10.1016/j.cjca.2016.07.510
Copyright © 2016, Canadian Cardiovascular Society
 Primary prevention for:

1 LDL-C >=190 mg/dl

2 Diabetes and aged 40-75 years with LDL-C between 70- 189 mg/dl
3 No diabetes and estimated 10 year ASCVD risk of >= 7.5 %
and Who are between 40 to 75 years of age with LDL-C
between 70-189 mg/dl
What treatments are available for dyslipidemia?

Treatment categories for dyslipidemia:

 Lifestyle changes
 Physical activity
 Medical nutrition therapy
 Smoking cessation
 Pharmacologic therapy
 Statins
 Fibrates
 Omega-3 fish oil
 Niacin
 Bile acid sequestrants
 Cholesterol absorption inhibitors
 PCSK9 inhibitors
 MTP inhibitor
 Antisense apo B oligonucleotide
 Combination therapies
 ASCVD Risk Categories and LDL-C Treatment Goals
Treatment goals
Risk category Risk factors/10-year risk LDL-C Non-HDL-C Apo B
(mg/dL) (mg/dL) (mg/dL)
Progressive ASCVD including unstable angina in I
Individuals after achieving an LDL-C <70 mg/dL
Established clinical cardiovascular disease in
Extreme risk <55 <80 <70
individuals with DM, stage 3 or 4 CKD, or HeFH
History of premature ASCVD (<55 male, <65
female)
Established or recent hospitalization for ACS,
coronary, carotid or peripheral vascular disease,
10-year risk >20%
Very high risk <70 <100 <80
DM or stage 3 or 4 CKD with 1 or more risk
factor(s)
HeFH
≥2 risk factors and 10-year risk 10%-20%
High risk DM or stage 3 or 4 CKD with no other risk factors <100 <130 <90

Moderate risk ≤2 risk factors and 10-year risk <10% <130 <130 <90
Low risk 0 risk factors <130 <160 NR
Reduced Alcohol Intake
 A Model of Steps in
Therapeutic Lifestyle Changes (TLC)

Visit 2 Visit 3
Evaluate LDL Evaluate LDL Visit N
Visit I 6 wks response 6 wks response Q 4-6 mo
Monitor
Begin Lifestyle If LDL goal not
If LDL goal not Adherence
Therapies achieved,
achieved, to TLC
intensify consider
• Emphasize LDL-Lowering Tx adding drug Tx
reduction in • Initiate Tx for
• Reinforce reduction
saturated fat & Metabolic
in saturated fat and
cholesterol Syndrome
cholesterol
• Encourage • Intensify
• Consider adding
moderate physical weight
plant stanols/sterols
activity management &
• Increase fiber intake physical
• Consider referral to
a dietitian • Consider referral to activity
a dietitian • Consider
referral23
to a dietitian
ACC/AHA
 Secondary prevention for:
1 Patients with known coronary heart disease (CHD;
including myocardial infarction, angina, and prior
coronary revascularization)
2 Other cardiovascular disease (CVD; including stroke,
transient ischemic attack, and peripheral arterial
disease)
3 Combinations of risk factors that result in a 10-year
risk of ASCVD events of more than 20 %
4 Chronic kidney disease with estimated GFR
<45ml/min/1.73m2
5 Risk equivalent for CV in diabetic patients:
 Classification of Elevated Triglyceride Levels
TG levels that are even moderately elevated (≥150 mg/dL) may identify individuals at
risk for the insulin resistance syndrome. TG levels ≥200 mg/dL may indicate a
substantial increase in ASCVD risk. Hypertriglyceridemia is also commonly associated
with a procoagulant state and hypertension.

TG category TG concentration (mg/dL) TG goal

Normal <150

Borderline high 150-199

<150 mg/dL
High 200-499

Very high ≥500

Lipid-Lowering Drug Therapies, Starting Dosages, and Dosage Ranges
Fibrates
Usual recommended Method of
Agent Dosage range administration
starting daily dosage
Fibrates
Fenofibrate 48-145 mg 48-145 mg Oral
Gemfibrozil 1,200 mg 1,200 mg Oral
Fenofibric acid 45-135 mg 45-135 mg Oral

Metabolic Effects:
• Primarily ↓ TG 20%-35%, ↑ HDL-C 6%-18% by
stimulating lipoprotein lipase activity
• Fenofibrate may ↓ TC and LDL-C 20%-25%
• Lower VLDL-C and LDL-C; reciprocal rise in
LDL-C transforms the profile into a less
atherogenic form by shifting fewer LDL
particles to larger size
• Fenofibrate ↓ fibrinogen level
Lipid-Lowering Drug Therapies, Starting Dosages, and Dosage Ranges
Omega-3 Fatty Acids
Usual recommended Method of
Agent Dosage range
starting daily dosage administration
Omega-3-acid ethyl esters 4 g per day 4 g per day Oral
(Lovaza)
Icosapent ethyl (Vascepa) 4 g per day 4 g per day Oral

Metabolic Effects:
• ↓ TG 27%-45%, TC 7%-10%, VLDL-C 20%-42%, apo B 4%, and non-HDL-C 8%-14% in
individuals with severe hypertriglyceridemia most likely by reducing hepatic VLDL-TG
synthesis and/or secretion and enhancing TG clearance from circulating VLDL particles. Other
potential mechanisms of action include: increased ß-oxidation; inhibition of acyl-CoA; 1,2-
diacylglyceral acyltransferase; decreased hepatic lipogenesis; and increased plasma
lipoprotein activity.
• Icosapent ethyl ↓ LDL-C 5%, whereas, omega-3-acid ethyl esters ↑ LDL-C 45%
 Lipid-Lowering Drug Therapies, Starting Dosages, and Dosage Ranges
Bile Acid Sequestrants
Usual recommended Method of
Agent Dosage range administration
starting daily dosage
Bile acid sequestrants
Cholestyramine 8-16 g 4-24 g Oral
Colestipol 2g 2-16 g Oral
Colesevelam 3.8 g 3.8-4.5 g Oral

Metabolic Effects:
• Primarily ↓ LDL-C 15%-25% by binding bile
acids and preventing their reabsorption in
the ileum (causing hepatic cholesterol
depletion and LDL-receptor upregulation)
• Colesevelam ↓ glucose and hemoglobin
A1C (~0.5%); FDA-approved to treat T2DM
Main Considerations:
• May ↑ serum TG
• Frequent constipation and/or bloating, which can
reduce adherence
• Many potential drug interactions (decreased drug
absorption), less so with colesevelam (see product
labeling)
• May reduce absorption of folic acid and fat-soluble
vitamins such as vitamins A, D, and K
 Lipid-Lowering Drug Therapies, Starting Dosages, and Dosage Ranges
Cholesterol Absorption Inhibitors
Usual recommended Method of
Agent Dosage range administration
starting daily dosage
Cholesterol absorption inhibitors
Ezetimibe 10 mg 10 mg Oral

Combination therapies (single-pill)

Ezetimibe/simvastatin 10/20 mg 10/10 to 10/80 mg Oral

Metabolic Effects drugs remain (e.g., myopathy/

• Primarily ↓ LDL-C 10%-18% by inhibiting intestinal rhabdomyolysis, cholelithiasis)
absorption of cholesterol and decreasing delivery to
the liver, leading to upregulation of hepatic LDL
receptors
• ↓ Apo B 11%-16%
• In combination with statins, additional ↓ LDL-C 25%,
total ↓ LDL-C 34%-61%
• In combination with fenofibrate, ↓ LDL-C 20%-22%
and ↓ apo B 25%-26% without reducing ↑ HDL-C
Main Considerations
• Myopathy/rhabdomyolysis (rare)
• When coadministered with statins or
fenofibrate, risks associated with those
ALGORITMA TATALAKSANA
DISLIPIDEMIA
Alur II
 Kasus
• Pasien laki-laki usia 50 tahun dengan DM tipe2,
Merokok 1 bungkus sehari selama lebih dari 20
tahun, dan menderita hipertensi tekanan darah
160/90
– TC : 300
– LDL 230
– TG 300
– HDL 45
• Klasifiskasi RISK?
• Tatalaksana?
• 1 tahun kemudian pasien ini menderita stroke
• Klasifikasi RISK?
• Tatalaksana?
• 2 tahun kemudian, LDL pasien diketahui
dibawah 70. Tetapi pasien MRS dengan
Unstable angina Pektoris
• Risk?
• Tatalaksana?
• Target LDL?
• Pasien laki-laki usia 78 tahun dengan DM tipe2,
Merokok 1 bungkus sehari selama lebih dari 20
tahun, dan menderita hipertensi tekanan darah
160/90
– TC : 300
– LDL 230
– TG 300
– HDL 45
• RISK?
• Terapi?