17 - Lipid

OO

Pickup J, Williams G. Lipid Disorders in diabetes mellitus. Text Book of Diabetes. 1997:p. 55.1-31Pickup J, Williams G. Lipid Disorders in diabetes mellitus. Text Book of Diabetes. 1997:p. 55.1-31

HOHO

HH

CHCH33 CHCH33

CC

CHCH33

CHCH22CHCH22 CHCH22 CC

CHCH33

CHCH33

HH

KolesterolKolesterol

HH33CC (CH(CH22))77 CCHH

CC (CH(CH22))77 CC

OO

OO CHCH

CHCH22

CHCH22

OO CC (CH(CH22))1414 CHCH33

OO CC

OO

(CH(CH22))1616 CHCH33

TrigliseridTrigliserid

FosfolipidFosfolipid

C HC H22.O.CO.R.O.CO.R

R.COO.CHR.COO.CH

C HC H22OO PP OCHOCH22.CH.CH22.N.N++

CHCH33

CHCH33

CHCH33

OO

OO

LIPID PLASMALIPID PLASMA

Lipid plasma tidak larut dalam airLipid plasma tidak larut dalam airUntuk melarutkan perlu Untuk melarutkan perlu Apolipoprotein = Apolipoprotein = Apoprotein = ApoApoprotein = ApoKompleks Kompleks lipid plasma – lipid plasma – apoprotein apoprotein disebut disebut lipoproteinlipoproteinLipoproteinLipoprotein = kolesterol, = kolesterol, trigliserida, trigliserida, fosfolipid, dan apoproteinfosfolipid, dan apoprotein

LIPOPROTEINLIPOPROTEIN

++KKTGTG FF

ApoApo

==

ApApoo

ApApoo

ApApooKK

TGTG FF

LIPOPROTEINLIPOPROTEIN

Apolipoprotein + Lipid = Apolipoprotein + Lipid = Lipoprotein Lipoprotein

APAKAH LIPOPROTEIN ?APAKAH LIPOPROTEIN ?

Feher MD, Richmond W. Lipids and Lipid Disorders Second ed. Bayer. Feher MD, Richmond W. Lipids and Lipid Disorders Second ed. Bayer. 1996 1996

Feher MD, Richmond W. Lipids and Lipid Disorders Second ed. Bayer. 1996 Feher MD, Richmond W. Lipids and Lipid Disorders Second ed. Bayer. 1996

PARTIKEL KOLESTEROL HDL

Apo A-1Apo A-2

Apo C

Apo E

PhospholipidTrigliceride

Cholesterol Ester

Unesterified cholesterol

Diameter : 75-100 Ǻ

JENIS LIPOPROTEINJENIS LIPOPROTEIN

Lipoprotein class

Relative size, triglyceride and

cholesterol content

Major apoproteins

ChylomicronsChylomicrons BB4848, E, , E, CIICII

VLDLVLDL BB100100, E, , E, CIICII

IDLIDL BB100100, E, E

LDLLDL BB100100

HDHDLL

AI,AIIAI,AII

TriglycerideTriglyceride CholesterolCholesterol

THE METABOLIC PATHWAY THE METABOLIC PATHWAY OF LIPOPROTEINSOF LIPOPROTEINS

Endogenous pathwayEndogenous pathwayExogenous pathwayExogenous pathwayReverse cholesterol Reverse cholesterol transporttransport

Shepherd J. Eur Heart J Supplements 2001;3(suppl Shepherd J. Eur Heart J Supplements 2001;3(suppl

E):E2-E5E):E2-E5

ExogenousExogenous

Lipoprotein Metabolism Lipoprotein Metabolism EndogenouEndogenou

ss

HDL

LiverLiver

VLDL

MacrophageMacrophage

VLDL IDL LDL

RCTPRCTP

RCTP = reverse cholesterol transport pathway

Stool

remnants

kilomikron

Intestine

Food

Cholesterol

Cholesterol

IDL

Liver

VLDLVLDL

Macrophage

VLDL

Cholesterol

Reverse cholesterol transportReverse cholesterol transport

HDLNascent HDL

Kwiterovich PO, Jr. The metabolic pathways of high-density lipoprotein, low-Kwiterovich PO, Jr. The metabolic pathways of high-density lipoprotein, low-density lipoprotein, and triglycerides: A current review. Am J Cardiol 2000; 86: density lipoprotein, and triglycerides: A current review. Am J Cardiol 2000; 86: 5L-10L 5L-10L

LDLTriglyceride

Cholesteryl ester

LDL Receptor

Scavenger receptor-A / CD 36

ABC-1 transporter

SRB-1 receptor

THE METABOLIC PATHWAY THE METABOLIC PATHWAY OF LIPOPROTEIN OF LIPOPROTEIN

IN IN

TYPE 2 DIABETES MELLITUS TYPE 2 DIABETES MELLITUS

AND AND

METABOLIC SYNDROME METABOLIC SYNDROME

LipoproteinLipoprotein Metabolism Metabolism in Insulinin Insulin ResistanceResistance

Insulin

IR

Adipocytes

FFALiver

(CETP)(CETP)

(CETP)(CETP)

LDLsmalal denset

(lipoprotein or Hepatic lipase i)

ApoA1

Kidney

TGTG

HDLTGTG

Kwiterovich PO, Jr. The metabolic pathways of high-density lipoprotein, low-density lipoprotein, Kwiterovich PO, Jr. The metabolic pathways of high-density lipoprotein, low-density lipoprotein, and triglycerides: A current review. Am J Cardiol 2000;86:5L-10L and triglycerides: A current review. Am J Cardiol 2000;86:5L-10L

LDL

VLDLlarge

CECE

FFA : Free Fatty AcidFFA : Free Fatty AcidCE : Cholesteryl EsterCE : Cholesteryl EsterCETP : Cholesteryl Ester Transfer CETP : Cholesteryl Ester Transfer ProteinProtein

CECE

DISLIPIDEMIADISLIPIDEMIA

Dislipidemi diabetes tipe 2 / resistensi Dislipidemi diabetes tipe 2 / resistensi insulininsulin

Resistensi insulinResistensi insulin mengakibatkan FFA mengakibatkan FFA meningkat meningkat hati, menjadi sumber VLDL hati, menjadi sumber VLDL

VLDL–LDL, pertukaran TG dan kolesterol VLDL–LDL, pertukaran TG dan kolesterol LDL LDL kecil padatkecil padatApoA1 dikeluarkan oleh ginjal, sehingga HDL– ApoA1 dikeluarkan oleh ginjal, sehingga HDL– kolesterol rendahkolesterol rendah

KesimpulanKesimpulan: : TG tinggi, HDL-kol rendah, TG tinggi, HDL-kol rendah, LDL-kol padat, kecil tinggiLDL-kol padat, kecil tinggi

Management of Management of dyslipidaemiadyslipidaemia

All three lipid profilesAll three lipid profiles

-kolesterol LDL, kolesterol HDL, dan -kolesterol LDL, kolesterol HDL, dan trigliserid –trigliserid –

play a role in the formation of play a role in the formation of atherosclerosisatherosclerosis

50

40

30

20

10

150 200 250 3000(3.87) (5.17) (6.46) (7.75)

Jum

lah

kem

atia

n 1 0

-tahu

n (P

AK

) ,kem

a tia

n pe

r 10 0

0

0

Kadar serum kolesterol (mg/dl / mmol/L)Kadar serum kolesterol (mg/dl / mmol/L)

Hubungan antara kadar serum kolesterol dan risiko penyakit arteri koronerHubungan antara kadar serum kolesterol dan risiko penyakit arteri koronerDari penelitian Multiple Risk Factor Intervention Trial (MRFIT)Dari penelitian Multiple Risk Factor Intervention Trial (MRFIT)

FarnierFarnier M, Davignon J. Am J Cardiol. 1998;82:3J-10J M, Davignon J. Am J Cardiol. 1998;82:3J-10J

150

100

50

0

PA

K /

100

0

1018

1722 25

73

55

156

< 130 130 - 160 160 - 190 > 190

Insiden PAK / 1000 orang dalam 4 tahun menurut kadar Insiden PAK / 1000 orang dalam 4 tahun menurut kadar trigliserid dan LDL-kolesterol. trigliserid dan LDL-kolesterol.

LDL-kolesterol

Assman G. Am J Cardiol 1992;70:10H-Assman G. Am J Cardiol 1992;70:10H-13H13H

Trigliserid < 200 mg/dlTrigliserid < 200 mg/dl

Trigliserid Trigliserid >> 200 mg/dl 200 mg/dl

Insidens PAK Insidens PAK (per 1.000 dalam (per 1.000 dalam 6 tahun)6 tahun)

80

120

< 35 35 - 55 > 55HDL-kolesterol (mg/dl)

Hubungan HDL-kolesterol dengan insiden penyakit arteri koroner (PAK): Dari Prospective Cardiovascular Munster (PROCAM) Study. HDL-kolesterol secara meyakinkan berhubungan dengan risiko PAK ( p < 0.001).

100

60

40

20

0

PROCAM Study PROCAM Study

CLASSIFICATION OF CLASSIFICATION OF

LDL-cholesterol, Total-LDL-cholesterol, Total-cholesterol, HDL-cholesterol cholesterol, HDL-cholesterol

and Triglycerides and Triglycerides

NCEP-ATP IIINCEP-ATP III

KLASIFIKASI TOTAL, LDL, HDL-KLASIFIKASI TOTAL, LDL, HDL-KOLESTEROL, DAN TRIGLISERID MENURUT KOLESTEROL, DAN TRIGLISERID MENURUT NCEP ATP III NCEP ATP III

JAMA 2001;285:24862-497JAMA 2001;285:24862-497

LDL kolesterolLDL kolesterol< 100< 100 mg/dlmg/dl100 – 129100 – 129 mg/dlmg/dl130 – 159130 – 159 mg/dlmg/dl160 – 189160 – 189 mg/dlmg/dl>> 190 190 mg/dlmg/dl

Total kolesterolTotal kolesterol< 200< 200 mg/dlmg/dl200 – 239200 – 239 mg/dlmg/dl>> 240 240 mg/dlmg/dl

HDL kolesterolHDL kolesterol< 40< 40 mg/dlmg/dl>> 60 60 mg/dlmg/dl

OptimalOptimalMendekati optimalMendekati optimalSedikit tinggi (Borderline) Sedikit tinggi (Borderline) TinggiTinggiSangat tinggiSangat tinggi

DiinginkanDiinginkanSedikit tinggi (Borderline) Sedikit tinggi (Borderline) TinggiTinggi

RendahRendahTinggiTinggi

TRIGLISERIDA (NCEP-ATP III)TRIGLISERIDA (NCEP-ATP III)

OptimalOptimal < 150 mg/dl< 150 mg/dl

Sedikit tinggi(borderline) Sedikit tinggi(borderline) 150 - 199 mg/dl150 - 199 mg/dl

Tinggi Tinggi 200 - 499 mg/dl200 - 499 mg/dl

Sangat tinggi Sangat tinggi > 500 mg/dl > 500 mg/dl

Risk assessment: first step Risk assessment: first step in the management of in the management of

dyslipidaemiadyslipidaemia

Langkah pertama menentukan risikoLangkah pertama menentukan risiko PKV PKV seseorang adalah dengan menghitung seseorang adalah dengan menghitung berapa faktor risiko yang dimiliki berapa faktor risiko yang dimiliki penderita tersebut (risk assessment) penderita tersebut (risk assessment)

Faktor risiko dikelompokkan atas tiga Faktor risiko dikelompokkan atas tiga kelompokkelompok

risiko rendah, risiko sedang, dan risiko risiko rendah, risiko sedang, dan risiko

tinggi tinggi

Major Risk Factors (Exclusive of LDL-Major Risk Factors (Exclusive of LDL-cholesterol) That Modify LDL Goalscholesterol) That Modify LDL Goals

• Cigarette smokingCigarette smoking• Hypertension Hypertension (blood pressure > 140/90 (blood pressure > 140/90 mmHg, mmHg, or on antihypertension)or on antihypertension)

• Low HDL cholesterolLow HDL cholesterol (< 40 mg/dl)* (< 40 mg/dl)*• Family history of premature (CHD in male first-degree Family history of premature (CHD in male first-degree relative < relative < 55 years; CHD in female 55 years; CHD in female first-first- degree relative < 65 degree relative < 65 yearsyears

• AgeAge male > 45 years, female > 55 male > 45 years, female > 55 yearsyears

JAMA 2001;285:24862-497JAMA 2001;285:24862-497

•HDL cholesterol HDL cholesterol >> 60 mg/dl counts as a negative risk 60 mg/dl counts as a negative risk factor, factor, its presence removes 1 risk factor from the total countits presence removes 1 risk factor from the total count

Three categories of risk that modifyThree categories of risk that modify

LDL cholesterol goalsLDL cholesterol goals

JAMA 2001;285:24862-497JAMA 2001;285:24862-497

Risk groupRisk group LDL-C goals (mg/dl)LDL-C goals (mg/dl)

Subjects with CHD or equivalent Subjects with CHD or equivalent (high risk)(high risk)

Faktor risiko multipel ( Faktor risiko multipel ( >> 2) 2) (moderate risik)(moderate risik)

0 - 1 Risk Factor0 - 1 Risk Factor

(low risik)(low risik)

< 100< 100

< 130< 130

< 160< 160

Mortality from coronary heart Mortality from coronary heart disease in subjects with type 2 disease in subjects with type 2

diabetes and in non-diabetic subjects diabetes and in non-diabetic subjects with and without prior myocardial with and without prior myocardial

infarction infarction Haffner SM, et al. Haffner SM, et al.

N Engl J Med N Engl J Med 19981998; 339: 229–234; 339: 229–234

3,5%3,5%

18,8%18,8% 20,2%20,2%

45,0%45,0%

00

55

1010

1515

2020

2525

3030

3535

4040

4545

5050

No DM, No MINo DM, No MI No DM, MINo DM, MI DM, No MIDM, No MI DM, MIDM, MI

7-y

ear

incid

en

ce o

f 7-y

ear

incid

en

ce o

f M

IM

I7-y

ear

incid

en

ce o

f 7-y

ear

incid

en

ce o

f M

IM

I

Type 2 diabetes mellitus (DM) and coronary artery disease (CAD). The 7 year Type 2 diabetes mellitus (DM) and coronary artery disease (CAD). The 7 year incidence of fatal or nonfatal myocardial infraction (MI) is essentially the incidence of fatal or nonfatal myocardial infraction (MI) is essentially the same in patients who have diabetes without a history of CAD and in patients same in patients who have diabetes without a history of CAD and in patients with CAD who are not diabetic. P < 0,001 for the difference between with CAD who are not diabetic. P < 0,001 for the difference between patients with and without MI in both group.patients with and without MI in both group.

Type 2 diabetes mellitus (DM) and coronary artery disease (CAD). The 7 year Type 2 diabetes mellitus (DM) and coronary artery disease (CAD). The 7 year incidence of fatal or nonfatal myocardial infraction (MI) is essentially the incidence of fatal or nonfatal myocardial infraction (MI) is essentially the same in patients who have diabetes without a history of CAD and in patients same in patients who have diabetes without a history of CAD and in patients with CAD who are not diabetic. P < 0,001 for the difference between with CAD who are not diabetic. P < 0,001 for the difference between patients with and without MI in both group.patients with and without MI in both group.

Non Non diabeticdiabetic

Non Non diabeticdiabetic

DiabetiDiabeticc

DiabetiDiabeticc

Haffner SM, et al. N Engl J Med Haffner SM, et al. N Engl J Med 19981998;339:229-34;339:229-34Haffner SM, et al. N Engl J Med Haffner SM, et al. N Engl J Med 19981998;339:229-34;339:229-34

PENGERTIAN YANG DISAMAKANPENGERTIAN YANG DISAMAKAN

JAMA 2001;285:24862-497JAMA 2001;285:24862-497

• Penyakit aterosklerotik lain seperti penyakit Penyakit aterosklerotik lain seperti penyakit arteri perifer, aneurisma aorta abdominalis,arteri perifer, aneurisma aorta abdominalis, dan penyakit arteri karotis simptomatik dan penyakit arteri karotis simptomatik • Diabetes melitus terutama tipe 2Diabetes melitus terutama tipe 2• Mereka dengan faktor risiko multipel yang Mereka dengan faktor risiko multipel yang dalam waktu 10 tahun mempunyai risiko PAK dalam waktu 10 tahun mempunyai risiko PAK > 20 %> 20 % Secara praktis : diabetes melitus, strok, Secara praktis : diabetes melitus, strok, penyakit arteri periferpenyakit arteri perifer

ADULT TREATMENT PANEL ADULT TREATMENT PANEL REPORTSREPORTS

ATP III update 2004ATP III update 2004Since the publication of ATP III, 5 major clinical trials Since the publication of ATP III, 5 major clinical trials with statin therapy and clinical endpoints have been with statin therapy and clinical endpoints have been published published

Heart Protection Study Heart Protection Study (HPS)(HPS) Prospective Study of Pravastain in the Elderly at Risk Prospective Study of Pravastain in the Elderly at Risk (PROSPER)(PROSPER) Antihypertensive and Lipid-Lowering Treatment to Prevent Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial – Lipid-Lowering Trial Heart Attack Trial – Lipid-Lowering Trial (ALLHAT LLT)(ALLHAT LLT) Anglo-Scandinavian Cardiac Outcomes Trial – Lipid-Lowering Anglo-Scandinavian Cardiac Outcomes Trial – Lipid-Lowering ArmArm (ASCOT-LLA) (ASCOT-LLA) Pravastatin or Atorvastatin Evaluation and Infection – Throm-Pravastatin or Atorvastatin Evaluation and Infection – Throm- bolysis in Myocardial Infraction 22 bolysis in Myocardial Infraction 22 (PROVE IT-TIMI 22)(PROVE IT-TIMI 22) Primary Prevention of Cardiovascular Disease With Atorvas-Primary Prevention of Cardiovascular Disease With Atorvas- tatin in Type 2 Diabetes in thetatin in Type 2 Diabetes in the Collaborative Atorvastatin Collaborative Atorvastatin Diabetes StudyDiabetes Study ((CADRS)CADRS)

PREVENTION OF CORONARY HEART PREVENTION OF CORONARY HEART DISEASE IN TYPE 2 DIABETES DISEASE IN TYPE 2 DIABETES

MELLITUSMELLITUS

Heart Protection Study with SimvastatinHeart Protection Study with Simvastatin 40 mg40 mg

RESULTS RESULTS Lowering LDL-cholesterol Lowering LDL-cholesterol from < 116 mg/dl to < 77 from < 116 mg/dl to < 77

mg/dlmg/dl

The lower the better ?The lower the better ?

Baseline LDL-Baseline LDL-C (mg/dl)C (mg/dl)

Statin Statin (n (n

=10,269)=10,269)

Placebo Placebo (n =10,267)(n =10,267)

< 100< 100

100 – 129100 – 129

>> 130 130

All All patientspatients

282 (16.4%)282 (16.4%)

668 (18.9%)668 (18.9%)

1,083 1,083 (21.6%)(21.6%)

2,033 2,033 (19.8%)(19.8%)

358 (21.0%)358 (21.0%)

871 (24.7%)871 (24.7%)

1,356 (26.9%)1,356 (26.9%)

2,585 (25.2%)2,585 (25.2%)

Event Rate Event Rate RatioRatio

Statin Statin BetterBetter

0.40.4 0.60.6 0.80.8 1.01.0 1.21.2 1.41.4

Statin Statin WorseWorse

0.76 (0.72 – 0.81) 0.76 (0.72 – 0.81) p<0.0001p<0.0001

Major vascular events by baseline low-density lipoprotein cholesterol (LDL-Major vascular events by baseline low-density lipoprotein cholesterol (LDL-C) level in the Heart Protection Study (HPS). Numbers in parentheses C) level in the Heart Protection Study (HPS). Numbers in parentheses represent event rates for the subset of 3,421 patients with entry LDL-C represent event rates for the subset of 3,421 patients with entry LDL-C levels < 100 mg/dl (2.6 mmol/l). See Figure 1 for an explanation of event levels < 100 mg/dl (2.6 mmol/l). See Figure 1 for an explanation of event rate ratio figures. CI = confidence interval. rate ratio figures. CI = confidence interval.

Ballantyne CM. Am J Cardiol 2003;92 (suppl):3K-9KBallantyne CM. Am J Cardiol 2003;92 (suppl):3K-9K

HEART PROTECTION STUDY WITH HEART PROTECTION STUDY WITH SIMVASTATIN (HPS)SIMVASTATIN (HPS)

PREVENTION OF CORONARY HEART PREVENTION OF CORONARY HEART DISEASE IN TYPE 2 DIABETES DISEASE IN TYPE 2 DIABETES

MELLITUSMELLITUS Heart Protection Study with Heart Protection Study with

SimvastatinSimvastatinConclusionsConclusions

The present study provides direct evidence The present study provides direct evidence that cholesterol-lowering therapy is beneficial that cholesterol-lowering therapy is beneficial for people with diabetes even if they do not for people with diabetes even if they do not already have manifest coronary disease or already have manifest coronary disease or high cholesterol concentrationshigh cholesterol concentrations

Statin therapy Statin therapy should now be considered should now be considered routinely for all diabetic patientsroutinely for all diabetic patients at sufficiently at sufficiently high risk of major vascular events, irrespective high risk of major vascular events, irrespective of their initial cholesterol concentrationsof their initial cholesterol concentrations

C-REACTIVE PROTEIN LEVELS AND C-REACTIVE PROTEIN LEVELS AND OUTCOMES AFTER STATIN OUTCOMES AFTER STATIN THERAPYTHERAPY

Ridker PM, Cannon CP, Morrow D, Rifai N, Lynda M, Rose MS, Ridker PM, Cannon CP, Morrow D, Rifai N, Lynda M, Rose MS, Carolyn H, McCabe BS, Preffer MA, Braunwald E. Carolyn H, McCabe BS, Preffer MA, Braunwald E.

N Engl J Med 2005; 352: 20 – 28N Engl J Med 2005; 352: 20 – 28

PROVE - ITPROVE - IT

From the PROVE – IT studyFrom the PROVE – IT studyDivided into two groups:Divided into two groups: LDL – cholesterolLDL – cholesterol >> 70 mg/dl 70 mg/dl

< 70 mg/dl< 70 mg/dl hsCRPhsCRP >> 2 mg/L 2 mg/L

< 2 mg/L< 2 mg/L

Is thereIs there a difference in recurrent a difference in recurrent myocardial infarction andmyocardial infarction and death from death from

coronary causes between these groups?coronary causes between these groups?

Subjects and methodsSubjects and methods

RATIONAL FOR OPTIMAL VERY RATIONAL FOR OPTIMAL VERY LOW LDL-CHOLESTEROL GOAL (< LOW LDL-CHOLESTEROL GOAL (<

70mg/dl)70mg/dl)

Lesson from HPSLesson from HPSLesson from PROVE IT studyLesson from PROVE IT study

A question raised from these studies: A question raised from these studies: is LDL-C < 100 mg/dl sufficient low in is LDL-C < 100 mg/dl sufficient low in

high-risk patients who already have low high-risk patients who already have low LDL-C LDL-C

at base line?at base line?

Circulation. July, 2004;110:227-239Circulation. July, 2004;110:227-239

WHAT ARE NEW?WHAT ARE NEW?

THE VERY HIGH RISK PATIENTSTHE VERY HIGH RISK PATIENTS

Established CVD plus:Established CVD plus:

1.1.Multiple major risk factors (Multiple major risk factors (especiallyespecially diabetesdiabetes))

2.2.Severe and poorly controlled risk factors Severe and poorly controlled risk factors (especially continued (especially continued cigarette smokingcigarette smoking))

3.3.Multiple risk factors of the Multiple risk factors of the metabolic metabolic syndromesyndrome (especially high triglycerides (especially high triglycerides >> 200 200 mg/dl plus non-HDL-C mg/dl plus non-HDL-C >> 130 mg/dl with low 130 mg/dl with low HDL-C < 40 mg/dlHDL-C < 40 mg/dl

4.4.On the basis of PROVE IT, patients with On the basis of PROVE IT, patients with acute acute coronary syndromescoronary syndromesGrundy SM et al. Circulation. July, 2004; 110: Grundy SM et al. Circulation. July, 2004; 110:

227-239227-239

PENATALAKSANAAPENATALAKSANAANN

Perubahan gaya hidupPerubahan gaya hidup (therapeutic lifestyle changes )(therapeutic lifestyle changes ) Perencanaan makan (diet)Perencanaan makan (diet) Olahraga Olahraga Berhenti merokokBerhenti merokok Batasi alkoholBatasi alkohol

Obat penurun lipidObat penurun lipid

OLAHRAGA OLAHRAGA TERATURTERATUR

OBAT PENURUN OBAT PENURUN LIPIDLIPID

* bezafibrat, cipofibrat dan fenofibrat menurunkan LDL-kolesterol * bezafibrat, cipofibrat dan fenofibrat menurunkan LDL-kolesterol lebih banyak daripada gemfibrozil lebih banyak daripada gemfibrozil

Persentasi penurunan LDL-kolesterol dan Persentasi penurunan LDL-kolesterol dan trigliserid, serta kenaikan HDL-kolesteroltrigliserid, serta kenaikan HDL-kolesterol

ObatObat LDL-KLDL-K HDL-KHDL-K TGTG

StatinStatin

ResinResin

Fibrate*Fibrate*

Nicotinic acidNicotinic acid

EzetimibeEzetimibe

18 - 55%18 - 55%

15 - 30%15 - 30%

5 - 25%*5 - 25%*

5 - 25%5 - 25%

10 - 15%10 - 15%

5 - 15%5 - 15%

3 - 5%3 - 5%

10 - 20%*10 - 20%*

15 - 35%15 - 35%

--

7 - 30%7 - 30%

- / - /

20 - 50%*20 - 50%*

20 - 50%20 - 50%

--

SASARAN LDL - KOLESTEROL SASARAN LDL - KOLESTEROL PENGOBATAN PERUBAHAN GAYA HIDUP PENGOBATAN PERUBAHAN GAYA HIDUP (DIET, OLAHRAGA), DAN PENGOBATAN (DIET, OLAHRAGA), DAN PENGOBATAN

STATINSTATIN

JAMA 2001;285:2487-2497

Kelas Kelas risikorisiko

Sasaran Sasaran LDL LDL

(mg/dl)(mg/dl)

Kadar LDL Kadar LDL dimana dimulai dimana dimulai diet - olahraga diet - olahraga

(mg/dl)(mg/dl)

Kadar LDLdimana Kadar LDLdimana dimulai obat dimulai obat

(mg/dl)(mg/dl)

PAK atau PAK atau yangyangdisamakandisamakan

>> 2 faktor 2 faktor risikorisiko

0 - 1 faktor 0 - 1 faktor risikorisiko

< < 100100

< < 130130

< < 160160

>> 100 100

>> 130 130

>> 160 160

>> 130 130

(100-129 dapat (100-129 dapat dipertimbangkdipertimbangkan obat)an obat)

>> 160 160

>> 190 190

Pria umur 50 tahun, ke dokter untuk pemeriksaan kesehatan. Ia tidak merokok, melakukan olah raga teratur. Kedua orang tua masih hidup.

Pada pemeriksaan ditemukan sbb: TB 150 cm, BB 76 kg, TD 185/95 mmHg. Pemeriksaan fisik lain baik

Ia membawa hasil laboratorium sbb: pemeriksaan rutin baik, GDP 124 mg/dl, total -kol 198 mg/dl, LDL- kol 138 mgdl, HDL 50 mg/dl, TG 156 mg/dl.

Diagnosa? Berapa sasaran LDL-kol?

CONTOH KASUS (1)CONTOH KASUS (1)

Wanita umur 56 tahun, ke dokter untuk Wanita umur 56 tahun, ke dokter untuk pemeriksaan kesehatan. Ia tidak merokok, pemeriksaan kesehatan. Ia tidak merokok, melakukan olah raga teratur. Kedua orang tua melakukan olah raga teratur. Kedua orang tua masih hidup.masih hidup.

Pada pemeriksaan ditemukan sbb: TB 150 cm, BB Pada pemeriksaan ditemukan sbb: TB 150 cm, BB 65 kg, TD 150/90 mmHg. Pemeriksaan fisik lain 65 kg, TD 150/90 mmHg. Pemeriksaan fisik lain baikbaik

Ia membawa hasil laboratorium sbb: pemeriksaan Ia membawa hasil laboratorium sbb: pemeriksaan reduksi positif, GDP 256 mg/dl, A1C 9,0%, total -reduksi positif, GDP 256 mg/dl, A1C 9,0%, total -kol 180 mg/dl, LDL- kol 110 mg/dl, HDL 50 kol 180 mg/dl, LDL- kol 110 mg/dl, HDL 50 mg/dl, TG 156 mg/dl.mg/dl, TG 156 mg/dl.

Diagnosa? Berapa sasaran LDL-kol?Diagnosa? Berapa sasaran LDL-kol?

CONTOH KASUS (2)CONTOH KASUS (2)