7. lipid patofisiologi gizi

8/16/2019 7. Lipid Patofisiologi Gizi

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LIPID MANAGEMENT Why,when and how ?( Based on NCEP ; ATP III )

Dr Putu Moda Arsana !PD " #EMD

De!art$ent o% Interna& Med''ne

Braw'aya *n'+ers'ty

M a & a n


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Po-o- .ahasan

• Apa yang dimaksud dengan lipid dandislipidemia ?

• Mengapa dislipidemia harus diobati ?

• Apakah ada bukti bahwa pengobatandislipidemia bermanfaat ?

• Kapan pengobatan harus dimulai ?

• Berapa sasaran lipid yang harus dicapai ?• Bagaimana melakukan penatalaksanaan

dislipidemia yang rasional ?


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LIPID

• Mo&e-u& oran'- yan t'da- &arut da&a$a'r

• e.a'an .esar terd'r' dar' h'dro -ar.on

• D'.a' $enad' / L'!'d sederhana / asa$ &e$a- L'!'d -o$!&e-s / Ester asa$ &e$a-( a.unan antara asa$ &e$a- denana&-oho&; $onoay&&yero& atautr'ay&&yero& )


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0*NGI LIPID

• e.aa' su$.er dan adananener'

• Me$.entu- te-stur tu.uh• 0uns' !e&'ndun $e-an'-

• Bahan untu- s'ntes's hor$on

• Bahan untu- s'ntes's d'nd'n se&• Bahan untu- s'ntes's !rosta&and'n

dll


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*MBE1 LIPID

• D'et 2 $a-anan ( e-soen )

• 'ntes's o&eh tu.uh ( endoen )


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T1ANP31TAI LIPID

• 4a&ur e-soen ( $enan-ut &'!'d yan

.erasa& dar' d'et )• 4a&ur endoen ( $enan-ut &'!'d yan

.erasa& dar' s'ntes's o&eh hat' )

⇒

L'!'d d'an-ut o&eh L'!o!rote'n


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LIP3P13TEIN

• #o$!&e-s &'!'d denan !rote'n

• Terd'r' dar' /0os%o&'!'dA!o&'!o!rote'n#ho&estero& .e.as

#ho&estero& esterTr'&'ser'da


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LIP3P13TEIN

• *ntu- trans!ortas' L'!'d ( Tr'&'ser'dadan -ho&estero& )

• Bentu- .entu- L'!o!rote'n /Chy&o$'rons5ery Low Dens'ty L'!o!rote'n ( 5LDL )Inter$ed'ate Dens'ty L'!o!rote'n ( IDL )Low Dens'ty L'!o!rote'n ( LDL )6'h Dens'ty L'!o!rote'n ( 6DL )


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L'!o!rote'n C&asses and In%&a$$at'on

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.

HDLHDLLDLLDLC!lomicro"#$C!lomicro"#$%LDL$ a"&%LDL$ a"&teir cata'olicteir cata'olic

rem"a"t#rem"a"t#

> 30 nm> 30 nm 20–22 nm20–22 nm

(ote"tiall! )roi"*lammator!(ote"tiall! )roi"*lammator!

9–15 nm9–15 nm

(ote"tiall! a"ti-(ote"tiall! a"ti-

i"*lammator!i"*lammator!


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LIP3P13TEIN METAB3LIM


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Muscle Adipose

FFA

Capillaries

ChylomicronChylomicron

remnant

Muscle Adipose

FFA

Capillaries

Dietarylipids

Bileacids

+

Cholesterol

Peripheraltissues

EndogenousExogenous

LDLR

ApoB

ApoE

ApoC’s


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Reverse cholesteroltransport

Freecholesterol

Apo A

CE

!"

Chylomicrons

Peripheral cells

#mallintestine

Li$er

%ascent&DL

LCA!'LDL

Mature

&DL LDLR

LDLRLDLDL

C E ! P

C E ! P

Macrophage


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HDL

LDL

IDL

VLDL

Chylomicron

Chylomicronremnants

5 10 20 40 60 80 1000

0.95

1.006

1.02

1.06

1.10

1.20

Diameter, mm

D e n s i t y , g m

L

!he density and si(e)distri*ution o the ma,or classes o

lipoprotein


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!he Basic Components o Cholesterol #ynthesis and Excretion

Bile

!riglycerides

Plasma

#itosterolernia

ABC "-

ABC ".

'ery)lo/)densiti lipoprotein

!riglycerides

Artery

MuscleMuscle

FatFat

LDL

CholesterolCholesterolester coreester core

PhospholipidsPhospholipids

Apolipoprotein B)011Apolipoprotein B)011

LDLreceptor

Autosomal recessi$ehypercholesterolemia

Familial ligand)deecti$eapolipoprotein B)011

Familialhypercholesterolemia


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2$er$ie/ o lipoprotein meta*olism /ith special reerence to the

role o &DL)cholesterol

&DL)CLCA!

!"

CE

CE !"CE

CE!P

FFA

Adipose

tissue

Cell in

peripheral tissues

LDL)C receptor

LDL)C receptor

CE

FC

%e/synthesis

LDL)C Adipose andother tissues

FFALPL

'LDL)C

!"

FC

CE

L'ER

L'ER

!"

CE


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A!a 'tu d's&'!'de$'a ?

• Tota& ho&estero&

• LDL 7 ho&estero&

• Tr'&'ser'da• ( $a&& dense 7 LDL )

• ( Non 6DL 7 ho&estero& )

• 6DL 7 ho&estero& ↓


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Apa akibat dari dislipidemia ?


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LDLLDL

LDLLDLEndotheliumEndothelium

Vessel LumenVessel Lumen+o"oc!te+o"oc!te

+acro)a,e+acro)a,e

&e#io"&e#io"+olecle#+olecle#

Maro!haes and 0oa$ Ce&&s E8!ress Growth0ators and Prote'nases

/oam Cell/oam Cell

IntimaIntima

+o&i*ie&+o&i*ie&

LDLLDLC!toki"e#C!toki"e#

Cell (roli*eratio"Cell (roli*eratio"

+atri De,ra&atio"+atri De,ra&atio"

Grot /actor#Grot /actor#

+etallo)rotei"a#e#+etallo)rotei"a#e#

o## . N Enl ! "ed 1999;340:115-126.

+C(-1+C(-1


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Atherosclerosis: A Progressive Disease

Li!!y ". Circulation. 2001#104$%65&%'2# (oss (. N Engl J Med. 1999#%40$115&126.

Monocyte LDL)C

Adhesion

molecule

Macrophage

Foam cell

2xidi(ed

LDL)C

Pla3ue rupture

#mooth muscle

cells

CRP

Pla3ue insta*ilityand throm*us

2xidationnlammationEndothelialdysunction


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A!a-ah ada .u-t' .ahwa &'!'d

.er.ahaya dan da!at$enye.a.-an adanya !enya-'t

-ard'o+as-u&er ?


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• #a!an !eno.atan harus d'$u&a' ?

• Bera!a sasaran ho&estero& yanharus d'a!a' ?

• Baa'$ana $e&a-u-an !eno.atan

d's&'!'de$'a ?• 4en's o.at a!a yan sesua' ?

Pertanyaan 99


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Lan-ah &an-ah( NCEP ; ATP III )

• Tentu-an %a-tor res'-o yan ada

• 6'tun :; year r's- %or C6D atau r's-

e


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0a-tor res'-o

• Maor, 'nde!endent r's- %ators

• L'%e " ha.'t r's- %ators

• E$er'n r's- %ators


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Maor 1's- 0ators ( E8&us'+e o% LDLCho&estero& ) That Mod'%y LDL Goa&s

• C'arette s$o-'n• 6y!ertens'on (BP ≥:=2> $$6 or on

ant'hy!ertens'+e $ed'at'on)

• Low 6DL ho&estero& (= $2dL)@ • 0a$'&y h'story o% !re$ature C6D

– C6D 'n $a&e %'rst deree re&at'+e years– C6D 'n %e$a&e %'rst deree re&at'+e years

• Ae ($en≥

= years; wo$en≥

years)

) HD cholesterol ≥!" mg#d counts as a $negati%e& risk factor'its presence remo%es one risk factor from the total count(


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L'%e"6a.'t 1's- 0ators

• 3.es'ty (BMI≥

)• Phys'a& 'nat'+'ty

• Atheroen' d'et


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E$er'n 1's- 0ators

• L'!o!rote'n (a)

• 6o$oyste'ne• Prothro$.ot' %ators

• Pro'n%&a$$atory %ators

• I$!a'red %ast'n &uose• u.&'n'a& atheros&eros's


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6'tun : year r's- %or C6D

0ra$'nha$s a&u&ator


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0ra$'nha$ !o'nt sores

• Age

• )otal cholesterol

• HD – cholesterol

• *mokers

• *ystolik blood pressure


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Points

Total cholesterolmg/dL

Age20-39 y

Age40-49 y

Age50-59 y

Age60-69 y

Age70-79 y

< 60 0 0 0 0 0

60 ! 99 4 3 2 0

200 ! 239 7 5 3 0

240 ! 279 9 6 4 2

≥ 2"0 " 5 3

Points

Age20-39 y

Age40-49 y

Age50-59 y

Age60-69 y

Age70-79 y

#on smo$er 0 0 0 0 0

%mo$er " 5 3

!a*le Estimate o 01)year ris4 or Men5Framingham Point #cores6

Age, y Points

20 – 34 -9

35 – 39 -440 – 44 0

45 – 49 3

50 – 54 6

55 – 59 8

60 – 64 10

65 – 69 11

70 – 74 12

75 - 79 13

HDL,mg/dL

Points

≥60 -1

50 – 59 0

40 – 49 1

< 40 2

Pointtot!

10-ye""is#, $

< 0 -< 1

0 1

1 1

2 1

3 1

4 1

5 2

6 2

7 3

8 4

9 5

10 6

11 8

12 10

13 12

14 16

15 20

16 25

≥ 7 ≥ 30

%ystolic &P' mm (g )* +ntreated )* treated

< 20 0 0

20 ! 29 0 3

30 ! 39 5

40 ! 59 6

≥ 60 2 "


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Points

Total cholesterolmg/dL

Age20-39 y

Age40-49 y

Age50-59 y

Age60-69 y

Age70-79 y

< 60 0 0 0 0 0

60 ! 99 4 3 2

200 ! 239 " 6 4 2

240 ! 279 " 5 3 2

≥ 2"0 3 0 7 4 2

Points

Age20-39 y

Age40-49 y

Age50-59 y

Age60-69 y

Age70-79 y

#on smo$er 0 0 0 0 0

%mo$er 9 7 4 2

!a*le Estimate o 01)year ris4 or 7omen5Framingham Point #cores6

Age, y Points

20 – 34 -7

35 – 39 -3

40 – 44 0

45 – 49 3

50 – 54 6

55 – 59 8

60 – 64 10

65 – 69 12

70 – 74 14

75 - 79 16

HDL,

mg/dL

Points

≥60 -1

50 – 59 0

40 – 49 1

< 40 2

Pointtot!

10-ye""is#, $

< 9 -< 1

9 110 1

11 1

12 1

13 2

14 2

15 316 4

17 5

18 6

190 8

20 11

21 14

22 17

23 22

24 27

≥25 ≥30

%ystolic &P' mm (g )* +ntreated )* treated

< 20 0 0

20 ! 29 3

30 ! 39 2 4

40 ! 59 3 5

≥ 60 4 6


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#ateor' res'-o

% &HD o" "is# e'(i)!ent Di*etes me!!it(s

P+D 10 ye" "is# o" &HD ≥ 20 $

% 2 o" mo"e "is# to"s

% 0 – 1 "is# to"


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LDL Cho&estero& Goa&s and Cut!o'nts %or Thera!eut' L'%esty&e Chanes (TLC)and Dru Thera!y 'n D'%%erent 1's- Cateor'es

Risk CategoryLDL Goal(mg/dL)

LDL Level atWhich to nitiate

!herape"ticLi#estyle

Changes (!LC)(mg/dL)

LDL Level atWhich

to ConsiderDr"g !herapy

(mg/dL)

C$D or C$D Risk%&"ivalents('year risk

*+,)

-' ≥

'≥

'.

(''+0: dr"goptional)

+1 Risk 2actors

('year risk+,)

-'. ≥

'.

'year risk '

+,:≥

'.

'year risk

-',:≥

'3

' Risk 2actor -'3 ≥

'3

≥

'0

('3'40: LDLlo5ering dr"g

optional)


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P'&'h !enata&a-sanaan 2!eno.atan yan sesua'


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ATP III L'!'d andL'!o!rote'n C&ass'%'at'on

LDL Cholesterol 5mg8dL6

*100 +timal

100-129 ear otimala!o/e otimal

1%0-159 orerline high

160-189 High

≥190 Very high

&DL Cholesterol 5mg8dL6

*40 Lo

≥60 High

!otal Cholesterol 5mg8dL6

*200 Desira!le

200-2%9 orerline high

≥240 High


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Pr'$ary Pre+ent'on

Goals o# !herapy

% Long-te"m ."e)ention 10 ye"s% o"t-te"m ."e)ention ≤10 ye"s


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Pr'$ary Pre+ent'on W'thLDL"Lower'n Thera!y

Pu.&' 6ea&th A!!roah

• +educed intakes of saturatedfat and cholesterol

• ,ncreased physical acti%ity

• -eight control


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Thera!eut' L'%esty&e Chanes 'nLDL"Lower'n Thera!y

Maor 0eatures

• ). Diet– +educed intake of cholesterol/raising nutrients

0same as pre%ious *tep ,, Diet1• *aturated fats 234 of total calories• Dietary cholesterol 25"" mg per day

– D/lowering therapeutic options• 6lant stanols#sterols 05 g per day1• 7iscous 0soluble1 fiber 08"–59 g per day1

• -eight reduction• ,ncreased physical acti%ity


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Thera!eut' L'%esty&e ChanesNutr'ent Co$!os't'on o% TLC D'et

:utrient +ecommended ,ntake• *aturated fat ess than 34 of total calories• 6olyunsaturated fat ;p to 8"4 of total calories

• Monounsaturated fat ;p to 5"4 of total calories• )otal fat 59–imately 894 of total calories

• .holesterol ess than 5"" mg#day• )otal calories 0energy1 Balance energy intake and

e>penditure to maintain desirable body weight#pre%ent weight gain

A 6 d l # 7t i


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3 (einorce rection

in satrate at an

cholesterol

3 Consier aing

lant stanolssterols3 Increase i!er intae

3 Consier reerral to

a ietitian

3 Initiate 7 or

eta!olic

:ynrome

3 Intensiy eightmanagement ;

hysical acti/ity

3 Consier reerral

to a ietitian

6 s 6 s < 4&6 mo

3 =mhasi>e

rection in

satrate at ;

cholesterol

3 =ncorage

moerate hysical

acti/ity

3 Consier reerral to

a ietitian

Visit I

egin Liestyle

7heraies

Visit 2

=/alate LDL

resonse

I LDL goal not

achie/e, intensiy

LDL&Loering 7

Visit %=/alate LDL

resonse

I LDL goal not

achie/e, consier

aing rg 7

A 6odel o# 7teps in!herape"tic Li#estyle Changes

(!LC)

onitor

?herence

to 7LC

Visit


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7. lipid patofisiologi gizi

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