10/4/2012 1 Lipidmetabolism & blodfetter Jan Borén Sahlgrenska Center for Cardiovascular and Metabolic Research Wallenberg Laboratory for Cardiovascular Research University of Gothenburg, Sweden Jan Borén Tel. 0733‐764264 [email protected]
10/4/2012
1
Lipidmetabolism & blodfetter
Jan Borén
Sahlgrenska Center for Cardiovascular and Metabolic Research Wallenberg Laboratory for Cardiovascular Research
University of Gothenburg, Sweden
Jan BorénTel. 0733‐764264
10/4/2012
3
Ett lipoprotein består av en central kärna av neutrallipid(triglycerider och cholesterol-estrar).Denna kärna är omgiven av ettmonolager av amfipatisk lipid(fosfolipider och cholesterol)
I det amfipatiska Monolagret “flyter” Proteindelen det s.k. apolipoproteinet
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Exogenous Lipid Transport
ApoB
apo
E
apoC-II
Fettsyror
Kapillär
Adipocyt(fettcell)
Chylomikron
ApoB
apoC-II
LDL-receptorn
LRP
Levern
Chylomikronremnant
Chylomikronen bildas i tarmen transporteras via lymfan till blodet. Ikapillärer i framförallt fettväv bryts en stor del av triglyceriderna icylomikronerna ner (katalys: lipoproteinlipas). En remnant partikel bildassom anrikas med apoE och tas upp i levern med LRP och LDL-receptorn.
10/4/2012
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(Adapted from Verschuren et al, 1995)
35
30
25
20
15
10
5
0
Dea
th r
ate
fro
m C
HD
/100
0 m
en
2.60 3.25 3.90 4.50 5.15 5.80 6.45 7.10 7.75 8.40 9.05
Serum total cholesterol (m m ol/L)
Northern Europe
United States
Southern Europe, inland
Southern Europe, M editerranean
Japan
Serbia
Relationship of serum cholesterol to m ortality
(Seven Countries Study)
Relationship of Serum Cholesterol to Mortality
GI TractLiver
Remnant
Chylomicron
VLDL IDLLDL
Oxidation
Arterial WallMacrophage
NascentPreBHDL
Lipid poorApoA-1
-HDL
TG
CE
CETP
Bile AcidsFC + PL
HL
LPL
HLPLTP
LCAT
Lipoprotein Metabolism
LPL
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8
Slide SourceLipids Online Slide Librarywww.lipidsonline.org
HDL MetabolismNascent HDL (lipid-poor apolipoprotein A1 [Apo A1]) is produced by the liver and intestine
intestine
peripheral cells
kidney
PLTP
LCAT
ABC1
particleuptake
liver
TGRLselectiveuptake
surfaceremnantscubilin
apo A1
HDL3
HDL2
pre-HDL
CETPSR-BIHL, EL
LPL
Von Eckardstein A et al. Curr Opin Lipidol 2000;11:627–637.
HDL Formation
Liver
ApoA
Pre--HDL
Discoidal/lipid poor
Cholesterol fromLiver and intestinal Cells via ABCA1
Pre--HDL
A A
Unesterified cholesterol-rich
Lecithin-cholesterol acyltransferase (LCAT)
HDL
1. Cholesterolto liver
Steroidogeniccells
2. Cholesterolfor steroid synthesis
Cholesterolto otherlipoproteins
3. Cholesterol-estertransfer protein(CETP)
A
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CETPLCAT
Free cholesterol
hydrolysis
Reverse Cholesterol Transport: Indirect
Extrahepatic tissues
Cholesterol esters
Pre--HDL
A
HDLACholesterol to VLDL, IDL,LDL
LiverCholesterol is reusedor excreted in bile
ABCA1
Direct
Reverse Cholesterol Transport : Direct
SR-BI (scavenger receptor, class B, type 2)
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PROCAM StudyMI-Incidence according to LDL-cholesterol and triglycerides
Endogenous lipoprotein metabolism
Atherosclerosis
LDL-receptorAdipose tissue
LDLLDL
IDL
LargeVLDL
SmallVLDL
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Retention of LDL in Aortic Intima from a Rabbit 2 h after Injection with Human LDL
Nievelstein et al. (1991) Arterio and Thromb.
Freeze-etch electron photomicrograph
Cholesterol Functions Membrane
component Precurser to
Bile acids Vitamin D Steroid hormones
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Sources of Cholesterol
Diet De novo synthesisCholesterol synthesizedin extrahepatic tissues
Liver cholesterolpool
Free cholesterolIn bile
Conversion to bile salts/acidsSecretion of HDLand VLDL
De novo Synthesis of Cholesterol Primary site: liver (80%) (~1g/d)
Secondary sites: intestine (10%), skin (5%), adrenal cortex, ovaries, testes
Overall equation:
10/4/2012
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Dietary Cholesterol
• Assume 400 mg intake / day
• 200 mg is absorbed
• 1000 mg is excreted
• 800 mg from de novo synthesis
Lowering cholesterol in diet has very little effect on blood cholesterol !!!
CAD26 C
N
ER-lumen
• In cholesterol loaded cells– Unprocessed SREBP resides in Endoplasmatic Reticulum (ER)– SREBP is tightly complexed with sterol sensor SREBP-cleavage activating
protein (SCAP)– SCAP is attached via its sterol-sensing domain (SSD) to Insulin-induced
gene (INSIG) retention protein– (INSIG-1 and -2)
N
C
SCAP SREBPINSIG
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CAD27
ER-lumen
N
C
• In cholesterol depleted cells– Conformation of SCAP is altered due alteration in
conformation of SSD (sterol sensitive domaine)
C
N
SCAP SREBPINSIG
CAD28
ER-lumen
N
C
C
N
SCAP
• In cholesterol depleted cells– Conformation of SCAP is altered due alteration in
conformation of SSD (sterol sensitive domaine)
SREBPINSIG
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CAD29
ER-lumen
N
C
C
N
SCAP SREBPINSIG
• In cholesterol depleted cells– Conformation of SCAP is altered due alteration in
conformation of SSD (sterol sensitive domaine)– Which enables the dissociation of INSIG
CAD30
Golgi-lumen
N
C
C
N
SCAP SREBP
• In cholesterol depleted cells– Conformation of SCAP is altered due alteration in
conformation of SSD (sterol sensitive domaine)– Which enables the dissociation of INSIG– SREBP is escorted to the Golgi apparatus
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CAD31
SREBP
Golgi-lumen
N
C
C
N
SCAP
• SREBP is cleaved in the Golgi apparatus– In Golgi apparatus SREBP is sequentially cleaved by two
proteases
– Site-1 protease (S1P) and Site-2 protease (S2P), respectively
– S1P is cholesterol sensitive (inhibited by cholesterol and SREBP is retained in Golgi if the content of cholesterol is high)
S1P
CAD32
SREBP
Golgi-lumen
C
C
N
SCAP
S1P
N
S2P
• SREBP is cleaved in the Golgi apparatus– In Golgi apparatus SREBP is sequentially cleaved by two
proteases
– Site-1 protease (S1P) and Site-2 protease (S2P), respectively
– S1P is cholesterol sensitive - low cholesterol content --> cleavage by S1P, followed by S2P cleavage
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CAD33
SREBP
Golgi-lumen
C
C
N
SCAP
S1P
S2P
• SREBP is cleaved in the Golgi apparatus– In Golgi apparatus SREBP is sequentially cleaved by
two membrane-bound proteases Site-1 protease (S1P) and Site-2 protease (S2P), respectively
– S1P is a serine protease– S2P is a zinc metalloproteinase
CAD34
Summary of SREBP maturation
CC
ER
C
Nucleus
N
N
Golgi
C
NCHOLESTEROL
125 kB65 kB
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CAD35
3 different SREBPsOsborne TF. J Biol Chem. 2000, 275, 32379–82
• Belong to the helix-loop-helix family of transcription factors
• First identified through their ability to bind to a sterol response element (SRE) on genes of cholesterolgenesis
• SREBP-1a and SREBP-1c regulate lipid synthetic genes
• SREBP-1a and SREBP-1c are transcribed from the same gene locus and differ only at their N-termini
• SREBP-2 is encoded by a separate gene
• SREBP-1a is dominant isoform in sterol-depleted cell lines
• SREBP-1c is the major isoform in rodent and human liver and is a key regulator of fatty acid and triglyceride synthesis
• SREBP-2 controls cholesterol synthesis at the cleavage site
• SREBP-1c regulates lipogenesis mainly by SREBP-1c mRNA level
Xanthomas Raised, waxy
appearing, often yellow skin lesions (shown here on knee) Associated with
hyperlipidemia Tendon xanthomas
common on Achilles and hand extensor tendons
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Xanthomasraised lesions related to hyperlipidemia
Eruptive Xanthomas-generally associated withhypertriglyceridemia
Xanthomas of the eyelid-generally associated withhypercholesterolemia
-80000
-60000
-40000
-20000
0
20021986Björck L, et al. Eur Heart J. 2009 Jan 13
13 180färre döda
56% förklaras av riskfaktorer:
Lägre kolesterol (39%)
Färre rökare (9%)
Lägre blodtryck (7%)
Mer motion (6%)
Mer diabetes (-5%)
Mer fetma (-2%)
35% förklaras av förbättrad behandling:
Hjärtinfarkt (6%)
Sekundär prevention (9%)
Hjärtsvikt (7%)
Angina (4%)
Hypertoni (4%)
Varför har antalet döda i kranskärlssjukdom halverats i Sverige 1986-2002?
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The Mevanolate Pathway2
The biosynthesis of cholesterol and isoprenoids (a group of compounds responsible for cell fluidity and cell proliferation)
+ HSCoA
H2CC
CH3HO
CH2
CO O
C SCoA
O
H2CC
CH3HO
CH2
CO O
H2C OH
2NADP+
2NADPH
HMG-CoA
mevalonate
HMG-CoA Reductase
5-pyrophosphomevalonate
isopentenyl pyrophosphate
geranyl pyrophosphate
farnesyl pyrophosphate
squalene
2,3-oxidosqualene
HO HO
lanosterol cholesterol
19 steps
In 1976…….. ML-236A, ML-236B, ML-236C: metabolites isolated from a
fungus (Penicillium citrinum) were found to reduce serum cholesterol levels in rats.
This work was done by Akira Endo, Masao Kuroda and Yoshio Tsujita at the Fermentation Research Laboratories, Tokyo, Japan.3
Preliminary experiments showed that these fungal metabolites had no effect on mevanolate or other steps in the biosynthetic pathway.
This led to the speculation that their action was somewhere between the mevanolate and the HMG-CoA
β
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Target: HMG-CoA Reductase (HMGR)
The enzyme that catalyzes the conversion of HMG-CoA to mevanolate.
This reaction is the rate-determining step in the synthetic pathway.
+ HSCoA
H2CC
CH3HO
CH2
CO O
C SCoA
O
H2CC
CH3HO
CH2
CO O
H2C OH
2NADP+
2NADPH
HMG-CoA
mevalonate
HMG-CoA Reductase
3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
Cholesterol and Bile Acid/Salt Metabolism Major excretory form of cholesterol
Steroid ring is not degraded in humans Occurs in liver
Bile acid/salts involved in dietary lipid digestion as emulsifiers
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Recycling of Bile Acids Enterohepatic
circulation 98% recycling of
bile acids Cholestyramine
Treatment Resin binds bile
acids Prevents recycling Increased uptake of
LDL-C for bile acid synthesis
CAD44
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ApoB and LpA-I, LpA-I:A-II Kinetics with Rosuvastatin
LDLrLiver
31%
IDL
VLDLApoB36%
LDL
47%
89%
58%
55%
TG 42%Apo C-III 23%HDL-C 10%CETPa 11%
LpAI
22%LpAI:AII
19%
Ooi et al Atherosclerosis 2008; 197: 139-46 Ooi et al J Clin Endo Metab 2008; 93: 430-37
20%
24%
LpAI
22%LpAI:AII
19%
20%
24%22%22%
-80000
-60000
-40000
-20000
0
20021986Björck L, et al. Eur Heart J. 2009 Jan 13
13 180färre döda
56% förklaras av riskfaktorer:
Lägre kolesterol (39%)
Färre rökare (9%)
Lägre blodtryck (7%)
Mer motion (6%)
Mer diabetes (-5%)
Mer fetma (-2%)
35% förklaras av förbättrad behandling:
Hjärtinfarkt (6%)
Sekundär prevention (9%)
Hjärtsvikt (7%)
Angina (4%)
Hypertoni (4%)
Varför har antalet döda i kranskärlssjukdom halverats i Sverige 1986-2002?
10/4/2012
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En liten bulle gör väl ingenting?
100 g choklad = 555 kcal
200 g chips = 1094 kcal
1 daimstrut = 337 kcal
33 cl coca-cola = 137 kcal
100 gram lösgodis = 400 kcal
1 kanelbulle = 280 kcal
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Pojke 11 år, 40 kg, som springer 8 km/h förbrukar ca 270 kcal/h
100 g choklad = 2 h200 g chips = 4 h1 daimstrut = 1,5 h33 cl coca-cola = 30 min100 gram lösgodis = 1 h 45 min1 kanelbulle = 1 h lek och skutt
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Age-adjusted Prevalence of Obesity and Diagnosed Diabetes Among U.S. Adults Aged 18 Years or Older
Obesity (BMI ≥30 kg/m2)
Diabetes
1994
1994
2000
2000
No Data <14.0% 14.0%–17.9% 18.0%–21.9% 22.0%–25.9% 26.0%
No Data <4.5% 4.5%–5.9% 6.0%–7.4% 7.5%–8.9% >9.0%
CDC’s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics
2010
2010
There’s no such thing as a sudden heart attack. It requires years of
preparation.
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Secretion and Metabolism of VLDL1 and VLDL2
apoB
TG
Small, dense LDL
IDL
IDL
VLDL1
VLDL2
VLDL2
LDL
LDL
VLDL1 Triglycerides are the Major Determinant of Plasma Triglycerides
0 1 2 3 4 50
1
2
3
VLDL1 TG
VLDL2 TG
Total TG [mmol/l]
Tri
glyc
erie
s [m
mol
/l]
VLDL1 TG or VLDL2 TG in Type 2 DM patients
Hiukka A et al. Diabetologia 2005;48:1207
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What Forces Drive the Overproduction of VLDL1 Particles in
Type 2 Diabetes and Insulin Resistance?
Liver Fat and Plasma Glucose Determine VLDL1 TG Production
Variable Beta SE Significance
Liver fat 0.22 0.092 0.025Plasma glucose 0.80 0.38 0.050Insulin 0.49Adiponectin 0.86Total abdominal fat 0.86Subcutaneous fat 0.50Intra-abdominal fat 0.57
Multivariate regression
Adiels M et al. Diabetologia 2006;49:755
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Magnetic Resonance Imaging
Intraperitoneal Fat Compartments
Apo E, MTP, ApoB SP, HL, CETP genotypes, etcRyys et al Diabetes 2000; 49:749
39% liver fat
Liver Fat content
Proton Spectroscopy
Sources of Fatty Acids for Liver and VLDL TG
GlucoseInsulin
CM
PlasmaNEFA
TG
DNL
FA
β-OX
VLDLTG
apoBLIVER
TG
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Hypothesis:
Acute suppression of VLDL1
production by insulin is regulated by liver fat
Low Liver Fat: Normal Production and Regulation of VLDL1 Particles
apoB
TG
Insulin
Low Liver Fat
VLDL1
VLDL2
VLDL2
Adiels M et al. Diabetologia 2007; In Press
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High Liver Fat: Overproduction and Dysregulation of VLDL1 Particles
apoB
TG
Insulin
VLDL1
VLDL2
VLDL2
High Liver Fat
Adiels M et al. Diabetologia 2007; In Press
Metabolic Syndrome: Dysregulation of ApoB and ApoAI Lipoproteins
LDLrLiver18%
IDL
VLDL
ApoB85%
LDL
54%
37%
85%
45%HDL AI16%
48%
25%
TG 200%45%
Riches et al Int J Obesity 1998;22:414 /Chan et al Metabolism 2002;51:1041/ Watts et al Diabetes 2003;53:803
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Proposed Mechanisms for Generation of Small, Dense LDL
CETP = cholesterol ester transfer protein, HL = hepatic lipase
Secretion and Metabolism of VLDL1 and VLDL2
Residence time
Small, dense LDL
apoB
TG
Small, dense LDL
IDL
IDL
VLDL1
VLDL2
VLDL2
LDL
LDL
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LDL Size by Diabetic Status and Gender
Adapted from Gray RS et al Arterioscler Thromb Vasc Biol 1997;17-2713-2720.
The Strong Heart Study
262.8
260.8
257.5
260.5
258.6
256.3
Women Men
Normal glucose tolerance
Impaired glucose tolerance
Diabetes
263
261
259
257
255
Atherogenic Lipoprotein Profile
LargeVLDL
Small denseLDL
HDL
Metabolic SyndromeType 2 Diabetes
IncreasedCAD Risk
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Large, buoyantparticles
Small, denseparticles
Apo-B 25% more apo-B "Normal" concentrationof LDL-C can bemisleading
The number of LDLparticles is increased
The concentration ofapo-B is increased
Why is Small dense LDL Associated with Increased ApoB?
Metabolic Syndrome: Dysregulation of ApoB and ApoAI Lipoproteins
LDLrLiver18%
IDL
VLDL
ApoB85%
LDL
54%
37%
85%
45%HDL AI16%
48%
25%
TG 200%45%
Riches et al Int J Obesity 1998;22:414 /Chan et al Metabolism 2002;51:1041/ Watts et al Diabetes 2003;53:803
10/4/2012
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Therapeutic Interventions
Lifestyle– Weight loss
– Diet-Exercise
Pharmacotherapy– Statins
– Ezetimibe
– Fish oils
– PPARs (, , )– Niacin
– CETP inhibitors “Did you say I should start dieting?”
Watts, Barrett, Chan. Curr Opin Lipidol 2008; 19: 395-404 . Watts, Ooi, Chan. Pharmacol Ther 2009; 123: 231-91
ApoB and ApoAI Kinetics with Weight Loss
LDLrLiver
IDL
VLDL
ApoB
LDL
34%
24%
42%
24%
24%
27%
Riches et al J Clin Endocrinol Metab 1999; 84: 2854-61, Ng et al Diabetes Care 2007 30:2945-50, Ng et al Clin Sci 2009;118: 79-85.
Chol 12% TG 43%Insulin 34%Adiponectin 18%
HDL AIHDL AII 9%
AI 13%AII 23%
AI 13%AII 12%
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Effect of Weight Loss on Liver Fat Content and VLDL Secretion in Obese Men
Chan et al 2009
ApoB and LpA-I, LpA-I:A-II Kinetics with Rosuvastatin
LDLrLiver
31%
IDL
VLDLApoB36%
LDL
47%
89%
58%
55%
TG 42%Apo C-III 23%HDL-C 10%CETPa 11%
LpAI
22%LpAI:AII
19%
Ooi et al Atherosclerosis 2008; 197: 139-46 Ooi et al J Clin Endo Metab 2008; 93: 430-37
20%
24%
LpAI
22%LpAI:AII
19%
20%
24%22%22%
10/4/2012
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-80000
-60000
-40000
-20000
0
20021986Björck L, et al. Eur Heart J. 2009 Jan 13
13 180färre döda
56% förklaras av riskfaktorer:
Lägre kolesterol (39%)
Färre rökare (9%)
Lägre blodtryck (7%)
Mer motion (6%)
Mer diabetes (-5%)
Mer fetma (-2%)
35% förklaras av förbättrad behandling:
Hjärtinfarkt (6%)
Sekundär prevention (9%)
Hjärtsvikt (7%)
Angina (4%)
Hypertoni (4%)
Varför har antalet döda i kranskärlssjukdom halverats i Sverige 1986-2002?
ApoB and ApoAI Kinetics with Fish Oils
LDLrLiver
IDL
VLDL
ApoB
LDL
28%
HDL AIHDL AII 9%
13%
30%
49%
Chan et al Am J Clin Nutr 2003; 77: 300 / Chan et al Am J Clin Nutr 2006; 84: 37-43
TG 25%
AI 9%AII 23%
AI 9%AII 12%
10/4/2012
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Summary: Interventions – VLDL ApoBIntervention Secretion Catabolism Concentration
Wt loss
Fish Oils
Statin -
CETPi
Ezetimibe -
Niacin -
PPAR -
PPAR -
PPAR
Proportions of lipid levels at recommended targets among US adults with dyslipidemia on treatment
LDL-C Non-HDL-C HDL-C Triglyceride% % % %
Total cohort
Male
Female
Diabetes
MetS
CVD
61.0
57.4
65.4
40.4
68.5
50.4
57.7
53.5
62.9
46.5
42.6
63.5
73.3
74.3
71.9
64.1
57.9
73.9
60.6
61.6
59.7
56.0
43.8
71.6
Ghandehari H et al. Am Heart J 2008;156;112-119
10/4/2012
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The proportions at recommended level of all lipids among US adults on treatment
60
40
20
0All Men Women DM Mets CVD
Less than 20% of people with diabetes, Mets and CVDwere at recommended goal for all lipids
Ghandehari H et al. Am Heart J 2008;156;112-119
Behandling med lipidsänkande läkemedel
Bedömning av lipidvärden
Indikatorer för ökad risk
Triglycerider
>2,0 mmol/L
HDL kolesterol
<1,0 mmol/L
Triglycerider >2 mmol/L och HDL-kolesterol <1,0 mmol/L kan stärka indikationerna för behandling.
* Hos patienter med mycket hög risk kan behandlingsindikation föreligga även vid lägre värden
Önskvärd nivå
Kolesterol
<5,0 mmol/L *
LDL kolesterol
<3,0 mmol/L *
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Behandling med lipidsänkande läkemedel
Motiverade lipidanalyser
• Totalkolesterol
• HDL-kolesterol
• LDL-kolesterol
• Triglycerider
Upprepat prov efter fasta önskvärt
Lipidanalyser
Apolipoprotein B och A I kan tillföra ytterligare information för den specialintresserade
Behandling med lipidsänkande läkemedel
Befolkningsinriktad screening saknar vetenskapligt underlag!
Målgrupper för mätning av blodlipider
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Behandling med lipidsänkande läkemedel
Målgrupper för mätning av blodlipider
• Vid: manifest kranskärlssjukdom/annan aterosklerotisk kärlsjukdom
• Personer med ökad risk - diabetes mellitus, rökning, hypertoni, övervikt, kronisk njursjukdom
• Förekomst av aterosklerotisk hjärt-kärl sjukdom/ uttalad hyperkolesterolemi i familjen
Behandling med lipidsänkande läkemedel
Patienter med diabetes
• Kardiovaskulär sjukdom är den viktigaste orsaken till morbiditet och mortalitet vid diabetes.
• Diabetiker klassas därför i Riskgrupp 1
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Behandling med lipidsänkande läkemedel
Bedömning av lipidvärden
Indikatorer för ökad risk
Triglycerider
>2,0 mmol/L
HDL kolesterol
<1,0 mmol/L
Triglycerider >2 mmol/L och HDL-kolesterol <1,0 mmol/L kan stärka indikationerna för behandling.
* Hos patienter med mycket hög risk kan behandlingsindikation föreligga även vid lägre värden
Önskvärd nivå
Kolesterol
<5,0 mmol/L *
LDL kolesterol
<3,0 mmol/L *
Behandling med lipidsänkande läkemedel
Läkemedelsval
Lipidrubbning Rekommenderat
läkemedel
Alternativt
läkemedel
Kombinations-
behandling
Isolerad
hyperkolesterolemi
Statin Resin Statin + Resin
Alt. Statin +
ezetimib
Kombinerad
hyperlipidemi
Statin Fibrat Statin + Fibrat
Uttalad isolerad
hypertriglyceridemi
Fibrat Nikotinsyra
Omega-3
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Behandling med lipidsänkande läkemedel
Hälsoekonomi
Statinbehandling oavsett ålder och kön är kostnadseffektiv vid behandling efter hjärtinfarkt, koronarkärlsingrepp och angina pectoris.
Primärprevention:– acceptabel kostnadseffektivitet endast vid behandling av personer
med särskilt hög risk
– Statinbehandling vid diabetes och familjär hyperkolesterolemi synes vara kostnadseffektiv
Fall beskrivning 1
Man 42 år kommer till vårdcentral med lätt reumatiska problem (ont i leder). Mamman har RA. Oklart på pappans sida då pappan dog tidigt i ”hjärt-problem”. Vid undersökning känns knutor över leder och förtjockad akillessena.
Utredning? Vad tänka på?
10/4/2012
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Fall beskrivning 2
Kvinna kommer till läkare efter att hälsoundersökning påvisat förhöjda blodfetter:
S-kol 6.1 mmol/LS-Tg 4.2 mmol/LS-HDL 0.7 mmol/L
Vad tänka på – vad fråga – vilka råd och/eller behandling?
Fall beskrivning 3
Barn med flera utvecklingsskador skall opereras. Barnet står på Intralipid. Vid operation påvisas ”vit vätska i buk och lungor”. Misstanke på felaktig sond med Intralipid?
Vad tänka på – vad analysera?
10/4/2012
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Fall beskrivning 4
Man kommer till distriktsläkaren. Berättar att familjen har ”tidig hjärtdöd” med lågt HDL kolesterol. För att förbättra detta dricker han en halv flaska vin per dag.
Vad säger Du?
Alcohol Increases HDL-C Level
• Alcohol increases HDL-C level in a dose-dependent manner.
• Half bottle of wine per day (39 g alcohol) for 6 weeks significantly increased mean HDL-C level by 7 mg/dL in 12 healthy subjects.1
– Wine intake did not significantly affect Total-C, Total-TG, or LDL-C.1
• One beer per day (13.5 g alcohol) for 6 weeks significantly increased mean HDL-C level by 2 mg/dL in 20 healthy subjects.2
– Beer intake did not significantly affect LDL-C, VLDL-C, TG, or apolipoproteins.
1. Thornton J et al. Lancet 1983;ii:819–8222. McConnell MV et al. Am J Cardiol 1997;80:1226–1228