3. Terminology
Hyperlipidemia
Concentration of lipid in
the blood exceeds the
upper range of normal in a
12 hr fasting blood sample
Includes both
hypercholesterolemia and
hypertriglyceridemia
Dyslipidemia
Dyslipidemia –
derangement in blood
lipid concentration or
composition
Almost always due to
hyperlipidemia
Dyslipidemia – major role
in atherosclerosis and CAD
5. The lipoprotein fractions
Chylomicrons
Very Low density
lipoproteins (VLDL)
Intermediate density
Lipoproteins (IDL)
Low density
Lipoproteins (LDL)
High density
Lipoproteins (HDL)
7. Lipoproteins – physiological functions
absorption of
- dietary cholesterol
- long-chain fatty acids
- fat-soluble vitamins
transport of
- triglycerides
- cholesterol
- fat-soluble vitamins
- from the liver to peripheral tissues
transport of cholesterol
- from peripheral tissues to the liver
8. Apolipoproteins - functions
proteins associated with lipoproteins.
lipoprotein assembly and function.
activate enzymes in lipoprotein metabolism.
ligands for cell surface receptors.
9. The story of lipids – the normal
physiology
Chylomicrons transport fats from the intestinal
mucosa to the liver
In the liver, the chylomicrons release triglycerides
and some cholesterol and become low-density
lipoproteins (LDL).
LDL then carries fat and cholesterol to the body’s
cells.
High-density lipoproteins (HDL) carry fat and
cholesterol back to the liver for excretion.
10. Why study of lipoproteins and
apolipoproteins are important?
Atherosclerosis and dyslipoproteinemias have a very
close association
All the cardiovascular risk models advocate lipoprotein
studies in risk stratification and prognostication
Recently, non – HDL fraction, apo B , ratio of apo B to
apo A 1, number and size of small, dense LDL particles
are all emerging as risk markers for CAD.
Subendothelial retention of LDL -initiating factor for
atherosclerotic plaque formation
11. Source: Yusuf S et al. Lancet. 2004;364:937-952
36
12
7
10
20
33
0
20
40
60
80
100
Smoking Fruits/
Veg
Exercise Alcohol Psycho-
social
Lipids All 9 risk
factors
PAR
(%)
14
18
90
Diabetes Abdominal
obesity
Hyper-
tension
Lifestyle factors
50
INTERHEART Study
n=15,152 patients and 14,820 controls in 52 countries
MI=Myocardial infarction, PAR=Population
attributable risk (adjusted for all risk factors)
Attributable Risk Factors
for a First Myocardial Infarction
12. Classification - hyperlipidemia
Primary
Secondary
defect in genes and /or enzymes involved in
lipoprotein metabolism
1st case report of Familial hypercholesterolemia
In 1938 Carl Mu¨ller, a Norwegian clinician, described FH
as an “inborn error of metabolism” that produces high
blood cholesterol and myocardial infarctions (heart
attacks) in young people
14. Alternative classification
I . Primary
Primary Disorders of Elevated ApoB -Containing
Lipoproteins
Inherited Causes of Low Levels of ApoB -Containing
Lipoproteins
Genetic Disorders of HDL Metabolism
Miscellaneous-
Elevated Plasma Levels of Lipoprotein(a)
Elevated small dense LDL particles
II . Secondary forms of hyperlipidemia
15. Primary Disorders of Elevated
Apo B -Containing Lipoproteins
Lipid disorders
associated with elevated
LDL and normal
triglycerides
Lipid disorders
associated with elevated
triglycerides
16. Lipid disorders associated with elevated LDL
and normal triglycerides
1. Familial Hypercholesterolemia (FH)
2. Familial Defective ApoB-100 (FDB)
3. Autosomal Dominant Hypercholesterolemia Due to
Mutations in Pcsk9 (ADH-Pcsk9 or ADH3)
4. Autosomal Recessive Hypercholesterolemia (ARH)
5. Sitosterolemia
6. Polygenic Hypercholesterolemia
18. Familial hypercholesterolemia
tendon xanthomas –hands, wrists, elbows, knees, heels
or buttocks
Total cholesterol levels > 500 mg/Dl
Accelerated atherosclerosis – begins in aortic root and
extends into coronary ostia
Receptor negative-untreated patients don’t survive
beyond 2nd decade
Receptor defective- better prognosis
19. Familial Defective Apob-100 (FDB)
Dominantly inherited disorder
Elevated plasma LDL levels with normal triglycerides, tendon
xanthomas, increased incidence of premature ASCVD
mutations in the LDL receptor–binding domain of apoB-100
LDL binds the receptor with reduced affinity -> removed from
the circulation at a reduced rate
Clinically identical to heterozygous FH but have lower plasma
levels of LDL
20. Autosomal Dominant
Hypercholesterolemia - physiology
AD disorder ; gain-of-function mutations in PCSK9
PCSK9 is a secreted protein that binds to the LDL receptor
causing its degradation
LDL is internalized along with the receptor after binding
In the low pH of the endosome LDL dissociates from the
receptor and the receptor returns to the cell surface
The LDL is delivered to the lysosome
21. Autosomal Dominant
Hypercholesterolemia- pathology
When PCSK9 binds to the receptor, the complex is internalized
and the receptor is redirected to the lysosome rather than to the
cell surface
The missense mutations enhance the activity of PCSK9
The number of hepatic LDL receptors is reduced
indistinguishable clinically from patients with FH
22. Autosomal Recessive
Hypercholesterolemia (ARH)
LDL Receptor Adaptor Protein (LDLRAP) is involved in LDL
receptor–mediated endocytosis in the liver.
In the absence of LDLRAP, lipoprotein-receptor complex fails to
be internalized
Hypercholesterolemia, tendon xanthomas, premature CAD
Hyperlipidemia responds partially to treatment with HMG-CoA
reductase inhibitors
Usually require LDL apheresis to lower plasma LDL-C
23. Sitosterolemia
Autosomal recessive disease
severe hypercholesterolemia, tendon xanthomas, premature
ASCVD (Atherosclerotic CardioVascular Disease)
mutations in either of two members of the ATP-binding cassette
(ABC) half transporter family, ABCG5 and ABCG8
genes are expressed in enterocytes and hepatocytes
24. Sitosterolemia
intestinal absorption of
sterols is increased and
biliary excretion of the sterols
is reduced
increased plasma and tissue
levels of both plant sterols
and cholesterol
Dysmorphic red blood cells
and megathrombocytes
hemolysis - distinctive
clinical feature of this disease
respond to reductions in
dietary cholesterol content
do not respond to statins.
Bile acid sequestrants and
cholesterol absorption
inhibitors - effective
25. Polygenic Hypercholesterolemia
Elevated LDL with a normal plasma level of triglyceride in the
absence of secondary causes of hypercholesterolemia
Plasma LDL levels are generally not as elevated as they are in
other primary hypercholesterolemias
Family studies to differentiate polygenic hypercholesterolemia
from single-gene disorders
26. Lipid Disorders Associated with
Elevated Triglycerides
1. Familial Chylomicronemia Syndrome (Type I
Hyperlipoproteinemia; Lipoprotein Lipase and
ApoC-II Deficiency)
2. Familial Dysbetalipoproteinemia (Type III
Hyperlipoproteinemia)
3. Apo A-V Deficiency
4. GPIHBP1 Deficiency
5. Hepatic Lipase Deficiency
6. Familial Hypertriglyceridemia (FHTG)
7. Familial Combined Hyperlipidemia (FCHL)
27. Familial Chylomicronemia
Syndrome
LPL (Lipoprotein Lipase) is required for the hydrolysis of
triglycerides in chylomicrons and VLDLs
apoC-II is a cofactor for LPL
Genetic deficiency or inactivity of LPL or apo C II results in
impaired lipolysis and elevations in plasma chylomicrons
The fasting plasma is turbid
Very high triglyceride levels
28. Familial Chylomicronemia
Syndrome
Present in childhood with features suggestive of acute pancreatitis
Lipemia retinalis
Eruptive xanthomas
Hepatosplenomegaly
Premature CHD not a feature
29. Familial Chylomicronemia
Syndrome- diagnosis
IV heparin injection - endothelial-bound LPL is released
LPL activity is profoundly reduced in both LPL and apo C-II
deficiency
normalizes after the addition of normal plasma (providing a
source of apoC-II)
30. Familial Chylomicronemia
Syndrome
dietary fat restriction with fat-soluble vitamin supplementation
medium-chain triglycerides
Fish oils
Fresh frozen plasma – source of apo C
Plasmapheresis in pregnancy
31. HYPERTRIGLYCERIDEMIA
- OTHER CAUSES
APO A V DEFICIENCY
Apo A-V required for the
association of VLDL and
chylomicrons with LPL
Deficiency presents as
hyperchylomicronemia
GPIHBP1 Deficiency
LPL is attached to a protein
on the endothelial surface of
capillaries called GPIHBP1
mutations that interfere with
GPIHBP1 synthesis or folding
cause severe
hypertriglyceridemia
32. Hepatic Lipase Deficiency
autosomal recessive disorder
elevated plasma levels of cholesterol and triglycerides (mixed
hyperlipidemia) due to the accumulation of circulating lipoprotein
remnants
association of this genetic defect with ASCVD is not clearly known
Lipid-lowering therapy with statins along with other drugs
33. Familial Dysbetalipoproteinemia –
FDBL (Type III
Hyperlipoproteinemia)
mixed hyperlipidemia; due to genetic variations in apoE
Patients homozygous for the E2 allele (the E2/E2 genotype)
comprise the most common subset of patients with FDBL
precipitating factors usually present
hyperlipidemia, xanthomas, premature coronary disease,
peripheral vascular disease
34. Familial Dysbetalipoproteinemia
(Type III Hyperlipoproteinemia)
The disease seldom presents in women before menopause
Two distinctive types of xanthomas- tuberoeruptive and palmar
Broad beta band on electrophoresis
Premature CHD
Dramatic response to weight reduction and dietary changes; statins
Treatment of other metabolic conditions
35. Familial Hypertriglyceridemia
(FHTG)
The diagnosis of FHTG is suggested by the triad of
Elevated levels of plasma triglycerides (250–1000 mg/dL)
Normal or only mildly increased cholesterol levels (<250 mg/dL)
Reduced plasma levels of HDL-C
Plasma LDL-C levels are generally not increased and are often
reduced due to defective metabolism of the triglyceride-rich
particles
36. Familial Hypertriglyceridemia
(FHTG)
type IV and type V of
Fredrickson classification
autosomal dominant disorder of
unknown etiology
VLDL is elevated
Precipitating factors
not associated with increased risk
of ASCVD
secondary causes of
hypertriglyceridemia to be
ruled out
Monitor pancreatitis
37. Familial Combined Hyperlipidemia
(FCHL)
autosomal dominant
one of three phenotypes
Elevated plasma levels of
LDL-C
Elevated plasma levels of
triglycerides due to elevation
in VLDL
Elevated plasma levels of
both LDL-C and triglyceride
classical feature of FCHL -
lipoprotein profile can switch
among these three
phenotypes in the same
individual over time
Associated with other
metabolic risk factors
Family history of
hyperlipidemia and/or
premature CHD
38. Familial Combined Hyperlipidemia
(FCHL)
significantly elevated plasma levels of apoB
(Hyperapobetalipoproteinemia)
Increased small, dense LDL particles are characteristic of this
syndrome
Overproduction of VLDL by liver – cause not known
39. Inherited Causes of Low Levels of
Apo B Containing Lipoproteins
Familial Hypobetalipoproteinemia (FHB)
MOST COMMON INHERITED FORM OF
HYPOCHOLESTEROLEMIA
low total cholesterol and LDL-C due to mutations in
apoB
LDL levels < 80 mg%
Protection from CHD
Parents have abnormal lipid fractions
40. Pcsk9 Deficiency
Loss of function mutations
PCSK9 normally promotes the degradation of the LDL
receptor
Absence cause increased activity of LDL receptor and
low LDL levels ( 40% reduction)
Protection from CHD increases as plasma LDL levels
decrease
41. Abetalipoproteinemia
autosomal recessive
disease
loss-of-function
mutations in the gene
encoding microsomal
triglyceride transfer
protein (MTP)
transfers lipids to nascent
chylomicrons and VLDLs
in the intestine and liver
Parents have normal lipid
levels
diarrhea and failure to
thrive
Neurologic
manifestations
Pigmented
retinopathydefective
absorption and transport
of fat soluble vitamins –
vitamin E
low-fat, high-caloric,
vitamin-enriched diet
42. Genetic Disorders of HDL Metabolism
Inherited causes of low levels of HDL-C
1. Gene Deletions in the Apo A V-AI-CIII-AIV Locus
and Coding Mutations in ApoA-I
2. Tangier Disease (ABCA1 Deficiency)
3. LCAT Deficiency
4. Primary Hypoalphalipoproteinemia
Inherited causes of high levels of HDL-C
1. CETP Deficiency
2. Familial Hyperalphalipoproteinemia
43. Gene Deletions in the ApoAV-AI-CIII-AIV
Locus and Coding Mutations in ApoA-I
Absence of mature HDL
Free cholesterol increase in HDL and in tissues
corneal opacities and planar xanthomas
Premature CHD
44. Tangier Disease (ABCA1
Deficiency)
autosomal recessive
ABCA1, a cellular transporter that facilitates efflux of
unesterified cholesterol and phospholipids from cells
to apoA-I
extremely low circulating plasma levels of HDL-C (<5
mg/dL) and apoA-I (<5 mg/dL).
hepatosplenomegaly , pathognomonic enlarged
grayish yellow or orange tonsils, mononeuritis
multiplex
Premature CHD not so common – because LDL levels
also low
45. LCAT Deficiency
Autosomal recessive
defective formation of mature HDL
2 types – complete and partial
Progressive corneal opacification
Low levels of HDL
COMPLETE FORM – hemolytic anemia, progressive
renal insufficiency and ESRD
PREMATURE CHD not seen
46. Primary Hypoalphalipoproteinemia
(isolated low HDL Syndrome)
defined as a plasma HDL-C level below the tenth
percentile in the setting of relatively normal
cholesterol and triglyceride level
no apparent secondary causes of low plasma HDL-C
no clinical signs of LCAT deficiency or Tangier
disease.
Premature CHD not a consistent feature
47. Inherited causes of high levels
of HDL-C
CETP DEFICIENCY
Loss-of-function mutations
CETP facilitates transfer of cholesteryl esters from
HDL to apoB-containing lipoproteins
CETP deficiency results in an increase in the
cholesteryl ester content of HDL,decreased clearance
of HDL and a reduction in plasma levels of LDL-C
The relationship of CETP deficiency to ASCVD
remains unresolved
48. defined as a plasma HDL-C level above the ninetieth
percentile
mutations in endothelial lipase
Relation to reduced CHD risk and increased longevity
not consistent
Inherited causes of high levels
of HDL-C
Hyperalphalipoproteinemia
50. Management-
What are the
recommendations?
Checking lipids
Nonfasting lipid panel
measures HDL and total cholesterol
Fasting lipid panel
Measures HDL, total cholesterol and triglycerides
LDL cholesterol is calculated:
LDL cholesterol = total cholesterol – (HDL + triglycerides/5)
51. When to check lipid panel
Two different Recommendations
Adult Treatment Panel (ATP III) of the National Cholesterol
Education Program (NCEP)
Beginning at age 20: obtain a fasting (9 to 12 hour) serum lipid profile
consisting of total cholesterol, LDL, HDL and triglycerides
Repeat testing every 5 years for acceptable values
United States Preventative Services Task Force
Women aged 45 years and older, and men ages 35 years and older undergo
screening with a total and HDL cholesterol every 5 years.
If total cholesterol > 200 or HDL <40, then a fasting panel should be obtained
Cholesterol screening should begin at 20 years in patients with a history of
multiple cardiovascular risk factors, diabetes, or family history of either
elevated cholesteral levels or premature cardiovascular disease.
52. Goals for Lipids
LDL
< 100 →Optimal
100-129 → Near optimal
130-159 → Borderline
160-189→ High
≥ 190 → Very High
Total Cholesterol
< 200 → Desirable
200-239 → Borderline
≥240 → High
HDL
< 40 → Low
≥ 60 → High
Serum Triglycerides
< 150 → normal
150-199 → Borderline
200-499 → High
≥ 500 → Very High
53. Determining Cholesterol Goal
JNC 7 Risk Factors
Cigarette smoking
Hypertension (BP ≥140/90 or on anti-hypertensives)
Low HDL cholesterol (< 40 mg/dL)
Family History of premature coronary heart disease
(CHD) (CHD in first-degree male relative <55 or CHD in first-
degree female relative < 65)
Age (men ≥ 45, women ≥ 55)
54. Risk Category LDL-C Goal Initiate TLC
Consider
Drug Therapy
High risk:
CHD or CHD risk equivalents
(10-year risk >20%)
<100 mg/dL
(optional goal:
<70)
100 mg/dL >100 mg/dL
(<100 mg/dL: consider drug
options)
Moderately high risk:
2+ risk factors*
(10-year risk 10% to 20%)
<130 mg/dL
(optional goal:
<100)
130 mg/dL >130 mg/dL
(100-129 mg/dL: consider
drug options)
Moderate risk:
2+ risk factors*
(10 year risk <10%)
<130 mg/dL 130 mg/dL >160 mg/dL
Lower risk:
0-1 risk factor*
<160 mg/dL 160 mg/dL >190 mg/dL
(160-189 mg/dL: LDL-C
lowering drug optional)
Source: Grundy S et al. Circulation 2004;110:227-239
ATP=Adult Treatment Panel, CHD=Coronary heart disease, LDL-C=Low
density lipoprotein cholesterol, TLC=Therapeutic lifestyle changes
*Risk factors for CHD include: cigarette smoking, hypertension (blood pressure >140/90 mmHg or on
antihypertensive medication, HDL-C <40 mg/dl (>60 mg/dl is a negative risk factor), family history of
premature CHD, age >45 years in men or >55 years in women
ATP III LDL-C Goals and
Cut-points for Drug Therapy
55. Level (mg/dl) Classification
<200 Desirable
200-239 Borderline High
>240 High
Level (mg/dl) Classification
>40 Minimum goal*
40-50 Desired goal*
>50 High
Level (mg/dl) Classification
<150 Normal
150-199 Borderline High
200-499 High
>500 Very High
Total Cholesterol HDL-Cholesterol
Triglyceride
Source: Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults. JAMA 2001;285:2486-2497
ATP III Classification of Other Lipoprotein Levels
*These goals apply to men. For women, the minimum goal is >50 mg/dL
HDL=High density lipoprotein
56. TREATMENT
Lifestyle changes- diet, exercise and yoga
mediterranean diet
Drugs
New therapies
LDL apheresis, monoclonal antibodies,Apo A –I
mimetics
57. Soluble fiber
Soy protein
Stanol esters
Dietary Adjuncts
Ezetimibe
Cholesterol absorption inhibitor
Cholestyramine
Colesevelam
Colestipol
Bile acid sequestrants
Atorvastatin
Fluvastatin
Lovastatin
Pitavastatin
Pravastatin
Rosuvastatin
Simvastatin
3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG-
CoA) reductase inhibitors [Statins]
Drug(s)
Class
Nicotinic acid Niacin
Drug therapies available
Newer therapies CETP inhibitors, APO A analogues, monoclonal
antibodies
59. Lipid Research Clinics-Coronary Primary Prevention
Trial (LRC-CPPT)
Placebo
8.6
Cholestyramine
9
6
3
0
7.0
P<0.05
19% RRR
Rate
of
MI
or
CHD
death
(%)
Source: The LRC-CPPT Investigators. JAMA 1984;251:351-364
CHD=Coronary heart disease, MI=Myocardial infarction,
RRR=Relative risk reduction
3,806 men with primary hypercholesterolemia randomized to cholestyramine
(24 grams) or placebo for 7.4 years
A bile acid sequestrant provides benefit in those with high cholesterol levels
Bile Acid Sequestrant Evidence:
Primary Prevention
60. 4.0
3.0
2.0
1.0
25 45 65
HDL-C (mg/dL)
CHD
risk
ratio
2.0
1.0
0
4.0
Framingham Study
Source: Kannel WB. Am J Cardiol 1983;52:9B–12B
CHD=Coronary heart disease, HDL-
C=High-density lipoprotein cholesterol
CHD Risk According to HDL-C Level
61. Source: Brown BG et al. NEJM 2001;345:1583-1592
HDL-Atherosclerosis Treatment Study (HATS)
*
*Includes cardiovascular death, MI, stroke, or need for coronary revascularization
Nicotinic Acid Evidence:
Secondary Prevention
CAD=Coronary artery disease, HDL-C=High density lipoprotein
cholesterol, LDL-C=Low density lipoprotein cholesterol
160 men with CAD, low HDL-C, and normal LDL-C randomized to simvastatin
(10-20 mg) + niacin (1000 mg bid), simvastatin (10-20 mg) + niacin (1000 mg
bid) + antioxidants, antioxidants, or placebo for 3 years
A statin plus niacin provides benefit to men with CAD and low HDL-C levels
**p<0.01, but low absolute event rates
**
**
Placebo (n=34)
Niacin/Simvastatin (n=33)
Placebo + Vitamins (n=39)
Niacin/Simvastatin + Vitamins (n=40)
62. Atherothrombosis Intervention in Metabolic Syndrome with
Low HDL/High Triglycerides: Impact of Global Health
Outcomes (AIM-HIGH) Trial
Nicotinic Acid Evidence:
Secondary Prevention
Time (years)
Primary
outcome
(%)**
0
10
20
0 1 2 3 4
Monotherapy
Combination Therapy
HR 1.02, p=0.79
16.2%
16.4%
3414 patients with established CV disease randomized to niacin (up to 2000
mg/day) or placebo on a background of statin therapy for a mean of 3 years*
Niacin provides no benefit to those with CV disease and low HDL-C levels
Source: AIM-HIGH Investigators. NEJM 2011;365:2255-2267
*The study was stopped prematurely
CV=Cardiovascular, HDL-C=High density lipoprotein cholesterol
**Composite of death from CHD, nonfatal MI, ischemic stroke, hospitalization for ACS,
or symptom-driven coronary/cerebral revascularization
63. Cholesterol Ester Transfer Protein Evidence:
Secondary Prevention
Investigation of Lipid Level Management to Understand its
Impact in Atherosclerotic Events (ILLUMINATE) Trial
15,067 patients at high CV risk randomized to torcetrapib (60 mg/day) plus
atorvastatin versus atorvastation alone for a median of 1.5 years*
The CETP inhibitor, torcetrapib, is associated with increased CV risk
Primary
end
point**
(%)
Atorvastatin
5.0
Atorvastatin and
Torcetrapib
9
6
3
0
6.2
P=0.001
All-cause
mortality
(%)
Atorvastatin
0.8
Atorvastatin and
Torcetrapib
3
2
1
0
1.2
P=0.006
Source: Barter PJ et al. NEJM 2007;357:2109-2122
CETP=Cholesterol ester transfer protein, CV=Cardiovascular
*The trial was stopped prematurely
**Composite of death from coronary heart disease, nonfatal myocardial
infarction, stroke, or hospitalization for unstable angina
64. Cholesterol Ester Transfer Protein Evidence:
Secondary Prevention
Dal-OUTCOMES Trial
Source: Barter PJ et al. NEJM 2007;357:2109-2122
ACS=Acute coronary syndrome, CETP=Cholesterol ester
transfer protein, CV=Cardiovascular
*The trial was stopped prematurely
**Composite of death from coronary heart disease, nonfatal myocardial infarction,
ischemic stroke, unstable angina, or cardiac arrest with resuscitation
15,871 patients with a recent ACS randomized to dalcetrapib (600 mg/day)
or placebo for a median of 2.6 years
The CETP inhibitor, dalcetrapib, is associated with no CV benefit
Primary
end
point**
(%)
Placebo
8.3
Dalcetrapib
9
6
3
0
8.0
P=0.52
65. Source: Knopp RH et al. Am J Med 1987;83:50-9
-20*
+11*
-38*
+15*
-45*
-50
-40
-30
-20
-10
0
10
20
30
40
50
Type IIa hyperlipidemia Type IIb hyperlipidemia
Mean
%
change
from
baseline
HDL=High density lipoprotein, LDL=Low density
lipoprotein, TG=Triglyceride
180 patients with type IIa or IIb hyperlipidemia randomized to fenofibrate
(100 mg three times daily) or placebo for 24 weeks
LDL TG
HDL
TG
HDL
Fibrate Evidence:
Effect on Lipid Parameters
-6*
LDL
*p<0.01
66. Source: Yokoyama M et al. Lancet 2007;369:1090-1098
Japan Eicosapentaenoic acid Lipid Intervention Study (JELIS)
*Composite of cardiac death, myocardial infarction, angina, PCI, or CABG
Years
Omega-3 Fatty Acids Evidence:
Primary and Secondary Prevention
18,645 patients with hypercholesterolemia randomized to EPA (1800 mg) with a
statin or a statin alone for 5 years
Omega-3 fatty acids provide CV benefit, particularly in secondary prevention
CV=Cardiovascular, EPA=Eicosapentaenoic acid
67. Therapy Dose (g/day) Effect
Dietary soluble fiber 5-10 (psyllium) LDL-C 10-15%
Soy protein 20-30 LDL-C 5-7%
Stanol esters 1.5-2 LDL-C 15-20%
Sources:
Kwiterovich Jr PO. Pediatrics 1995;96:1005-1009
Lichtenstein AH. Curr Atheroscler Rep 1999;1:210-214
Miettinen TA et al. Ann Med 2004;36:126-134
Dietary Adjuncts Evidence:
Efficacy at Reducing LDL-C
LDL-C=Low density lipoprotein cholesterol
68. HDL-C=High-density lipoprotein cholesterol, LDL-C=Low-density lipoprotein
cholesterol, TC=Total cholesterol, TG=Triglyceride
Good
- 9%
+ 1%
- 18%
- 13%
Ezetimibe
Good
- 14-29%
+ 4-12%
- 25-50%
- 19-37%
Statins*
Good
- 30%
+ 11-13%
- 4-21%
- 19%
Fibrates
Reasonable
to Poor
- 30-70%
+ 14-35%
- 10-20%
- 10-20%
Nicotinic acid
Poor
Neutral or
+ 3%
- 10-18%
- 7-10%
Bile acid
sequestrants
Patient
tolerability
TG
HDL-C
LDL-C
TC
Therapy
Effect of Pharmacotherapy
on Lipid Parameters
*Daily dose of 40mg of each drug, excluding rosuvastatin
69.
70. SUMMARY
The role of lipoproteins
increasing day by day
Watch out for the
dyslipidemic triad-
increased TG,
decreased HDL and
increase in small
dense LDL
Primary
hyperlipidemias are
not so uncommon
Diet , exercise , yoga
- mediterranean
Hypolipidemic agents
used according to the
lipid goal to be achieved
Watch for adverse effects
Newer treatments- LDL
apheresis/apo A
analogues
71. Editorial : A System for Phenotyping Hyperlipoproteinemia
DONALD S. FREDRICKSON and ROBERT S. LEES
CIRCULATION: 1965;31:321-327
