Cholesterol:
The Expanded Lipid Profile
Ben Brown MD
December 19, 2011
Thanks also to Wendy K and Fasih H
Outline
 What is the expanded lipid panel?
 Why order it?
 How to order it?
 What to do with results?
 Cases
 Questions
Cases
1. 54 y/o woman with no risk factors and an LDL
of 189. She does not want meds.
2. 35 y/o Latino male with new onset DM and a
“perfect” lipid panel.
3. 40 y/o male who comes in and tells you that
his Dad and brother both had their first MI at
45y/o. His lipids look more or less normal.
4. Bonus Case from Wendy
5. A 72 y/o woman obese, HTN, IGT,
depression. What is my risk of heart disease
or stroke?
Why bother with more?
1.
2.
Not all lipids are the same risk:

impact of LDL size & number

HDL subtypes
In selected patients: Other Risk
Factors missed with typical lipid
panel

Lp(a)

hsCRP
 FHx early CADz and
close to normal lipids
 Metabolic Syndrome
and need more info
to change
 High Lipids and wants
to avoid statins or
difficulty tolerating
Question?
In addition to the standard lipid profile, What is included
in the expanded lipid panel?
A.
LDL subtypes (apoB)
B.
HDL subtypes (2 and 3)
C. LPa
D.
hsCRP
E.
Homocysteine
F.
All of the above
G. It depends
What is there and How to Order?
Expanded Lipid Profiles
 Quest: expanded lipid panel (or lipid- or
homocyt- with homocysteine)
 Lipoprotein Particle Analysis (LPP) Spectracell
 Berkeley HeartLab (BHL)
 NMR: Liposcience
 VAP: Atherotec
 Hunter: Cardiovascular Risk/Metabolic Syndrome
LDL: particle size and number
Bigger is Better
 Small LDL is the bad guy
why?

it goes across the
endothelium more readily
 absorbed by
macrophages more
readily = foam cells…bad
Less is more (better)
 ApoB ( one per particle)
scientifically accepted
measurement for LDL
particle number. Can be
used to Monitor statin
therapy.
Apo B (LDL pattern)
Nl <60
Small LDL= pattern B
Case 1
According to ATP 3 Guidelines what would you
recommend for our 54 y/o woman with no risk
factors and an LDL of 189?
A.
Life style with a goal of LDL 160
B.
Life style with a goal of LDL 130
C. Start a Statin
D.
Start Bile Acid Binder or Niacin
Case 1
According to ATP 3 Guidelines what would you
recommend for our 54 y/o woman with no risk
factors and an LDL of 189?
A.
Life style with a goal of LDL 160
B.
Life style with a goal of LDL 130
C. Start a Statin
D.
Start Bile Acid Binder or Niacin
ATP 3 Guidelines-surprisingly
generous
Google: ATP 3 Guidelines at a glance
ATP3 Guidelines
Step 3:risk factors
Her expanded panel results
 LDL=189, TG=102, HDL =63
 apoB 20 (low)
 hsCRP 0.5 (normal)
 HDL2 (normal)
 HDL3 (normal)
What if her Apo B or hsCRP or AIC
was high?
 Lp(a) low
 Later an AIC was 5.0
Treatment of small dense LDL
Treat LDL cholesterol and think
Metabolic or Inflammation
 Insulin Resistance (glycocylation)
 Check AIC and treat accordingly
 Note: I start metformin early in someone who does not make LS
changes easily (provider choice).
 Inflammation (oxidation)
 Check hsCRP
 Think of antioxidants
 Will cover with hsCRP
HDL
HDL 2 (a and b)
HDL 3
 Again bigger is better
 Smaller less protective
 Reverse cholesterol
(signal of inefficient transport)
transport
 Antioxidant effect
 Increases with exercise, fish
oil, niacin, fibric acid, statin
and niacin combo’s,
moderate alcohol
consumption.
Case 2
35 y/o Latino male with new
onset DM and a “perfect”
lipid panel.
Expanded Panel
 TC 168
 HDL 2 low/3 normal
 HDL 41
 Hs CRP 1.7
 TG 115
 Lp(a) normal
 LDL 104
What would you do?
 Apo B high
Treatment of Low HDL 2
 Exercise
 Niacin
 Moderate alcohol consumption (both 2 and 3)
 Stop smoking
 ?Fish oil
 ?statin, Fibric Acids, Bile acid binder might start
for high apoB
 Mediterranean Diet, fish oils, consider probiotic
for his high CRP
LipoProtein (a)
• Lp(a) is an
inherited
abnormal protein
attached to LDL.
• Normal level < 30
mg/dL
• Lp(a) increases
coagulation and
triples CVD risk.
Treatment options:
 Niacin
 NAC 600 mg
twice daily
Case 3
 40 y/o male who
comes in and tells
you that his Dad
and brother both
had their first MI at
45y/o. His lipids
look more or less
normal.
Expanded panel
results
 Lp(a) high (104)
 Others normal
What would you do?
Lp(a)
Bonus case: Wendy’s patient
 58 yo woman, slender, healthy eater with h/o ischemic
stroke age 58. Year later, ischemic bowel.
Inflammation
Hs-CRP
 Inflammatory
marker
 Better then ESR
and leucocytes for
predicting
vascular events
 Low Risk level < 1.0
mg/L
Lp-PLA2
 Slightly more
specific for
vascular
inflammation
 Low risk <200
mg/ml
hsCRP
Treatment of increased hsCRP
 Look for cause: inflammation, infection, trauma.
 Consider checking Lp-PLA2 (endothelial
inflammation)
 Anti-inflammatory regimen
 Diet (Mediterranean anti-inflammatory or mod





elim)
Exercise (any is better)
Fish oils (dose by EPA/DHA 2-6g a day)
Probiotics (10 billion org a day)
Vit D (check level and treat to 50)
Decrease Stress and support good sleep (cortisol)
4th Patient
•
72 y/o woman obese, HTN,
IGT, depression.
•
“What is my risk of heart
disease or stroke?”
•
How do you answer this
question?
•
Very Concrete thinker
•
Can you do it in a way that
furthers the patients
motivation to change and is
affordable?
Thoughts after test
Advanced Risk Markers
Routine lipid panel
•
•
•
At Goal
–
HDL = 65
–
VLDL = 18
–
Chol/HDL ratio =3.2
–
TG’s = 90
moderate risk
–
TC = 211
–
LDL = 128
–
Non-HDL chol = 146
•
High Risk
–
hsCRP = 4.88 [<1]
–
sd-LDL = 36.2 [20]
Moderate Risk
–
Apo B 113 [<60]
–
Homocysteine 11.2 (<10)
At Goal
–
Lp-PLA2 185.4 (<200)
How to treat
•
NCEP –ATC diet with goal
of dropping 5-10% weight
•
Lower carbohydrate,
higher fiber diet
•
Omega 3 fats; substitute
olive oil
•
Screen for DM,
hypothyroidism
•
Lower LDL*
ECW tricks: 3 other tests
you may want…
Summary
 High apoB = Small dense LDL ~ metabolic syndrome
 check AIC, treat LDL earlier, LS changes, consider earlier
metformin, check hsCRP
 Low HDL (especially low High HDL 2)
 Exercise, Niacin, moderate ETOH
 High Lp(a) bad
 Niacin, NAC
 High hsCRP (cardio CRP) > 1.0
 r/o infection, inflammation, trauma. Repeat test/ck lp-PLA2
 Anti-inflam regimen (diet, ex, stress, fish oil, probiotic,
antioxidants)
 Homocysteine: a definite risk factor, interventions lower it,
?if that makes a difference unless they have the condition
hyperhomocysteinuria (rare).
Homocysteine
 Methylation (if high also check
B12/folate/methylmalonic acid)
 Functions primarily to protect DNA
 How to help
 For most Mediterranean Diet adequate, if still a
problem may need supplementation
 B6 25 micrograms/d
 B12 1000micrograms/d
 Folate 800micrograms/d (may need as methyl THF)
Progression of Drug Therapy
in Primary Prevention
Initiate
LDLlowering
drug
therapy
• Start statin or
bile acid
sequestrant
or nicotinic
acid
6 wks
If LDL goal
not
achieved,
intensify
LDL-lowering
therapy
• Consider
higher dose of
statin or add a
bile acid
sequestrant or
nicotinic acid
6 wks
If LDL goal not
achieved,
intensify drug
therapy or
refer to a lipid
specialist
• If LDL goal
achieved,
treat other
lipid risk
factors
Q 4-6
mo
Monitor
response
and
adherence
to therapy
Lipids Background
Cholesterol Functions
1. Plasma Membranes
2. Myelinated structures in the CNS
3. Inner Mitochondrial Membranes
4. Bile Acids
5. Steroid Hormones and Sex Hormones
6. Ergosterol (UV skin) Vit D3
Lipids Background
Lipids in Atherosclerosis Dys-Function
1. Endothelium and damage
2. LDL and Macrophages
3. Oxidized LDL and Foam Cells

Also glycosylated and acetylated LDL
4. Plaque and rupture
5. HDL as scavenger
Cholesterol General
(TC/HDL)
Total Cholesterol/HDL ratio
Best Lipid predictor of CHD in Framingham Study
TC/HDL ratio 1 unit =  CHD risk by 60%
Eg TC/HDL ratio of <4 is normal
6 = 120% increased risk
3 = 60% decreased risk
JAMA: 2009
68 Studies: 300,000 patients
Mean fu 6 years
Risk for coronary disease was Risk for coronary disease was
associated with higher values of associated with higher values
of
•non–HDL-C and LDL-C,
•higher ratios of non–HDL-C/HDL-C •non–HDL-C and LDL-C,
•higher ratios of non–HDL•apo B/A1 (LDL/HDL)
C/HDL-C
•lower values of HDL-C.
•apo B/A1
•not associated with triglyceride •lower values of HDL-C.
levels
•not associated with
•No difference in risk prediction was triglyceride levels
•No difference in risk prediction
observed between fasting and nonwas observed between fasting
fasting measurements.
and nonfasting measurements.
Di Angelantonio E et al. for the Emerging Risk Factors Collaboration. Major lipids,
apolipoproteins, and risk of vascular disease. JAMA 2009 Nov 11; 302:1993.
IM4U Treatment Pyramid
Environment
Relationships
Internal Environment
Life Style
Natural Therapies
Drugs
Surgery
Rescue
Resources
IM4U Treatment Pyramid
(expanded)
Environment
Relationships
Belief-Attitude-Identity-Spirituality
Food-Movement-RelaxationSleep-Habits
Structural-MetabolicEnergetic
Drugs
Surgery
Rescue
Resources
Drug Therapy
1) HMG CoA Reductase Inhibitors (Statins)
 Reduce LDL-C 18–55% & TG 7–30%
 Raise HDL-C 5–15%
 Major side effects
 Myopathy
 Increased liver enzymes
 Contraindications
 Absolute: liver disease
 Relative: use with certain drugs
HMG CoA Reductase
Inhibitors (Statins) (continued)
Demonstrated Therapeutic Benefits
 Reduce major coronary events
 Reduce CHD mortality
 Reduce coronary procedures (PTCA/CABG)
 Reduce stroke
 Reduce total mortality
Statins: Drug-Nutrient Side Effects
Nutrients Depleted
Coenzyme Q10: Statins inhibit the enzyme
HMG CoA reductase that is required to
make cholesterol and Coenzyme Q10.
 Could explain myalgia, exercise intolerance,
myoglobuinuria
Also, Selenium, Zinc, Copper
Lower serum PUFA’s and alter the relative
% of omega 6:3 fats
Arch Neurol 2004;61(6):889
Nutr Metab Cardiovasc Dis 2005; 15(1): 36
Drug Therapy
2) Bile Acid Sequestrants
Ex: cholestyramine, colestipol, colesevelam
 Major actions
 Reduce LDL-C 15–30%
 Raise HDL-C 3–5%
 May increase TG
 Contraindications
 Dysbetalipoproteinemia
 Raised TG (especially >400 mg/dL)
Bile Acid Sequestrants (continued)
 Demonstrated Therapeutic Benefits
 Reduce major coronary events
 Reduce CHD mortality
 Side effects
 GI distress/constipation
 Decreased absorption of other drugs
 Decreases beta-carotene, calcium, folate, Fe,
Mg, Vit B12, D, E, K & zinc (cholestyramine)
Drug Therapy
3) Nicotinic Acid
 Major actions
 Lowers LDL-C 5–25%
 Lowers TG 20–50%
 Raises HDL-C 15–35%
 Side effects: flushing, hyperglycemia,
hyperuricemia, upper GI distress,
hepatotoxicity
 Contraindications: liver disease, severe
gout, peptic ulcer
Nicotinic Acid
Drug Form
Dose Range
Immediate release
(crystalline)
1.5–3 g
Extended release
1–2 g
Sustained release
1–2 g
Nicotinic Acid (continued)
Demonstrated Therapeutic Benefits
 Reduces major coronary events
 Possible reduction in total mortality
Drug Therapy
4) Fibric Acids
Example: gemfibrozil, fenofibrate, clofibrate
 Major actions
Lower LDL-C 5–20% (with normal TG)
 May raise LDL-C (with high TG)
 Lower TG 20–50%
 Raise HDL-C 10–20%

 Contraindications: Severe renal or hepatic
disease
Fibric Acids (continued)
 Demonstrated Therapeutic Benefits
 Reduce progression of coronary lesions
 Reduce major coronary events
 Side effects: dyspepsia, gallstones,
myopathy
 Drug-nutrient interactions: Decrease
CoQ10 also, Vitamin E, (fenofibrate
incr’s homocysteine)