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Cholesterol: The Expanded Lipid
ProfileBen Brown MDDecember 19, 2011Thanks 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
Cases1. 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. Not all lipids are the same risk:
impact of LDL size & number HDL subtypes
2. 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 numberBigger 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)
Lp(a) low
Later an AIC was 5.0
What if her Apo B or hsCRP or AIC was high?
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
HDLHDL 2 (a and b)
Again bigger is better
Reverse cholesterol transport
Antioxidant effect
Increases with exercise, fish oil, niacin, fibric acid, statin and niacin combo’s, moderate alcohol consumption.
HDL 3
Smaller less protective
(signal of inefficient transport)
Case 2
35 y/o Latino male with new onset DM and a “perfect” lipid panel.
TC 168
HDL 41
TG 115
LDL 104
Expanded Panel
Apo B high
HDL 2 low/3 normal
Hs CRP 1.7
Lp(a) normal
What would you do?
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)Treatment options:• Lp(a) is an
inherited abnormal protein attached to LDL.
• Normal level < 30 mg/dL
• Lp(a) increases coagulation and triples CVD risk.
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.
InflammationHs-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
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
Advanced Risk Markers
• 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
If LDL goal not achieved, intensifyLDL-lowering therapy
If LDL goal not achieved, intensify drug therapy or refer to a lipid specialist
Monitor response and adherence to therapy
• Start statin or bile acid sequestrant or nicotinic acid
• Consider higher dose of statin or add a bile acid sequestrant or nicotinic acid
6 wks
6 wks
Q 4-6 mo
• If LDL goal achieved, treat other lipid risk factors
Initiate LDL-lowering drug 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
Total Cholesterol/HDL ratio (TC/HDL)
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: 200968 Studies: 300,000 patients
Mean fu 6 years
Risk for coronary disease was associated with
higher values of •non–HDL-C and LDL-C,
•higher ratios of non–HDL-C/HDL-C
•apo B/A1•lower values of HDL-C. •not associated with triglyceride levels
•No difference in risk prediction was observed
between fasting 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.
Risk for coronary disease was associated with higher values of •non–HDL-C and LDL-C,•higher ratios of non–HDL-C/HDL-C•apo B/A1 (LDL/HDL)•lower values of HDL-C. •not associated with triglyceride levels•No difference in risk prediction was observed between fasting and non-fasting measurements.
IM4U Treatment Pyramid
Environment ResourcesRelationships
IM4U Treatment Pyramid (expanded)
Environment ResourcesRelationships
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):889Nutr 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 1.5–3 g(crystalline)
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)