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Cholesterol: The Expanded Lipid Profile Ben Brown MD December 19, 2011 Thanks also to Wendy K and Fasih H.

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Presentation on theme: "Cholesterol: The Expanded Lipid Profile Ben Brown MD December 19, 2011 Thanks also to Wendy K and Fasih H."— Presentation transcript:

1 Cholesterol: The Expanded Lipid Profile Ben Brown MD December 19, 2011 Thanks also to Wendy K and Fasih H

2 Outline  What is the expanded lipid panel?  Why order it?  How to order it?  What to do with results?  Cases  Questions

3 Cases y/o woman with no risk factors and an LDL of 189. She does not want meds y/o Latino male with new onset DM and a “perfect” lipid panel 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?

4 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

5 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

6 What is there and How to Order?

7 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

8 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.

9 Apo B (LDL pattern) Nl <60

10 Small LDL= pattern B

11 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

12 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

13 ATP 3 Guidelines-surprisingly generous Google: ATP 3 Guidelines at a glance

14 ATP3 Guidelines Step 3:risk factors

15 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?

16 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

17 HDL HDL 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)

18 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?

19 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

20 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

21 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?

22 Lp(a)

23 Bonus case: Wendy’s patient  58 yo woman, slender, healthy eater with h/o ischemic stroke age 58. Year later, ischemic bowel.

24 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

25 hsCRP

26

27 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)

28 4 th 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?

29 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-PLA (<200)

30 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*

31 ECW tricks: 3 other tests you may want…

32 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).

33 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  B micrograms/d  Folate 800micrograms/d (may need as methyl THF)

34 Progression of Drug Therapy in Primary Prevention If LDL goal not achieved, intensify LDL-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 Q 4-6 mo If LDL goal achieved, treat other lipid risk factors Initiate LDL- lowering drug therapy

35 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

36 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

37 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

38 JAMA: 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.

39 IM4U Treatment Pyramid Internal Environment Life Style Natural Therapies Drugs Surgery Rescue EnvironmentResourcesRelationships

40 IM4U Treatment Pyramid (expanded) Belief-Attitude-Identity-Spirituality Food-Movement-Relaxation- Sleep-Habits Structural-Metabolic- Energetic Drugs Surgery Rescue EnvironmentResourcesRelationships

41 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

42 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

43 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

44 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)

45 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)

46 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

47 Nicotinic Acid Drug FormDose Range Immediate release1.5–3 g (crystalline) Extended release1–2 g Sustained release1–2 g

48 Nicotinic Acid (continued) Demonstrated Therapeutic Benefits  Reduces major coronary events  Possible reduction in total mortality

49 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

50 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)

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