hypertriglyceridemia
TRANSCRIPT
- 1. Hypertriglyceridemia Why dont we address it atthe next visit? Jenny Gordon March 26, 2004
2. 3. Overview
- Case Presentations
- Pathophysiology- review the lipids
- Triglyceride Disorders
- Secondary causes of Hypertriglyceridemia
- Cardiac Risk factor
- Current guidelines
- Treatment options
4. Patient M.B.
- 40 y/o male comes in to establish care, CPE, wants to make some healthy changes. H/O ETOH abuse, quit 6 months ago. Quit smoking 6 days ago. Concerned about cholesterol, heart disease , etc.
- FH-neg for CAD, HTN, DM , CA
- PMH- ETOH x 25 yrs, Smoking-25pack years
- Meds-Nicotine Patch, MVI
5. Patient M.B.
- PE-
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- BP 153/85, P 84, Wt 181 lb
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- Physical exam unremarkable except for partial dentures and mild abdominal obesity
- Labs-
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- CBC, Chem 7, LFTs wnl
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- Tchol 275, HDL 31, LDL 176, TG 34
- Plan- Diet and Exercise, nutrition visit, recheck chol 3 months
6. Patient M.B.
- Returns 2 months later- he has started smoking, wants to quit again. Has seen nutrition and made some diet changes-eating oatmeal and fruit for breakfast-getting dental surgery, so needs to eat soft foods.
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- Plan Zyban, Patch , SFGH smoking cessation class
- Returns 1 month later-not smoking ,eating oatmeal and bran, wants to focus on diet changes after smoking cessation
7. Patient M.B.
- Returns 2 mo later- still not smoking or drinking
- BP130/86
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- T Chol 258, HDL 49, LDL 129, TG 398
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- Not ready to take medication, really wants to try diet change wholeheartedly now. Pt wants to try a vegetarian diet for 3 months and see if he can decrease his TG. Discussed starting lipid lowering meds if still high at that point.
8. Patient R.P.
- 57 y/o female seen very briefly in ACC for URI
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- Review of labs shows TG 620, TSH 15.2, HgA1c 13.9
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- What is causing her high TGs?
9. Questions I Had
- Were they REALLY fasting or not?
- Is it a risk factor for heart disease or not? What do triglycerides do in the body?
- Do I need any other labs? To rule out any other things?
- Should I treat with meds? Which ones?
- Why is it so hard to spell Hypertriglyceridemia?
- Maybe we should address this at the next visit
- ???
10. Review the Lipids (briefly!)
- Lipids (cholesterol and triglycerides)
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- insoluble in plasma
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- circulating lipid is bound to lipoprotein
- lipoprotein
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- esterified and unesterified cholesterol
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- triglycerides
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- phospholipids
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- Protein -known as apolipoproteins or apoproteins.
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- serve as cofactors for enzymes and ligands for receptors.
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11. Review the Lipids (briefly!)
- Chylomicrons -Chol and TG
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- A-I, A-II, A-IV, B-48, C-I,C-II, C-III, and E.
- VLDL- TG and less chol
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- B-100, C-I, C-II, C-III, and E.
- IDL- Chol esters and TG.
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- B-100, C-III, and E.
- LDL- chol esters
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- B-100.
- HDL- Chol esters.
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- A-I, A-II, C-I, C-II, C-III, D, and E.
12. Atherogenic lipids
- VLDL
- IDL
- LDL especially small dense LDL
13. Elevated Triglycerides
- Normal500 mg/dL
14. Fredrickson Classification 15. Disorders of TG Metabolism 16. Borderline High Triglycerides (150199 mg/dL)
- Acquired causes
- Overweight and obesity
- Physical inactivity
- Cigarette smoking
- Excess alcohol intake
- High carbohydrate intake
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- (>60% of total energy)
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- Secondary causes
- Genetic causes
- Various genetic polymorphisms
17. High Triglycerides (200499 mg/dL)
- Acquired causes
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- Same as for borderline high triglycerides (usually combined with foregoing causes)
- Secondary causes
- Genetic patterns
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- Familial combined hyperlipidemia
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- Familial hypertriglyceridemia
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- Polygenic hypertriglyceridemia
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- Familial dysbetalipoproteinemia
18. Very High Triglycerides (>500 mg/dL)
- Usually combined causes
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- Same as for high triglycerides
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- Familial lipoprotein lipase deficiency
- Familial apolipoprotein C-II deficiency
19. Secondary causes of Hypertriglyceridemia
- Type 2 diabetes mellitus
- Cholestatic liver diseases
- Nephrotic syndrome
- Chronic renal failure
- Hypothyroidism
- Cigarette smoking
- Obesity
- Drugs (Tamoxifene, glucocorticoids, cyclosporine, Estrogen, Protease inhibitors)
20. Additional Labs to order
- Thyroid function tests
- Creatinine
- Fasting glucose
21. Chylomicronemia syndrome triglycerides >2000 mg/dL)
- Eruptive skin xanthomas
- Hepatic steatosis
- Lipemia retinalis
- Mental changes
- High risk for pancreatitis
22. Eruptive Xanthoma 23. Palmare Striatum 24. A Risk Factor for Heart Disease?
- Hokanson and Austins meta-analysis of prospective population-based studies
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- association between the serum triglyceride concentration and cardiovascular disease
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- pooled analysis of 46,413 men enrolled in 16 studies
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- univariate risk ratio (RR) for triglyceride of 1.32 (95 percent CI 1.26 to 1.39) for men
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- five studies of nearly 10,800 women were associated with a univariate RR of 1.76 (95 percent CI 1.50 to 2.07).
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- With adjustment for HDL and other risk factors, correlation was still significant
25. A Risk Factor for Heart Disease?
- Physician's Health Study
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- The risk of myocardial infarction (MI) was highest among men with the highest tertile for both triglyceride and the TC/HDL-C ratio
- Helsinki Heart Study
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- CHD risk was highest in the cohort with a triglyceride level >201 mg/dL and an LDL-cholesterol/HDL-cholesterol ratio >5.0. A benefit from lipid-lowering from gemfibrozol was confined to this high-risk subgroup
26. A Risk Factor for Heart Disease?
- Copenhagen Male Study
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- gradient of CHD risk with increasing serum triglycerides
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- even after adjustment for other major CHD risk factors, including LDL-cholesterol.
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- The protective effect of a high HDL-C concentration above 68 mg/dL was not seen in the highest third of triglyceride levels.
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27. A Risk Factor for Heart Disease?
- It still remains debated whether treating hypertriglyceridemia really independentlylowers CHD risk, however almost everyone can agree that elevated triglycerides are a very important marker for
- 1. Metabolic Syndrome
- 2. Atherogenic dyslipidemia ( high small dense LDL, low HDL, high atherogenic remnants)
28. Associated Abnormalities
- Low levels of HDL-C
- The presence of small, dense LDL particles.
- The presence of atherogenic triglyceride-rich lipoprotein remnants
- Insulin resistance
- Increases in coagulability and viscosity
29. TG and Small dense LDL 30. Why High TG causes Low HDL and High small dense LDL
- High levels of VLDL
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- VLDL exchanges its TG for Chol from HDL
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- Chol rich VLDL- very atherogenic!
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- Chol depleted HDL-can easily dissociate from apo A-1 and be cleared
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- VLDL exchanges its TG for Chol from LDL
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- LDL gets denser and smaller-Very atherogenic
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31. Identify Metabolic Syndrome
- Any three of the following
- -Triglycerides150 mg/dL
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- HDL cholesterol 500)
- Goals of therapy:
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- Triglyceride lowering to prevent acute pancreatitis (first priority)
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- Prevention of CHD (second priority)
- Triglyceride lowering to prevent pancreatitis:
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- Very low-fat diet when TG >1000 mg/dL (500) cont
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- Triglyceride-lowering drugs (fibrate or nicotinic acid): most effective
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- Statins: not first-line agent for very high triglycerides (statins not powerful triglyceride-lowering drugs)
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- Bile acid sequestrants: contraindicatedtend to raise triglycerides
42. Summary of Non-Hdl goals 43. Lipid Lowering Drugs 44. 45. Main Points
- Hypertriglyceridemia is a marker for metabolic syndrome, increased CHD, and multiple associated lipid abnormalities that further increase CHD risk
- Treatment involves
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- Review meds
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- Look for acquired causes and secondary causes (TSH, Cr, Fasting Glucose)
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- Therapeutic Lifestyle changes
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- Meds- statins, niacin,fibrates,
46. References
- ATP-III, Third Report of the National Cholesterol education program expert panel. Nhlb.nih.gov
- Gotto,A., et al, High Density lipoprotein cholesterol and triglycerides as therapeutic targets.., Am Heart Journal, December, 2002.
- Watson,K., et al, Lipid abnormalities in insulin resistance states, Rev Cardiovasc Med. 2003, Vol 4, No 4
47. References cont
- Hokansen,J. et al, Plasma triglyceride level is a risk factor for cardiovascular disease, Jou Cardiovascular RiskApril 1996
- Collins, R., et al, Heart protection study of cholesterol lowering with simvastatin in 5963 people with diabetes., Lancet, 2003 Vol 361 p2005-2016.
- Up To Date online-multiple topics
- Broset, Tom, Lipid clinic SFGH Gladstone Cardiovascular Institute
48. 49.
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- Very low-fat diet when TG >1000 mg/dL (500) cont
- HDL cholesterol 500)