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-

• BP 153/85, P 84, Wt 181 lb

• Physical exam unremarkable except for partial dentures and mild abdominal obesity

Labs-

• CBC, Chem 7, LFTs wnl

• 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.

• 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

• T Chol 258, HDL 49, LDL 129, TG 398

• 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

• Review of labs shows TG 620, TSH 15.2, HgA1c 13.9

• 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)

• insoluble in plasma

• circulating lipid is bound to lipoprotein

lipoprotein

• esterified and unesterified cholesterol

• triglycerides

• phospholipids

• Protein -known as apolipoproteins or apoproteins.

• • serve as cofactors for enzymes and ligands for receptors.

11. Review the Lipids (briefly!)

Chylomicrons -Chol and TG

• A-I, A-II, A-IV, B-48, C-I,C-II, C-III, and E.

VLDL- TG and less chol

• B-100, C-I, C-II, C-III, and E.

IDL- Chol esters and TG.

• B-100, C-III, and E.

LDL- chol esters

• B-100.

HDL- Chol esters.

• 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

• • (>60% of total energy)

Secondary causes

Genetic causes

Various genetic polymorphisms

17. High Triglycerides (200499 mg/dL)

Acquired causes

• Same as for borderline high triglycerides (usually combined with foregoing causes)

Secondary causes

Genetic patterns

• Familial combined hyperlipidemia

• Familial hypertriglyceridemia

• Polygenic hypertriglyceridemia

• Familial dysbetalipoproteinemia

18. Very High Triglycerides (>500 mg/dL)

Usually combined causes

• • Same as for high triglycerides

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

• association between the serum triglyceride concentration and cardiovascular disease

• pooled analysis of 46,413 men enrolled in 16 studies

• univariate risk ratio (RR) for triglyceride of 1.32 (95 percent CI 1.26 to 1.39) for men

• five studies of nearly 10,800 women were associated with a univariate RR of 1.76 (95 percent CI 1.50 to 2.07).

• With adjustment for HDL and other risk factors, correlation was still significant

25. A Risk Factor for Heart Disease?

Physician's Health Study

• 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

• 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

• gradient of CHD risk with increasing serum triglycerides

• • even after adjustment for other major CHD risk factors, including LDL-cholesterol.

• • The protective effect of a high HDL-C concentration above 68 mg/dL was not seen in the highest third of triglyceride levels.

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

• VLDL exchanges its TG for Chol from HDL

• • Chol rich VLDL- very atherogenic!

• • Chol depleted HDL-can easily dissociate from apo A-1 and be cleared

• VLDL exchanges its TG for Chol from LDL

• • LDL gets denser and smaller-Very atherogenic

31. Identify Metabolic Syndrome

Any three of the following

-Triglycerides150 mg/dL

• HDL cholesterol 500)
  • Goals of therapy:
  • • Triglyceride lowering to prevent acute pancreatitis (first priority)
  • • Prevention of CHD (second priority)
  • Triglyceride lowering to prevent pancreatitis:
  • • Very low-fat diet when TG >1000 mg/dL (500) cont
      • • Triglyceride-lowering drugs (fibrate or nicotinic acid): most effective
      • • Statins: not first-line agent for very high triglycerides (statins not powerful triglyceride-lowering drugs)
      • • 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
      • • Review meds
      • • Look for acquired causes and secondary causes (TSH, Cr, Fasting Glucose)
      • • Therapeutic Lifestyle changes
      • • 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.