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Hypertriglyceridemia

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Eruptive skin xanthomas. Hepatic steatosis. Lipemia retinalis. Mental changes ... Eruptive Xanthoma. Palmare Striatum. A Risk Factor for Heart Disease? ... – PowerPoint PPT presentation

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Title: Hypertriglyceridemia


1
Hypertriglyceridemia
  • Why dont we address it at the next visit?
  • Jenny Gordon
  • March 26, 2004

2
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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.

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Atherogenic lipids
  • VLDL
  • IDL
  • LDL especially small dense LDL

13
Elevated Triglycerides
  • Normal lt150 mg/dL
  • Borderline high 150199 mg/dL
  • High 200499 mg/dL
  • Very high gt500 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
  • (gt60 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(gt500 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 syndrometriglycerides gt2000
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 gt201 mg/dL and an
    LDL-cholesterol/HDL-cholesterol ratio gt5.0. 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 independently lowers
    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
  • - Triglycerides 150 mg/dL
  •  HDL cholesterol lt40 mg/dL in men and lt50 mg/dL
    in women
  •  Blood pressure 130/ 85 mmHg
  •  Fasting glucose 110 mg/dL
  • waist circumference in men gt40 in and in women 35
    in

32
TG and Insulin Resistance
33
TG and Insulin Resistance
34
Treat Metabolic Syndrome
  • Treat HTN
  • Treat Obesity/Abdominal Obesity
  • Weight reduction
  • Diet and exercise
  • ASA if high CHD risk for prothrombotic state
  • Treat lipid abnormalities
  • Treat insulin insensitivity (Controversial)

35
Treating Lipids in Insulin Resistance
36
Guidelines for treatment
  • ATP-III focuses on non-HDL( Total Chol- HDL) as
    secondary goal after LDL has been addressed .
    Why?
  • TG is more variable day to day than non-HDL
  • Non-HDL may actually turn out to be a more
    powerful predictor of CHD risk than LDL
  • Reflects highly atherogenic VLDL LDL

37
Borderline TG (150-199)
  • Primary goal achieve LDL-C goal
  • Life-habit changes first-line therapy
  • Body weight control
  • Regular physical activity
  • Smoking cessation
  • Restriction of alcohol use (when consumed in
    excess)
  • Avoid high carbohydrate intakes
  • Drug therapy Triglycerides in this range not a
    direct target of drug therapy

38
High TG (200-499)
  • Primary goal achieve LDL-C goal
  • Secondary goal achieve non-HDL-C goal 30 mg/dL
    higher than LDL-C goal
  • First-line therapy for high triglycerides
    TLC-emphasize weight reduction and exercise
  • Second-line therapy drugs to achieve non-HDL-C
    goal
  • Statins lowers both LDL-C and VLDL-C
  • Fibrates lowers VLDL-triglycerides and VLDL-C
  • Nicotinic acid lowers VLDL-triglycerides and
    VLDL-C

39
High TG (200-499) cont..
  • Alternate approaches to drug therapy for lowering
    non-HDL-C
  • High doses of statins (lower both LDL-C and
    VLDL-C)
  • Moderate doses of statins and triglyceride-lowerin
    g drug (fibrate or nicotinic acid)
  • Caution increased frequency of myopathy with
    statins fibrates

40
Very High TG (gt500)
  • 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 gt1000 mg/dL (lt15 of
    total calories as fat)
  • Institute weight reduction/physical activity
  • Fish oils

41
Very High TG (gt500) 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
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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 Risk April 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

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