Treatment of Lipid Disorders Ulrich K. Schubart AECOM/JMC

Treatment of Treatment of Lipid DisordersLipid Disorders

Ulrich K. SchubartUlrich K. Schubart

AECOM/JMCAECOM/JMC

Proposed Mechanisms of Event Reduction by Lipid Lowering Therapy

• Improved endothelium dependent vasodilation

• Stabilization of atherosclerotic lesions

- Especially non-obstructive , vulnerable plaques

• Reduction in inflammatory stimuli

- Lipoproteins and modified lipoproteins

• Reduced thrombotic and increased fibrinolytic potential

• Prevention, slowed progression, or regression of

atherosclerotic lesions

adapted from Libby P. Circulation1995; 91:2844-2850

% Reductions in CV Events depends upon:

• Percent cholesterol (and LDL) lowering

• Absolute Level of Baseline cholesterol

• Duration of cholesterol lowering

• Presence of other lipid abnormalities

Dietary Therapy for Elevated Blood Cholesterol

30% of total calories

55% of total calories

~ 15% of total calories

To achieve and maintaindesirable weight

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 1993;269:3015-3023.

Nutrient*

* Calories from alcohol not included.

<10% oftotal calories

< 300 mg/day

Total fat

Saturated fatty acids

Carbohydrates

Protein

Cholesterol

Total calories

< 7% oftotal calories

< 200 mg/day

Recommended intake

Step I Diet Step II Diet

Drugs to lower LDL Drugs to lower LDL CholesterolCholesterol

• Statins (HMG-CoA Reductase Inhibitors) Statins (HMG-CoA Reductase Inhibitors) 25-55%25-55%

• Bile Acid ResinsBile Acid Resins 15-30%15-30%

• Cholesterol Absorption Inhibitors 15-20%

• NiacinNiacin 15-25%15-25%

• CombinationsCombinations >60%>60%

• EstrogenEstrogen 10-15%10-15%

% LDL Reduction% LDL Reduction

Synergistic effects of diet Synergistic effects of diet and drug therapy and drug therapy

• This is the equivalent of doubling the daily dose of a statin

• Therefore, successful dietary therapyreduces drug therapy by over 50%

• Dietary therapy reduces LDL cholesterol by 7-10%

Common Final Mechanism of Statin/BAR/CAI reduction in LDL-C

apo B-100

apo C

apo E

VLDL

VLDLRemnant

LDL

Liver

VLDLPRODUCTION

LDL CLEARANCE

LIPOLYSIS

CONVERSION

Other sites

SHUNT PATHWAYCE

+

Currently Available HMG CoA Reductase Inhibitors

Generic Trade Dose % LDL Cost LipitorAtorvastatin 10-80 mg 37-55

ZocorSimvastatin 5-80 mg 24-51% Formulary

MevacorLovastatin 10-80 mg 19-40% Dependent

PravacholPravastatin 10-40 mg 20-30%

Fluvastatin Lescol 20-80 mg 15-25%

Resuvastatin Crestor 10-40 mg 46-55%

Side Effects of HMG CoA Reductase Inhibitors

• Myopathy (0.1%)

• Abnormal Liver Function Tests (1-2%)

• Gastrointestinal Distress and Diarrhea

• CNS – Insomnia

• Diabetes

Statins and MyopathyStatins and Myopathy

• Liver Disease• Multisystem Disease• Drugs: - Cyclosporin; tacrolimus - Fibrates - Erythromycin - Itraconazole, ketoconazole - Mibefradil (Posicor) - ? Protease inhibitors

Precipitating Factors:

Check CKCheck CK

priorprior to initiating statin therapy to initiating statin therapy

Statins and MyopathyStatins and Myopathy

Significant Inhibitors of Significant Inhibitors of

CYP3A4:CYP3A4:Potential for interaction Potential for interaction

with statinswith statinsAntibiotics clarithromycin* erythromycin* metronidazole

Antifungals ketoconazole* itraconazole** miconazole

Protease Inhibitors indinivir ritonavir nelfinivir

CCB’s mibefradil**

Immunosuppressant cyclosporin A*

H2 Blockers cimetidine

Antidepressants fluoxetine fluvoxamine

Food grapefruit grapefruit juice

HypertriglyceridemiaHypertriglyceridemiaTreatmentTreatment

Hypocaloric, low fat (10-20%), alcohol Hypocaloric, low fat (10-20%), alcohol restricted diet. Avoid saturates, simple restricted diet. Avoid saturates, simple Carbs. Exercise and weight loss.Carbs. Exercise and weight loss.

In DM: Optimize glycemic controlIn DM: Optimize glycemic control Consider metformin or thiazolidenedione for Consider metformin or thiazolidenedione for

IGT/insulin resistanceIGT/insulin resistance Assess meds: oral estrogens/OCPs, steroids, Assess meds: oral estrogens/OCPs, steroids,

Retin A, thiazides or B blockersRetin A, thiazides or B blockers Drugs: 1 : Drugs: 1 : Fibrates or NiacinFibrates or Niacin (unless DM) (unless DM)

2 : High dose statins, Fish Oils 2 : High dose statins, Fish Oils

HypertriglyceridemiaDrug Therapy: High Risk Patients

Triglycerides

Treat to prevent/reverse ASCVD

Treat to preventpancreatitis

<800 mg/dl > 1,000 mg/dl

R/OSecondary Hyperlipidemia

Diet/Lifestyle Modification

HypertriglyceridemiaHypertriglyceridemiaDrug Therapy - High Risk Drug Therapy - High Risk

CADCADTG 200 TG 200-400 TG 400

Statin Statin CombinedDrugTherapy

Useful Combinations:Hypercholesterolemia: Mixed HLD:

Statins+Resins/Ezitamibe

Statins/Ezit+Niacin, or

Statins/Ezit+ Fibrates*

Resin Niacin Consider HighNiacin Gemfibrozil Dose Statins

HypertriglyceridemiaHypertriglyceridemia The bottom lineThe bottom line

• Triglycerides 150 -1000. Treat to prevent CAD*

• Triglycerides > 1000. Treat to prevent pancreatitis

* If in doubt measure Apo B 100. Median 100 mg/dl; > 125 mg/dl likely atherogenic

ATP III: Management ofATP III: Management of

Diabetic DyslipidemiaDiabetic Dyslipidemia Primary target of therapy: identification of LDL-C; Primary target of therapy: identification of LDL-C;

goal for persons with diabetes: <100 mg/dL goal for persons with diabetes: <100 mg/dL Therapeutic options:Therapeutic options:

LDL-C 100–129 mg/dL: increase intensity of TLC; add LDL-C 100–129 mg/dL: increase intensity of TLC; add drug to modify atherogenic dyslipidemia (fibrate or drug to modify atherogenic dyslipidemia (fibrate or nicotinic acid); intensify risk factor controlnicotinic acid); intensify risk factor control

LDL-C LDL-C 130 mg/dL: simultaneously initiate TLC and 130 mg/dL: simultaneously initiate TLC and LDL-C–lowering drugsLDL-C–lowering drugs

TG TG 200 mg/dL: non–HDL-C* becomes secondary 200 mg/dL: non–HDL-C* becomes secondary targettarget

JAMA. 2001;285:2486-2497.

Note: Diabetic dyslipidemia is essentially atherogenic dyslipidemia in persons with type 2 diabetes.*Non–HDL-C goal is set at 30 mg/dL higher than LDL-C goal.

Fibric Acid Derivatives • Gemfibrozil (Lopid) 600-1200 mg/day Clofibrate (Atromid S) 1000-2000 mg/day Fenofibrate (Tricor) 54-160 ug/ day

• Mechanism: Increases clearance of triglyceride-rich lipoproteins (Chylos, VLDL, remnants) through downregulation of Apo CIII and increased LPL activity

• Effects on Lipids:

TG 20-50 %HDL-C 10-15 %LDL-C variable

Fibric Acid Derivatives - Indications

• Severe Hypertriglyceridemia (TG > 1000 mg/dl)

• ? Combination therapy for mixed hyperlipidemia or

moderate hypertriglyceridemia

• Reduces risk of CHD in subjects with High TG /Low HDL-C

• May raise homocysteine levels

Fibric Acid Derivatives

• Side EffectsMyopathyHepatitis (increases in transaminases)Gallstones, Nausea, Diarrhea

•Contraindications Absolute: Relative:

Gallstones Use with statins Hepatic Insufficiency Inhibitors of CYP 3A4 Pregnancy

Niacin - IndicationsNiacin - Indications

• Mixed hyperlipidemia

• Hypertriglyceridemia

• Low HDL (hypoalphalipoproteinemia)

• Combination therapy for hypercholesterolemia, mixed hyperlipidemia

Niacin - Mechanism of Action

• Inhibition of hormone-sensitive lipase in fat cells

• Reduction of VLDL production rates from liver• Activation of LPL and accelerated TG rich lipoprotein clearance.

• Increased clearance of remnants and LDL

• Mechanism of HDL-C increase unknown, but may be related to decreased TG- cholesterol exchange

Niacin - Side effects

• Flushing, pruritis - almost universal, harmless

• Insulin resistance/ worsened glucose tolerance

• Hyperuricemia/ gout

• Hepatitis (fulminant hepatic failure with SR niacin)

• Dyspepsia, Exaccerbation of IBD

• Toxic ambliopia (rare)

Niacin - Contraindications

• Active liver disease, alcoholism• Hx of neural tube defect or hyperhomocysteinemia• Gout or active hyperuricemia

• Active peptic ulcer disease (caution if prior Hx)

• Inflammatory bowel disease

• Pregnancy

• Poorly controlled diabetes

Niacin - Prescribing Hints• Dose 1.5 - 6 gms/ day divided t.i.d. IR niacin

• Max dose 2.0 gm/day SR niacin (and give folate)

• Titrate dose up slowly

• Benefit on HDL seen at < 1.5 gms/day; TG effect dose dependent.

• Take with meals; pretreat ~1 hour earlier with NSAID

• Avoid alcohol (flushing, hepatitis)

_

Bile Acid Binding ResinsBile Acid Binding Resins

Cholestyramine (Questran) Cholestyramine (Questran)

Colestipol (Colestid)Colestipol (Colestid)

Colesevelam (Welchol)Colesevelam (Welchol)

• Indicated for treatment of hypercholesterolemia• Proven efficacy to prevent CHD• Safest agent for reducing cholesterol (except bran foods and garlic)• Ideal for the young, healthy patient

Ge et al Cell Metab 2008

Other Drugs, etc • Estrogen replacement therapy

oral estrogens vs transdermalselective estrogen receptor modulators (raloxifene)- risk of TG’s with oral estrogens

• Vitamin E (400 - 800 I.U./ day)• Vitamin C 1-2 gm/day• Folic acid (1-2 mg/day), B 2-5 mg/day• Aspirin• ACE inhibitors• LDL apheresis

Statins in CAD

Statin Tx Metaanalysis Lancet 2005

Statin Tx Metaanalysis Lancet 2005

Statin Tx Metaanalysis Lancet 2005

Statins forPrimary Prevention

Air Force/Texas Coronary Air Force/Texas Coronary Atherosclerosis Prevention Study Atherosclerosis Prevention Study

(AFCAPS/TexCAPS)(AFCAPS/TexCAPS)

Randomized, double-blind trial to Randomized, double-blind trial to compare lovastatin with placebo for compare lovastatin with placebo for prevention of first acute major coronary prevention of first acute major coronary event in men and women without event in men and women without clinically evident atherosclerotic CVDclinically evident atherosclerotic CVD

5,608 men and 997 women with 5,608 men and 997 women with average Total-C and LDL-C and below-average Total-C and LDL-C and below-average HDL-Caverage HDL-C

Downs JR et al. JAMA 1998;279:1615–1622

Primary EndpointPrimary EndpointFirst Acute Major Coronary First Acute Major Coronary

EventEvent

N=3304 N=3270 N=3228 N=3184 N=3134 N=1688

Lovastatin

N=3301 N=3251 N=3211 N=3159 N=3092 N=1644

Placebo

# At RiskLovastatinPlacebo

Years of Follow-up0 1 2 3 4 5 5+ Years

Cum

ulat

ive

Inci

denc

e

37% Risk Reduction(p = 0.00008)

0.00

0.01

0.02

0.03

0.04

0.05

0.07

0.06

Downs JR et al. JAMA 1998;279:1615–1622

Air Force/Texas Coronary Air Force/Texas Coronary Atherosclerosis Prevention Study Atherosclerosis Prevention Study

(AFCAPS/TexCAPS)(AFCAPS/TexCAPS)Event Rates by Baseline HDL-C Event Rates by Baseline HDL-C

TertileTertile

0

2

4

6

8

10

12

14

16

34 35–39 40

Lovastatin

Placebo

Even

t ra

te p

er

1,0

00

pati

ent-

years

at

risk

HDL-C (mg/dL)

Downs JR et al. JAMA 1998;279:1615–1622

-44%risk reduction

-45%risk reduction

-15%risk reduction

Heart Protection StudyHeart Protection Study Primary prevention with risk factors

(hypertension, diabetes, and CVA)

2x2 factorial design simvastatin 40 mg/day, antioxidant cocktail (600 mg vitamin E, 250 mg vitamin C, 20 mg beta carotene)

N = 20,000; subgroups include: Women (n ~ 5,000) Elderly (>65, n ~ 10,000) Diabetics (n ~ 6,000) Stroke (n ~ 3,000) Hypertension (n ~ 8,000) Noncoronary vascular disease (n ~ 7,000) Low to average blood cholesterol (n ~ 8,000)

FPI – 1996, fully enrolled, results 2001 Heart Protection Collaborative Group. Lancet 2002;360:7–22. Study

HPS: Primary and HPS: Primary and Secondary Prevention Secondary Prevention

ImplicationsImplications

Adapted from Illingworth. Med Clin North Am. 2000;84:23.At: http://www.hpsinfo.org.

50 21070 190170150130110900

5

10

15

20

25

% w

ith

CA

D e

ven

t

WOSCOPS

AFCAPS

CARE

4S

LIPID

HPS

HPS

LDL-C (mg/dL)

Simvastatin: Major Vascular Events Simvastatin: Major Vascular Events in Upper and Lower Thirds of Baseline LDLin Upper and Lower Thirds of Baseline LDL

(Heart Protection Study)(Heart Protection Study)

15

20

25

30

60 80 100 140 160

Average LDL Cholesterol (mg/dl)

120

Upperthird LDL

% w

ith

Majo

r V

asc

ula

r Even

ts

Lowerthird LDL

Statin-allocated

Placebo-allocated

Baseline LDL Baseline LDL (mg/dl)(mg/dl)

Statin Statin (10,269)(10,269)

Placebo Placebo (10,267)(10,267)

<100<100 282282 358358

100–129100–129 668668 871871

130130 10831083 13561356

All patientsAll patients 20332033(19.8%)(19.8%)

25852585(25.2%)(25.2%)

24% SE 324% SE 3reductionreduction

(2P<0.00001)(2P<0.00001)

0.4 0.6 0.8 1.0 1.2 1.4

HPS: Statin Benefit is EntirelyHPS: Statin Benefit is EntirelyIndependent of Baseline LDLIndependent of Baseline LDL

www.hpsinfo.org

Risk ratio and 95% CIRisk ratio and 95% CI

Statinbetter

Statin worse

Simvastatin: Major Vascular Events Simvastatin: Major Vascular Events by Yearby Year

0

5

10

15

20

25

30

0 1 2 4 5Years of Follow-up

63

Placebo

Simvastatin

Peop

le S

uff

eri

ng

Even

ts

(%)

5 (3) 20 (4)

46 (5)

54 (7)

60 (18)

35 (5)

Benefit/1000 (SE)

Heart Protection Study Collaborative Group. Lancet 2002;360:7–22.

Cause of DeathCause of Death

SimvastatinSimvastatin (10,269) (10,269)

Placebo Placebo (10,267)(10,267)

VascularVascular

CoronaryCoronary 587587 707707

Other vascularOther vascular 194194 230230

ANY VASCULARANY VASCULAR 781 (7.6%)781 (7.6%) 937 (9.1%)937 (9.1%)

NonvascularNonvascular

NeoplasticNeoplastic 359359 345345

RespiratoryRespiratory 9090 114114

Other medicalOther medical 8282 9090

NonmedicalNonmedical 1616 2121

NONVASCULARNONVASCULAR 547 (5.3%)547 (5.3%) 570 (5.6%)570 (5.6%)

ALL CAUSESALL CAUSES 1328 (12.9%)1328 (12.9%) 1507 (14.7%)1507 (14.7%)

Simvastatin: Cause-Specific Simvastatin: Cause-Specific MortalityMortality

0.6 0.8 1.0 1.2 1.40.4

Risk ratio and 95% CIRisk ratio and 95% CI

STATINBetter

PLACEBOBetter

17% SE 4reduction(2P<0.0001)

5% SE 6reduction (NS) 13% SE 4

reduction(2P<0.001)

TaggartLancet2009

Statins in DiabetesMetaanalysis Lancet 2008

Statinsin Diabetes

MetaanalysisLancet 2008

Statinsin Diabetes

MetaanalysisLancet 2008

Statinsin Diabetes

MetaanalysisLancet 2008

Statins in CKDMetaanalysis

BMJ 2008

Statins in CKDMetaanalysis

BMJ 2008

Statins in CKDMetaanalysis

BMJ 2008

Fibrate TrialsCVD Mortality

Metaanalysis: Ajoy Saha et al Am Heart J 2007

Fibrate TrialsNon-fatal MI

Metaanalysis: Ajoy Saha et al Am Heart J 2007

Fibrate TrialsAll Outcomes

Metaanalysis: Ajoy Saha et al Am Heart J 2007

COMBINATION LIPID THERAPYFor Patients with Metabolic Syndrome

Zhao et al. Am J Cardiol 2009

COMBINATION LIPID THERAPYWith and Without Metabolic Syndrome

Zhao et al. Am J Cardiol 2009

Zhao et al. Am J Cardiol 2009

COMBINATION LIPID THERAPYWith and Without Metabolic Syndrome

Sharma et al

Framingham CHD Score for Men

Framingham CHD Score for Men

Conroy et al.Eur Heart J

2003

Conroy et al.Eur Heart J

2003

Hayward et al Ann Int Med 2010

Hayward et al Ann Int Med 2010

Case StudiesCase Studies

24 yo ♂ construction worker.24 yo ♂ construction worker. Sx: vague joint pains which he treats with NSAIDS without much relief and which Sx: vague joint pains which he treats with NSAIDS without much relief and which

he attributes to work he attributes to work PMH: “high cholesterol”PMH: “high cholesterol” FHx: F died of MI at 40. 2 paternal aunts with MI aged 60,70. 2 sisters A&W.FHx: F died of MI at 40. 2 paternal aunts with MI aged 60,70. 2 sisters A&W. Diet: Likes fast food. Non smokerDiet: Likes fast food. Non smoker PE: BMI 25. BP 130/80PE: BMI 25. BP 130/80

+ arcus, xanthelasma+ arcus, xanthelasma

soft Ssoft S22

thickened achilles tendonsthickened achilles tendons Lab:Lab: Chol Chol 360360 TSH 2.9TSH 2.9

TGTG 100100 glucose 100glucose 100LDLLDL 290290 urine urine μμalb - negalb - negHDLHDL 5050

Dx:Dx: ?other diagnostic and lab tests ?other diagnostic and lab tests Rx:Rx: ?Diet?Diet

?Drug therapy?Drug therapyLipoprotein electrophoresis (Kaneka, HELP)Lipoprotein electrophoresis (Kaneka, HELP)

An Employment Physical

34 yo ♂ ICU Physician of Asian Indian background34 yo ♂ ICU Physician of Asian Indian background Sx:: None. Does c/o of decreased exercise toleranceSx:: None. Does c/o of decreased exercise tolerance PMH: Hyperlipidemia in past: - 2 years ago: Chol 200, TG 250, HDL 40, PMH: Hyperlipidemia in past: - 2 years ago: Chol 200, TG 250, HDL 40,

LDL 110; wt 165#LDL 110; wt 165# SHx:SHx: 20 lb weight gain since finishing Medical School. Was avid 20 lb weight gain since finishing Medical School. Was avid

runner/biker in past. Now works night shift, rarely exercises, eats lots of runner/biker in past. Now works night shift, rarely exercises, eats lots of pizza, hamburgers, frozen foods due to stress and lack of time. Non pizza, hamburgers, frozen foods due to stress and lack of time. Non smoker.smoker.

FHx: F CABG aged 50, one paternal uncle with high cholesterol on Zocor. FHx: F CABG aged 50, one paternal uncle with high cholesterol on Zocor. Sister with hypertriglyceridemia, 2 brothers A&W, no known problems..Sister with hypertriglyceridemia, 2 brothers A&W, no known problems..

Diet: Likes fast food, icecream. Non smokerDiet: Likes fast food, icecream. Non smoker PE: BMI 27. Wt. 170. WHR 0.92. BP 135/85PE: BMI 27. Wt. 170. WHR 0.92. BP 135/85

o/w unremarkableo/w unremarkable Lab:Lab:

Chol Chol 252252 TSH 2.9TSH 2.9 Lp(a)Lp(a) 10 mg/dl10 mg/dl

TGTG 210210 glucose 105glucose 105 apoBapoB 125 mg/dl125 mg/dl

LDLLDL 175175 urine urine μμalb – 15 ug/galb – 15 ug/g VLDL-CVLDL-C 53 mg/dl (beta 53 mg/dl (beta quant)quant)

HDLHDL 3535 Hyc – 7 Hyc – 7 μμmole/L mole/L Dx:Dx: ?other diagnostic and lab tests ?other diagnostic and lab tests Rx:Rx: ?Diet?Diet

?Drug therapy?Drug therapy

Evaluation for Hyperlipidemia

54 yo AA♀ Diabetic 54 yo AA♀ Diabetic Sx: polyuria, polydipsia. 10# weight loss over last 3-6 months. Pain in the Sx: polyuria, polydipsia. 10# weight loss over last 3-6 months. Pain in the

legs when walking.legs when walking. PMH: DM2 Dx’d 5 years ago. Post menopausal x 5 years. HTN x 3 years.PMH: DM2 Dx’d 5 years ago. Post menopausal x 5 years. HTN x 3 years.

Meds: Meds: glyburide glyburide 10 mg qd10 mg qd x 5 years x 5 years

premarin/proverapremarin/provera0.625/10 mg0.625/10 mg x 5 years x 5 years

HCTZHCTZ 25 mg qd25 mg qd x 3 years x 3 years

metoprolol metoprolol 50 mg bid50 mg bid x 6 months x 6 months SHx:SHx: On a 1800 kcal ADA low fat diet but is “frequently hungry”. On a 1800 kcal ADA low fat diet but is “frequently hungry”.

Weight maxed out at 230# 1 year ago. Weight maxed out at 230# 1 year ago. Non smokerNon smoker FHx: M with PVD who is diabetic and smokes. Currently on Tricor.FHx: M with PVD who is diabetic and smokes. Currently on Tricor. PE: BMI 28. Wt. 190. WHR 0.93. BP 140/85PE: BMI 28. Wt. 190. WHR 0.93. BP 140/85

+ arcus corniae+ arcus corniae

liver edge 2 FB below RCMliver edge 2 FB below RCM

+ bruit over R femoral artery+ bruit over R femoral artery

o/w unremarkableo/w unremarkable Lab:Lab:

Chol Chol 310310 TSH 2.9TSH 2.9 Alk Phos 185Alk Phos 185

TGTG 450450 glucose 210glucose 210 VLDL-CVLDL-C 144 mg/dl (beta 144 mg/dl (beta quant)quant)

LDLLDL -- HbA1C 9.5%HbA1C 9.5% LP Electrophoresis: broad beta bandLP Electrophoresis: broad beta band

HDLHDL 3030 urine urine μμalb – 150 ug/galb – 150 ug/g

Dx:Dx: ?other diagnostic and lab tests ?other diagnostic and lab tests Rx:Rx: ?Diet?Diet

?Drug therapy?Drug therapy

Evaluation for Hyperlipidemia

21 yo ♀ 21 yo ♀ Px: pancreatitis, lipemic serum. Px: pancreatitis, lipemic serum. HPI:HPI: Has noted abd pains increasing over last 3-6 months. Noted mild Has noted abd pains increasing over last 3-6 months. Noted mild

SOB, difficulty concentrating in school and pruritic rash over her sides SOB, difficulty concentrating in school and pruritic rash over her sides and buttocks prior to onset of abd pain. No history of gallstones.and buttocks prior to onset of abd pain. No history of gallstones.

PMH: PMH: Appendicitis in El Salvador at age 13.Appendicitis in El Salvador at age 13.

Meds: Meds: Orthotricyclin x 6 months.Orthotricyclin x 6 months. ROS:ROS: Onset abd pains around puberty when eating fatty meals. Pain Onset abd pains around puberty when eating fatty meals. Pain

seemed to wax and wane in monthly intervals and was worse when she seemed to wax and wane in monthly intervals and was worse when she ate more at celebrations. Stopped eating porc and fried foods after ate more at celebrations. Stopped eating porc and fried foods after appendicitis and has felt well since. appendicitis and has felt well since.

SHx:SHx: Comes from a small town in the highlands of El Salvador. No Comes from a small town in the highlands of El Salvador. No ETOH. Eats low fat diet. Has remained slim all her life. No regular ETOH. Eats low fat diet. Has remained slim all her life. No regular exercise except regular walking. Recently married but wants to finish exercise except regular walking. Recently married but wants to finish school before starting a family.school before starting a family.

FHx: F died at age 50 of “abdominal pain”. He liked to drink alcohol. Has FHx: F died at age 50 of “abdominal pain”. He liked to drink alcohol. Has 10 brothers and sisters. All in good health except her brother who came to 10 brothers and sisters. All in good health except her brother who came to US with her and was recently hospitalized with pancreatitis. US with her and was recently hospitalized with pancreatitis.

PE: PE: BMI 18. Wt. 110. BP 100/65BMI 18. Wt. 110. BP 100/65

Fundiscopic exam: lipemia retinalisFundiscopic exam: lipemia retinalis

fading eruptive xanthomata over the buttocks and flanks.fading eruptive xanthomata over the buttocks and flanks.

distended abdomen with peritoneal findings. distended abdomen with peritoneal findings.

Evaluation for Hypertriglyceridemia

continuedcontinued

Lab: Lab: Chol Chol 252252 TSH 2.9TSH 2.9 Lipase 15Lipase 15TGTG 52005200 glucose 155glucose 155 Na 125 K 3.8 Cl 99 CO2 20Na 125 K 3.8 Cl 99 CO2 20LDLLDL -- HbA1C 4.6%HbA1C 4.6%HDLHDL 1515

Dx:Dx: ?other diagnostic and lab tests ?other diagnostic and lab tests Refrigeration testRefrigeration test Lipoprotein electrophoresis (chylomicrons)Lipoprotein electrophoresis (chylomicrons) Apolipoprotein electrophoresis (apo C2)Apolipoprotein electrophoresis (apo C2)

Rx:Rx: acute – starvation plus insulin/glucose to maintain normoglycemiaacute – starvation plus insulin/glucose to maintain normoglycemia – – Consider plasma for known apo CII deficiencyConsider plasma for known apo CII deficiencydiscontinue/reverse predisposing drugs and/or causes of discontinue/reverse predisposing drugs and/or causes of

hyperlipidemiahyperlipidemia?Diet- very low fat < 20g fat/day. Supplement with MCT fat ?Diet- very low fat < 20g fat/day. Supplement with MCT fat

soluble vitamins prnsoluble vitamins prn?Drug therapy?Drug therapy fibratesfibrates niacinniacin +/- statins+/- statins consider fish oils, androgenic progestins/steroids in ♀/♂consider fish oils, androgenic progestins/steroids in ♀/♂

Evaluation for Hypertriglyceridemia

Continued

Other Therapy:Other Therapy:consider anti-oxidant therapy: consider anti-oxidant therapy:

Vit E 300 IU/qdVit E 300 IU/qdVit C 500/qdVit C 500/qdΒΒ-carotene 9000 i.u.qd-carotene 9000 i.u.qdmethionine 500 mg qd in divided doses. methionine 500 mg qd in divided doses.

Heaney AP et al. et al. Prevention of recurrent pancreatitis in familial lipoprotein lipase deficiencyPrevention of recurrent pancreatitis in familial lipoprotein lipase deficiencywith high-dose antioxidant therapy.with high-dose antioxidant therapy.JCEMJCEM. 1999 Apr;84(4):1203-5. . 1999 Apr;84(4):1203-5.

Evaluation for Hypertriglyceridemia