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WORK SHOP: DYSLIPIDEMIAWORK SHOP: DYSLIPIDEMIA

Apiradee SriwijitkamolDivision of Endocrinology and Metabolism

Department of MedicineFaculty of Medicine Siriraj Hospiral

Case 1

25 year old womanCame for check upShe had family history of dyslipidemia.Her brother had CABG last year.PELab: CH 560, TG 340,

HDL-C 30

What is the diagnosis?A. Combined dyslipidemiaB. Familial dyslipidemiaC. Secondary dyslipidemia

Case 2

25 year old womanCame for check upShe had no family history of dyslipidemia.PE: P 60/min, myoedema +ve, diffuse

thyroid enlargement 40 gLab: CH 360, TG 240, HDL-C 30


Case 3

35 year old manHad skin lesion as shownHe had family history of diabetes.PE: Lab: CH 260, TG 540, HDL-C 30

FPG 180, A1C 8%


Approach to Dyslipidemia

Familial DyslipidemiaSecondary DyslipidemiaPrimary Dyslipidemia


Familial Dyslipidemia

Tendon xanthomas

Tuberous xanthomas

Xanthelasma

Corneal arcus

Signs of longstanding high LDL-C

Eruptive xanthomas Palmar xanthomas

Lipemia Retinalis

Signs of High trigeridemia

Fredrickson classification of lipid disorders

Typical lipid levelsFredericksonphenotype Lipoprotein abnormality

I

IIa

IIb

III

IV

V

Chylomicron

LDL

LDL, VLDL

Remnant of VLDL (IDL), Chylomicron

VLDL

VLDL, Chylomicron

TG

TC

TC,TG,ApoB

TC,TG

TG

TG

Chylomicron Test

•Persistent lipemia•After 12 hr fast•Place in the refrigerator (4°C) for 6-10 hour

•creamy layer: defect in chylomicron metabolism•Turbid: disorder of VLDL catabolism•Clear: disorder of LDL catabolism

Fredrickson classification of lipid disorders

Typical lipid levelsFredericksonphenotype Lipoprotein abnormality

I

IIa

IIb

III

IV

V

Chylomicron

LDL

LDL, VLDL

Remnant of VLDL (IDL), Chylomicron

VLDL

VLDL, Chylomicron

TG

TC

TC,TG,ApoB

TC,TG

TG

TG


Secondary Dyslipidemia

Secondary causes of Dyslipidemia

Diabetes mellitusAlcohol overuseChronic kidney diseaseHypothyroidismPrimary biliary cirrhosis and other cholestaticliver diseasesDrugs such as– Thiazides– β-blockers– Retinoids– highly active antiretroviral agents– estrogen and progestins– glucocorticoids.

Case 1

25 year old womanCame for check upShe had family history of dyslipidemia.Her brother had CABG last year.PELab: CH 560, TG 340,

HDL-C 30

Tuberous xanthomas


Case 2

25 year old womanCame for check upShe had no family history of dyslipidemia.PE: P 60/min, myoedema +ve, diffuse

thyroid enlargement 40 gLab: CH 360, TG 240, HDL-C 30

Diagnosis: Hypothyroidism


Case 3

35 year old manHad skin lesion as shownHe had family history of diabetes.PE: Lab: CH 260, TG 540, HDL-C 30

Eruptive xanthoma


Case 4

45 year old manTaxi driverFamily Hx of CVD: fatherSmoking 1 pack/yrBMI 18, WC 80BP 150/90CH 250, TG 350, HDL 50, LDL 130FPG 93

What should be treated first?A. LDL-CB. TriglyceridesC. HDL-C

Case 5

45 year old manTeacherBMI 30, BP 130/90CH 380, TG 1,200, HDL 35, LDL 205FPG 180, A1C 8.0%

What should be treated first?A. LDL-CB. TriglyceridesC. HDL-C

Case 4 (again)


What is his LDL-C goal?A. 70B. 100C. 130D. 160

Case 5 (again)



Case 6

45 year old manTeacherNo family history of DM or dyslipidemiaBMI 30, BP 130/90CH 240, TG 200, HDL 30, LDL 170FPG 103



NCEP GUIDELINE

Approach to the Patient at Risk for CHD

- Count risk factors;if more than 2, use Framinghamrisk score

- Rule outsecondary hyperlipidemia

11Assess the

Patient’s RiskStatus

- Determine goal LDL-C according to global risk

22

Get LDL-Cto Goal

33

Get Non HDL-Cto Goal

First Step: Risk Assessment

Multiple (2 ormore) Risk factors

That confers a Risk of 10-20% in 10 years)

HTSmokingLow HDLAgeFamily history of

premature CHD

ModMod

Zero to 1Risk factors

10-year risk < 10%

LowLow

DMPADAAASymptomatic

carotid a. diseaseMultiple risk

factors that confer a risk of >20% in 10 yearsCKD

HighHigh

CHD or CHD riskEquivalent

Note: Risk estimates were derived from the experience of the Framingham Heart Study, a predominantly Caucasian population in Massachusetts, USA.

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.

Assessing CHD Risk in MenStep 1: Age

Years Points20-34 -935-39 -440-44 045-49 350-54 655-59 860-64 1065-69 1170-74 1275-79 13

Step 2: Total Cholesterol

TC Points at Points at Points at Points at Points at(mg/dL) Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79

<160 0 0 0 0 0160-199 4 3 2 1 0200-239 7 5 3 1 0240-279 9 6 4 2 1≥280 11 8 5 3 1

HDL-C(mg/dL) Points

≥60 -150-59 040-49 1<40 2

Step 3: HDL-Cholesterol

Systolic BP Points Points(mm Hg) if Untreated if Treated

<120 0 0120-129 0 1130-139 1 2140-159 1 2≥160 2 3

Step 4: Systolic Blood Pressure

Step 5: Smoking Status

Points at Points at Points at Points at Points atAge 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79

Nonsmoker 0 0 0 0 0Smoker 8 5 3 1 1

AgeTotal cholesterolHDL-cholesterolSystolic blood pressureSmoking statusPoint total

Step 6: Adding Up the Points

Point Total 10-Year Risk Point Total 10-Year Risk<0 <1% 11 8%0 1% 12 10%1 1% 13 12%2 1% 14 16%3 1% 15 20%4 1% 16 25%5 2% ≥17 ≥30%6 2%7 3%8 4%9 5%

10 6%

Step 7: CHD Risk

ATP III Framingham Risk Scoring

Point Total 10-Year Risk Point Total 10-Year Risk<9 <1% 20 11%9 1% 21 14%

10 1% 22 17%11 1% 23 22%12 1% 24 27%13 2% ≥25 ≥30%14 2%15 3%16 4%17 5%18 6%19 8%

Assessing CHD Risk in Women



Step 1: Age

Years Points20-34 -735-39 -340-44 045-49 350-54 655-59 860-64 1065-69 1270-74 1475-79 16

TC Points at Points at Points at Points at Points at(mg/dL) Age 20-39 Age 40-49 Age 50-59 Age 60-69Age 70-79

<160 0 0 0 0 0160-199 4 3 2 1 1200-239 8 6 4 2 1240-279 11 8 5 3 2≥280 13 10 7 4 2

HDL-C(mg/dL) Points

≥60 -150-59 040-49 1<40 2



<120 0 0120-129 1 3130-139 2 4140-159 3 5≥160 4 6







Step 7: CHD Risk







premature CHD

ModMod


10-year risk < 10%

LowLow

DMPADAAASymptomatic



HighHigh

CHD or CHD riskEquivalent Moderate

10-year risk < 10%

Moderately high10-year risk 10-20%

Very highCombinations




11Assess the



22

Get LDL-Cto Goal

or optional

100 mg/dL*

or optional

70 mg/dL*

NCEP ATP III: LDL-C Goals (2004 Modifications)

Grundy SM et al. Circulation 2004;110:227-239.

High Risk

CHD or CHD risk equivalents

(10-yr risk >20%)

LD

L-C

level

100

160

130

190

Lower Risk

< 2 risk factors

Moderately High Risk

≥ 2 risk factors

(10-yr risk 10-20%) goal

160mg/dL

goal

130mg/dL

70 -

goal

100 mg/dL

Moderate Risk

≥ 2 risk factors

(10-yr risk <10%)

goal

130 mg/dL

Existing LDL-C goals

Proposed LDL-C goals




11Assess the



22

Get LDL-Cto Goal

33

Get Non HDL-Cto Goal

Non-HDL-C: Secondary Target after LDL-C

Non-HDL-Cholesterol

= (Total Cholesterol)-(HDL-Cholesterol)

Goal = (goal of LDL-Cholesterol) + 30 mg/dl

Case 4 (again)




Assessing CHD Risk in MenStep 1: Age

Years Points20-34 -935-39 -440-44 045-49 350-54 655-59 860-64 1065-69 1170-74 1275-79 13


TC Points at Points at Points at Points at Points at(mg/dL) Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79

<160 0 0 0 0 0160-199 4 3 2 1 0200-239 7 5 3 1 0240-279 9 6 4 2 1≥280 11 8 5 3 1

HDL-C(mg/dL) Points≥60 -1

50-59 040-49 1<40 2



<120 0 0120-129 0 1130-139 1 2140-159 1 2≥160 2 3







Point Total 10-Year Risk Point Total 10-Year Risk<0 <1% 11 8%0 1% 12 10%1 1% 13 12%2 1% 14 16%3 1% 15 20%4 1% 16 25%5 2% ≥17 ≥30%6 2%7 3%8 4%9 5%

10 6%

Step 7: CHD Risk


or optional

100 mg/dL*

or optional

70 mg/dL*



High Risk


(10-yr risk >20%)

LD

L-C

level

100

160

130

190

Lower Risk

< 2 risk factors


≥ 2 risk factors


160mg/dL

goal

130mg/dL

70 -

goal

100 mg/dL

Moderate Risk

≥ 2 risk factors

(10-yr risk <10%)

goal

130 mg/dL




Case 5 (again)


or optional

100 mg/dL*

or optional

70 mg/dL*



High Risk


(10-yr risk >20%)

LD

L-C

level

100

160

130

190

Lower Risk

< 2 risk factors


≥ 2 risk factors


160mg/dL

goal

130mg/dL

70 -

goal

100 mg/dL

Moderate Risk

≥ 2 risk factors

(10-yr risk <10%)

goal

130 mg/dL




Case 6


New Criteria for Diagnosis MSNCEP, IDF, AHA

3 out of 5Diagnosis

< 40 (M)or 50 (F)

HDL-C (mg/dl)> 150TG (mg/dl)

> 130/85BP (mmHg)100FPG (mg/dl)

WC >90 (M)or 80 (F)

Obesity

Criteria

Alberti KG. Circulation. 2009;120:1640.

Metabolic syndrome increase risk of cardiovascular events regardless of Framingham risk score

Girman CJ, et al. Am J Cardiol. 2004;93:136-141.





premature CHD

ModMod


10-year risk < 10%

LowLow

DMPADAAASymptomatic



HighHigh

CHD or CHD riskEquivalent Moderate

10-year risk < 10%

Moderately high10-year risk 10-20%

Very highCombinations


Case 4 (again again)


What is the management?A. Lifestyle modificationB. StatinC. FibratesD. Ezetimibe




Case 6 (again)




Management of Dyslipidemia

• Reinforce reductionin saturated fat andcholesterol

• Consider addingplant stanols/sterols

• Increase fiber intake• Consider referral to

a dietitian

• Initiate Tx forMetabolicSyndrome

• Intensify weightmanagement &physical activity

• Consider referral to a dietitian

6 wks 6 wks Q 4-6 mo

• Emphasizereduction insaturated fat &cholesterol

• Encouragemoderate physicalactivity

• Consider referral toa dietitian

Visit IBegin LifestyleTherapies

Visit 2Evaluate LDLresponseIf LDL goal notachieved, intensifyLDL-Lowering Tx

Visit 3Evaluate LDLresponseIf LDL goal notachieved, consideradding drug Tx

A Model of Steps in Therapeutic Lifestyle Changes

MonitorAdherenceto TLC

Visit N

All Dietary Recommendations

Nutrient Recommended Intake

Saturated fat* <7% of total calories

Polyunsaturated fat Up to 10% of total calories

Monounsaturated fat Up to 20% of total calories

Total fat 25% - 35% of total calories

Carbohydrate (esp. complex carbs) 50% - 60% of total calories

Fiber 20 – 30 g/d

Protein ~15% of total calories

Cholesterol <200 mg/d

*Trans fatty acids also raise LDL-C and should be kept at a low intake.Note: Regarding total calories, balance energy intake and expenditure to maintain desirable body weight

New Options to Lower LDL-C

Avoid

− Trans fatty acids*

Add

− Dietary fiber

− Plant sterol/stanol ester margarines

Expert Panel. JAMA. 2001;285:2486-2497.

*Keep trans fatty acids low

Trans fat

8 grams

5 grams

7 grams

42 grams: trans fat 3 grams

A

B

C

D

Fat•Fat 1 portion = 45 Calories

•1 portion = 1 teaspoon or 5 grams

•Example of 1 portion:

•Oil 1 teaspoon

•Peanut 10 grains

•Fried bacon 1 piece

Fats

↑ LDL and ↓ HDLMost margarines; partially hydrogenated vegetable oil; deep-fried chips; many fast foods; most commercial baked goods

Trans

↑ LDL and HDLWhole milk, butter, cheese, and ice cream; red meat; chocolate; coconuts, coconut milk, and coconut oil

Saturated

↓ LDL; ↑ HDLCorn, soybean, safflower, and cottonseed oils; fish

Polyunsaturated

↓ LDL; ↑ HDLOlives oil, canola oil, peanut oil; cashews, almonds, peanuts, and most other nuts; avocados

Monounsaturated

Effects on lipid profiles

SourceType of fat

Dietary Adjuncts

TLC for patients with LDL-C = 160

Walden CE, et al. Arterioscler Thromb Vasc Biol. 1997;17:375-382.Jenkins DJ, et al. Curr Opin Lipidol. 2000;11:49-56.Cato N. Stanol meta-analysis. Personal communication, 2000.

––3636TotalTotal

––1616Plant Plant stanolsstanols/sterols (2 g/d)/sterols (2 g/d)

––88Viscous fiber (10Viscous fiber (10––25 g/d)25 g/d)

––1212Low saturated fat/dietary Low saturated fat/dietary cholesterolcholesterol

LDLLDL--C C ↓↓ (mg/(mg/dLdL))Dietary ComponentDietary Component



LDL-C goal = 100


Drug Class MechanismInterfere with cholesterol synthesis, upregulate LDL receptors, reduce VLDL-C, increase HDL-C, reduce non–HDL-C

Reduces VLDL-C production, decreases uptake of HDL-C

Activate PPARα, increase lipoprotein lipase activity, decrease VLDL-C production

Statins

Niacin

Fibrates

Prevent reabsorption of bile acids, upregulate LDL receptors

Bile-acid binding resins

Cholesterol absorption inhibitors

Selectively inhibit intestinal cholesterol absorption

Medications for treatment ofDyslipidemia

Adapted from Gotto AM Jr. Management of lipid and lipoprotein disorders. In: Gotto AM Jr, Pownall HJ, eds. Manual of Lipid Disorders. Baltimore: Williams & Wilkins; 1992; Rubins HB, et al. N Engl J Med. 1999;341:410-418.* Adapted from NCEP ATP III. Circulation. 2002;106:3143-3421.

Resins ↓ 20%

Nicotinic acid ↓ 25%

Fibrates ↓ 15%

Statins ↓ 15%–60%

Selective cholesterol —absorption inhibitor*

Drug Class TC LDL HDL TG

Variable

↓ 20%–50%

↓ 20%–50%

↓ 10%–40%

No change

↑ 3%–5%

↑ 15%–35%

↑ 6%–15%

↑ 3%–15%

↑ 4%–9%

↓10%–20%

↓10%–15%

Variable

↓ 20%–60%

↓ 15%–20%

Effects on lipid profiles



LDL-C goal = 100


Case 6 (again)


LDL-C goal = 100



45 year old manTeacherBMI 30, BP 130/90CH 240, TG 200, HDL 30, LDL 170FPG 103

•He was prescribed simvastatin 20 mg/d•2-month later, he complaint muscle painat his arm and thigh that he’s never experienced before•His CPK is normal

What should you do?A. Prescribed muscle relaxant + NSAIDSB. Reduced dose of simvastatinC. Stop simvastatinD. Change to gemfibrozil

Side Effects of Approved Drug Classes for Treating Dyslipidemia

Piepho RW. Am J Cardiol. 2000;86(suppl):35L-40L.

GI effects/discomfort < 5% GI problems < 6% ↑ Liver enzymes < 2% ↑ Liver enzymes ≤ 5%Myopathy < 0.3% Gallstones < 2%

Myopathy ~ 0.2%

(cholestyramine and colestipol)Flushing up to 90% Constipation ~ 30%Itching ~ 40% Heartburn ~ 20%Hyperglycemia ~ 8% Bloating ~ 10%Hyperuricemia ~ 5% Nausea ~ 10%Hepatitis < 1%

Statins Fibrates

Niacin SR Formulation Bile-Acid Binding Resins

Selective Cholesterol Absorption Inhibitor

Drug interaction with Statin

FibratesCyclosporinAzole antifungiMacrolide antibioticVerapamilHIV protease inhibitorsAmiodarone


45 year old manTeacherBMI 30, BP 130/90CH 240, TG 200, HDL 30, LDL 170FPG 103

•He was prescribed simvastatin 20 mg/d•2-month later, he complaint muscle painat his arm and thigh that he’s never experienced before•His CPK is normal

What should you do?A. Prescribed muscle relaxant + NSAIDSB. Reduced dose of simvastatinC. Stop simvastatinD. Change to gemfibrozil

Conclusion

Management of Dyslipidemia– Type of dyslipidemia– First Treat LDL-C, except TG > 1000– What is LDL-C goal?– Lifestyle modification always– Consider proper lipid lowering agents– Drugs interaction?– Side effects?


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WORK SHOP: DYSLIPIDEMIA - rcpt.org...คณะแพทยศาสตร ศ ร ราชพยาบาล มหาว ทยาล ยมห ดล WORK SHOP: DYSLIPIDEMIA Case