Lipids 101Lipids 101Lipids 101Lipids 101

Cardiology Board Review Cardiology Board Review

Med-Peds Style!Med-Peds Style!

TherapeuticLifestyle

Changes (TLC) Drug

CHD and CHDRisk Equivalents 24.1 20.710-year risk >20%

2+ Risk Factors 10.9 8.310-year risk 10–20%

2+ Risk Factors 14.6 2.810-year risk <10%

0–1 Risk Factor 15.6 4.7

Total 65.3M 36.5M

35

30.2

29

7.5

Americans requiring treatment for Hyperlipidemia

Inherited Dyslipidemias

Disease Phenotype AbnormalLipid

Defect Clinical presentation RiskofCHD

FamilialHypercholesterolemia

II a ↑LDL Defect i n LDLrecept or or apo-B-100 may beheterozygou s orhomozygous

Tendinou s xanthom ,asXanthelasma, PlanarxanthomasCorneal arcus

+++

Famili al lipoprotei n lipasedeficiency

I , V ↑chylomicrons Lipoprotei n Lipasedeficiency

Eruptiv e xanthomas, Lipemiaretinali ,s Abdomin al Pai ,nHepat -o splenomegaly

0

FamilialHypertriglyceridemia

I , V ↑VLDL Unknown Oft en asymptomatic +

Combined Hyperlipidemia I ib ↑V ,LDL LDL Unknown Oft en asymptomat ic exceptCH , D Yellow-orang e palmarcreases

+++

Familialdysbetalipoproteinemia

III ↑VLDL Defective or absentapo-E

Tuberoerupti ve xanthom ,asHyperuricemia, Glucoseintolerance, Corne al opacities

+++

Lecitihi -n cholesterolacetyltransferasedeficiency

N/A ↓HDL Rapid apo-A- 1catabolism

Renal insufficiency, Hemolyticanemia

+

Tangie r disease N/A ↓HDL Rapid H DL catabolism Corneal opacitie ,spolyneuropath , y orangetonsils

0

Metabolic Syndrome• Abdominal obesity (>40” in men; >35”

in women• Atherogenic dyslipidemia

– Elevated triglycerides (>150mg/dl)– High LDL– Low HDL (<40 in men; <50 in

women)

• Raised blood pressure (>130/85)• Insulin resistance ( glucose

intolerance)– Fasting glucose >110mg/dl

• Prothrombotic state• Proinflammatory state

3 Orange Criteria = Diagnosis!

Risk Assessment

• Measure fasting LDL in all patients beginning at age 20yo.

• For patients with multiple (2+) risk factors– Recheck LDL every 5 years

• For patients with 0–1 risk factor– 5 year risk assessment not

required– Most patients have 10-year risk

<10%

Major Risk Factors (Exclusive of LDL) That Modify LDL

Goals• Cigarette smoking• Hypertension (BP 140/90 mmHg or

on antihypertensive medication)

• Low HDL cholesterol (<40 mg/dL)† • Family history of premature CHD

– CHD in male first degree relative <55 years

– CHD in female first degree relative <65 years

• Age (men 45 years; women 55 years)

CHD Risk Equivalents

• Other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease)

• Diabetes (10-year risk for CHD =20%)• Multiple risk factors that confer a 10-

year risk for CHD >20%

Lifestyle Risk Factors

• Obesity (BMI 30)• Physical inactivity• Atherogenic diet

Causes of Secondary Dyslipidemia

• Diabetes• Hypothyroidism• Obstructive liver disease• Chronic renal failure• Drugs that raise LDL cholesterol and

lower HDL cholesterol (progestins, anabolic steroids, and corticosteroids)

Primary Prevention With LDL-Lowering Therapy

Public Health Approach

• Reduced intakes of saturated fat and cholesterol

• Increased physical activity• Weight control

Secondary Prevention With LDL-Lowering Therapy

• Benefits: reduction in total mortality, coronary mortality, major coronary events, coronary procedures, and stroke

• LDL cholesterol goal: <100 mg/dL• Includes CHD risk equivalents• Consider initiation of therapy during

hospitalization(if LDL 100 mg/dL)

LDL Goals and Cutpoints for Therapeutic Lifestyle Changes

(TLC) and Drug Therapy

Risk CategoryLDL Goal(mg/dL)

LDL to Initiate Therapeutic

Lifestyle Changes (TLC)

(mg/dL)

LDL to Consider

Drug Therapy (mg/dL)

CHD or CHD Risk

Equivalents(10-year risk

20%)

<100 100130

(100–129: drug optional)

2+ Risk Factors

(10-year risk 20%)

<130 130

10-year risk 10–20%: 130

10-year risk <10%: 160

0–1 Risk Factor <160 160

190 (160–189: LDL-lowering drug

optional)

July 14, 2004: NCEP updated stratified cholesterol

guidelinesVery high risk individuals: patients

with CAD AND DM, uncontrolled HTN, or metabolic risk factors including obesity, high triglycerides, and low HDL. Smokers with CAD. Goal of therapy--LDL < 70 mg/dl

High-risk individuals: CAD or DM or multiple risks factors -- Goal of therapy--LDL < 100 mg/dl

July 14, 2004: NCEP updated stratified cholesterol

guidelinesModerately high risk: Multiple risk

factors for CAD with a 10% to 20% chance of having an MI or cardiac death within a decade. If the LDL level is between 100-129 mg/dl then a statin drug may be started. Goal of therapy--LDL < 100 mg/dl

Lower or moderate risk: Dietary changes and exercise unless LDL levels are very high

LDL-Lowering Therapy…How low do we go?

Baseline LDL: <100 mg/dL• Further LDL lowering not required

except in CHD and CHD risk equivalent then use LDL <70

• Therapeutic Lifestyle Changes (TLC)

• Consider treatment of other lipid risk factors– Elevated triglycerides– Low HDL cholesterol

HMG CoA Reductase Inhibitors (Statins)

• Reduce LDL-C 18–55% & TG 7–30%

• Raise HDL-C 5–15%• Major side effects

– Myopathy– Increased liver enzymes

• Contraindications– Absolute: liver disease– Relative: use with certain drugs

Bile Acid SequestrantsCholestyramine, Colestipol, Colesevelam

• Major Actions– Reduce LDL-C 15–30%– Raise HDL-C 3–5%– May increase TG

• Side effects– GI distress/constipation– Decreased absorption of other drugs

• Contraindications– Dysbetalipoproteinemia– Raised TG (especially >400 mg/dL)

Nicotinic Acid• Major actions

– Lowers LDL-C 5–25%– Lowers TG 20–50%– Raises HDL-C 15–35%

• Side effects: flushing, hyperglycemia, hyperuricemia, upper GI distress, hepatotoxicity

• Contraindications: liver disease, severe gout, peptic ulcer

Fibric AcidsGemfibrozil, Fenofibrate, Clofibrate

• Major actions– Lower LDL-C 5–20% (with normal

TG)– May raise LDL-C (with high TG)– Lower TG 20–50%– Raise HDL-C 10–20%

• Side effects: dyspepsia, gallstones, myopathy

• Contraindications: Severe renal or hepatic disease

DRUG TREATMENT PLAN

If LDL goal not achieved, Consider higher dose of statin or add a bile acid sequestrant or nicotinic acid

If LDL goal not achieved, intensify drug therapy or refer to a lipid specialist

If LDL goal achieved, treat other lipid risk factors

MONITOR

6 wks 6 wks Q 4-6 mo

Start statin or bile acid sequestrant or nicotinic acid AFTER 3 MONTHS OF TLC

Classification of Serum Triglycerides

• Normal <150 mg/dL• Borderline high 150–199 mg/dL• High 200–499 mg/dL• Very high 500 mg/dL

Management of Very High Triglycerides (500

mg/dL)• Goal of therapy: prevent acute

pancreatitis• Very low fat diets (15% of caloric

intake)• Triglyceride-lowering drug usually

required (fibrate or nicotinic acid)• Reduce triglycerides before LDL

lowering

Causes of Low HDL Cholesterol (<40

mg/dL)• Elevated triglycerides• Overweight and obesity• Physical inactivity• Type 2 diabetes• Cigarette smoking• Very high carbohydrate diet

(>60%)• beta-blockers, anabolic steroids,

progestational agents

Management of Low HDL Cholesterol

• LDL cholesterol is primary target of therapy

• Weight reduction and increased physical activity (if the metabolic syndrome is present)

• Non-HDL cholesterol is secondary target of therapy (if triglycerides 200 mg/dL)

• Consider nicotinic acid or fibrates (for patients with CHD or CHD risk equivalents)

Previous In-service Topics

Hyperlipidemia due to secondary causes

Statin associated myositisTarget LDL in DM and HTNWhich statin is least likely to be

metabolized by P450 and least likely to interact with anti-retrovirals.

Causes of hypertriglyceridemia

Food for Thought…"The average American may be fine with an LDL of

120, but when we're born we have an LDL of 25 or 30. If we put statins in the drinking water, would it help public health? Yes, but public health endeavors would help more.

Our obesity epidemic needs to be conquered not with medicine but with effective change for the whole population. If you're looking at cost-effectiveness, it’s time to teach young people to eat right and exercise. We can do that -- or we can start throwing 10 medicines at them when they are 40 or 50 years old."

-Lawerence S. Sperling, MD Director of Emory Heart Center Risk Reduction Program