Lipids 101

Cardiology Board Review Med-Peds Style!

Americans requiring treatment for Hyperlipidemia

CHD and CHD Risk Equivalents 10-year risk >20% 2+ Risk Factors 10-year risk 10 –20% 2+ Risk Factors 10-year risk <10% 0 –1 Risk Factor Total Therapeutic Lifestyle Changes (TLC) 24.1

10.9

14.6

15.6

35 30.2

65.3M

Drug 20.7

8.3

2.8

4.7

29 7.5

36.5M

Inherited Dyslipidemias Disea se Familial Hype rchole st er ole mia Familial l ipopr ot ein l ipa se def icie ncy Familial Hype rtri gl yc er idemia Comb ined Hyp er lipidemia Familial dysb eta lipopr ot eine mia Leciti hin- chole st er ol a cet yl tran sf era se def icie ncy Tan gier dise ase Phe noty pe Abnorma l Lipid II a I , V Def ect  LDL  chylo micr ons Def ect in LDL r ecept or or ap o- B 100 may be he ter oz ygous o r homoz ygous Lipoprot ein L ipase def icie ncy I , V I ib  VLDL  VLDL, LDL Unknown Unknown III N/A N/A    VLDL HDL HDL Clinic al p re se ntat ion Te ndinous xa nt homas, Xant hel asm a, Pla nar xa nt homas Cor ne a l ar cus Eru pt ive xant homa s, Lipemia r eti na lis, Abdominal Pa in, Hepa t o- splen omeg a ly Oft en as ympt oma t ic Risk of CHD +++ 0 + Def ect ive or abs ent a po- E Ra pid ap o- A- 1 catab olism Ra pid HDL c atab olism Oft en as ympt oma t ic e xcept CHD, Yell ow- ora nge pa lmar cr ea se s Tub er oer up ti ve xa nt homas, Hype rur icemia, Glu cose int ole ran ce , Cor ne al opa cit ie s Re na l insuff icie ncy , H e molyt ic a ne mia +++ +++ + Cor ne a l opa cit ie s, polyne ur opat hy, ora nge t onsils 0

Metabolic Syndrome

• Abdominal obesity (>40” in men; >35” in women • Atherogenic dyslipidemia 3 Orange Criteria = – Elevated triglycerides (>150mg/dl) Diagnosis!

– 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

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 Category CHD or CHD Risk Equivalents (10-year risk



20%) 2+ Risk Factors (10-year risk



20%) 0 –1 Risk Factor LDL Goal (mg/dL) <100 <130 <160 LDL to Initiate Therapeutic Lifestyle Changes (TLC) (mg/dL)



100 LDL to Consider Drug Therapy (mg/dL)



130 (100 –129: drug optional) 10-year risk 10 – 20%:



130



130



160 10-year risk <10%:



160



190 (160 –189: LDL lowering drug optional)

July 14, 2004: NCEP updated stratified cholesterol guidelines

Very 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 guidelines

Moderately 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 Sequestrants

Cholestyramine, 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 Acids

Gemfibrozil, 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

Start statin or bile acid sequestrant or nicotinic acid AFTER 3 MONTHS OF TLC 6 wks If LDL goal not achieved, Consider higher dose of statin or add a bile acid sequestrant or nicotinic acid 6 wks If LDL goal not achieved, intensify drug therapy or refer to a lipid specialist Q 4-6 mo If LDL goal achieved, treat other lipid risk factors M O I N T O R

Classification of Serum Triglycerides

• Normal • Borderline high • High • Very high <150 mg/dL 150 –199 mg/dL 200 –499 mg/dL  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 myositis  Target LDL in DM and HTN  Which 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