Mahesh Moolani, M.D. Diplomat American Board Of Internal Medicine and Lipidology What’s The Big FAT Deal?

Mahesh Moolani, M.D.

Diplomat American Board Of Internal Medicine and Lipidology

What’s The Big FAT Deal?

CHOLESTEROL

A soft waxy substance found among lipids (fats) in the bloodstream and all cells

Needed for digesting fats, making hormones, building cell walls

Carried in particles called lipoproteins that act as transport vehicles delivering cholesterol to various body tissues to be used, stored or excreted

Excess circulating cholesterol can lead to plaque formation- Atherosclerosis

HYPERLIPIDEMIA OR DYSLIPIDEMIA

(A consequence of abnormal lipoprotein metabolism)

Elevated Total Cholesterol (TC) Elevated Low-density lipoproteins (LDL) Elevated triglycerides (TG) Decreased High-density lipoproteins (HDL)

The story of lipids

Chylomicrons transport fats from the intestinal mucosa to the liver

In the liver, the chylomicrons release triglycerides and some cholesterol and become low-density lipoproteins (LDL).

LDL then carries fat and cholesterol to the body’s cells.

High-density lipoproteins (HDL) carry fat and cholesterol back to the liver for excretion.

The story of lipids (cont.) When oxidized LDL cholesterol gets

high, atheroma formation in the walls of arteries occurs, which causes atherosclerosis.

HDL cholesterol is able to go and remove cholesterol from the atheroma.

Atherogenic cholesterol → LDL, VLDL, IDL

Types of Cholesterol

LDL- (“bad” cholesterol) The major cholesterol carrier in the blood. Excess most likely to lead to plaque formation. Goal: LOW

HDL- (“good” cholesterol) Transports cholesterol away from arteries and back to the liver to be eliminated. Removes excess cholesterol from plaques, slowing growth. Goal: HIGH

TYPES (CONT.)

Triglycerides- the chemical form in which most fat exists in foods as well as in the body. Present in blood plasma and together with cholesterol, form the plasma lipids. Made in the body from other energy sources like carbohydrates. Calories ingested in a meal and not immediately used by tissues are converted to triglycerides..

PRIMARY DYSLIPIDEMIA ETIOLOGY SINGLE OR MULTIPLE GENE MUTATION –

RESULTING IN DISTURBANCE OF LDL, HDL AND TRIGYLCERIDE, PRODUCTION OR CLEARANCE.

Should be suspected in patients with premature heart disease family hxof atherosclerotic dx. Or serum cholesterol level >240mg/dl. Physical signs of hyperlipidemia.

Hereditary Causes of Hyperlipidemia Familial Hypercholesterolemia

Occurs in 1 in 500 individuals Mutation in LDL receptor, resulting in elevated levels of LDL at

birth and throughout life High risk for atherosclerosis, tendon xanthomas (75% of

patients), tuberous xanthomas and xanthelasmas of eyes. Familial Combined Hyperlipidemia

Increased secretions of VLDLs Dysbetalipoproteinemia

Affects 1 in 10,000 Increased risk for atherosclerosis, peripheral vascular disease Tuberous xanthomas, striae palmaris

Causes of SECONDARY Hyperlipidemia Diet Hypothyroidism Nephrotic

syndrome Anorexia nervosa Obstructive liver

disease Obesity Diabetes mellitus Pregnancy

Obstructive liver disease

Acute heaptitis Systemic lupus

erythematousus AIDS (protease

inhibitors)

SECONDARY DYSLIPIDEMIA (Most adult cases of dyslipidemia are secondary in nature in western civilizations)

Sedentary lifestyle Excessive consumption of cholesterol

– saturated fats and trans-fatty acids.

Specific Dyslipidemias: Very High LDL (> 190mg/dl)

Causes and Diagnosis

Genetic disordersMonogenic familial

hypercholesterolemiaFamilial defective apolipoprotein B-

100 (Apo B)Polygenic hypercholesterolemia

Family testing to detect affected relatives

Dietary sources of Cholesterol

Type of Fat Main Source Effect on Cholesterol levels

Monounsaturated Olives, olive oil, canola oil, peanut oil, cashews, almonds, peanuts and most other nuts; avocados

Lowers LDL, Raises HDL

Polyunsaturated Corn, soybean, safflower and cottonseed oil; fish

Lowers LDL, Raises HDL

Saturated Whole milk, butter, cheese, and ice cream; red meat; chocolate; coconuts, coconut milk, coconut oil , egg yolks, chicken skin

Raises both LDL and HDL

Trans Most margarines; vegetable shortening; partially hydrogenated vegetable oil; deep-fried chips; many fast foods; most commercial baked goods

Raises LDL

Why Do We Care?

According to the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Cholesterol in Adults

(NCEP ATP-III):

High LDL levels are a leading cause of coronary heart disease (CHD) and should be the main target of any cholesterol lowering regimen

Checking lipids

Nonfasting lipid panel measures HDL and total cholesterol

Fasting lipid panel Measures HDL, total cholesterol and

triglycerides LDL cholesterol is calculated:

LDL cholesterol = total cholesterol – (HDL + triglycerides/5)

When to check lipid panel Two different Recommendations

Adult Treatment Panel (ATP III) of the National Cholesterol Education Program (NCEP)

Beginning at age 20: obtain a fasting (9 to 12 hour) serum lipid profile consisting of total cholesterol, LDL, HDL and triglycerides

Repeat testing every 5 years for acceptable values

ATP III Lipid and Lipoprotein Classification

LDL Cholesterol (mg/dl) HDL Cholesterol (mg/dl)

<100 Optimal < 40 Low

100-129 Near/Above Optimal > 60 High (Desirable)

130-159 Borderline High

160-189 High

>190 Very High

Categories of Risk that Modify LDL Goals

CHD and CHD risk equivalents <100

Multiple (2+) risk factors <130

Zero to one risk factor <160

Major Risk Factors For CHD That Modify LDL GoalsCigarette smoking

Hypertension (BP >140/90 or on BP med)Low HDL cholesterol (<40mg/dl)Family Hx premature CHD- CHD in male 1st degree relative <55 years old- CHD in female 1st degree relative <65 years old

Age (men >45 yrs. women >55 yrs) HDL >60 counts as a “negative” risk factor. It’s presence

removes one risk factor from the total count

Risk Assessment for CHD

Diabetes regarded as a CHD equivalent

For patients with multiple (2+) risk factors

-Perform 10 year risk assessment

For patients with 0-1 risk factor-Most have 10 year risk assessment

<10%; risk assessment scoring unnecessary

Current ATP III Guidelines for Treating LDL Cholesterol

Risk Risk CategoryCategory

LDL GoalLDL Goal

(mg/dl)(mg/dl)

LDL level to LDL level to initiate TLCinitiate TLC

LDL level to LDL level to consider Rx consider Rx therapytherapy

CHD or CHD or EquivalentsEquivalents

<100<100

<70 Ideal<70 Ideal

> 100> 100 >> 130 130(100-129 Rx (100-129 Rx optional)optional)

2+ Risk 2+ Risk FactorsFactors

<130<130 > 130> 130 >> 130 (10 Year 130 (10 Year risk 10-20%)risk 10-20%)

>> 160 (Risk <10%) 160 (Risk <10%)

0-1 Risk 0-1 Risk FactorFactor

<160<160 > 160> 160 >> 190 190

(160-189 Rx (160-189 Rx optional)optional)

A Model of Steps in Therapeutic Lifestyle Changes (TLC)

Visit 1

Begin TLC

•Emphasize reduction in saturated fat & chol.

•Encourage moderate Physical activity

•Consider referral to dietician

Visit 2 (6 wks)

Eval. LDL response

Intensify Tx if not to goal

•Reinforce dietary recommendations

•Consider adding plant stanols/sterols

•Increase fiber intake

•Consider dietician

Visit 3 (6 wks)

Eval LDL response

Consider adding Rx if not to goal

•Evaluate for Metabolic syndrome

•Intensify wt mgmt & physical activity

•Consider dietician

Visit N

Monitor adherence to

TLC Q4-6 mos

Nutrient Recommendations of TLC Diet

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 25-30% of total calories Carbohydrates 50-60% of total calories Fiber 20-30 grams/day Protein Approx. 15% of total calories Cholesterol <200 mg/day Total calories Balance energy intake and

expenditure to maintain desirable body weight/

prevent weight gain

Food Pyramid

Medications for Hyperlipidemia

Drug Class Agents Effects (% change) Side Effects

HMG CoA reductase inhibitors

Lovastatin

Pravastatin

LDL (18-55), HDL (5-15)

Triglycerides (7-30)

Myopathy, increased liver enzymes

Cholesterol absorption inhibitor

Ezetimibe LDL( 14-18), HDL (1-3)

Triglyceride (2)

Headache, GI distress

Nicotinic Acid LDL (15-30), HDL (15-35)

Triglyceride (20-50)

Flushing, Hyperglycemia,

Hyperuricemia, GI distress, hepatotoxicity

Fibric Acids Gemfibrozil

Fenofibrate

LDL (5-20), HDL (10-20)

Triglyceride (20-50)

Dyspepsia, gallstones, myopathy

Bile Acid sequestrants

Cholestyramine LDL

HDL

No change in triglycerides

GI distress, constipation, decreased absorption of other drugs

Specific Dyslipidemias: Low HDL

Causes of Low HDL (<40 mg/dl)

Elevated triglycerides Overweight and obesity Physical Inactivity Type 2 diabetes Cigarette smoking Very high carb. intakes (>60% energy) Medications (some beta blockers,

anabolic steroids, progestational agents)

Specific Dyslipidemias: Elevated Triglycerides

Classification of Serum Triglycerides

Normal <150 mg/dl Borderline High 150-199

mg/dl High 200-499mg/dl Very High >500 mg/dl

Specific Dyslipidemias: Elevated Triglycerides

Causes of Elevated Triglycerides

Obesity and overweight Physical Inactivity Cigarette smoking Excess alcohol intake High carb. diets Several diseases (Type 2 DM, chronic renal

failure, nephrotic syndrome Medications (corticosteroids, estrogens,

retinoids, higher doses of beta blockers

Specific Dyslipidemias: Elevated Triglycerides

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 lowering LDL

Lipid Lowering Drugs

HMG-CoA Reductase Inhibitors (Statins)

Partially block an enzyme necessary for formation of cholesterol

Speed removal of LDL from blood 18%-60% reduction in LDL Most effective at lowering LDL; esp. HS dosing Liver enzymes MUST be monitored. Check

baseline, 3mos., then semi-annually (D/C if > 3x normal limits)

Side effects: Myalgias (D/C if total CK >10x normal), rhabdomyolysis

Metabolized by CP450 (watch for drug interactions)

Lipid Lowering Drugs

Bile Acid Sequestrants

Convert cholesterol to bile acids Bind bile acids and prevent

reabsorption in the gut May increase triglyceride levels Most common side effects: GI-

constipation Alternative for statins

Lipid Lowering Drugs

Cholesterol Absorption Inhibitor: Zetia Monotherapy or in combination with statin Reduces LDL number : esp. Lp(a)

Lipid-Regulating Agent: Omega 3 acid ethyl esters (Lovaza)

Omega 3 Fish oil (salmon, herring, mackerel, swordfish, albacore tuna, sardines, lake trout)

Only FDA approved supplement for tx of dyslipidemias

Decreases hepatic production of TG and VLDL Increases LDL size to large buoyant particles

Lipid Lowering Drugs

Nicotinic Acid/Niacin

Reduces production and release of LDL Effective in reduction of triglycerides

(<400mg/dl) Increases HDL Very effective in increasing LDL particle

size Monitor liver enzymes and glucose Most common side effect: FLUSHING (take

ASA/ibuprofen 30 min. prior and take with light snack). Decreased with time released formulas (Niaspan)

Lipid Lowering Drugs

Fibric Acid Derivatives/Fibrates

Very effective in reducing triglycerides (>400)

Increase HDL Containdications: Gallbladder disease,

hepatic disease, renal dysfunction Increase LDL particle size but not

quantity Caution with statins

Case Study 1

35 YO male, a police officer. 5’11’’, weight=258 (BMI=35, obese)

Hx: hypertension, anxiety. Has taken testosterone supplements in past, now uses “body building” shakes.

Family Hx: Father, paternal grandfather-DM

Labs: FBS=79, TSH normal

Case Study 1

Visit 1 Visit 2 Visit 3TC= 167 164 158TG=539 288 260HDL= 18 24 28LDL= ? 95 88Tricor started Niaspan Levaza (intolerant)

Case Study 2

39 YO male (hasn’t been in for 2 years) c/o frequent urination, excessive thirst, blurred vision.

Hx: Mod. Obesity, BMI= 33Family Hx: Mother DMMeds: NoneNon-fasting Accucheck= 297 (3 hrs PP)

Case Study 2

TCTC 705705 252252 212212 195195 144144

TrigTrig 67106710 149149 146146 128128 123123

HDLHDL 170170 3333 3636 3939 4242

LDLLDL ?? 190190 140140 131131 8282

A1CA1C 11.911.9 5.65.6 5.65.6

MedsMeds Tricor Tricor and and DM txDM tx

Zocor Zocor 20mg20mg

Zocor Zocor 40mg40mg

Add Add ZetiaZetia

Case Study 3

62 YO Female with CHD s/p CABG wanted me to manage lipids. Also has Hypertension.

Meds: Plavix, Atenolol, lisinopril, Atorvastatin (stopped by pt.-myalgias)

Current labs:TC= 248Trig= 144HDL= 41LDL= 156

Case Study 3

Changed atenolol to Coreg Started Pravachol 20mg Disease management/diet counseling Resume walking 3-4 days/week Repeat labs:TC=190 Increase Pravachol …178Trig= 130 to 40mg …128HDL= 39 …41LDL= 112 …98

Framingham Risk Prediction Score 47 YO Female Labs: TC= 178 Trig= 133 LDL= 110

HDL= 35 BP: 162/98 Hx: Smoker, non-diabetic

What is 10 Year CHD Risk?

Framingham Risk Prediction Score 47 YO Female Labs: TC= 178 Trig= 133 LDL= 110 HDL=

35 BP: 162/98 Hx: Smoker, non-diabetic

What is 10 Year CHD Risk?

10% Compared to average of 5% for her age group

Treatment of Dyslipidemias(Medication Comparison Chart)Which Medication(s) slows coronary

athersclerosis, lowers LDL, increases HDL but has no effect on triglycerides?

Treatment of Dyslipidemias(Medication Comparison Chart)Which Medication(s) slows coronary

athersclerosis, lowers LDL, increases HDL but has no effect on triglycerides?

Mevacor

NCEP ATP III Lipid Goals

What is the recommended LDL goal for a healthy normo-tensive, non-smoking 46 year old male whose father died of a massive MI at the age of 52?

NCEP ATP III Lipid Goals

What is the recommended LDL goal for a healthy normo-tensive, non-smoking 46 year old male whose father died of a massive MI at the age of 52?

<130 for 2 risk factors(age >45 and father with

premature CAD)

Final Question!!!!!

58 Year old Male (smoker)

Fam. Hx: Mother with NIDDM, sister died age 70 from MI

BP= 156/86 Pulse 78

Labs: TC= 310, TG= 250, HDL=29, LDL=156, FBS=88

What is Framingham 10 year Risk score? Based on score, what is LDL goal? Name 2 cholesterol medications (Brand) that

would be most appropriate for his treatment.

Final Question!!!!!

58 Year old Male (smoker)Fam. Hx: Mother with NIDDM, sister died age 70

from MIBP= 156/86 Pulse 78Labs: TC= 310, TG= 250, HDL=29, LDL=156,

FBS=88

What is Framingham 10 year Risk score? 27% Based on score, what is LDL goal? <100 Name 2 cholesterol medications (Brand) that

would be most appropriate for his treatment. Niaspan, any “statin” except Mevacor, any of the combination meds

Thank You

Questions?

Glenda Summerville