Screening, Diagnosis, and Treatment of Hyperlipidemia

Kimberly Williams, MDJune 20, 2011

Overview

Screening› Who needs screened?› How often?

Diagnosis Treatment Questions

› What do I do about triglycerides?› What if a patient isn’t at goal?› What about all those warnings on increasing

statin doses?› What about low HDL?

Why Screen?

Who to Screen? USPSTF

› Men 35 and older (Grade A) 20-35 with increased risk for CAD (Grade B)

› Women 45 and older (Grade A) 20-45 if at increased risk (Grade B)

› Increased risk defined as presence of any one of the following: Diabetes Previous personal history of CHD or non-coronary atherosclerosis (e.g.,

abdominal aortic aneurysm, peripheral artery disease, carotid artery stenosis)

A family history of cardiovascular disease before age 50 in male relatives or age 60 in female relatives

Tobacco use Hypertension Obesity (body mass index [BMI] >30)

› Total cholesterol and HDL-C on non-fasting or fasting Can check LDL-C, but requires fasting sample

› About every 5 years, more frequent if level close to needing treatment

Who to Screen?

NCEPIII (ATPIII)› Once every 5 years for all people 20 years and

older› Patients without CHD or equivalent, re-screen

every 5 years unless cholesterol is borderline (>160 with 0-1 risk factors or >130 with 2+ risk factors) then re-screen in 1-2 years

› Screen with fasting lipid panel (preferred) or total cholesterol and HDL

AAFP› Males 35 and older, Females 45 and older› Fasting lipid panel or total and HDL

Ranking of Effective Clinical Preventive Services

Diagnosis

Case Studies 35 year old female

› Depression, History of gestational diabetes, obese

Lipid panel› Total 234› TG 257› HDL 38› LDL 145

What do you do? When do you repeat her lipid panel?

Risk Category

LDL goal LDL level at which to initiate therapeutic lifestyle changes

LDL level at which to consider drug therapy

CHD, CHD equivalent or 10-year risk >20%

<100 >100 >130, optional 100-129

2 or more risk factors 10-year risk <20%

<130 >130 10yr risk 10-20% >13010yr risk <10%: >160

0-1 risk factors

<160 >160 >190, optional >160

ATP III LDL Goals

Case Studies

48 year old male› Smoker, otherwise healthy

Lipid panel› Total 234› TG 257› HDL 41› LDL 145

What do you do??

Risk Factors

CHD equivalents› DM› Symptomatic Carotid Artery Disease› Peripheral Artery Disease› AAA› +/- Renal Failure (Cr>1.5)—not ATPIII

Major CHD Risk Factors› Cigarette Smoking › HTN (>140/90 or antihypertensive meds)› Low HDL (<40)› Family history of premature CHD (1ST degree relative <55

men,<65 women)› Age (>45 men, > 55 women) › HDL >60 takes away one of the risk factors above

Risk Category

LDL goal LDL level at which to initiate therapeutic lifestyle changes

LDL level at which to consider drug therapy

CHD, CHD equivalent or 10-year risk >20%

<100 >100 >130, optional 100-129

2 or more risk factors 10-year risk <20%

<130 >130 10yr risk 10-20% >13010yr risk <10%: >160

0-1 risk factors

<160 >160 >190, optional >160

ATPIII LDL Goals

Treatment-Lifestyle Changes

Weight loss if overweight› BMI >25

Aerobic Exercise› Moderate exercise most days a week › 30min, 5x per week

Diet› Increase fruits and vegetables, 5+ servings per day› High Fiber› Decrease trans fats

Stick and full fat margarine, commercial baked goods, fried foods, fast food

Case Studies

61 year old male› Diabetic, former smoker (quit 10 years

ago, 30 pack year history)› Lipid panel

Total 230 TG 569 HDL 20 LDL 96, Direct LDL 124

What do you do??

Diabetes as a risk factor

ATP III considers DM a CHD equivalent Another suggestion for looking at DM

› Men over age 40 with type 2 DM and any other CHD risk factor, or over age 50 with or without other CHD risk factors

› Women over age 45 with type 2 DM and any other CHD risk factor, or over age 55 with or without other CHD risk factors

› Men or women of any age who have had DM (type 1 or type 2) for more than 20 years if they have another risk factor or more than 25 years without another risk factor

Risk Category

LDL goal LDL level at which to initiate therapeutic lifestyle changes

LDL level at which to consider drug therapy

CHD, CHD equivalent or 10-year risk >20%

<100 >100 >130, optional 100-129

2 or more risk factors 10-year risk <20%

<130 >130 10yr risk 10-20% >13010yr risk <10%: >160

0-1 risk factors

<160 >160 >190, optional >160

ATPIII LDL Goals

Case Studies

53 year old male› Smoker, HTN (on BP meds, now BP in

130s/70s)› Lipid panel

Total Cholesterol 198 TG 128 HDL 26 LDL 146

Risk Factors

CHD equivalents› DM› Symptomatic Carotid Artery Disease› Peripheral Artery Disease› AAA› +/- Renal Failure (Cr>1.5)—not ATPIII

Major CHD Risk Factors› Cigarette Smoking › HTN (>140/90 or antihypertensive meds) › Low HDL (<40) › Family history of premature CHD (1ST degree relative <55

men,<65 women)› Age (>45 men, > 55 women) › HDL >60 takes away one of the risk factors above

Risk Factor Calculator

If > 2 risk factors then need to use Framingham calculator

http://hp2010.nhlbihin.net/atpIII/calculator.asp?usertype=prof

Risk Category

LDL goal LDL level at which to initiate therapeutic lifestyle changes

LDL level at which to consider drug therapy

CHD, CHD equivalent or 10-year risk >20%

<100 >100 >130, optional 100-129

2 or more risk factors 10-year risk <20%

<130 >130 10yr risk 10-20% >13010yr risk <10%: >160

0-1 risk factors

<160 >160 >190, optional >160

ATPIII LDL Goals

Treatment

So, they need treatment….what do you choose and what dose?

What if they have insurance?

What if they have no insurance?

Treatment-Drug Therapy

Primary Prevention› Lowering Cholesterol in patient without CHD or

CHD equivalents Lifestyle Modification Statin therapy

20-30% reduction in CHD events seen in most trials Moderate dose (40mg lovastatin, pravastatin,

simvastatin, 20mg atorvastatin) Non-statin therapy

Some studies showed increase in noncardiovascular mortality

ATPIII would recommend if can’t tolerate statin or do not achieve goal with statin therapy alone

Treatment-Drug Therapy

Secondary Prevention—Known CHD or CHD equivalents› Initiate moderate dose statin therapy› If statin therapy is not tolerated, initiate

non-statin› Some suggest starting statins even if LDL

is at goal in pts with CHD/CHD equivalents

StatinsAtorvastatin

Fluvastatin

Lovastatin

Pitavastatin

Pravastatin

Rosuvastatin

Simvastatin

Brand Lipitor Lescol Mevacor Livalo Pravachol Crestor Zocor

LDL 38-54% 17-33% 29-48% 31-41% 19-40% 52-63% 28-48%

Dose 10-80 20-80 20-80 1-4 10-40 10-40 10-80

Time of admin

Evening Bedtime With meals Anytime Bedtime Anytime Evening

HDL * *** **

TG * *

Side effect

Lipophilic LessLipophilic

Lipophilic Lipophilic LessHydrophilic

LessHydrophilic

Lipophilic

Cost $100-140 $100 $4 WM $4 WM $140 $10/yr then $4/moKmart

Statin Efficacy

Statin Side Effects

They’re so good, we should just add them to the water right???

Well, maybe not…

Statin Side Effects

Hepatic Dysfunction› 0.5-3% occurrence of persistent elevation

of LFTs, may not be that much more than placebo

› Mixed recommendations on whether or not to monitor LFTs

› If elevated look for drug interactions, other causes of liver disease

› Consider decreasing dose or changing meds if persistently 3x upper limit of normal

Statin Side Effects

Muscle injury› 2-11% myalgias, 0.5% myositis, <0.1%

rhabdo› Myalgias can occur with normal CK› Usually occurs weeks-months after starting

statin and returns to normal days-weeks after stopping

› Less likely with pravastatin or fluvastatin› Hypothyroidism increase risk› Increased risk with gemfibrozil

Statin Side Effects

Proteinuria—mixed results Cognitive Function

› possible slowing, memory loss› Higher in lipophilic (Simvastatin,

rosuvastatin) Diabetes—probably small increased risk Neuropathy Cataracts Pregnancy and Breastfeeding

Statin Drug Interactions

Coumadin› Use pravastatin, fluvastatin, rosuvastatin

Avoid rosuvastatin with protease inhibitors

Gemfibrozil› Use pravastatin or fluvastatin

Cyclosporine› Use pravastatin

Plavix› Any statin OK

Statin Side Effects

Chronic Kidney Disease› Atorvastatin and Fluvastatin—no dose

adjustment Chronic Liver Disease

› Pravastatin at low dose, and complete abstinence of ETOH

› In patient with NASH—ok to use

What if the patient can’t tolerate statins?

What if not at goal with statin alone?

Non-Statin Therapy

Bile Acid Sequestrans› cholestyramine (Questran), colestipol

(Colestid), coleselvelam (Welchol)› Reduce LDL by 10-15%› Side effects—nausea, bloating, cramping› Work in conjunction with statin or nicotinic

acid› $80-$100/month

Non-Statin Therapy

Nicotinic Acid› 1500-2000mg› Reduce TG by 15-25%› Raises HDL by 30-35%› Monitor glycemic control carefully in diabetics› Flushing in 80% of patients, Nausea, puritis and

parasthesias in about 20%, reduced by taking 325mg of ASA 30min prior to Nicotinic Acid

› Can lead to hepatocellular injury, must monitor LFTs› OTC preparations not regulated

Slo-Niacin $25 Niaspan $100

Non-Statin Therapy

Ezetimibe› Reduce LDL by 17% at 10mg/day› Increases LDL lowering properties of statin,

but end-point benefit unclear› May increase incidence of myopathy

Fish Oil› > 3 g per day of EPA/DHA› Reduce TG by 25-30% or more› Raises HDL by 3%

Non-Statin Therapy

Fibrates› Gemfibrozil (Lopid), Fenofibrate (Tricor)› Reduce TG levels by 20-50%› Raise HDL by 11%› Gemfibrozil increases risk of muscle

toxicity with statin› Non TG hyperlipidemia, no real evidence

for decrease in mortality› Reduce coumadin dose by 30%

CASE STUDIES

51 year old male› HTN, Tobacco Abuse, depression, chronic

back pain› Simvastatin 40mg, Tricor 145mg› Lipid Panel

Total 163 TG 484 LDL 42 HDL 24

› What should you do about TG?

Hypertriglyceridemia

Definition of :› Normal <150 mg/dL (1.7 mmol/L)› Borderline high — 150 to 199 mg/dL (1.7 to 2.2 mmol/L)› High — 200 to 499 mg/dL (2.3 to 5.6 mmol/L)› Very high — ≥500 mg/dL (≥5.7 mmol/L)

Independent risk factor for CHD, possibly for other vascular events Associated with

› low levels of HDL› Insulin Resistance

Disorders that raise TG› Obestiy HIV antiretrovirals› DM Glucocortiocids› Nephrotic Syndrome Retinoids› Pregnancy› Hypothyroism› Estrogen› B-blockers

Treating High TG

200-500 (Mild to moderate)› Diet—”eat less,” avoid high carbs, high

fructose foods, increase fish consumption› If CHD risk factors, start Statin therapy

>500 aim at reducing TG› Fibrate first then fish oil› Diet—reduce fat in diet, reduce ETOH intake

If CHD risk factors and high TG› Fibrate first to bring TG down below 500

then statin

CASE STUDIES

70 year old, no health care, told BP was high in the past, and has been high at Wal-mart

Initial lipid panel› Total Cholesterol 344› TG 109› HDL 63› LDL 259 VLDL 22

Further testing and eval—Does have HTN, diabetes A1c 6.5

CASE STUDIES

70 year old continued› Started Simvastatin 40mg, walking 1

mile/day› Lipid panel 4 months later

Total Cholesterol 256 TG 118 HDL 65 LDL 167

› NOT AT GOAL, WHAT DO YOU DO?

Risk Category

LDL goal LDL level at which to initiate therapeutic lifestyle changes

LDL level at which to consider drug therapy

CHD, CHD equivalent or 10-year risk >20%

<100 >100 >130, optional 100-129

2 or more risk factors 10-year risk <20%

<130 >130 10yr risk 10-20% >13010yr risk <10%: >160

0-1 risk factors

<160 >160 >190, optional >160

ATPIII LDL Goals

Treating to goal or dose??

High-risk patients—Stable CHD or High CHD risk› Moderate dose of statin

Lovastatin, pravastain, simvastatin 40mg Atorvastatin 20mg Rosuvastatin 5-10mg

Very High risk › Established CHD PLUS Multiple major risk factors (especially

diabetes)  OR Severe and poorly controlled risk factors (especially continued smoking)  OR Multple risk factors of the metabolic syndrome (especially triglycerides ≥200 plus non-HDL-C ≥130 plus HDL-C <40)  OR Acute coronary syndrome

› Intensive statin thearpy Atorvastatin 40-80mg Rosuvastatin 20-40mg Simvastatin 80mg (higher side effects) Monitor closely for side effects

CASE STUDIES

46 year old male› Bipolar, schizophrenia, tobacco abuse,

hyperlipidemia› “Allergy” to pravastatin-blurred vision, loss of

vision, double vision› Zetia 10mg› Lipid Panel

Total Cholesterol 201 TG 131 LDL 149 VLDL 26 HDL 26

› Do you do anything about his HDL?

HDL—what do we do about it?

ATPIII › Benefit has really only been seen in

secondary prevention› Could consider in patients with strong

family history› Get LDL to goal› Intensify weight management, physical

activity and smoking cessation› Treat hypertriglyceridemia

CASE STUDIES

47 year old male› DM, HTN, Hyperlipidemia, Obesity› Simvastatin 40mg, Tricor 145mg› Lipid panel

Total Cholesterol 198 TG 128 HDL 26 LDL 146 VLDL 26

› LDL not at goal, what do you do?

Questions?