screening › who needs screened? › how often? diagnosis treatment questions › what do i do...
TRANSCRIPT
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?