Screening, Diagnosis, and Treatment of Hyperlipidemia

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Screening, Diagnosis, and Treatment of
Hyperlipidemia

• Kimberly Williams, MD
• June 20, 2011

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Overview

• Screening
• Who needs screened?
• How often?
• Diagnosis
• Treatment
• Questions
• What do I do about triglycerides?
• What if a patient isnt at goal?
• What about all those warnings on increasing
  statin doses?
• What about low HDL?

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Why Screen?
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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 gt30)
• 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

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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
  (gt160 with 0-1 risk factors or gt130 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

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Ranking of Effective Clinical Preventive Services
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Diagnosis
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Diagnosis FH
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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?

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ATP III LDL Goals
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 gt20 lt100 gt100 gt130, optional 100-129
2 or more risk factors 10-year risk lt20 lt130 gt130 10yr risk 10-20 gt130 10yr risk lt10 gt160
0-1 risk factors lt160 gt160 gt190, optional gt160
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Case Studies

• 48 year old male
• Smoker, otherwise healthy
• Lipid panel
• Total 234
• TG 257
• HDL 41
• LDL 145
• What do you do??

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Risk Factors

• CHD equivalents
• DM
• Symptomatic Carotid Artery Disease
• Peripheral Artery Disease
• AAA
• /- Renal Failure (Crgt1.5)not ATPIII
• Major CHD Risk Factors
• Cigarette Smoking ?
• HTN (gt140/90 or antihypertensive meds)
• Low HDL (lt40)
• Family history of premature CHD (1ST degree
  relative lt55 men,lt65 women)
• Age (gt45 men, gt 55 women) ?
• HDL gt60 takes away one of the risk factors above

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ATPIII LDL Goals
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 gt20 lt100 gt100 gt130, optional 100-129
2 or more risk factors 10-year risk lt20 lt130 gt130 10yr risk 10-20 gt130 10yr risk lt10 gt160
0-1 risk factors lt160 gt160 gt190, optional gt160
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Treatment-Lifestyle Changes

• Weight loss if overweight
• BMI gt25
• 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

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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??

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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

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ATPIII LDL Goals
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 gt20 lt100 gt100 gt130, optional 100-129
2 or more risk factors 10-year risk lt20 lt130 gt130 10yr risk 10-20 gt130 10yr risk lt10 gt160
0-1 risk factors lt160 gt160 gt190, optional gt160
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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

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Risk Factors

• CHD equivalents
• DM
• Symptomatic Carotid Artery Disease
• Peripheral Artery Disease
• AAA
• /- Renal Failure (Crgt1.5)not ATPIII
• Major CHD Risk Factors
• Cigarette Smoking ?
• HTN (gt140/90 or antihypertensive meds) ?
• Low HDL (lt40) ?
• Family history of premature CHD (1ST degree
  relative lt55 men,lt65 women)
• Age (gt45 men, gt 55 women) ?
• HDL gt60 takes away one of the risk factors above

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Risk Factor Calculator

• If gt 2 risk factors then need to use Framingham
  calculator
• http//hp2010.nhlbihin.net/atpIII/calculator.asp?u
  sertypeprof

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ATPIII LDL Goals
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 gt20 lt100 gt100 gt130, optional 100-129
2 or more risk factors 10-year risk lt20 lt130 gt130 10yr risk 10-20 gt130 10yr risk lt10 gt160
0-1 risk factors lt160 gt160 gt190, optional gt160
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Treatment

• So, they need treatment.what do you choose and
  what dose?
• What if they have insurance?
• What if they have no insurance?

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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 cant tolerate statin
  or do not achieve goal with statin therapy alone

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Treatment-Drug Therapy

• Secondary PreventionKnown 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

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Statins
Atorvastatin 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 Less Lipophilic Lipophilic Lipophilic Less Hydrophilic Less Hydrophilic Lipophilic
Cost 100-140 100 4 WM 4 WM 140 10/yr then 4/mo Kmart
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Statin Efficacy
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Statin Side Effects

• Theyre so good, we should just add them to the
  water right???
• Well, maybe not

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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

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Statin Side Effects

• Muscle injury
• 2-11 myalgias, 0.5 myositis, lt0.1 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

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Statin Side Effects

• Proteinuriamixed results
• Cognitive Function
• possible slowing, memory loss
• Higher in lipophilic (Simvastatin, rosuvastatin)
• Diabetesprobably small increased risk
• Neuropathy
• Cataracts
• Pregnancy and Breastfeeding

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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

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Statin Side Effects

• Chronic Kidney Disease
• Atorvastatin and Fluvastatinno dose adjustment
• Chronic Liver Disease
• Pravastatin at low dose, and complete abstinence
  of ETOH
• In patient with NASHok to use

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• What if the patient cant tolerate statins?
• What if not at goal with statin alone?

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Non-Statin Therapy

• Bile Acid Sequestrans
• cholestyramine (Questran), colestipol (Colestid),
  coleselvelam (Welchol)
• Reduce LDL by 10-15
• Side effectsnausea, bloating, cramping
• Work in conjunction with statin or nicotinic acid
• 80-100/month

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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

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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
• gt 3 g per day of EPA/DHA
• Reduce TG by 25-30 or more
• Raises HDL by 3

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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

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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?

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Hypertriglyceridemia

• Definition of
• Normal lt150 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

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Treating High TG

• 200-500 (Mild to moderate)
• Dieteat less, avoid high carbs, high fructose
  foods, increase fish consumption
• If CHD risk factors, start Statin therapy
• gt500 aim at reducing TG
• Fibrate first then fish oil
• Dietreduce fat in diet, reduce ETOH intake
• If CHD risk factors and high TG
• Fibrate first to bring TG down below 500 then
  statin

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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 evalDoes have HTN, diabetes
  A1c 6.5

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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?

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ATPIII LDL Goals
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 gt20 lt100 gt100 gt130, optional 100-129
2 or more risk factors 10-year risk lt20 lt130 gt130 10yr risk 10-20 gt130 10yr risk lt10 gt160
0-1 risk factors lt160 gt160 gt190, optional gt160
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Treating to goal or dose??

• High-risk patientsStable 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 lt40)  OR Acute
  coronary syndrome
• Intensive statin thearpy
• Atorvastatin 40-80mg
• Rosuvastatin 20-40mg
• Simvastatin 80mg (higher side effects)
• Monitor closely for side effects

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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?

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HDLwhat 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

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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?

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Questions?