Dyslipidemia resident survival guide

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Overview

Classification

There are several ways in which lipoprotein abnormalities are classified. Lipoprotein disorders can be classified according to:

  • The pattern of change in the lipoprotein levels, described as hyperlipidemia (increase in lipid levels) and hypolipidemia (decrease in lipid levels): However, this classification is problematic because the lipids and lipoproteins levels in some situation can be elevated in some types of lipoproteins and lipids and decreased in others.
  • Phenotype, or the specific type of lipid that is increased, as classified by Fredrickson: This classification is problematic because it does not include abnormalities in the level of HDL.
  • Etiology, as primary (genetic) or secondary to another condition: This classification can be problematic, because most conditions involve the intersection of genetics and lifestyle issues. However, there are a few well defined genetic conditions that are usually easy to identify.
  • Levels of measured lipids (cholesterol and triglycerides), described as hypercholesterolemia and hypocholesterolemia or hypertriglyceridimia and hypotriglyceridemia: This distinction is not specific because it does not reflect the specific lipoprotein(s) that are abnormally high or low.

Fredrickson Classification of Hyperlipoproteinemia

 
 
 
 
 
 
 
 
 
 
 
 
 
Hyperlipoproteinemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Type I:
Familial hyperchylomicronemia
 
 
Type II
 
Type III:
Dysbetalipoproteinemia
 
Type IV:
Primary hypertriglyceridemia
 
Type V:
Mixed hyperlipoproteinemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Type A:
Familial hypercholesterolemia
 
Type B:
Familial combined hyperlipidemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Type A
 
Type B
 
Type C
 
 
 
 


Fredrickson classification of Hyperlipidemias
Hyperlipoproteinemia Synonyms Problems Labs description Treatment
Type I Buerger-Gruetz syndrome, primary hyperlipoproteinaemia, or familial hyperchylomicronemia Decreased lipoprotein lipase (LPL) or altered ApoC2 Elevated chylomicrons Diet control
Type IIa Polygenic hypercholesterolaemia or familial hypercholesterolemia LDL receptor deficiency Elevated LDL only Bile acid sequestrants, statins, niacin
Type IIb Combined hyperlipidemia Decreased LDL receptor and increased ApoB Elevated LDL, VLDL and triglycerides Statins, niacin, gemfibrozil
Type III Familial Dysbetalipoproteinemia Defect in ApoE synthesis Increased IDL Drug of choice: Gemfibrozil
Type IV Endogenous Hyperlipemia Increased VLDL production and decreased elimination Increased VLDL Drug of choice: Niacin
Type V Familial Hypertriglyceridemia Increased VLDL production and decreased LPL Increased VLDL and chylomicrons Niacin, gemfibrozil

Unclassified forms

Non-classified forms are extremely rare:

  • Hypo-alpha lipoproteinemia
  • Hypo-beta lipoproteinemia (prevalence 0.01-0.1%)

Classification According to Etiology

 
 
 
 
 
 
 
 
 
 
Lipoprotein Disorders
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Primary
(Genetic)
 
 
 
 
 
 
 
 
 
 
 
 
 
Secondary
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LDL
 
Chylomicron Remnants
 
Lipoproteins Rich in Triglyceride
(Chylomicrons, VLDL, IDL)
 
HDL
 
Multiple lipoproteins
 
Alcohol
Diabetes
Drugs
Liver disease
Obesity
Renal disease
Smoking
Thyroid
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
High LDL:
-Familial hypercholesterolemia
-Familial defective apo B 100
-Autosomal dominant hypercholesterolemia (PCSK9)
-Autosomal recessive hypercholesterolemia
-Familial sistosterolemia
-Familial lipoprotein a lipoproteinemia

Low LDL:
-Abetalipoproteinemia
-Hypobetalipoproteinemia
-PCSK 9 deficiency
 
-Deficiency in hepatic lipase
-Type III dysbetalipoproteinemia
 
-Deficiency in lipoprotein lipase
-Deficiency in Apo C-II
-Deficiency in Apo A-V
-Familial combined hyperlipidemia
-Familial hypertriglyceridemia
- Chylomicron retention disease
 
High LDL:
-Cholesteryl ester transferase protein deficiency

Low HDL:
-Deficiency in Apo A-I
-Deficiency in lecithin cholesterol acyltransferase (LCAT)
-Familial hypoalphalipoproteinemia
-Nieman-Pick disease
-Tangier disease
 
- Familial combined hypolipidemia (ANGPTL3)

Classification According to Laboratory Results

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lipid Laboratory Tests
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total cholesterol
 
 
 
 
 
LDL-C
 
 
 
 
 
HDL-C
 
 
 
 
 
Triglycerides
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
High total cholesterol
 
Low total cholesterol
 
High LDL
 
Low LDL
 
High HDL
 
Low HDL
 
High triglyceride
 
Low triglyceride

Causes

Secondary causes of dyslipidemia may cause either an increase in total-cholesterol & low density lipoprotein-cholesterol (LDL-C) or an increase in total triglycerides & very low density lipoprotein cholesterol (VLDL-C). Common causes are listed below.

Increase in Total Cholesterol and LDL-C

  • Hypothyroidism
  • Nephrosis
  • Dysgammaglobulinemia (systemic lupus erythematosus, multiple myeloma)
  • Cholestatic hepatic diseases due to abnormal lipoproteins (e.g. primary biliary cirrhosis)
  • Administration of protease inhibitors (treatment for HIV infection)
  • Administration of progestin or anabolic steroids

Increase in Total Triglycerides and VLDL-C

  • Chronic kidney disease
  • Type 2 diabetes mellitus
  • Obesity
  • Excessive alcohol intake
  • Hypothyroidism
  • Administration of anti-hypertensive therapy (thiazide diuretics or B-blockers)
  • Administration of corticosteroids
  • Severe stress that increases endogenous corticosteroid concentration
  • Elevated concentrations of estrogen (administration of oral (not transdermal) estrogen therapy, oral contraceptives, or pregnancy)
  • Administration of protease inhibitors (treatment for HIV infection)


To view a comprehensive list of dyslipidemia causes, click here

Screening

Abbreviations: ASA: American society of anesthesiologists; BP: Blood Pressure; CCS: Canadian cardiovascular society; CrCl: Creatinine clearance; CXR: Chest X-ray; DNI: Do not intubate; DNR: Do not resuscitate; ECG: Electrocardiogram; eGFR: estimated glomerular filtration rate; HR:Heart rate; INR: International normalized ratio; LMWH: Low molecular weight heparin; LV: Left ventricle; LVED: Left ventricular ejection fraction; NOAC: Novel oral anticoagulant; NPO: Nothing per os; PMI: Point of maximal impulse; PT: Prothrombin time; RR: Respiratory rate; SpO2: Oxygen saturation; T: Temperature; VT: Ventricular tachycardia

 
 
 
 
 
 
 
 
 
 
 
Identify risk factors for CAD

Major risk factors:

❑ Advanced age

❑ ↑ total serum cholesterol

❑ ↑ non-HDL-C (calculated by: total cholesterol minus HDL-C)

❑ ↑ LDL-C (either measured or calculated by: total cholesterol minus HDL-c minus (total triglycerides/5))

❑ ↓ HDL-C

❑ Diabetes mellitus

❑ Hypertension

❑ Cigarette smoking

❑ Family history of CAD

Additional risk factors:

❑ Obesity, especially abdominal

❑ Family history of hyperlipidemia

❑ Small, dense LDL-C

❑ ↑ Apo-B

❑ ↑ LDL particle number (measured by ApoB)

❑ Fasting/postprandial hypertriglyceridemia

❑ Polycystic ovarian syndrome

❑ Dyslipidemic triad

Non-traditional risk factors:

❑ ↑ lipoprotein

❑ ↑ clotting factors

❑ Inflamamtory markers (e.g. hsCRP or Lipoprotein-associated phospholipase A2 (Lp-PLA2)

❑ Hyperhomocysteinemia

❑ ApoE4 isoform

❑ ↑ uric acid
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Determine the 10-year risk of coronary event using ANY of the following assessment tools:

❑ Framingham Risk Assessment Tool (To be redirected to Framingham Risk Assessment Tool, click here)

❑ Reynolds Risk Score (To be redirected to Reynolds Risk Score website, click here)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
High
(Framingham 10-year global risk > 20%)
 
Intermediate
(Framingham 10-year global risk between 10% and 20%)
 
 
 
Lower
(Framingham 10-year global risk < 10%)
 
Optimal
(Framingham 10-year global risk < 10% with optimal levels or risk factors and heart-healthy lifestyle)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Does the patient have type 2 diabetes mellitus?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Does the patient have ALL the following criteria for low-risk dyslipidemia during previous work-up?

❑ Low LDL-C < 100 mg/dL, AND

❑ HDL-C > 50 mg/dL, AND

❑ Triglycerides < 150 mg/dL
 
 
 
 
 
 
Adult patient
 
 
 
 
 
 
 
 
 
 
Pediatric patient (age at least 2 years)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes. The patient has ALL of the criteria for low-risk dyslipidemia
 
Either unknown history of lipid profile or No, the patient does not have ALL of the criteria for low-risk dyslipidemia (at least 1 criterion is not met)
 
 
 
 
Does that patient have risk factors for CAD (listed above)?
 
 
 
 
 
 
 
 
 
 
Does the patient have risk factors for CAD (listed above)?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screen every 2 years
 
Screen annually
 
No
 
 
 
Yes
 
 
 
 
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screen patient more frequently than patients with no risk factors based on clinical judgement (unknown optimal interval)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Male patient
 
 
 
 
 
 
 
 
 
Female patient
 
 
 
 
 
Screen every 3 to 5 years
 
Do not screen patient for dyslipidemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Age between 20 and 45 years
 
Age > 45 years to 65 years
 
Age > 65 years
 
Age between 20 years and 55 years
 
Age > 55 years to 65 years
 
Age > 65 years
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screen every 5 years
More frequent screening is recommended for patients with risk factors for CAD (shown above)
 
Screen every 1 to 2 years
More frequent screening is recommended for patients with risk factors for CAD (shown above)
 
Screen annually
 
Screen every 5 years
More frequent screening is recommended for patients with risk factors for CAD (shown above)
 
Screen every 1 to 2 years
More frequent screening is recommended for patients with risk factors for CAD (shown above)
 
Screen annually
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Complete Diagnostic Approach

Boxes in red signify that an urgent management is needed.

Abbreviations: ASA: American society of anesthesiologists; BP: Blood Pressure; CCS: Canadian cardiovascular society; CrCl: Creatinine clearance; CXR: Chest X-ray; DNI: Do not intubate; DNR: Do not resuscitate; ECG: Electrocardiogram; eGFR: estimated glomerular filtration rate; HR:Heart rate; INR: International normalized ratio; LMWH: Low molecular weight heparin; LV: Left ventricle; LVED: Left ventricular ejection fraction; NOAC: Novel oral anticoagulant; NPO: Nothing per os; PMI: Point of maximal impulse; PT: Prothrombin time; RR: Respiratory rate; SpO2: Oxygen saturation; T: Temperature; VT: Ventricular tachycardia

 
 
 
 
 
 
 
 
 
 
Obtain a Detailed History

History of present illness

❑ Address specific patient symptoms and complaints

❑ Obtain review of systems relevant to dyslipidemia and diseases associated with dyslipidemia

❑ Headache
❑ Dizziness
❑ Syncope/presyncope
❑ Blurry vision / double vision / reduced visual acquity
❑ Dysphagia
❑ Slurred speech
❑ Facial drooping
❑ Chest pain / Angina
❑ Palpitations
❑ Dyspnea
❑ Cough
❑ Abdominal pain
❑ Change in bowel movements
❑ Lower extremity pain, weakness, or tingling
❑ Peripheral edema
❑ Muscle pain

❑ Intake of dietary fat, saturated fat, fiber, and cholesterol intake

❑ Exercise patterns

❑ History of alcohol use

❑ History of smoking

Past Medical History
❑ History of previous medical diagnoses / past medical complaints / hospitalizations and surgeries

❑ History of CAD or myocardial infarction

❑ History of diabetes mellitus

❑ History of hypertension

❑ History of renal disease

❑ History of hepatic disease

❑ History of stroke (ischemic or hemorrhagic) or transient ischemic attack (TIA)

❑ History of hypothyroidism

Medications

❑ Current prescribed medications

❑ List of over-the-counter drugs

❑ Previous intake of medications and reason for discontinuation

❑ History of drug adverse effects

❑ History of herbs and supplement use

❑ Compliance to medications

Allergies

❑ Known drug allergies

❑ Known environmental/food allergies

Family history
❑ Family history of dyslipidemia

❑ Family history of premature CAD (i.e. Established CAD in father or 1st degree male relative before the age of 55 years OR established CAD in mother or 1st degree female relative before the age of 65 years)

❑ Family history of hypothyroidism

❑ Family history of stroke/TIA

❑ Family history of peripheral vascular disease

Social History
❑ Overall living situation

❑ Occupation

❑ Exercise

❑ Diet (general)

❑ Smoking history

❑ Alcohol use

❑ Recreational drug use

❑ Stress

❑ Sexual lifestyle & contraceptive methods

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assess for CAD Risk Factors

Major risk factors:

❑ Advanced age

❑ ↑ total serum cholesterol

❑ ↑ non-HDL-C (calculated by: total cholesterol minus HDL-C)

❑ ↑ LDL-C (either measured or calculated by: total cholesterol minus HDL-c minus (total triglycerides/5))

❑ ↓ HDL-C

❑ Diabetes mellitus

❑ Hypertension

❑ Cigarette smoking

❑ Family history of CAD

Additional risk factors:

❑ Obesity, especially abdominal

❑ Family history of hyperlipidemia

❑ Small, dense LDL-C

❑ ↑ Apo-B

❑ ↑ LDL particle number (measured by ApoB)

❑ Fasting/postprandial hypertriglyceridemia

❑ Polycystic ovarian syndrome

❑ Dyslipidemic triad

Non-traditional risk factors:

❑ ↑ lipoprotein

❑ ↑ clotting factors

❑ Inflamamtory markers (e.g. hsCRP or Lipoprotein-associated phospholipase A2 (Lp-PLA2)

❑ Hyperhomocysteinemia

❑ ApoE4 isoform

❑ ↑ uric acid
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Evaluate possible causes of secondary dyslipidemia if suggested by findings during history-taking and physical examination
To view a complete list of dyslipidemia causes, click here
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Determine the 10-year risk of coronary event using ANY of the following assessment tools:

❑ Framingham Risk Assessment Tool (To be redirected to Framingham Risk Assessment Tool, click here)

❑ Reynolds Risk Score (To be redirected to Reynolds Risk Score website, click here)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Examine the patient

Vital signs
❑ High blood pressure
Skin
❑ Xanthomas (eruptive, tuberous, tendinous)
❑ Xanthelesma
❑ Cool hairless extremities (suggestive of peripheral vascular disease)
❑ Other skin rashes that may be suggestive of secondary causes (e.g. systemic lupus erythematosus, drug eruptions, pregnancy rash)
HEENT
❑ Arcus senilis (corneal arcus)
Neck
❑ Carotid bruits
❑ Thyromegaly (when dyslipidemia is caused by thyroid disease)
Peripheral
❑ Diminished distal pulses

❑ Femoral bruits
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Order tests to rule out secondary causes of dyslipidemia
Common causes include:

❑ Hypothyroidism

❑ Order TSH, FT4, and FT3

❑ Nephrosis

❑ Order serum creatinine and urinalysis with either spot urine for proteins or 24-hour urinary collection for proteins, urinary protein to creatinine ratio

❑ Dysgammaglobulinemia

❑ Order ANA, anti-dsDNA antibodies, plasma and urine electrophoresis

❑ Cholestatic hepatic diseases

❑ Order GGT, ALP, and bilirubins

❑ Chronic kidney disease

❑ Order serum creatinine, BUN, urinalysis, and renal ultrasound

❑ Type 2 diabetes mellitus

❑ Order glycemia and HbA1c

❑ Excessive alcohol intake
❑ Drugs

❑ Any of the following: estrogen, progestin, protease inhibitors, beta-blockers, corticosteroids, anabolic steroids, protease inhibitors

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Order fasting lipid profile
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total cholesterol
Optimal: < 200 mg/dL
Borderline: 200-239 mg/dL
High/very high risk: ≥ 240 mg/dL
 
LDL-C
May be either calculated or measured. Measured LDL-C is preferable, especially among certain high-risk populations (elevated triglycerides > 250 mg/dL, diabetes mellitus, peripheral vascular disease).
To calculate LDL-C, use the following equation: LDL-C=(total cholesterol-HDL-C)/(triglycerides/5). Do NOT calculate LDL-C when triglycerides > 200 mg/dL (low to no validity of the equation). Instead, use measured LDL-C.

Optimal: < 100 mg/dL
Borderline: 130-160 mg/dL
High risk: 160-189 mg/dL
Very high risk: ≥ 190 mg/dL
 
HDL-C
An optimal HDL-C concentration is a negative CAD risk factor in both genders (subtract 1 risk factor for CAD)

Optimal: ≥ 60 mg/dL
Borderline: 40-50 mg/dL (men) OR 50-59 mg/dL (women)
High/very high risk: < 40 mg/dL (men) OR < 50 mg/dL (women)
 
Triglycerides
Optimal: < 150 mg/dL
Borderline: 150-199 mg/dL
High risk: 200-499 mg/dL
Very high risk: ≥ 500 mg/dL
 
Additional tests

Non-HDL
non-HDL is calculated by the following equation: non-HDL=total cholesterol - HDL-C
non-HDL-C provides additional risk assessment information compared with LDL-C alone.
Calculate non-HDL-C only in the following cases: Either moderate elevation of triglyceride (between 200 to 500 mg/dL), diabetes mellitus, insulin resistance syndrome, or established CAD

ApoB
ApoB reflects LDL-C particle number, which may be a more potent measure of CVD risk than either LDL-C or LDL-C particle size
Optimal: < 90 mg/dL for patients with at risk of CAD (including diabetes mellitus) OR < 80 mg/dL for patients with established CAD or diabetes mellitus plus at least 1 additional risk factor

Ratio of ApoB/ApoAI
May be useful in evaluating residual risk (independent of LDL-C) in patients at high risk of CAD or patients with either established CAD, diabetes mellitus, or insulin resistance

hsCRP
Order hsCRP for patients with borderline risk or patients with LDL-C < 130 mg/dL
hsCRP helps further stratify patient risk for CVD

LP-PLA2
May provide more specificity than hsCRP and may be ordered for further stratification of CVD risk
 
 
 
 
 
 
 
 
 

Treatment

 
 
Confirmed Dyslipidemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Set lipid goals

❑ Total cholesterol target: < 200 mg/dL

❑ LDL-C target: < 70 mg/dL for very high risk patients OR < 100 mg/dL for all other patients

❑ HDL-C target: As high as possible. At least > 40 mg/dL in both genders

❑ Non-HDL-C target: 30 mg/dL above LDL-C goal (target < 100 mg/dL for very high risk patients OR < 130 mg/dL for all other patients)

❑ Triglycerides target: < 150 mg/dL

❑ ApoB target: < 90 mg/dL for patients at risk of CAD (including patients with diabetes) or < 80 mg/dL for patients with established CAD or diabetes plus at least one additional CAD risk factor
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Control modifiable CAD risk factors

❑ Hypertension

❑ Diabetes mellitus

❑ Obesity

❑ Cigarette smoking
 
Recommend lifestyle modification

❑ Recommend physical activity

❑ At least 30 minutes of moderate-intensity physical activity 4 to 6 times weekly
❑ Examples include brisk walking, riding stationary bicycle, water aerobics, cleaning/scrubbing/ mowing lawn, and sporting activities

❑ Recommend medical nutrition therapy (reduced calorie intake)

❑ Advise patients to have at least 5 servings/day of vegetables and fruits
❑ Advise patients to have more than 6 servings/day of grains, at least 1/3 of which are whole grain
❑ Advise patients to limit intake of saturated fat, trans-fats, and cholesterol
❑ Smoking cessation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lipid goal achieved with lifestyle modification alone?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer pharmacologic monotherapy
Table of available classes, generic names, recommended daily doses, and dose ranges also available below algorithm. Click here.

Statins
Administration of any of the following statins is recommended to manage dyslipidemia

Lovastatin: Recommended starting daily dose 20 mg PO once daily at bedtime. Dose range: 10-80 mg

Pravastatin: Recommended starting daily dose 40 mg PO once daily at bedtime. Dose range: 10-80 mg

Simvastatin: Recommended starting daily dose 20-40 mg PO once daily at bedtime. Dose range: 5-80 mg (80 mg not approved for therapy unless patient has been on treatment for more than 1 year without myopathy)

Fluvastatin: Recommended starting daily dose 40 mg PO once daily at bedtime. Dose range: 20-80 mg

Atorvastatin: Recommended starting daily dose 10-20 mg PO once daily at bedtime. Dose range: 10-80 mg

Rosuvastatin: Recommended starting daily dose 10 mg PO once daily at bedtime. Dose range: 5-40 mg

Pitavastatin: Recommended starting daily dose 2 mg PO once daily at bedtime. Dose range: 2-4 mg

Safety Monitoring with Statins
If statin therapy is to be initiated, the following lab parameters should be monitored

❑ Liver transaminases (AST and ALT) should be measured among asymptomatic patients as follows:
❑ Before initiation of statin therapy (baseline)
❑ At 3 months following initiation of statin therapy due to high risk of hepatotoxicity within 3 months of therapy.
❑ Every 6 months thereafter

❑ Creatine kinase (CK) should be measured only among symptomatic patients who complain of muscle pain/weakness

Fibrates
Administration of any of the following fibrates is recommended to manage dyslipidemia
Fenofibrate: Recommended starting daily dose 48-145 mg PO once daily. Dose range: 48-145 mg

Gemfibrozil: Recommended starting daily dose 1200 mg PO once daily. Dose range: 1200 mg

Fenofibric acid: Recommended starting daily dose 45-135 mg PO once daily. Dose range: 45-135 mg

Safety Monitoring with Fibric Acid
If fibric acid therapy is to be initiated, the following lab parameters should be monitored

❑ Liver transaminases (AST and ALT) measured as follows:
❑ Before initiation of statin therapy (baseline)
❑ At 3 months following initiation of fibric acid therapy due to high risk of hepatotoxicity within 3 months of therapy.
❑ Every 6 months thereafter

Nacin

Immediate release: Recommended starting daily dose 250 mg PO once daily at bedtime. Dose range: 250-3000 mg
Extended release: Recommended starting daily dose 500 mg PO once daily at bedtime. Dose range: 50-2000 mg

Safety Monitoring with Niacin
If niacin therapy is to be initiated, the following lab parameters should be monitored

❑ Liver transaminases (AST and ALT) should be measured among asymptomatic patients as follows:
❑ Before initiation of niacin therapy (baseline)
❑ Every 3 months following initiation of niacin therapy for the first year
❑ Every 6 months thereafter

Bile acid sequestrants
Administration of any of the following bile acid sequestrants is recommended to manage dyslipidemia
Cholestyramine: Recommended starting daily dose 8-16 mg PO once daily at bedtime. Dose range: 4-24 mg
Colestipol: Recommended starting daily dose 2 mg PO once daily at bedtime. Dose range: 2-16 mg
Colesevelam: Recommended starting daily dose 3.8 mg PO once daily at bedtime. Dose range: 3.8-4.5 mg

Cholesterol absorption inhibitors

Ezetimibe: Recommended starting daily dose 10 mg PO once daily at bedtime. Dose range: 10 mg
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aim to reduce LDL

❑ Statin monotherapy at recommended initial daily dose (LDL reduction: 21% to 55%)

❑ Fibrate monotherapy at recommended initial daily dose (LDL reduction: 20% to 25%)

❑ Niacin monotherapy at recommended initial daily dose (LDL reduction: 10% to 25%)

❑ Bile acid sequestrant monotherapy at recommended initial daily dose (LDL reduction: 10% to 25%)

❑ Ezetimibe monotherapy at recommended initial daily dose (LDL reduction: 10% to 18%)
 
Aim to reduce triglycerides

❑ Fibrates monotherapy at recommended initial daily dose with or without omega-3 fish oil (triglyceride reduction: 20% to 35%)

❑ Niacin monotherapy at recommended initial daily dose with or without omega-3 fish oil (triglyceride reduction: 20% to 30%)
 
Aim to increase HDL

❑ Niacin monotherapy at recommended initial daily dose (HDL increase: 10% to 35%)

❑ Fibrates monotherapy at recommended initial daily dose (HDL increase: 6% to 18%)

❑ Statin monotherapy at recommended initial daily dose (HDL increase: 2% to 10%)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lipid goal achieved with optimal administration of antilipidemic monotherapy?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Does the patient have ANY of the following criteria to initiate combination pharmacotherapy?

❑ Markedly elevated cholesterol concentration, OR

❑ Mixed dyslipidemia (e.g. Hypertriglyceridemia and reduced HDL-C), OR

❑ Patient developed or at high risk of developing drug-associated, dose-dependent adverse effects
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Consider changing drug class
❑ Reassess liver transaminase when changing drug class for statin, niacin, and fibrates
 
❑ Consider increasing dose of antilipidemic agent within dose range for each drug
❑ Reassess liver transaminase when increase dose for any of statin, niacin, or fibrates
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lipid goal achieved with optimal administration of antilipidemic monotherapy?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer combination therapy

Administer ANY of the following combination therapies: ❑ Ezetimibe/simvastatin (1 pill): Recommended starting daily dose 10/20 mg PO once daily at bedtime. Dose range: 10/10 to 10/80 mg, OR

❑ Extended-release niacin/simvastatin (1 pill): Recommended starting daily dose 500/20 mg PO once daily at bedtime. Dose range: 500/20 to 1000/20 mg
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Follow-up

❑ Reassess lipid profile at 6 weeks following initiation of management

❑ If goal is not achieved following 6 weeks, reassess 6 weeks later. Continue 6-week interval until target lipid profile is achieved

❑ Once target lipid profile is achieved, generally reassess lipid profile within 6 months to 12 months

❑ Consider more frequent lipid profile reassessments in the following conditions
❑ Deterioration of diabetic control
❑ Administration of new drug that is known to affect lipid profile
❑ Progression of atherothrombotic disease
❑ Considerable weight gain
❑ Unexpected adverse derangement in any parameter of the lipid profile
❑ Development of new risk factor for CAD
❑ For all patients (symptomatic or asymptomatic) receiving either statin, fibric acid, or niacin, assess liver tranaminases (AST and ALT) at 3 months
❑ For patients receiving either statin or fibric acid: Repeat liver transaminase reassessment every 6 months thereafter.
❑ For patients receiving niacin: Repeat liver transaminase reassessment every 3 months for the first year, then every 6 months thereafter.
❑ For patients receiving statin therapy who are complaining of significant myalgia or muscle weakness
❑ Assess creatine kinase (CK) to confirm or rule out myopathy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Do's

  • Treat pediatric patients who are older than 8 years of age with either LDL-C > 190 mg/dL or LDL > 160 mg/dL plus any of the following conditions: either ≥ 2 CV risk factors even after lifestyle intervention, family history of premature CAD, or overweight/obese/insulin resistance.

Don'ts

  • Do not routinely order homocysteine, uric acid, plasminogen activator inhibitor 1, or other inflammatory markers.
  • Do not routinely perform non-invasive measures of atherosclerosis (e.g. carotid intima media thickness).
  • Do not treat dyslipidemia among post-menopausal women with hormonal replacement therapy.

References