Updated: 12/21/2019

Hypercholersterolemia / Hyperlipidemia

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Snapshot
  • A 45-year-old woman presents to her primary care physician for a routine visit. She reports feeling very tired over the past few months. She also reports gaining weight over the past year due to physical inactivity and poor dieting habits. She has a 4 pack-year history of smoking. On physical exam, she is overweight but otherwise without any abnormal findings. Given her risk factors, her physician recommends a screening lipid panel as well as thyroid function tests.
Introduction
  • Clinical definition
    • elevated serum levels of cholesterol
      • parameters are total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL)
  • Epidemiology
    • risk factors
      • obesity
      • smoking
      • hypertension
      • family history
      • older age
  • Etiology
    • familial hypercholesterolemia
    • physical inactivity
    • metabolic syndrome
    • diabetes
    • chronic kidney disease
    • hypothyroidism
    • drugs
      • steroids
      • protease inhibitors
  • Pathogenesis
    • hypercholesterolemia results from excess cholesterol from the diet, bile, or intestines
    • triglycerides enter the plasma from the liver (as very low-density lipoproteins, VLDLs) or intestines (as chylomicrons)
      • VLDLs are converted into LDLs
      • cells with LDL receptor then receive cholesterol from LDLs
    • HDL carries extra cholesterol back to the liver to be metabolized
  • Associated conditions
    • diabetes
    • hypertension
    • hypertriglyceridemia
    • atherosclerosis
  • Prognosis
    • associated with ↑ risk of cardiovascular disease
Presentation
  • Symptoms
    • typically asymptomatic
  • Physical exam
    • metabolic syndrome
      • high blood pressure
    • in severe cases, may see
      • xanthomas
        • yellow nodules or plaques, especially on the Achilles tendon or fingers
      • xanthelasma
        • yellow papules and plaques eyelids
      • corneal arcus
        • white opaque ring at the border of the cornea
Studies
  • Labs
    • fasting lipid panel
      • total cholesterol
        • > 200 mg/dL is abnormal
      • LDL cholesterol
        • > 130 mg/dL is abnormal
      • HDL cholesterol
      • triglycerides
    • rule out secondary causes of hyperlipidemia
      • fasting blood glucose
      • hemoglobin A1c
      • thyroid stimulating hormone
      • alkaline phosphatase
      • urinalysis
        • to assess for proteinuria
  • Making the diagnosis
    • based on laboratory studies
Differential
  • Hypothyroidism
    • distinguishing factors
      • abnormal thyroid function tests
      • often presents with other symptoms of hypothyroidism, including weight gain, cold intolerance, and lethargy
Treatment
  • Management approach
    • screening
      • men at 40 years of age
      • women at 50 years of age
      • men and women 20 years of age with risk factors for coronary artery disease (CAD)
      • family history of familial hypercholesterolemia
    • target numbers
      • low-density lipoprotein < 100 mg/dL
        • < 70 mg/dL for those with diabetes
      • high-density lipoprotein  40 mg/dL
      • triglycerides <150 mg/dL
  • Conservative
    • dietary modification
      • indication
        • all patients
      • modalities
        • minimize saturated fats, trans fats, sugars, and red meats
    • increased physical activity
      • indication
        • all patients
  • Medical
    • statins
      • indications
        • hyperlipidemia
        • coronary artery disease
        • stroke
        • > 10% 10-year risk for coronary artery disease
        • lowers mortality
      • side effects
        • liver toxicity
    • ezetimibe
      • indication
        • adjuvant therapy to statins in patients with acute coronary syndrome
    • PCSK9 inhibitors
      • indications
        • hyperlipidemia even with statins at maximum dose
      • drugs
        • alirocumab
        • evolocumab
Complications
  • Heart disease
 

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Questions (1)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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