Dyslipidemias: Clinical Features & Evaluation Flashcards Preview

DEMS: Unit II > Dyslipidemias: Clinical Features & Evaluation > Flashcards

Flashcards in Dyslipidemias: Clinical Features & Evaluation Deck (14):
1

Lipids most important to development of atherosclerosis

 

  • LDL and HDL most important lipoproteins in terms of atherosclerosis
    • Also involved: remnants, lipoprotein a, VLDL (especially in DM)
  • Risk stratifying patients based on LDL-C level has beneficial effects on CVD risk (treat with statins)

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2

Determination of LDL cholesterol levels

  • Calculate with Friedewald formula
    • LDL-C = Total cholesterol - HDL-C - (triglycerides / 5)

 

  • Total cholesterol (TC) = HDL-C + LDL-C + VLDL-C
    • TC, HDL-C, triglycerides easily measured
    • When fasting, VLDL-C = triglycerides / 5
      • As long as triglycerides are <400mg/dL

3

Secondary causes of hyperlipidemia

  • Diets high in saturated and trans fat
  • Hypothyroidism
  • Nephrotic syndrome
  • Obstructive liver disease
  • Cyclosporine

4

Individualization of risk for ASCVD (risk factors)

  • Age (males > females)
  • Caucasian vs. African American
  • Higher total cholesterol
  • Lower HDL-C
  • Current cigarette smoking
  • Systolic BP > 140 
    • Or on antihypertensives
  • Diabetes

5

2 causes of increased LDL-C

  1. Increased LDL-C production
  2. Decreased LDL catabolism

6

Causes of increased VLDL production

  • Insulin resistance - most common
    • Increases in FFA flux from adipose tissue
  • Drugs - protease inhibitors, oral estrogens, nephrotic syndrome, chronic renal failure
  • Alcohol
    • Enhances fatty acid production from ethanol-derived carbons
  • Genetics
    • lipoprotein lipase (LPL)
    • Apo A5

7

Causes of decreased lipoprotein catabolism

  • Decreases in LPL levels or activity
  • Primary defects:
    • LPL deficiency
    • apo C2 deficiency (specific apoprotein activator of LPL)
    • glycosylphosphatidylinostitol-anchored high-density lipoprotein-binding protein 1 (binds LPL to endothelium) deficiency
  • Familial dysbetalipoproteinemia

8

Polygenic/multifactorial causes of hypertriglyceridemia

  • Possible when several disorders of lipoprotein triglyceride synthesis and/or catabolism are simultaneously present AND fat remains in diet
  • When triglycerides are >1000mgdl --> additional increase attributable to chylomicrons
  • Absolute LPL deficiency or two+ disorders of triglyceride metabolism: fasting triglyceride levels up to 30,000mg/dl

9

Increased Non-HDL-C

  • Encompasses all apo-B-100 containing lipoproteins (VLDL, IDL, LDL)
    • Non-HDL-Cholesterol = TC - HDL
  • Correlate closely with central/visceral obesity
  • Strong predictor of ASCVD events/death

10

Causes of increased Non-HDL-C

  • Familial dysbetalipoproteinemia (FD, broad beta disease)
    • Disturbances in IDL and remnant catabolism
    • Manifest: approximately equivalent increase in both LDL-C and triglycerides 
    • Most often occurs due to genetic variation in Apo E
      • ApoE2 isoform --> increased risk 
    • Defective binding of ApoE2 to hepatic receptors recognizing VLDL/chylomicron remnants

11

Low HDL-C

  • Associated with increased risk for ASCVD (high levels protective)
  • Explained by many properties of HDL: reverse cholesterol transport, anti-oxidant/anti-inflammatory effects
  • Can be secondary to:
    • Altered composition (hypertriglyceridemia): ApoA1 level unchanged
    • Reduction in HDL particles: ApoA1 level reduced

12

Genetic causes of low HDL-C

  • Male gender
  • Mutations in ATP binding cassette 1
    • Tangier disease: autosomal co-dominant --> accumulation of cholesterol in peripheral organs (orange tonsils)
    • Familial HDL deficiency: autosomal dominant
  • Lecithin:cholesterol acyl transferase (LCAT) deficiency
    • Homozygous mutations --> corneal opacities & low HDL
  • Familial hypoalphalipoproteinemia: autosomal dominant
    • Mutations in ApoA1 gene --> premature ASCVD 

13

Acquired causes of low HDL-C

  • Diet: Decreased fat (high carbohydrate) intake, obesity
  • Drugs: Beta blockers, diuretics, progestins, androgens, protease inhibitors
  • Hypertriglyceridemic disorders
  • Others: sedentary lifestyle, smoking

14

Development/progression of atherosclerosis

  • Altered plasma levels of lipids --> effect on arterial wall
  • Atherosclerosis begins as fatty streak --> progresses to more advanced disease (fibrous/calcified plaque or complicated lesion)