Chemistry
Cardiac related
Hyperlipidemia

Author: Alaa Abdelrazik, MBBCh, MSc, M.D., Ph.D. (see Authors page)

Revised: 19 September 2017, last major update September 2017

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: chemistry hyperlipidemia [title] "loattrfree full text"[sb]
Cite this page: Abdelrazik, A. Hyperlipidemia. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/chemistryhyperlipidemia.html. Accessed April 24th, 2018.
Definition / general
  • Term used to denote excess of lipids, mainly cholesterol and triglycerides (TG), in the blood
  • Strong relationship between high plasma lipids and coronary heart disease
  • Lowering LDL and raising HDL decrease the progression of coronary atherosclerosis, the process responsible for majority of cardiovascular diseases (CVD)
Pathophysiology
    Lipid metabolism
  • Cholesterol and triglycerides are not water soluble and circulate bound to lipoproteins
  • These consist of nonpolar core of TG and cholesteryl esters surrounded by a layer of phospholipids, cholesterol and proteins known as apolipoproteins (see Diagrams / tables below)

    Classification of lipoproteins
  • Chylomicrons: large particles that carry dietary fat (mainly TG) from the intestine to the liver
  • Very low density lipoprotein (VLDL): carries endogenous TG synthesized in the liver to the tissues
  • Low density lipoprotein (LDL): is formed from intermediate density lipoprotein (IDL) by hepatic lipase
    • It carries cholesterol from liver to tissues
  • High density lipoprotein (HDL): carries cholesterol from tissues to liver
Diagrams / tables

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Schematic of a chylomicron

Types of hyperlipidemia
    Primary hyperlipidemia:
  • There are many types of familial dyslipidemia; common forms include:

  • Familial hyeprcholestrolemia (FH):
    • Autosomal dominant
    • LDL receptor defects
    • In heterozygotes, cholesterol levels are in the range of 6 - 12 mmol/L, while in homozygotes, levels can be as high as 20 mmol/L
    • Clinical features: tendon xanthoma, corneal arcus and xanthelasma (see Clinical images)

  • Polygenic hypercholesterolemia:
    • Most common form of familial hyperlipidemia
    • Plasma cholesterol is not as high as FH and is influenced by environmental factors such as diet

  • Familial combined hyperlipidemia:
    • Results in elevated cholesterol and TG
    • Associated with diabetes, obesity, cutaneous manifestations of hyperlipidemia and premature ischemic heart disease (IHD)

  • Familial chylomicronemia:
    • Failure to metabolise the chylomicrons due to deficiency of lipoprotein lipase or apoC-II
    • Presents with pancreatitis, hepatosplenomegaly and eruptive xanthomata

  • Familial hypertriglyceridemia:
    • Autosomal dominant
    • Associated with eruptive xanthomas, diabetes and pancreatitis

Secondary hyperlipidemia:
  • Alcoholism
  • Diabetes
  • Cushing syndrome
  • Renal failure
  • Cholestasis
  • Nephrotic syndrome
  • Hypothyroidism
  • Drugs: β blockers, thiazides, steroids and antiretrovirals
Management
  • Exclude secondary causes of dyslipidemia
  • Lifestyle modifications (Am Fam Physician 2010;81:1097):
    • Diet
      • Reduce total fat intake to 30% or less of total energy and intake of dietary cholesterol to less than 300 mg/day
      • Eat at least 5 portions of fruits and vegetables per day and ≥ 2 portions of fish per week
      • Reduce alcohol consumption to 2 drinks per day for men and 1 drink per day for women
    • Smoking cessation
    • Encourage physical activity

  • Assess the following before starting treatment:
    • Blood pressure
    • Body mass index (BMI)
    • Total cholesterol, non HDL cholesterol, HDL cholesterol and triglycerides
    • HbA1c
    • Renal function and eGFR
    • Transaminase levels
    • Thyroid stimulating hormone

  • Primary prevention (treatment of those with no evidence of disease):
    • Treat with statins if lipids remain high despite nondrug therapy and 10 year CVD risk is ≥ 10%

  • Secondary prevention (treatment of those who have proven CVD):
    • Start treatment immediately, irrespective of initial cholesterol levels
    • Patients with diabetes are considered as secondary prevention

  • Hypercholesterolemia
    • Statins are the drugs of choice for the treatment of hypercholesterolemia
      • They inhibit HMG CoA reductase required for cholesterol synthesis in the liver
      • Possible side effects: myalgia, myositis, abdominal pain and abnormal liver function tests
      • Statins are contraindicated in pregnancy, breastfeeding and active liver disease
    • Bile acid sequestrants: they act by binding bile acids, preventing their reabsorption, which promotes hepatic conversion of cholesterol into bile acids
      • Gastrointestinal side effects are common
      • Ezetimibe (Zetia or Ezetrol) inhibits the intestinal absorption of cholesterol
      • Fibrates act mainly by decreasing serum triglycerides
        • They tend to be less effective than statins at lowering cholesterol
        • They also increase HDL concentration

  • Hypertriglyceridemia:
    • Responds best to fibrates, nicotinic acid or fish oil
Clinical images

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Xanthelasma palpebrarum

Board review question #1
    When do you start treatment with statins?

  1. 10 year CVD risk is ≥ 10%
  2. 10 year CVD risk is ≥ 15%
  3. 10 year CVD risk is ≥ 20%
  4. 10 year CVD risk is ≥ 30%
  5. 10 year CVD risk is ≥ 50%
Board review answer #1
A. 10 year CVD risk is ≥ 10%