Chemistry, toxicology & urinalysis
General chemistry
Metabolism
Hyperlipidemia
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Table of Contents
Definition / general | Pathophysiology | Diagrams / tables | Types of hyperlipidemia | Management | Clinical images | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Abdelrazik A. Hyperlipidemia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/chemistryhyperlipidemia.html. Accessed April 25th, 2024.
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
Images hosted on other servers:
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
- Diet
- 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
- Statins are the drugs of choice for the treatment of hypercholesterolemia
- Hypertriglyceridemia:
- Responds best to fibrates, nicotinic acid or fish oil
Clinical images
Images hosted on other servers:
Xanthelasma palpebrarum
Additional references
Board review style question #1
- When do you start treatment with statins?
- 10 year CVD risk is ≥ 10%
- 10 year CVD risk is ≥ 15%
- 10 year CVD risk is ≥ 20%
- 10 year CVD risk is ≥ 30%
- 10 year CVD risk is ≥ 50%
Board review style answer #1
