Introduction to Dyslipidemia and Lipid Metabolism

Introduction to Dyslipidemia

• Dyslipidemia is elevated total cholesterol, low-density lipoprotein (LDL) cholesterol, or triglycerides, or a low high-density lipoprotein (HDL) cholesterol
• These abnormalities can lead to coronary, cerebrovascular, and peripheral vascular arterial disease

Lipid Transport and Metabolism

• Cholesterol is a crucial substance made by the body's cells
• It maintains cell structure, aids in bile acid and hormone production
• Triglycerides and phospholipids are also essential lipids
• Lipoproteins (lipid-protein complexes) transport these lipids in the bloodstream

Lipoprotein Classification

• Lipoproteins vary in size and density based on lipid and protein content
• Chylomicrons, VLDL, IDL, LDL, and HDL are different lipoprotein classes
• Their size and density affect their movement during centrifugation
• Lipoproteins are classified by their density: Chylomicrons, VLDL, IDL, LDL, and HDL

Familial Dyslipidemia Types

• Different types of familial dyslipidemia exist, each with distinct characteristics
• Type I: Hyperchylomicronemia (elevated chylomicrons and triglycerides)
• Type IIa: Hypercholesterolemia (elevated LDL cholesterol)
• Type IIb: Combined hyperlipidemia (elevated both LDL and triglycerides)
• Type III: Dysbetalipoproteinemia (elevated IDL remnants)
• Type IV: Hypertriglyceridemia (elevated triglycerides)
• Type V: Mixed hypertriglyceridemia (elevated both triglycerides and cholesterol)

Clinical Presentation and Diagnosis

• Dyslipidemia often asymptomatic, but corneal arcus and xanthomas might be seen in patients
• Extreme elevations of LDL or triglycerides lead to pancreatitis or tuberoeruptive xanthomas
• Lipid profiles (total cholesterol, non-HDL, LDL, HDL cholesterol, triglycerides) are essential screenings for all adults over 20 every 5 years.
• Children with high cholesterol risk factors should be screened too

Indications for Additional Tests

• Tests should be used for conditions that may create lipid irregularities
• Conditions like those in Table 12-2 (specific examples not included in the summary) should be screened

National Lipid Association Classifications

• National Lipid Association provides cholesterol and triglyceride classification levels (in mg/dL and mmol/L). Specific LDL, HDL, total cholesterol ranges are listed.
• Classification is essential for determining risk levels and treatments.

Treatment

• Lifestyle modifications (diet, exercise, weight reduction) are first-line therapies
• These changes should include reducing total fat to 30% of total energy intake, saturated fat to 10% and cholesterol to 300mg daily and increasing fruits, vegetables, fiber, and fish oil intake.
• Medications are considered for high-risk patients or those who do not achieve desired results from lifestyle modifications

Statins

• Statins are widely used lipid-lowering medications.
• Adverse effects listed can include liver problems, muscle weakness, and rare cases of rhabdomyolysis
• Monitoring of liver function tests and creatine kinase levels is important

Cholesterol Absorption Inhibitors

• Ezetimibe reduces LDL cholesterol but can also result in some increase in HDL levels and a slight decrease in triglycerides
• Ezetimibe is primarily used when statin treatment doesn't bring adequate reduction in cholesterol

Bile Acid Sequestrants

• These medications bind to bile acids in the gut, causing these acids to be excreted and resulting in increased LDL receptors and reduced serum cholesterol

Niacin

• Niacin (vitamin B3) is used for lower LDL cholesterol and increased HDL.
• Potential for significant flushing and liver issues.
• Extended-release niacin is better tolerated

Fibrates

• Fibrates primarily lower triglycerides and raise HDL levels.
• Gemfibrozil is a less preferred fibrate when combined with statin for fear of affecting the statin glucuronidation
• Monitoring of liver function tests and creatine kinase levels is essential

Omega-3 Fatty Acids

• Omega-3 fatty acids reduce triglycerides and may have additional cardiovascular benefits.Excessive consumption can be problematic for patients on anticoagulants and/or antiplatelets