What are the different types of hyperlipidemia?

Types of Hyperlipidemia

Hyperlipidemia can be classified into several distinct types based on the specific lipid abnormalities, with each type having different clinical implications, risk profiles, and treatment approaches. 1

Primary Classification of Hyperlipidemia

Based on Lipid Abnormality:

1. Hypercholesterolemia

   • Elevated LDL cholesterol with normal triglycerides
   • Examples: Familial Hypercholesterolemia (Heterozygous and Homozygous), Familial Defective Apolipoprotein B, Polygenic Hypercholesterolemia

2. Hypertriglyceridemia

   • Elevated triglycerides with normal or mildly elevated cholesterol
   • Severity classification 1, 2:
     • Mild: 150-199 mg/dL
     • Moderate: 200-999 mg/dL
     • Severe: 1,000-1,999 mg/dL
     • Very severe: ≥2,000 mg/dL

3. Mixed (Combined) Hyperlipidemia

   • Elevations in both LDL cholesterol and triglycerides
   • Example: Familial Combined Hyperlipidemia

4. Dysbetalipoproteinemia (Type III)

   • Accumulation of IDL and chylomicron remnants
   • Typical profile: Total cholesterol 250-500 mg/dL; Triglycerides 250-600 mg/dL 1

5. Hypoalphalipoproteinemia

   • Decreased HDL cholesterol levels

Specific Familial Disorders

Familial Hypercholesterolemia

• Homozygous: Markedly elevated LDL cholesterol (>500 mg/dL)
• Heterozygous: Moderately elevated LDL cholesterol (190-350 mg/dL)
• Caused by mutations in LDL receptor gene, apolipoprotein B gene, or PCSK9 gene

Familial Combined Hyperlipidemia

• Type IIa: Elevated LDL cholesterol
• Type IV: Elevated VLDL cholesterol and triglycerides
• Type IIb: Elevated LDL cholesterol, VLDL cholesterol, and triglycerides
• Often accompanied by reduced HDL cholesterol
• Most commonly manifests with obesity 1

Familial Hypertriglyceridemia

• Elevated VLDL cholesterol and triglycerides (200-1000 mg/dL)
• Usually autosomal dominant inheritance

Severe Hypertriglyceridemia

• Elevated chylomicrons, VLDL cholesterol, and severely elevated triglycerides (>1000 mg/dL)
• Associated with increased risk of pancreatitis 1

Rare Genetic Disorders Presenting as Chylomicronemia Syndrome

1. Lipoprotein Lipase (LPL) Deficiency (Type I)

   • Autosomal recessive, extremely rare (1 in 1 million)
   • Triglyceride-to-cholesterol ratio 10:1
   • Triglycerides >1000 mg/dL with increased chylomicrons
   • Clinical features: lipemia retinalis, hepatosplenomegaly, eruptive xanthomas 1

2. Apolipoprotein CII Deficiency

   • Autosomal recessive
   • Absence of needed cofactor for LPL
   • Similar lipid profile to LPL deficiency
   • Attacks of pancreatitis can be reversed by plasmapheresis 1

3. Apolipoprotein AV Homozygosity

   • Mutations leading to truncated apolipoprotein AV
   • Late onset, incomplete penetrance
   • Unusual resistance to conventional treatment 1

4. GPIHBP1 Mutations

   • Expressed in childhood
   • Reduces binding to LPL and hydrolysis of chylomicron triglycerides
   • May have lipemia retinalis and pancreatitis 1

Secondary Causes of Hyperlipidemia

Secondary causes should always be evaluated and treated 1:

• Excessive alcohol intake
• Uncontrolled diabetes mellitus
• Endocrine conditions (hypothyroidism, Cushing's syndrome)
• Renal or liver disease
• Pregnancy
• Autoimmune disorders
• Medications (thiazides, beta blockers, estrogen, isotretinoin, corticosteroids, antiretroviral protease inhibitors, antipsychotics)

Special Conditions

Lipodystrophy

• Can be inherited (rare) or acquired (e.g., HIV-associated)
• Characterized by loss of adipose tissue
• Often associated with hypertriglyceridemia and low HDL-C
• Severity related to extent of fat loss 1

Clinical Implications

• Mild/Moderate Hypertriglyceridemia (150-999 mg/dL): Risk factor for cardiovascular disease
• Severe/Very Severe Hypertriglyceridemia (≥1000 mg/dL): Significant risk for acute pancreatitis 1, 2
• Hypercholesterolemia: Strong correlation to coronary heart disease risk 3

Diagnostic Approach

1. Measure fasting lipid profile (total cholesterol, LDL-C, HDL-C, triglycerides)
2. Evaluate for secondary causes
3. Assess family history for premature cardiovascular disease
4. Consider specialized testing for familial disorders:
   • Apolipoprotein analysis
   • Genetic testing for specific mutations
   • Lipoprotein electrophoresis

Understanding the specific type of hyperlipidemia is crucial for determining appropriate treatment strategies and assessing cardiovascular risk. Each type requires a tailored approach to management, with consideration of both lifestyle modifications and pharmacological interventions based on severity and associated risk factors.