What classifies hyperlipidemia?

Classification of Hyperlipidemia

Hyperlipidemia is classified based on specific abnormalities in lipid profiles, including elevated total cholesterol, LDL cholesterol, triglycerides, or combinations of these abnormalities, with specific threshold values determining diagnosis.

Primary Classification of Hyperlipidemia

Hyperlipidemia is broadly classified into three main categories based on the specific lipid abnormalities:

1. Hypercholesterolemia:

   • Characterized by elevated LDL cholesterol levels
   • LDL cholesterol ≥ 130 mg/dL (3.35 mmol/L) 1
   • Total cholesterol ≥ 200 mg/dL (5.2 mmol/L) 1

2. Hypertriglyceridemia:

   • Characterized by elevated triglyceride levels
   • Triglycerides ≥ 150 mg/dL (1.7 mmol/L) 1
   • Severe hypertriglyceridemia: ≥ 500 mg/dL (5.6 mmol/L)

3. Mixed Hyperlipidemia:

   • Combination of elevated LDL cholesterol and elevated triglycerides 2
   • Often associated with metabolic syndrome or familial combined hyperlipidemia

Specific Lipid Parameters and Thresholds

LDL Cholesterol

• Primary target for lipid management 3
• Classification thresholds:
  • Optimal: < 100 mg/dL (2.6 mmol/L)
  • Near optimal: 100-129 mg/dL (2.6-3.3 mmol/L)
  • Borderline high: 130-159 mg/dL (3.4-4.1 mmol/L)
  • High: 160-189 mg/dL (4.1-4.9 mmol/L)
  • Very high: ≥ 190 mg/dL (4.9 mmol/L)

HDL Cholesterol

• Low HDL is a cardiovascular risk factor
• Low HDL defined as:
  • < 40 mg/dL (1.0 mmol/L) in men
  • < 45 mg/dL (1.2 mmol/L) in women 1

Non-HDL Cholesterol

• Calculated as total cholesterol minus HDL cholesterol
• Includes all atherogenic lipoproteins
• Target levels are typically 30 mg/dL higher than corresponding LDL targets 1

Triglycerides

• Classification thresholds:
  • Normal: < 150 mg/dL (1.7 mmol/L)
  • Borderline high: 150-199 mg/dL (1.7-2.2 mmol/L)
  • High: 200-499 mg/dL (2.3-5.6 mmol/L)
  • Very high: ≥ 500 mg/dL (5.6 mmol/L) 1

Genetic Disorders of Lipid Metabolism

1. Familial Hypercholesterolemia (FH):

   • Heterozygous FH: LDL ≥ 190 mg/dL without family history of premature CVD or ≥ 160 mg/dL with family history 1
   • Homozygous FH: Extremely elevated LDL cholesterol levels, often > 500 mg/dL
   • Prevalence: approximately 1 in 200-500 persons 1

2. Familial Combined Hyperlipidemia (FCHL):

   • Multiple phenotypes within same family
   • Elevated LDL, elevated triglycerides, or both
   • Associated with overproduction of VLDL particles 1

3. Familial Hypertriglyceridemia (FHTG):

   • Primary elevation of triglycerides
   • Often associated with metabolic syndrome 1

4. Lipodystrophy:

   • Inherited or acquired disorders characterized by loss of adipose tissue
   • Associated with hypertriglyceridemia and low HDL-C 1

Secondary Causes of Hyperlipidemia

Secondary dyslipidemia can be caused by:

1. Medical conditions:

   • Diabetes mellitus (particularly type 2)
   • Obesity and insulin resistance
   • Hypothyroidism
   • Chronic kidney disease
   • Liver disease
   • Cushing's syndrome 1

2. Medications:

   • Corticosteroids
   • Some antiretroviral therapies
   • Immunosuppressants (cyclosporine)
   • Isotretinoin and etretinate 1

3. Lifestyle factors:

   • Excessive alcohol consumption
   • High-carbohydrate diets (particularly simple carbohydrates)
   • Physical inactivity 1

Calculation Methods for Lipid Parameters

LDL cholesterol can be calculated using the Friedewald formula:

• In mg/dL: LDL-C = Total cholesterol - HDL-C - (Triglycerides/5)
• In mmol/L: LDL-C = Total cholesterol - HDL-C - (Triglycerides/2.2)

This calculation is valid only when triglycerides are < 400 mg/dL (4.5 mmol/L) 1.

Clinical Implications

The classification of hyperlipidemia guides treatment decisions and risk stratification:

• For high cardiovascular risk patients: LDL-C target < 70 mg/dL (1.8 mmol/L)
• For moderate risk patients: LDL-C target < 100 mg/dL (2.5 mmol/L)
• For low risk patients: LDL-C target < 115 mg/dL (3.0 mmol/L) 1, 3

Important Considerations

• A complete fasting lipid profile (total cholesterol, LDL-C, HDL-C, and triglycerides) should be obtained for proper classification 2
• Non-HDL cholesterol is increasingly recognized as an important target, especially in patients with elevated triglycerides 1
• The presence of small, dense LDL particles (common in insulin resistance and metabolic syndrome) increases cardiovascular risk even when LDL-C levels are not markedly elevated 1
• Lipoprotein(a) may be an independent risk factor but is not routinely used for classification 1