What is hyperlipidemia?

Hyperlipidemia Definition

Hyperlipidemia is defined as elevated levels of lipids in the blood, including elevations in total cholesterol, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, or some combination thereof, as well as lower levels of high-density lipoprotein cholesterol (HDL-C). 1

Types of Hyperlipidemia

Hyperlipidemia can be classified into two main categories:

1. Primary (Genetic) Hyperlipidemia

• Familial Hypercholesterolemia: Characterized by highly elevated LDL-C levels (≥190 mg/dL), genetic mutation, or both. Occurs in approximately 1 in 200-500 persons in North America and Europe 1
• Familial Combined Hyperlipidemia: Features elevations in both VLDL and LDL levels 2
• Familial Hypertriglyceridemia: Presents with elevated serum triglycerides without marked hypercholesterolemia 2
• Remnant (Type III) Hyperlipidemia: Characterized by cholesterol and triglyceride-rich VLDL 2
• Familial Hypoalphalipoproteinemia: Associated with isolated low HDL cholesterol levels 1

2. Secondary (Acquired) Hyperlipidemia

Secondary causes include:

• Lifestyle factors: Overweight/obesity, physical inactivity, excessive alcohol intake, diets rich in simple carbohydrates 1
• Medical conditions: Diabetes mellitus, metabolic syndrome, hypothyroidism, renal disease, liver disease, pregnancy, autoimmune disorders 1, 3
• Medications: Thiazides, beta-blockers, estrogen, isotretinoin, corticosteroids, bile acid-binding resins, antiretroviral protease inhibitors, immunosuppressants, antipsychotics 1, 3

Diagnostic Criteria

According to the Endocrine Society, hypertriglyceridemia is classified as 1:

• Mild: 150-199 mg/dL (1.7-2.3 mmol/L)
• Moderate: 200-999 mg/dL (2.3-11.3 mmol/L)
• Severe: 1,000-1,999 mg/dL (11.3-22.6 mmol/L)
• Very severe: ≥2,000 mg/dL (≥22.6 mmol/L)

For total lipid profile, the American Diabetes Association defines the following categories 4:

Risk	LDL cholesterol	HDL cholesterol	Triglyceride
High	≥130 mg/dL	<40 mg/dL	≥400 mg/dL
Borderline	100-129 mg/dL	40-59 mg/dL	150-399 mg/dL
Low	<100 mg/dL	≥60 mg/dL	<150 mg/dL

Note: For women, HDL cholesterol threshold values should be increased by 10 mg/dL

Clinical Significance and Risks

The importance of hyperlipidemia relates to its association with cardiovascular disease:

• Mild to moderate hypertriglyceridemia may be a risk factor for cardiovascular disease 1
• Severe and very severe hypertriglyceridemia increase the risk of pancreatitis 1, 5
• Elevated LDL-C and non-HDL-C levels are causally important in atherosclerosis 2
• Low HDL-C levels are associated with increased cardiovascular risk 4

Evaluation of Hyperlipidemia

When evaluating hyperlipidemia, clinicians should:

1. Obtain a complete fasting lipid profile including total cholesterol, LDL-C, HDL-C, and triglycerides 4
2. Calculate non-HDL cholesterol (total cholesterol minus HDL), which represents all atherogenic lipoproteins and may be a better predictor of cardiovascular risk than LDL alone in some populations 4
3. Evaluate for secondary causes of hyperlipidemia 1, 3
4. Assess for other cardiovascular risk factors, including family history of dyslipidemia and cardiovascular disease, central obesity, hypertension, abnormal glucose metabolism, and liver dysfunction 1
5. Consider screening family members, particularly in cases of suspected familial hyperlipidemia 2

Common Pitfalls in Diagnosis

• Failure to identify secondary causes: Always evaluate for common secondary causes before diagnosing primary hyperlipidemia 2, 3
• Overlooking combined disorders: Patients may have multiple lipid abnormalities that require comprehensive assessment 4
• Focusing solely on LDL-C: Non-HDL-C and triglycerides are important risk factors that should not be overlooked 4, 6
• Inadequate fasting: Triglyceride levels should be measured in a fasting state for accurate assessment 4

Hyperlipidemia represents a significant risk factor for cardiovascular disease and, in severe cases, pancreatitis. Proper identification, classification, and management are essential for reducing morbidity and mortality associated with these conditions.