What are the types of dyslipidemia?

Types of Dyslipidemia

Dyslipidemia encompasses any abnormality in plasma lipid levels or lipoprotein composition, classified into primary (genetic) and secondary (acquired) forms, with specific patterns including isolated hypercholesterolemia, hypertriglyceridemia, mixed dyslipidemia, low HDL-cholesterol, and atherogenic dyslipidemia. 1

Primary (Familial) Dyslipidemia

Primary dyslipidemia results from single or multiple gene mutations affecting lipid metabolism 2, 3:

Familial Hypercholesterolemia

• Heterozygous form: Elevated LDL-cholesterol, occurring in approximately 1 in 200-500 persons in North America and Europe 4
• Homozygous form: Markedly elevated LDL-cholesterol (≥500 mg/dL), extremely rare 4
• Familial defective apolipoprotein B: Elevated LDL-cholesterol due to defective apoB 4

Familial Combined Hyperlipidemia (FCHL)

This presents in three distinct patterns 4:

• Type IIa: Isolated LDL-cholesterol elevation
• Type IV: Elevated VLDL and triglycerides
• Type IIb: Combined elevation of LDL-cholesterol, VLDL, and triglycerides, often with low HDL-cholesterol 4

Hypertriglyceridemia Syndromes

• Familial hypertriglyceridemia: Triglycerides 200-1000 mg/dL with elevated VLDL 4
• Severe hypertriglyceridemia: Triglycerides ≥1000 mg/dL with elevated chylomicrons and VLDL, risk of pancreatitis 4
• Chylomicronemia syndrome: Rare genetic disorders including LPL deficiency, apolipoprotein CII deficiency, and apolipoprotein AV mutations, presenting with triglycerides >1000 mg/dL, lipemia retinalis, eruptive xanthomas, and hepatosplenomegaly 4

Other Primary Forms

• Polygenic hypercholesterolemia: Elevated LDL-cholesterol from multiple genetic variants 4
• Familial hypoalphalipoproteinemia: Isolated low HDL-cholesterol 4
• Dysbetalipoproteinemia: Total cholesterol 250-500 mg/dL with triglycerides 250-600 mg/dL, elevated IDL and chylomicron remnants 4

Secondary Dyslipidemia

Secondary dyslipidemia accounts for 30-40% of all cases and results from underlying diseases or medications 2:

Disease-Related Secondary Dyslipidemia

Diabetes mellitus (both Type 1 and Type 2) 4:

• Characterized by hypertriglyceridemia, low HDL-cholesterol, and small dense LDL particles 4, 5
• Results from hepatic VLDL overproduction and defective chylomicron clearance 4
• Prevalence of dyslipidemia is 2-3 times higher in diabetic patients compared to those with normal glucose tolerance 4

Obesity and metabolic syndrome 4:

• Atherogenic pattern: hypertriglyceridemia (elevated chylomicrons and VLDL), low HDL-cholesterol, small dense LDL, and oxidized LDL 4
• Elevated apolipoprotein B and apoB/apoA ratio 4

Hypothyroidism 2:

• Causes hypercholesterolemia
• Must be treated before initiating lipid-lowering therapy to avoid serious adverse events like rhabdomyolysis 2

Lipodystrophy syndromes 4:

• Congenital generalized lipodystrophy: severe hypertriglyceridemia with eruptive xanthomas and pancreatitis risk 4
• Familial partial lipodystrophy (Dunnigan variety): severe hypertriglyceridemia, worse in women 4
• HIV-associated lipodystrophy: increased triglycerides in VLDL, LDL, and HDL due to reduced clearance 4, 1

Chronic kidney disease: Accelerated atherosclerosis risk requiring aggressive lipid management 4

Medication-Induced Dyslipidemia

• Estrogen therapy: Can cause massive triglyceride elevation, especially in familial hypertriglyceridemia 6
• Thiazide diuretics: Associated with triglyceride elevation 6
• Beta-blockers: Can raise plasma triglycerides 6

Multifactorial Dyslipidemia

Multifactorial dyslipidemia involves both polygenic predisposition and environmental factors 4, 1:

• Defined by LDL-cholesterol ≥130 mg/dL or total cholesterol ≥200 mg/dL not attributable to familial hypercholesterolemia 4
• Strongly associated with obesity, which causes slight LDL-cholesterol elevation but more pronounced triglyceride elevation and HDL-cholesterol reduction 4

Atherogenic Dyslipidemia Pattern

The atherogenic lipid triad represents a particularly high-risk pattern 1, 3:

• Increased VLDL remnants
• Increased small dense LDL particles
• Reduced HDL-cholesterol 1
• Highly prevalent in patients with diabetes or metabolic syndrome 3

Clinical Significance

Critical distinction: Dyslipidemia can occur with normal total lipid levels but abnormal lipoprotein composition or function 1. This emphasizes that management must address specific lipid abnormality patterns, not just absolute levels 1. Misclassification can lead to missed important abnormalities in lipoprotein composition or function 1.