Lipids
Lipids — including cholesterol, triglycerides, and phospholipids — are essential for cellular structure, hormone synthesis, and energy metabolism. Because they cannot dissolve in blood, lipids are transported through the plasma by water-soluble carrier particles called lipoproteins.
Lipoproteins
Lipoproteins are generally categorized by density and size and include:
- Low-density lipoprotein (LDL)
- Very-low-density lipoprotein (VLDL)
- Intermediate-density-lipoprotein (IDL)
- High-density lipoprotein (HDL)
- Chylomicrons
- Lipoprotein(a) [Lp(a)]
Dyslipidemia
Dyslipidemia refers to abnormal lipid and lipoprotein levels in the bloodstream, including elevated blood cholesterol, low HDL, hypertriglyceridemia, and elevated Lp(a), that vary in clinical significance and implications for ASCVD risk.
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Phenotypic Classification of Dyslipidemias
Contemporary lipid management emphasizes phenotypic classification — identifying specific patterns of lipid and lipoprotein abnormality rather than relying on total cholesterol or a single marker. This approach enables more precise diagnosis and more targeted treatment.
Hypercholesterolemia
Typically describes elevations in LDL-C and/or Lp(a) with normal triglycerides. High HDL-C can also raise total cholesterol. A rare cause unrelated to LDL or HDL is LpX, most commonly seen in individuals with cholestatic liver disease.
Low Cholesterol
Low total and LDL-C is uncommon and usually reflects an inherited condition or an acquired cause such as severe liver disease. Low LDL-C itself does not cause harm, but may indicate an underlying condition that warrants investigation. A rare genetic condition resulting in absent ApoB can impair transport of fat-soluble vitamins and is associated with neurologic and other complications.
Hypertriglyceridemia
Elevated triglycerides with normal LDL-C. Classified by severity:
- Mild-to-moderate: 150–499 mg/dL
- Severe: ≥500 mg/dL
- Extreme: ≥880 mg/dL
Mixed Dyslipidemia
Elevated LDL-C and triglycerides, with or without reduced HDL-C. ApoB levels vary and can help clarify the underlying lipoprotein pattern.
Low HDL-C
Often coexists with elevated triglycerides and other lipid abnormalities. May result from inherited abnormalities in HDL-regulating genes or from metabolic conditions such as insulin resistance and obesity.
High HDL-C
Levels above 80 mg/dL are uncommon and can be associated with specific genetic conditions. The cardiovascular impact of very high HDL-C is unpredictable and should not be assumed to be protective.
Atherogenic Dyslipidemia
A particularly high-risk pattern characterized by elevated triglycerides, low HDL-C, and small dense LDL particles. ApoB tends to be disproportionately elevated relative to LDL-C — a discordance that standard lipid panels can miss.
Diagnostic Testing
Standard Lipid Panel: Measures total cholesterol, HDL-C, triglycerides, and provides an estimation of LDL-C. Also provides non–HDL-C, which is calculated as TC–HDL-C. The foundation of lipid assessment in most clinical settings.
Apolipoprotein B: An ApoB measurement measures the total number of atherogenic particles in circulation, since each LDL, VLDL, and Lp(a) particle carries exactly one ApoB molecule. ApoB adds clinical value, particularly when standard panels may underestimate atherogenic burden, particularly in patients with elevated triglycerides, metabolic syndrome, or insulin resistance. Measuring ApoB may also enhance ASCVD risk assessment, guide decisions on the initiation of lipid lowering therapy, and characterize inherited lipid disorders. For more information, visit our ApoB topic page.
Lipoprotein(a): Individuals with elevated Lp(a) are at increased ASCVD risk. A measurement of Lp(a) measures Lp(a) concentration in the blood. A measurement of Lp(a) is recommended at least once in all adults for ASCVD risk assessment. For more information, visit our Lp(a) topic page.
Clinician FAQs
What is the benefit of phenotypic classification in dyslipidemia? Phenotypic classification enables more precise diagnosis by identifying which lipoproteins are abnormal and in what pattern. This guides treatment selection more effectively than relying on a single threshold or marker.
When should advanced lipoprotein testing be ordered? Consider ApoB and Lp(a) testing in patients with elevated triglycerides, abdominal or visceral adiposity, metabolic syndrome, insulin resistance, or diabetes — especially when standard lipid values may not reflect true cardiovascular risk.
What are the limitations of standard lipid panels? Standard panels measure cholesterol content within lipoprotein fractions but do not account for particle number. In patients with atherogenic dyslipidemia or metabolic syndrome, LDL-C can underestimate cardiovascular risk — making advanced markers such as ApoB a valuable addition.
Can dyslipidemia be present even with a “normal” LDL-C? Yes. Atherogenic dyslipidemia, for example, is characterized by a pattern — high triglycerides, low HDL-C, small dense LDL — that may not be apparent from LDL-C alone. Phenotypic classification and, where appropriate, ApoB testing help surface these cases.
Content developed by the National Lipid Association. For full clinical guidelines and resources, visit the NLA Knowledge Center.