When should apolipoprotein A2 (ApoA2) be ordered?

When to Order Apolipoprotein A2 (ApoA2)

Apolipoprotein A2 testing is not recommended for routine clinical practice, as there are no established clinical indications, treatment targets, or evidence-based guidelines supporting its use in cardiovascular risk assessment or management.

Current Guideline Recommendations

No major cardiovascular guidelines recommend routine ApoA2 measurement. The American Heart Association, American College of Cardiology, and European Society of Cardiology guidelines do not include ApoA2 testing in their lipid assessment algorithms 1.

What Guidelines Actually Recommend Instead:

• ApoB testing may be considered in patients with borderline or intermediate 10-year ASCVD risk (5-19.9%), particularly when triglycerides are ≥200 mg/dL, with ApoB ≥130 mg/dL serving as a risk-enhancing factor 1, 2, 3
• ApoA1 testing (not ApoA2) can be measured as an alternative to HDL-C, particularly in patients with metabolic syndrome, diabetes, or chronic kidney disease 1, 2
• The ApoB/ApoA1 ratio has some evidence for risk stratification, but ApoA2 is not part of this calculation 1, 2

Why ApoA2 Testing Lacks Clinical Utility

Absence of Treatment Targets

No consensus treatment goals exist for ApoA2 levels. Unlike LDL-C, non-HDL-C, or ApoB, which have established targets based on cardiovascular risk categories, ApoA2 has no defined therapeutic thresholds 1.

Limited Evidence Base

• The evidence for therapeutic interventions targeting ApoA2 elevation is weak to nonexistent 1, 2
• The therapeutic focus should be on lowering ApoB rather than raising ApoA1 or ApoA2, as the evidence base for ApoB reduction is substantially stronger 1, 2, 3
• Research studies show conflicting results regarding ApoA2's clinical significance 4, 5, 6

Research Context Only

While recent research suggests ApoA2 may have prognostic value in specific populations (such as patients undergoing PCI), these findings are preliminary and have not been incorporated into clinical guidelines 5. One study found ApoA2 was inversely associated with cardiovascular events in PCI patients, but this represents emerging research rather than established clinical practice 5.

What to Order Instead

Standard Lipid Assessment

Order a fasting lipid panel (total cholesterol, triglycerides, HDL-C, LDL-C) every 5 years in adults, or more frequently if cardiovascular risk factors are present 1.

Advanced Testing When Indicated

Consider these alternatives to ApoA2 testing:

• ApoB measurement: For patients with triglycerides ≥200 mg/dL, metabolic syndrome, diabetes, or chronic kidney disease where LDL-C may underestimate atherogenic particle burden 1, 2, 3
• Lipoprotein(a): At least once in each adult's lifetime to identify those at very high lifetime risk, especially with family history of premature ASCVD 1
• Non-HDL-C: Easily calculated (total cholesterol minus HDL-C) and useful when triglycerides are elevated 1

Critical Clinical Pitfalls

• Do not order ApoA2 testing expecting actionable results, as no treatment algorithms exist based on ApoA2 levels 1, 2
• Do not confuse ApoA2 with ApoA1: ApoA1 is the major HDL apolipoprotein with some clinical utility, while ApoA2 is the second-most abundant HDL protein with no established clinical role 2, 7
• Traditional measures (LDL-C, total cholesterol) remain the primary treatment targets supported by the strongest evidence base from clinical trials 1, 2