What does a low Alpha-fetoprotein (AFP) level and an elevated High-Sensitivity C-Reactive Protein (HS CRP) level indicate?

Clinical Significance of Low Alpha-fetoprotein and Elevated HS-CRP

Low Alpha-fetoprotein (AFP) levels in adults and elevated High-Sensitivity C-Reactive Protein (HS-CRP) levels indicate potential risk for cardiovascular disease, with the elevated HS-CRP specifically suggesting ongoing inflammation that may contribute to atherosclerosis.

Alpha-fetoprotein (AFP) Interpretation

Normal AFP Levels in Adults

• AFP is primarily a fetal-specific glycoprotein produced by the fetal liver that rapidly declines after birth 1
• Normal AFP levels in adults are typically less than 10 ng/ml, with mean levels around 3.04 ng/ml ± 1.9 SD 1
• Men tend to have statistically higher levels than women, and levels may increase slightly with age 1

Clinical Significance of Low AFP

• Low AFP levels in adults are generally considered normal and not clinically significant 1
• In pregnant women, however, low maternal serum AFP (MSAFP) can be associated with increased risk of chromosomal abnormalities, particularly Down syndrome 2
• The American Society of Human Genetics notes that low MSAFP levels during pregnancy (specifically around 0.72 MOM - multiples of median) can indicate increased risk for Down syndrome 2

High-Sensitivity C-Reactive Protein (HS-CRP) Interpretation

Clinical Significance of Elevated HS-CRP

• HS-CRP is an independent marker of cardiovascular risk that predicts incident myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death 2, 3
• HS-CRP levels can be categorized into risk groups 2, 3:
  • Less than 1 mg/L: Lower cardiovascular risk
  • 1-3 mg/L: Moderate cardiovascular risk
  • Greater than 3 mg/L: Higher cardiovascular risk

Clinical Applications of HS-CRP Testing

• HS-CRP may be used at the physician's discretion in patients judged to be at intermediate risk (10-20% risk of coronary heart disease per 10 years) for cardiovascular disease 2
• It provides additional prognostic value at all levels of cholesterol, Framingham coronary risk score, severity of metabolic syndrome, and blood pressure 3
• Patients with persistently unexplained marked elevation of HS-CRP (>10 mg/L) after repeated testing should be evaluated for non-cardiovascular causes 2

Clinical Implications of Combined Findings

Cardiovascular Risk Assessment

• The combination of normal/low AFP (which is expected in adults) and elevated HS-CRP primarily points toward increased cardiovascular risk 2
• Elevated HS-CRP reflects a persistent inflammatory response that may mediate progressive atherosclerotic cardiovascular disease 2
• Recent evidence suggests that inflammatory biomarkers like HS-CRP are not only markers but also mediators of atherothrombotic disease 2

Management Considerations

• For patients with elevated HS-CRP, consider cardiovascular risk stratification using established guidelines 2
• Serial testing of HS-CRP should not be used to monitor treatment effects (Class III, Level of Evidence: C) 2
• Application of secondary prevention measures should not depend solely on HS-CRP determination (Class III, Level of Evidence: A) 2

Important Caveats

• Inflammatory markers other than HS-CRP should not be measured for coronary risk determination 2
• Elevated HS-CRP may also be associated with non-cardiovascular conditions causing inflammation 2
• The benefits of therapy based solely on HS-CRP levels remain uncertain 2
• In patients with chronic kidney disease, elevated inflammatory markers including HS-CRP are associated with poorer outcomes 2

In summary, while low AFP in adults is generally normal, elevated HS-CRP warrants attention as an independent risk factor for cardiovascular disease and may guide further evaluation and preventive strategies.