Can a high Angiotensin-Converting Enzyme (ACE) reading be associated with high N-terminal pro b-type natriuretic peptide (NT-proBNP) levels?

Relationship Between High ACE Levels and NT-proBNP Levels

High ACE (Angiotensin-Converting Enzyme) levels are inversely related to NT-proBNP levels, as ACE inhibition therapy leads to reduction in NT-proBNP levels in patients with heart failure. 1

Mechanism of Relationship

• ACE plays a key role in the renin-angiotensin-aldosterone system (RAAS), which affects cardiac function and blood pressure
• When ACE is inhibited through medications (ACE inhibitors):
  • NT-proBNP levels decrease significantly 1
  • This reduction occurs in parallel with hemodynamic improvements 2
  • The decrease in NT-proBNP is associated with reduction in filling pressures and reversal of pathological cardiac remodeling 1

Evidence for the Relationship

• Long-term treatment with ACE inhibitors leads to reduction in blood natriuretic peptide levels 1
• This finding is supported by studies showing that ramipril (an ACE inhibitor) treatment in heart failure patients results in decreased ANP levels (another natriuretic peptide) in parallel with hemodynamic improvements 2
• The relationship is further demonstrated by the fact that:
  • ACE inhibitors reduce NT-proBNP levels by decreasing ventricular wall stress
  • Higher doses of ACE inhibitors are associated with greater reductions in NT-proBNP levels 1

Clinical Implications

Monitoring Heart Failure Treatment

• NT-proBNP levels can be used to monitor response to ACE inhibitor therapy 3
• A reduction >30% in NT-proBNP in response to heart failure treatment indicates good prognosis 3
• Serial measurements of NT-proBNP can help assess treatment efficacy of ACE inhibitors and other heart failure medications 3

Therapeutic Considerations

• Sacubitril/valsartan (ARNI) is superior to traditional ACE inhibitors in reducing NT-proBNP levels 3
• For patients with elevated NT-proBNP levels, treatment with ACE inhibitors should be considered as part of guideline-directed medical therapy 3
• In biomarker-guided heart failure trials, higher doses of ACE inhibitors were used in the NT-proBNP-guided treatment arms 1

Important Caveats

• NT-proBNP levels are affected by multiple factors beyond ACE activity:

  • Age and sex (higher thresholds needed for older patients) 3
  • Renal dysfunction (higher levels with decreased renal function) 3
  • Atrial fibrillation (can elevate NT-proBNP independent of heart failure) 4
  • Obesity (associated with lower NT-proBNP levels) 1

• When interpreting NT-proBNP levels in relation to ACE:

  • Consider comorbidities that may affect both markers
  • Evaluate in context of clinical presentation
  • Use age and sex-specific cutoffs when applicable 3

Conclusion

The relationship between ACE and NT-proBNP is primarily inverse - when ACE activity is high, NT-proBNP tends to be lower, and when ACE is inhibited through medications, there is an initial reduction in NT-proBNP levels due to improved cardiac hemodynamics and reduced ventricular wall stress. This relationship forms the basis for using NT-proBNP as a biomarker to monitor response to ACE inhibitor therapy in heart failure patients.