Key result
Serum levels of adrenomedullin were significantly higher in heart failure patients compared to controls (MD 6.024; 95% CI 1.691-10.356), with levels increasing alongside NYHA class progression.
Why the study?
Studies assessing the potential of ADM, Pro-ADM, and MR-Pro-ADM for diagnosing and staging heart failure severity have yielded conflicting results.
Do adrenomedullin and its precursors accurately diagnose heart failure and correlate with NYHA severity?
Meta-Analysis (n=15,405)
Do adrenomedullin and its precursors accurately diagnose heart failure and correlate with NYHA severity?
Mean Difference: 6.024 (95% CI 1.691–10.356)
Adrenomedullin and its precursors are significantly elevated in heart failure and correlate with NYHA severity, though MR-Pro-ADM has lower diagnostic accuracy than established biomarkers.
Adrenomedullin tracks heart failure severity; hypothesis-generating for biomarker utility, needs prospective validation.
BACKGROUND: Several studies have examined the potential of adrenomedullin (ADM), pro-adrenomedullin (Pro-ADM), and mid-regional-pro-ADM (MR-Pro-ADM) as biomarkers for diagnosing and assessing the severity of heart failure (HF), with conflicting results. We aimed to investigate their diagnostic utility and their correlation with HF severity based on the New York Heart Association (NYHA) classification. METHODS: We searched PubMed, EMBASE, and Scopus using a predefined search string. The quality assessment of included studies was conducted using the Newcastle Ottawa Scale (NOS), and the primary outcome was the mean difference (MD) in serum levels of ADM, Pro-ADM, and MR-Pro-ADM, in addition to the area under the curve (AUC). RESULTS: A total of 28 articles fulfilled our inclusion criteria and were included in our qualitative and quantitative synthesis, with a total of 15,405 subjects. Significant MD in ADM levels in HF patients vs. controls (6.024 [95 % CI 1.691, 10.356]), NYHA I vs. controls (-1.202 [95 % CI -2.111, -0.292]), NYHA IV vs. controls (-7.536 [95 % CI -12.680, -2.393]), NYHA III vs. NYHA IV (-4.438 [95 % CI -7.612, -1.263]), and NYHA I-II vs NYHA III-IV (-2.351 [95 % CI -4.361, -0.341]) were observed. Moreover, a significant MD was observed in pro-ADM levels in NYHA I-II patients vs. controls (-0.960 [95 % CI -1.479, -0.440]), NYHA III-IV vs. controls (-1.979 [95 % CI -2.958, -1.000]), and NYHA I-II vs. NYHA III-IV (-0.966 [95 % CI -1.407, -0.526]). Furthermore, MR-Pro-ADM levels were significantly different in NYHA I-II vs. NYHA III-IV (-0.428 [95 % CI -0.492, -0.365]). MR-Pro-ADM predicted HF with an AUC of 0.781 (95 % CI 0.755, 0.806). CONCLUSIONS: Among HF patients, there was a significant increase in ADM levels compared to control subjects, and these levels increased with the progression of NYHA classes. Similarly, both Pro-ADM and MR-Pro-ADM displayed higher concentrations in NYHA class III-IV HF patients compared to those in NYHA class I-II. However, MR-Pro-ADM exhibited lower accuracy in predicting HF compared to established biomarkers.
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Cruciat et al. (2024) conducted a meta-analysis in Heart failure (n=15,405). Adrenomedullin (ADM), Pro-ADM, and MR-Pro-ADM levels vs. Controls or lower NYHA classes was evaluated on Mean difference (MD) in serum levels of ADM, Pro-ADM, and MR-Pro-ADM, and area under the curve (AUC) (MD 6.024, 95% CI 1.691, 10.356). Serum levels of adrenomedullin were significantly higher in heart failure patients compared to controls (MD 6.024; 95% CI 1.691-10.356), with levels increasing alongside NYHA class progression.
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