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. 2023 Jun 2;12(6):364-371.
doi: 10.1093/ehjacc/zuad029.

Mid-regional pro-adrenomedullin and lactate levels for risk stratification in patients with out-of-hospital cardiac arrest

Thomas A Zelniker  1   2 , Dominik Schwall  2 , Fardin Hamidi  1   2 , Simone Steinbach  2 , Pascal Scheller  2 , Sebastian Spaich  2 , Guido Michels  3 , Evangelos Giannitsis  2 , Hugo A Katus  2   4 , Norbert Frey  2   4 , Michael R Preusch  2   4
Affiliations

Mid-regional pro-adrenomedullin and lactate levels for risk stratification in patients with out-of-hospital cardiac arrest

Thomas A Zelniker et al. Eur Heart J Acute Cardiovasc Care. .

Abstract

Aims: Adrenomedullin (ADM) is a free-circulating peptide that regulates endothelial barrier function and vascular tone. Here, we sought to study the relationship of ADM in combination with lactate and the risk of death in patients with out-of-hospital cardiac arrest (OHCA).

Methods and results: Mid-regional pro-adrenomedullin (MR-proADM) and lactate concentrations were measured in patients with OHCA who survived at least 24 h after the return of spontaneous circulation. The outcome of interest was all-cause death. Patients were characterized by the quartiles (Q) of MR-proADM and lactate concentrations. Cox models were adjusted for age, sex, shockable rhythm, bystander resuscitation, simplified acute physiology score II (SAPS II), and estimated glomerular filtration rate (eGFR). A total of 232 patients were included in the present study (28% women, 67 years, SAPS II 80). The median MR-proADM and lactate levels at 24 h were 1.4 nmol/L [interquartile range (IQR) 0.8-2.8 nmol/L] and 1.8 mmol/L (IQR 1.3-3.4 mmol/L), respectively. Mid-regional pro-adrenomedullin concentrations correlated weakly with lactate levels (r = 0.36, P < 0.001). High (Q4) vs. low (Q1-Q3) MR-proADM concentrations were significantly associated with an increased rate of death at 28 days (75.9 vs. 45.4%; P < 0.001). After multivariable adjustment (including lactate levels at 24 h), higher MR-proADM levels were significantly associated with an increased risk of death [Q4 vs. Q1-Q3: adjusted hazard ratio (adj-HR) 1.67, 95% confidence interval (CI) 1.12-2.50; adj-HR for a 1-unit increase in a standardized biomarker 1.44, 95% CI 1.19-1.73]. This relationship remained significant even after further adjustment for baseline NT-proBNP and high-sensitivity troponin T levels. The combination of high MR-proADM and high lactate (Q4) concentrations identified patients at a particularly elevated risk (adj-HR 3.50; 95% CI 1.92-6.39).

Conclusion: Higher MR-proADM concentrations are associated with an increased risk of death in patients with OHCA, and the combination of high MR-proADM and lactate levels identifies patients at a distinctly elevated risk.

Keywords: Lactate; MR-proADM; Out-of-hospital cardiac arrest; Risk stratification.

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Conflict of interest statement

Conflict of interest: T.A.Z. reports grants from the Austrian Science Funds and the German Research Foundation, honoraria for serving on advisory boards from Boehringer Ingelheim, and personal and lecture fees from Alkem Lab. Ltd, AstraZeneca, Bayer AG, Boehringer Ingelheim, and Sun Pharmaceutical Industries, and educational grants from Eli Lilly and Company. E.G. reports lecture fees from Daiichi Sankyo, AstraZeneca, and Roche Diagnostics. He has received honoraria for consultancy from Roche Diagnostics, Boehringer Ingelheim, Novo Nordisk, Brahms Deutschland, and Daiichi Sankyo. N.F. reports honoraria for serving on advisory boards from Boehringer Ingelheim, and lecture fees from AstraZeneca, Bayer, Novartis, and Pfizer. D.S., F.H., S.St., P.S., S.Sp., G.M., and M.R.P. report no conflicts of interest.

Figures

Graphical abstract
Graphical abstract
(A) Cumulative incidence curves for all-cause death stratified by the top quartile (Q) vs. Q1–Q3 of mid-regional pro-adrenomedullin (MR-proADM). Patients with MR-proADM levels in the top quartile vs. those in Q1–Q3 had significantly higher death rates at 7 days (55.2 vs. 19.0%, P < 0.001) and at 28 days (75.9 vs. 45.4%, P < 0.001). (B) Kaplan–Meier event rates at 28 days stratified by MR-proADM and lactate levels for all-cause death. Patients with both markers in the top quartile had significantly higher rates of death. This risk persisted after multivariable adjustment (adjusted hazard ratio 3.50; 95% confidence interval 1.92–6.39).
Figure 1
Figure 1
Cumulative incidence curve with the respective Kaplan–Meier event rates at 7 and 28 days for all-cause death stratified by the top quartile (Q4) vs. Q1–Q3 of mid-regional pro-adrenomedullin levels.
Figure 2
Figure 2
Adjusted hazard ratios for mid-regional pro-adrenomedullin concentrations modelled as a continuous variable per 1 standard deviation increase in biomarker and stratified by the top quartile (Q4) vs. Q1–Q3 of adrenomedullin levels for all-cause death.
Figure 3
Figure 3
Estimated adjusted log-hazard ratios and 95% confidence limits for all-cause death in relation to continuous mid-regional pro-adrenomedullin concentrations modelled using natural cubic splines. The dashed vertical lines indicate the 25th, 50th, and 75th percentiles. The rug plot illustrates the marginal distribution of adrenomedullin concentrations. Cox regression models were adjusted for age, sex, the type of first monitored electrocardiogram rhythm, presence of bystander resuscitation, estimated glomerular filtration rate, and lactate levels.
Figure 4
Figure 4
Kaplan–Meier event rates at 28 days and adjusted hazard ratios for all-cause death stratified by mid-regional pro-adrenomedullin and lactate concentrations.
See this image and copyright information in PMC

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