MR-proADM as a Prognostic Marker in Patients With ST-Segment-Elevation Myocardial Infarction-DANAMI-3 (a Danish Study of Optimal Acute Treatment of Patients With STEMI) Substudy

Alexander C Falkentoft, Rasmus Rørth, Kasper Iversen, Dan E Høfsten, Henning Kelbæk, Lene Holmvang, Martin Frydland, Mikkel M Schoos, Steffen Helqvist, Anna Axelsson, Peter Clemmensen, Erik Jørgensen, Kari Saunamäki, Hans-Henrik Tilsted, Frants Pedersen, Christian Torp-Pedersen, Klaus F Kofoed, Jens P Goetze, Thomas Engstrøm, Lars Køber, Alexander C Falkentoft, Rasmus Rørth, Kasper Iversen, Dan E Høfsten, Henning Kelbæk, Lene Holmvang, Martin Frydland, Mikkel M Schoos, Steffen Helqvist, Anna Axelsson, Peter Clemmensen, Erik Jørgensen, Kari Saunamäki, Hans-Henrik Tilsted, Frants Pedersen, Christian Torp-Pedersen, Klaus F Kofoed, Jens P Goetze, Thomas Engstrøm, Lars Køber

Abstract

Background: Midregional proadrenomedullin (MR-proADM) has demonstrated prognostic potential after myocardial infarction (MI). Yet, the prognostic value of MR-proADM at admission has not been examined in patients with ST-segment-elevation MI (STEMI).

Methods and results: The aim of this substudy, DANAMI-3 (The Danish Study of Optimal Acute Treatment of Patients with ST-segment-elevation myocardial infarction), was to examine the associations of admission concentrations of MR-proADM with short- and long-term mortality and hospital admission for heart failure in patients with ST-segment-elevation myocardial infarction. Outcomes were assessed using Cox proportional hazard models and area under the curve using receiver operating characteristics. In total, 1122 patients were included. The median concentration of MR-proADM was 0.64 nmol/L (25th-75th percentiles, 0.53-0.79). Within 30 days 23 patients (2.0%) died and during a 3-year follow-up 80 (7.1%) died and 38 (3.4%) were admitted for heart failure. A doubling of MR-proADM was, in adjusted models, associated with an increased risk of 30-day mortality (hazard ratio, 2.67; 95% confidence interval, 1.01-7.11; P=0.049), long-term mortality (hazard ratio, 3.23; 95% confidence interval, 1.97-5.29; P<0.0001), and heart failure (hazard ratio, 2.71; 95% confidence interval, 1.32-5.58; P=0.007). For 30-day and 3-year mortality, the area under the curve for MR-proADM was 0.77 and 0.78, respectively. For 3-year mortality, area under the curve (0.84) of the adjusted model marginally changed (0.85; P=0.02) after addition of MR-proADM.

Conclusions: Elevation of admission MR-proADM was associated with long-term mortality and heart failure, whereas the association with short-term mortality was borderline significant. MR-proADM may be a marker of prognosis after ST-segment-elevation myocardial infarction but does not seem to add substantial prognostic information to established clinical models.

Clinical trial registration: URL: http:/www.ClinicalTrials.gov/. Unique identifiers: NCT01435408 and NCT01960933.

Keywords: ST‐segment–elevation myocardial infarction; biomarker; midregional proadrenomedullin; myocardial infarction; prognosis.

© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1
Figure 1
CONSORT study flow diagram. MR‐proADM indicates midregional proadrenomedullin; TIMI‐flow, angiographic thrombolysis in myocardial infarction flow.
Figure 2
Figure 2
Overall survival among patients with STEMI, according to quartiles of admission MR‐proADM. The MR‐proADM levels were as follows: first quartile ≤0.52 nmol/L, second quartile 0.53 to 0.64 nmol/L, third quartile 0.65 to 0.78 nmol/L and fourth quartile ≥0.79 nmol/L. MR‐proADM indicates midregional proadrenomedullin; STEMI, ST‐segment–elevation myocardial infarction.
Figure 3
Figure 3
Univariate and multivariable cox analysis for all‐cause mortality according to quartiles of MR‐proADM among patients with STEMI. Model 1 was adjusted for age and sex. Model 2 was adjusted additionally for age, sex, time since onset of symptoms, left ventricular ejection fraction, heart rate, estimated glomerular filtration rate, TIMI‐flow before primary PCI, anterior myocardial infarction, log2‐transformed peak concentrations of hs‐cTnT, and medical history of following variables: diabetes mellitus, hypertension, history of smoking, previous myocardial infarction, previous stroke, and congestive heart failure. CI indicates confidence interval; HR, hazard ratio; hs‐cTnT, high‐sensitivity cardiac troponin T; MR‐proADM, midregional proadrenomedullin; PCI, primary percutaneous coronary intervention; STEMI, ST‐segment–elevation myocardial infarction; TIMI‐flow, angiographic thrombolysis in myocardial infarction flow.

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