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.
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).
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.
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.
URL: http:/www.ClinicalTrials.gov/. Unique identifiers: NCT01435408 and NCT01960933.
Falkentoft AC
，Rørth R
，Iversen K
，Høfsten DE
，Kelbæk H
，Holmvang L
，Frydland M
，Schoos MM
，Helqvist S
，Axelsson A
，Clemmensen P
，Jørgensen E
，Saunamäki K
，Tilsted HH
，Pedersen F
，Torp-Pedersen C
，Kofoed KF
，Goetze JP
，Engstrøm T
，Køber L
... -
《Journal of the American Heart Association》
Multimarker Risk Stratification in Patients With Acute Myocardial Infarction.
Several biomarkers have individually been shown to be useful for risk stratification in patients with acute myocardial infarction (MI). The optimal multimarker strategy remains undefined.
Biomarkers representing different pathobiological axes were studied, including myocardial stress/structural changes (NT-pro B-type natriuretic peptide [NT-proBNP], midregional proatrial natriuretic peptide [MR-proANP], suppression of tumorigenicity 2 [ST2], galectin-3, midregional proadrenomedullin [MR-proADM], and copeptin), myonecrosis (troponin T), and inflammation (myeloperoxidase [MPO], high sensitivity C-reactive protein [hsCRP], pregnancy-associated plasma protein A [PAPP-A], and growth-differentiation factor-15 [GDF-15]), in up to 1258 patients from Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28), a randomized trial of clopidogrel in ST-elevation MI (STEMI). Patients were followed for 30 days. Biomarker analyses were adjusted for traditional clinical variables. Forward step-wise selection was used to assess a multimarker strategy. After adjustment for clinical variables and using a dichotomous cutpoint, 7 biomarkers were each significantly associated with a higher odds of cardiovascular death or heart failure (HF) through 30 days, including NT-proBNP (adjusted odds ratio [ORadj], 2.54; 95% CI, 1.47-4.37), MR-proANP (2.18; 1.27-3.76), ST2 (2.88; 1.72-4.81), troponin T (4.13; 1.85-9.20), MPO (2.75; 1.20-6.27), hsCRP (1.96, 1.17-3.30), and PAPP-A (3.04; 1.17-7.88). In a multimarker model, 3 biomarkers emerged as significant and complementary predictors of cardiovascular death or HF: ST2 (ORadj, 2.87; 1.61-5.12), troponin T (2.34; 1.09-5.01 and 4.13, 1.85-9.20, respectively for intermediate and high levels), and MPO (2.49; 1.04-5.96). When added to the TIMI STEMI Risk Score alone, the multimarker risk score significantly improved the C-statistic (area under the curve, 0.75 [95% CI, 0.69-0.81] to 0.82 [0.78-0.87]; P=0.001), net reclassification index (0.93; P<0.001), and integrated discrimination index (0.09; P<0.001).
In patients with STEMI, a multimarker strategy that combines biomarkers across pathobiological axes of myocardial stress, myocyte necrosis, and inflammation provides incremental prognostic information for prediction of cardiovascular death or HF.
O'Donoghue ML
，Morrow DA
，Cannon CP
，Jarolim P
，Desai NR
，Sherwood MW
，Murphy SA
，Gerszten RE
，Sabatine MS
... -
《Journal of the American Heart Association》
Mid-regional pro-adrenomedullin in patients with acute dyspnea: Data from the Akershus Cardiac Examination (ACE) 2 Study.
Mid-regional pro-adrenomedullin (MR-proADM) is a surrogate marker for adrenomedullin; a hormone that attenuates myocardial remodeling. Accordingly, we hypothesized that MR-proADM could provide diagnostic and prognostic information in patients with acute dyspnea.
We measured MR-proADM by a commercial ELISA on hospital admission in 311 patients with acute dyspnea and compared the utility of MR-proADM with N-terminal pro-B-type natriuretic peptide (NT-proBNP). Blood samples were also available after 24h (n=232) and before discharge (n=94). The principal diagnosis of the index hospitalization was determined by an adjudication committee. MR-proADM concentrations on hospital admission were higher in patients with acute heart failure (HF; n=143) vs. patients hospitalized with non-HF-related dyspnea (n=168): 1.31 (Q1-3 0.97-1.89) vs. 0.85 (0.59-1.15) nmol/L; p<0.001. The receiver-operating characteristics area under the curve (ROC-AUC) for MR-proADM to diagnose HF was 0.77 (95% CI 0.72-0.82) and 0.86 (0.82-0.90) for NT-proBNP. During a median follow-up of 816days, 66/143 patients (46%) with acute HF and 35/84 patients (42%) with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) died; p=0.58 between groups. In multivariate Cox regression analyses, admission MR-proADM concentrations were associated with mortality in patients with acute HF (HR 5.90 [3.43-10.13], p<0.001), but not in patients with AECOPD. Admission MR-proADM concentrations also improved risk stratification in acute HF as assessed by the net reclassification index. MR-proADM concentrations decreased from admission to later time points.
Admission MR-proADM concentrations provide strong prognostic information in patients with acute HF, but modest diagnostic information in patients with acute dyspnea.
Pervez MO
，Lyngbakken MN
，Myhre PL
，Brynildsen J
，Langsjøen EC
，Høiseth AD
，Christensen G
，Omland T
，Røsjø H
... -
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