MR-proANP improves prediction of mortality and cardiovascular events in patients with STEMI.

Atrial natriuretic peptide (ANP) is released from the atria (on cleavage of proANP) in response to elevated intra-atrial pressure and wall stretch. Clinical data on proANP are still limited, mainly due to limitations in assaying the protein, which recently have been solved. ProANP is elevated in cardiovascular disease and predicts outcome in heart failure. However, knowledge of the prognostic value in acute myocardial infarction remains limited. We prospectively included 680 patients with STEMI treated with primary-PCI, from September 2006 to December 2008. Blood samples were drawn immediately before PCI. Plasma MR-proANP was measured using an automated processing assay. Endpoints were all-cause mortality (n = 137) and the combined endpoint (n = 170) of major adverse cardiovascular events (MACE) defined as cardiovascular mortality and admission due to recurrent MI, ischaemic stroke or heart failure. During 5-year follow-up, MR-proANP was associated with increased risk of all-cause mortality and MACE (both p < 0.001). After adjustment for confounding risk factors (age, gender, hypertension, diabetes, hypercholesterolaemia, smoking, previous MI, BMI, eGFR, CRP, peak-TnI, symptom-to-balloon time, multivessel disease, complex lesion, LAD-lesion and use of glycoprotein inhibitor), MR-proANP remained an independent predictor of all-cause mortality and MACE - hazard ratio: 1.68 (95% CI 1.35-2.10; p < 0.001) and 1.68 (95% CI 1.39-2.03; p < 0.001) per standard deviation increase in MR-proANP. MR-proANP significantly increased C-statistics and reclassified 26% of the patients for all-cause mortality and 34% for MACE into higher or lower risk categories, matching actual event rates more accurately. Plasma MR-proANP independently predicts all-cause mortality and MACE in patients with STEMI.

Lindberg S ，Jensen JS ，Pedersen SH ，Galatius S ，Goetze JP ，Mogelvang R ... -  《-》

Interplay Between Adiponectin and Pro-Atrial Natriuretic Peptide and Prognosis in Patients With ST-Segment Elevation Myocardial Infarction.

Natriuretic peptides (NPs) may regulate adipocyte metabolism including adiponectin. Infusion of atrial natriuretic peptide (ANP) increases plasma adiponectin in patients with heart failure. However, this relation has not been examined in a clinical setting or in myocardial infarction (MI). Accordingly, we investigated the interplay between proANP and adiponectin and the prognostic implications in patients with MI. We prospectively included 680 patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention from September 2006 to December 2008. Blood samples were drawn immediately before percutaneous coronary intervention. Additionally, we included 40 patients with 4 obtained blood samples during STEMI. Adiponectin and proANP were measured in all plasma samples. All patients were followed for 5 years. End points were all-cause mortality (n = 137) and the combined end point (n = 170) of major adverse cardiovascular events (MACEs). Plasma adiponectin and proANP were strongly associated at admission (r = 0.34, p <0.001). In patients with increasing proANP during STEMI, adiponectin also increased (0.5 ± 0.3 vs -0.1 ± 0.1 mg/L, p = 0.026). During follow-up, patients with higher adiponectin at admission had increased risk of all-cause mortality and MACE (both, p <0.001). After adjustment for confounding risk factors by Cox regression analysis, adiponectin remained an independent predictor of all-cause mortality and MACE: hazard ratio 1.31 (95% confidence interval 1.07 to 1.60; p = 0.009) and 1.31 (95% confidence interval 1.09 to 1.57; p = 0.004), respectively, for each SD increase. However, the association vanished when proANP was included in the analysis. In conclusion, adiponectin is associated with an increased risk of all-cause mortality and MACE. However, concomitantly elevated proANP levels appear to confound the association between adiponectin and worsened outcome.

Lindberg S ，Jensen JS ，Hoffmann S ，Pedersen SH ，Iversen AZ ，Galatius S ，Frystyk J ，Flyvbjerg A ，Goetze JP ，Bjerre M ，Mogelvang R ... -  《-》

High osteopontin levels predict long-term outcome after STEMI and primary percutaneous coronary intervention.

Bjerre M ，Pedersen SH ，Møgelvang R ，Lindberg S ，Jensen JS ，Galatius S ，Flyvbjerg A ... -  《-》

Soluble form of membrane attack complex independently predicts mortality and cardiovascular events in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention.

The complement system is an important mediator of inflammation, which plays a pivotal role in atherosclerosis and acute myocardial infarction (AMI). Animal studies suggest that activation of the complement cascade resulting in the formation of soluble membrane attack complex (sMAC), contributes to both atherosclerosis and plaque rupture and may be the direct cause of tissue damage related to ischemia/reperfusion injury. However clinical data of sMAC during an AMI is sparse. Accordingly the aim was to investigate the prognostic role of sMAC in patients with ST-segment elevation myocardial infarction (STEMI). We included 725 STEMI-patients admitted to a single, high-volume invasive heart centre, treated with primary percutaneous coronary intervention (PCI), from September 2006 to December 2008. Blood samples were drawn immediately before PCI. Plasma sMAC was measured using an in-house immunoassay. Endpoints were all-cause mortality (n = 62) and the combined endpoint (n = 122) of major cardiovascular events (MACE) defined as cardiovascular mortality and admission due recurrent AMI or heart failure. Follow-up time was 12 months. During 12 months of follow-up 62 patients died from all causes and 122 patients reached the combined end-point of MACE. Patients with high sMAC (>75th percentile) had increased risk of both all-cause mortality and MACE. Even after adjustment for confounding risk factors by Cox-regression analyses, high levels of sMAC remained an independent predictor of all-cause mortality (hazard ratio 1.81 [95% CI 1.06-3.06; P = .029]) and MACE (hazard ratio 1.70 [95% CI 1.16-2.48; P = .006]). High plasma sMAC independently predicts all-cause mortality and MACE in STEMI-patients treated with PCI.

Lindberg S ，Pedersen SH ，Mogelvang R ，Galatius S ，Flyvbjerg A ，Jensen JS ，Bjerre M ... -  《-》

NT-proANP and NT-proBNP circulating levels as predictors of cardiovascular outcome following coronary stent implantation.

Natriuretic peptides are diagnostic/prognostic biomarkers in major cardiovascular diseases. We aimed at assessing the predictive role of N-terminal pro-A-type (NT-proANP) and pro-B-type (NT-proBNP) natriuretic peptides levels toward cardiovascular outcome in both stable and unstable coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) in a non-primary PCI setting. A total of 395 patients undergoing PCI with stent implantation for either stable angina (SA) or non ST-elevation acute coronary syndrome (NSTE-ACS) were enrolled. Pre-procedural NT-proANP and NT-proBNP levels were measured. Occurrence of major adverse cardiac events (MACEs), composite of cardiac death, non-fatal myocardial infarction, and clinically driven target lesion revascularization (c-TLR), was the endpoint of the study. Follow up mean time was 48.53±14.69months. MACEs occurred in forty-four patients (11%) during follow up. Both NT-proANP levels [3170 (2210-4630) vs 2283 (1314-3913) fmol/mL, p=0.004] and NT-proBNP levels [729 (356-1353) vs 511 (267-1006) fmol/mL, p=0.04] were significantly higher in patients with MACEs compared to patients without MACEs. Similar results were found when considering hard MACEs (myocardial infarction and cardiac death). NT-proANP levels were significantly higher in patients with c-TLR compared with patients without c-TLR [3705 (2766-5184) vs 2343 (1340-3960) fmol/mL, p=0.021]. At multivariate analysis, NT-proANP levels were a significant predictor of MACEs (HR 1.09, 95% CI 1.03-1.18, p=0.04). Kaplan-Meyer curves revealed that patients with elevated NT-proANP levels (>2.100fmol/mL) had a lower MACE free survival (p=0.003). Both NT-proANP and NT-proBNP levels were higher in CAD patients experiencing MACEs following PCI in a non-primary setting. Notably, only NT-proANP levels significantly affected prognosis after PCI.

Niccoli G ，Conte M ，Marchitti S ，Montone RA ，Fracassi F ，Grippo R ，Roberto M ，Burzotta F ，Trani C ，Leone AM ，Bianchi F ，Di Castro S ，Volpe M ，Crea F ，Rubattu S ... -  《-》