Influence of functional deficiency of complement mannose-binding lectin on outcome of patients with acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.
OBJECTIVE
Experimental data point towards a favourable effect of low serum concentrations of complement mannose-binding lectin (MBL) on myocardial ischaemia/reperfusion (I/R) injury. As comparable data on the role of MBL in human I/R injury is lacking, we investigated the influence of low serum MBL concentrations on mortality of patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).


RESULTS
Mannose-binding lectin was determined in 890 acute STEMI patients that were prospectively recruited in the APEX-AMI trial. This trial had a primary endpoint of death through Day 30 and secondary endpoints of death through Day 90 and the composite of death, cardiogenic shock, or congestive heart failure (CHF) through Days 30 and 90. Samples were taken immediately before PCI and the analysis of MBL limited to patients having received placebo. Patients with serum MBL levels of or below 100 ng/mL were considered to be functionally deficient. Of the 890 patients, 127 had functional MBL deficiency (14.3%). Characteristics of patients with MBL deficiency and those with MBL levels >100 ng/mL did not differ. In patients with MBL deficiency, there was 1 death (0.79%) compared with 42 deaths (5.51%) in patients with MBL levels >100 ng/mL (P = 0.0233) representing an absolute and relative lower mortality in MBL deficient patients of 4.7 and 85%, respectively. Functional MBL deficiency, however, was not associated with decreased risk of the combined endpoints of death and shock or death, shock, and CHF, respectively.


CONCLUSIONS
Functional deficiency of complement MBL is associated with reduced mortality in patients with STEMI undergoing PCI. This unique finding suggests that a component of the innate immune system affects mortality in STEMI patients undergoing primary PCI.


BACKGROUND
clinicaltrials.gov, Identifier: NCT00091637.
Trendelenburg
Marten
M
Internal Medicine and Clinical Immunology Laboratory, University Hospital Basel, Petersgraben, Basel, Switzerland. marten.trendelenburg@unibas.ch
Theroux
Pierre
P
Stebbins
Amanda
A
Granger
Christopher
C
Armstrong
Paul
P
Pfisterer
Matthias
M
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D051056:Complement Inactivating Agents / Q000627:therapeutic use; D003165:Complement System Proteins / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D037601:Mannose-Binding Lectin / Q000172:deficiency*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000401:mortality; D011446:Prospective Studies; D012770:Shock, Cardiogenic / Q000401:mortality; D057127:Single-Chain Antibodies / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D051056:Complement Inactivating Agents; D037601:Mannose-Binding Lectin; D057127:Single-Chain Antibodies; D003165:Complement System Proteins; C402724:pexelizumab; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form