N-terminal pro-brain natriuretic peptide (NT-proBNP) is increased early after acute myocardial infarction. We assessed the relationship of NT-proBNP with left ventricular function and mass as well as with renal function, hemodynamic, and anthropometric variables in 625 outpatients in the chronic phase after myocardial infarction and 465 siblings without infarction (control). NT-proBNP was measured by nonextracted, enzyme-linked, sandwich immunoassay. NT-proBNP was correlated with left ventricular ejection fraction, mass index, and renal function, in addition to infarction history, gender, and age, in univariate and multivariate analysis (all P<0.01). Increases in NT-proBNP observed in subjects with infarction (96.6+/-13.7 versus 31.2+/-1.8 pmol/L in control subjects, P<0.001) were particularly pronounced in the presence of significant left ventricular dysfunction (182.8+/-41.9 pmol/L), left ventricular hypertrophy (214.5+/-61.7 pmol/L), and renal dysfunction (210.3+/-51.4 pmol/L, all P<0.01). Patients with an ejection fraction <35% were detected by NT-proBNP with a sensitivity, specificity, and negative predictive value of 75%, 62%, and 99%, respectively, at an optimal cutoff of 44 pmol/L. Patients with an ejection fraction <35% and concomitant left ventricular hypertrophy were detected with a sensitivity, specificity, and negative predictive value of 90%, 80%, and 99.9%, respectively, at a cutoff of 76 pmol/L. Similar results were obtained for patients with an ejection fraction <35% and concomitant renal dysfunction at a cutoff of 162 pmol/L. NT-proBNP is a biochemical marker of integrated cardio-renal function in the chronic phase after myocardial infarction and a potential diagnostic tool for the detection and exclusion of significant left ventricular dysfunction. Cutoff concentrations have to be chosen according to renal function to optimize the predictive value of NT-proBNP.