OBJECTIVES: This study was designed to determine whether measurement of plasma pro-B-type natriuretic peptide (proBNP) could be used in discriminating between cardiac and pulmonary dyspnea in the general population. BACKGROUND: Natriuretic peptides are useful markers in ruling out acute cardiac dyspnea in the emergency department, but their diagnostic significance in evaluating chronic dyspnea in the general population is unknown. METHODS: Within the Copenhagen City Heart Study, a large, community-based population study, dyspnea was evaluated by spirometry, oxygen saturation, echocardiography, and plasma proBNP. RESULTS: Of 2,929 participants, 959 reported dyspnea. The plasma proBNP concentration was higher in the group with dyspnea (mean 17.8 pmol/l; 95% confidence interval [CI] 16.3 to 19.4 pmol/l) than in the group without (10.6 pmol/l; 95% CI 10.0 to 11.4 pmol/l; p < 0.001). In the group with dyspnea, left ventricular hypertrophy and/or systolic dysfunction was associated with a 2.6-fold increase in plasma proBNP concentration (p < 0.001), whereas pulmonary dysfunction was not associated with increased plasma proBNP (p = 0.66). Using multivariable regression analysis, a model to estimate the expected concentration of plasma proBNP based on age and gender was established for dyspneic subjects: an actual plasma proBNP concentration below half of the expected value ruled out left ventricular systolic and diastolic dysfunction (sensitivity 100%, 95% CI 100% to 100%; specificity 15%, 95% CI 12% to 17%). CONCLUSIONS: In the general population with dyspnea, plasma proBNP concentrations are increased in left ventricular dilatation, hypertrophy, systolic dysfunction, or diastolic dysfunction, but are unaffected by pulmonary dysfunction.