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To evaluate brain natriuretic peptide (BNP) as marker of left ventricular (LV) dysfunction and hypertrophy in a population-based sample of 610 middle-aged subjects (50–67 years) who were further characterized with respect to hemodynamic and anthropometric parameters and by echocardiography.Left ventricular (LV) systolic function, LV mass-index, age, gender, heart rate, and medication with beta adrenergic receptor blockers were significant and independently correlated with BNP (multivariate analysis, P < 0.05 each). As compared to subjects with normal LV function and mass-index (control), subjects with LV dysfunction (LV fractional shortening < 28%) or hypertrophy (LV mass-index > 110 g/m2 in women and > 134 g/m2 in men) were characterized by increased BNP. The increase in BNP associated with LV hypertrophy (n = 69, +101% versus control, P < 0.0001) was similar in magnitude to that associated with LV dysfunction (n = 39, +98% versus control, P < 0.03). These increases were markedly exceeded in subjects with severe LV dysfunction (n = 11, LV fractional shortening < 22%, BNP +197% versus control, P < 0.01), particularly in the presence of concomitant hypertrophy (n = 7, +227%, P < 0.01). The predictive values of BNP varied considerably with the degree of LV dysfunction and the presence or absence of concomitant LV hypertrophy. With 0.81, the highest area under the receiver operator characteristic curve was obtained for the detection of severe LV dysfunction and concomitant hypertrophy and sensitivity, specificity, positive and negative predictive value for this condition were 71, 86, 7 and 99.5%, respectively, for a cut-off of 34 pg/ml.The current study provides new insight into regulation and diagnostic value of BNP in middle-aged subjects and demonstrates important independent effects of LV function and mass upon BNP plasma concentrations. Although measurement of BNP cannot be recommended for the detection of marginally impaired LV function in the population, it may be helpful to suggest or exclude severe LV dysfunction with concomitant hypertrophy.