This cross-sectional study was performed to establish the rationale for BNP testing for identifying subjects at high risk of congestive heart failure (CHF) in a screening setting. Plasma BNP concentrations were measured in 8,178 community-dwelling residents (mean age, 62 +/- 12 years; 3,194 males). First, in order to determine age- and sex-related reference values for plasma BNP levels, subjects having factors known to influence plasma BNP levels were excluded. The remaining 3,410 subjects were eligible for the reference study. Second, to verify BNP testing for screening for subjects at high risk of CHF, the clinical characteristics of subjects showing abnormally high plasma BNP levels (> or = 97.5 percentile for each age- and sex-specific value of the reference cohort) were examined. In the reference subjects, plasma BNP levels increased with age in both genders, and were higher in women than in men. In the original cohort, age- and sex-specific reference values for high plasma BNP levels were related to the presence of major ECG abnormalities, hypertension, mildly elevated serum creatinine levels, and a history of coronary heart disease. The results of the present study indicate that individuals with high plasma BNP levels in the community have accumulating risk factors for CHF. This suggests that plasma BNP measurement may be a useful screening test for identification of individuals at high risk of CHF within a Japanese general population.