Background: Pre-clinical diastolic dysfunction (DD) is common in the community and is predictive of all-cause mortality and future heart failure (HF). As advanced Doppler echocardiographic techniques are needed to detect DD, a biomarker which could detect pre-clinical DD would facilitate early recognition and more aggressive intervention. Whether measurement of plasma concentrations of brain natriuretic peptide (BNP) can accurately identify those with pre-clinical DD is unclear. As BNP is higher in females and elderly persons without cardiovascular disease or DD, discriminatory values for diagnostic testing may be altered by age and sex. Objectives: To determine the predictive characteristics of BNP for detection of pre-clinical DD in the general population and in a high risk subset (age≥65 with known hypertension or coronary disease) and to determine if age and sex influence the concentration of BNP which discriminates between those with and without pre-clinical DD. Methods: Randomly selected residents (n = 2042) of Olmsted County Minnesota age ≥45 years underwent comprehensive Doppler echocardiography, medical record review and BNP testing (Biosite assay). Subjects with previous HF diagnosis, inconclusive diastolic assessment or missing BNP were excluded (final n = 1580). Diastolic function was characterized as any DD (abnormal relaxation, pseudonormal or restrictive pattern) or moderate-severe DD (pseudonormal or restrictive pattern). The area (AUC) under the reciever operating characteristic curve, the optimal discriminatory BNP, the + and - likelihood ratios (LR) and the % of the screened population needing echocardiography because of an abnormal BNP were calculated . Results: While the AUC and the LR were similar in elderly subjects, males, females and the high risk group, the optimal discriminatory value for BNP was higher in subjects over age 65 and in females. The + LR were<5 and the – LR were >0.2 indicating limited shifts in disease probability based on the results of the BNP test. Conclusion: When used to detect pre-clinical DD, measurement of plasma BNP does not meet criteria of a robust diagnostic test. An alternate biomarker(s) to detect pre-clinical DD is needed. Tabled 1BNP for detection of any or moderate-severe pre-clinical DDAny DDPrevalence (%)AUCOptimal BNP (pg/ml)+ LR/−LR% EchoAll (n = 1580)27.30.6625.91.61/0.6344.3Age≥65 yr (n = 572)52.60.6041.81.33/0.7649.4Males (n = 725)28.70.6820.21.97/0.5739.6Females (n = 855)26.10.6539.71.79/0.6139.8High risk (n = 369)63.60.6245.31.38/0.7252.2Moderate-Severe DDAll (n = 1580)6.90.7836.44.56/0.6534.0Age≥65 yr (n = 572)12.30.7558.03.13/0.6235.6Males (n = 725)6.70.7920.64.00/0.6339.0Females (n = 855)7.10.7853.14.88/0.6629.2High risk (n = 369)16.70.73113.63.69/0.4923.2 Open table in a new tab