BackgroundA physiological third heart sound (S3) is common in youth but allegedly very rare after the age of 40 years. The mechanism of its disappearance is not known. The aim of this work was to study the prevalence and predictors of physiological S3in a population-based sample of persons approaching 40 years of age.Methods and ResultsA random sample of 120 persons born in 1954 was invited; 93 (42 men) entered the study. Their physical activity, alcohol and tobacco consumption, and salt intake were quantified by diary follow-up. The presence of an S3was determined by auscultation and confirmed by phonocardiography. Left ventricular (LV) size, mass, and systolic function were assessed by M-mode echocardiography and LV filling by Doppler velocimetry of transmitral flow. An audible S3was detected in 22 subjects, 1 of whom had heart disease. The prevalence of physiological S3was 23.1%. Subjects with physiological S3 had a lower body mass index (22.3 ±2.8 versus 24.6±4.1 kg/m2[mean±SD],P= .005), lower heart rate (63±7 versus 68±10 beats per minute,P= .015), higher peak early diastolic transmitral velocity (67±10 versus 58±8 cm/s,P= .002), and higher acceleration of early diastolic velocity (717±148 versus 622±122 cm/s2,P= .012) than those without S3. No differences were noted in the lifestyle characteristics, blood pressure, or LV mass and systolic function. Body mass index and peak early diastolic transmitral velocity were independent predictors of physiological S3in logistic regression analysis.ConclusionsNearly one fourth of persons approaching their forties still have an audible physiological S3. The presence of S3is predicted by leanness and a high early diastolic LV inflow velocity; the disappearance of S3is unlikely to be secondary to increasing blood pressure and relative LV hypertrophy, as is widely presented, but reflects a more primary age-related alteration of LV early diastolic function.