Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): The project was funded by grants from The Liaison Committee for Education, Research and Innovation in Central Norway, St. Olavs University Hospital (Trondheim, Norway), Nord-Trøndelag Hospital Trust (Levanger, Norway), and Simon Fougner Hartmann's Family Fund (Copenhagen, Denmark). Background The left atrium (LA) and ventricle (LV) are closely linked and adapt to meet metabolic demands. Reduced LV end-diastolic volume (LVEDV) and increased LA end-systolic volume (LAESV) is common in patients with diastolic dysfunction and with higher age. The remodeling of LA and LV in response to endurance exercise is thought to be balanced, and thus, the LA:LV ratio could help discriminate pathologic from physiologic LA enlargement. Purpose We aimed to describe the relative LA and LV chamber remodeling associated with the clinical characteristics age, sex, maximal oxygen consumption (VO2peak), HbA1C, body mass index, systolic blood pressure, and diastolic dysfunction. Methods Healthy participants included in a large longitudinal population study underwent clinical evaluation and cardiopulmonary exercise testing (CPET) in 2006–2008, followed by comprehensive echocardiography and CPET in 2017–18. Exclusion criteria were: 1) submaximal performance during CPET, 2) atrial fibrillation, or 3) presence of heart failure or a history of myocardial infarction. All examinations were performed by highly experienced personnel. All echocardiographic exams and analyses were performed by personnel affiliated a European Association of Cardiovascular Imaging accredited echo-laboratory. Results In total, 1,349 participants were included. Mean (SD) age was 58 (12) years, and 52% were women. The LA:LV ratio was higher with higher age due to lower LVEDV and stable LAESV (Figure 1). Age alone explained 12% (p<0.001) of variance for the LA:LV ratio and men had higher LA:LV ratios than women (0.55 vs. 0.50, p <0.001). All examined clinical characteristics showed significant associations with LA:LV ratios in univariate regression analyses. In adjusted analyses, increased VO2peak was significantly associated with increased LA:LV ratio, but with a small effect-size without clinical significance. In the subsample with indexed LAESV >34mL/m2, increased VO2peak was significantly associated with increased LA:LV-ratio in adjusted analyses (p <0.001). Ten-year change in VO2peak was not significantly associated with LA:LV ratio in adjusted models for the total population, nor in the subgroup with indexed LAESV >34 mL (p = 0.181). Multiple logistic regression showed that higher LA:LV ratio was associated with increased risk of diastolic dysfunction with an OR (95% CI) of 2.4 (1.5, 4.0) per SD increase in LA:LV-ratio, adjusted for age, sex, systolic blood pressure, HbA1c, and BMI (p < 0.001). LA strain measures, E/e’ ratio, and TR velocity were significantly associated with the LA:LV ratio, while other diastolic function parameters were not. Conclusion The LA:LV ratio increases with higher age due to reduced LVEDV and stable LAESV. VO2peak was not a robust predictor of LA:LV ratio in this population. Future studies should evaluate the relative remodeling of LA and LV with repeated measurements of echocardiographic indices and CPET to better define the role of this ratio.