Coronary artery disease (CAD) and diabetes mellitus (DM) can induce changes in myocardial structure and function, thereby increasing the risk of heart failure (HF). We aimed to identify the alterations in echocardiographic variables and circulating biomarkers associated with DM, CAD, or both and to assess the effect of spironolactone on them. The “Heart OMics in AGEing” (HOMAGE) trial evaluated the effect of spironolactone on circulating markers of fibrosis over 9 months of follow-up in people at risk for HF. From the initial population (N = 527) of the HOMAGE trial, a total of 495 participants (mean age 74 years, 25