A landmark study reveals that exercise-induced multi-organ physiologic deficits strongly predict incident heart failure with preserved ejection fraction (HFpEF). Using invasive cardiopulmonary testing, metabolomics, and genomics across over 6,000 individuals, researchers identified seven distinct exercise deficits that, when combined, confer nearly 4-fold higher cardiovascular risk and implicate shared metabolic pathways with obesity, diabetes, and renal disease.