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A substantial proportion of patients with HFpEF exhibits coronary microvascular disease (CMD), and the combination of CMD with left ventricular diastolic dysfunction is associated with worse outcomes. Distinct patient clusters within HFpEF populations are based on clinical and biomarker profiles, each with unique prognoses and comorbidity patterns. Most patients with HFpEF present with multiple comorbidities, adding to the disease's complexity. Since risk factors directly affect the coronary microvasculature\u2014and considering the bidirectional paracrine signaling between cardiomyocytes and the microvasculature\u2014there is significant pathophysiological overlap between HFpEF and CMD. Therefore, in this review, we aim to summarize epidemiological evidence for the overlap in patients with CMD and HFpEF, identify shared biomarkers pathophysiological pathways underlying the co\u2010occurrence of CMD and HFpEF, and discuss how cardiometabolic interventions may simultaneously address both CMD and HFpEF. Established and emerging treatments for HFpEF and CMD target these shared mechanisms. A deeper understanding of these interrelated pathways may pave the way for novel therapeutic strategies to alleviate the burden of HFpEF and refine patient management.<\/jats:p>","DOI":"10.14814\/phy2.70521","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T19:39:41Z","timestamp":1755718781000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Coronary microvascular disease in heart failure with preserved ejection fraction"],"prefix":"10.14814","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6997-1898","authenticated-orcid":false,"given":"Payel","family":"Sen","sequence":"first","affiliation":[{"name":"Institute for Surgical Research Walter Brendel Center of Experimental Medicine, University Clinic Munich  Munich Germany"},{"name":"Interfaculty Center for Endocrine and Cardiovascular Disease Network Modelling and Clinical Transfer (ICONLMU) University Clinic 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