A comprehensive review of ischemic heart disease: pathophysiology, current treatments, natural products-based therapies, and nanotherapeutics.

Ischemic heart disease (IHD) is one of the major cardiovascular disorders leading to global morbidity and mortality and represents a huge burden on individuals and the healthcare system worldwide. Classically, it is attributed to obstructive atherosclerotic plaques in the epicardial coronary arteries; however, it is now understood to be a heterogeneous disease that also includes microvascular dysfunction, vasospasm, and ischemia with non-obstructive coronary arteries (INOCA). IHD is triggered by modifiable and non-modifiable risk factors, and its diagnosis relies on clinical assessment, electrocardiography, cardiac biomarkers, and advanced imaging techniques. Extensive investigations and trials have established the management of IHD, including lifestyle modifications, pharmacological therapies, and revascularization, while novel interventional, regenerative, and molecularly targeted therapies are under active investigation. This review provides a comprehensive overview of IHD, integrating its epidemiology, risk factors, pathophysiology, diagnostics, and therapeutics. IHD pathogenesis is complex, involving coronary atherosclerosis, plaque disruption, thrombosis, and myocardial ischemia-reperfusion injury that are modulated by oxidative stress, inflammation, and other signaling pathways. The review also addresses the molecular mechanisms and therapeutic potential of natural bioactive compounds, including polyphenols, terpenoids, and alkaloids, which exhibit antioxidant, anti-inflammatory, and cardioprotective effects. In addition, it highlights the multifaceted nature of IHD and underscores the need for integrated, mechanism-driven approaches to improve prevention, early detection, and personalized treatment for this global health burden.