PCSK9-remmers bij cardiaal syndroom X: nieuw perspectief op microvasculaire angina

Cardiac syndrome X (CSX), historically used to describe angina with normal coronary angiography and now largely encompassed within microvascular angina and INOCA, is an ischemic disorder characterized by angina pectoris without narrowing of coronary arteries. CSX, which primarily affects postmenopausal women, is driven by coronary micro-vascular dysfunction, endothelial impairment, oxidative stress, and chronic low-grade inflammation. Notably, the Conventional anti-anginal therapies often yield limited symptom relief, underscoring the need for novel mechanism-based approaches. Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) has emerged as a pivotal mediator linking dyslipidemia to endothelial dysfunction, oxidative injury, and vascular inflammation. Elevated PCSK9 suppresses endothelial nitric oxide synthase, enhances reactive oxygen species generation, promotes cytokines such as IL-6 and TNF-α, and increases platelet activation. Therefore, PCSK9 inhibitors such as alirocumab, evolocumab, and inclisiran, have been shown to improve endothelial function, reduce arterial stiffness, and attenuate oxidative and inflammatory stress. Consequently, PCSK9 inhibition may be a promising therapeutic strategy for CSX. Thus, this review aimed to discuss and explain the potential role of PCSK9 in the pathogenesis of CSX, and how PCSK9 inhibitors could be effective in managing patients with CSX.