Biomarkers of Coronary Microvascular Dysfunction in Patients With Microvascular Angina: A Narrative Review

Abstract

The current gold standard for diagnosis of coronary microvascular dysfunction (CMD) in the absence of myocardial diseases, whose clinical manifestation is microvascular angina (MVA), is reactivity testing using adenosine or acetylcholine during coronary angiography. This invasive test can be difficult to perform, expensive, and harmful. The identification of easily obtainable blood biomarkers which reflect the pathophysiology of CMD, characterized by high reliability, precision, accuracy, and accessibility may reduce risks and costs related to invasive procedures and even facilitate the screening and diagnosis of CMD. In this review, we summarized the results of several studies that have investigated the possible relationships between blood biomarkers involved with CMD and MVA. More specifically, we have divided the analyzed biomarkers into 3 different groups, according to the main mechanisms underlying CMD: biomarkers of “endothelial dysfunction,” “vascular inflammation,” and “oxidative stress.” Finally, in the last section of the review, we consider mixed mechanisms and biomarkers which are not included in the 3 major categories mentioned above, but could be involved in the pathogenesis of CMD.

Low-grade endotoxemia and NOX2 in patients with coronary microvascular angina

“…In accordance with this, LPS directly correlated with NOX2, suggesting a role for LPS as a trigger for oxidative stress [8]. The high levels of H 2 O 2 and the close relation with sNOX2 observed in this study suggest that systemic oxidative stress in MVA could derive from LPS-induced NADPH oxidase activation as hypothesized by previous papers [8,27].…”

“…It has been demonstrated that it mainly embraces two aspects: firstly, inadequate vasodilatation to a stimulus, and secondly, exaggerated vasoconstriction (coronary microvascular spasm) [7]. Experimental studies suggested a major role of oxidative stress in the initiation and progression of microvascular dysfunction in MVA [8]. NADPH oxidase-2 (NOX2) is considered one of the main sources of superoxide anion in humans, a modulator of the arterial tone [9][10][11][12], and an enzyme directly implicated in microvascular dysfunction [13].…”

Complete Blood Count-Derived Indices as Prognostic Factors of 5-Year Outcomes in Patients With Confirmed Coronary Microvascular Spasm

“…The longterm prognosis of coronary microcirculatory dysfunction is often thought to be relatively benign. Nevertheless, standard medical management including vasodilators is often ineffective and sometimes cannot prevent myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) or fatal arrhythmias (1)(2)(3).…”

“…The mechanism for the links between increased RDW or PDW values and the CVD prognosis remain unclear. Nevertheless, recent studies indicated that an interplay between endothelial dysfunction, chronic inflammatory response as well as oxidative stress might explain this association ( 2 , 3 , 11 ).…”

Classification, Diagnosis, and Treatment of Coronary Microvascular Dysfunction

“…Compared with these methods, the introduction into clinical practice of blood biomarker detection in patients with suspected MVA can facilitate the diagnosis of this pathological condition, offering several advantages, such as a reduction in costs, less risk of physical harm, a greater availability/accessibility, and prognostic value [ 8 ].…”