Circulating metabolic and inflammatory biomarkers in MINOCA: pathophysiologic mechanisms and clinical implications

Metabolic dysregulation and systemic inflammation are key contributors to the development of myocardial infarction with non-obstructive coronary arteries (MINOCA). MINOCA accounts for 5-15% of all acute myocardial infarctions, with a prognosis comparable to obstructive coronary artery disease. Despite its clinical significance, current risk assessment and management remain inadequate, as traditional methods focused on epicardial obstruction overlook the systemic disturbances underlying MINOCA. This gap has driven interest in circulating biomarkers reflecting the mechanisms of microvascular dysfunction and myocardial injury. We conducted a comprehensive search of PubMed, EMBASE, and the Cochrane Library from inception to May 2025, reviewing mechanistic and clinical studies on metabolic and inflammatory biomarkers in MINOCA. Evidence indicates that insulin resistance, hyperglycemia, dyslipidemia, thyroid dysfunction, hyperuricemia, renal impairment, hepatic dysfunction, and elevated inflammatory biomarkers independently contribute to endothelial dysfunction, coronary microvascular impairment, and vasomotor disturbances. These disruptions independently predict adverse cardiovascular outcomes. Specific metabolic biomarkers with demonstrated prognostic value include the stress hyperglycemia ratio, triglyceride-glucose index, atherogenic index of plasma, remnant cholesterol, lipoprotein(a), free triiodothyronine-to-free thyroxine ratio, serum uric acid, total bilirubin, fibrinogen-to-albumin ratio, and estimated glomerular filtration rate, while key inflammatory biomarkers include C-reactive protein, systemic inflammation response index, white blood cell count to mean platelet volume ratio, systemic immune-inflammation index, perivascular fat attenuation index, and interleukin-6. These findings are synthesized into a unified cardiometabolic-immune framework linking biomarker profiles to underlying pathophysiological mechanisms. We highlight the need for prospective multicenter validation, standardized protocols, and randomized trials targeting metabolic-inflammatory pathways to develop personalized management strategies for this underrecognized population.