BACKGROUND: Coronary microvascular disease (CMVD) is an important contributor to ischemic heart disease. Symptomatic patients without obstructive coronary lesions may still have microvascular ischemia, which is associated with an increased risk of major adverse cardiovascular events. The diagnosis of CMVD relies on coronary function testing or noninvasive imaging techniques, which are not universally available and may limit routine clinical implementation. OBJECTIVES: Growing evidence supports the notion that biological processes such as inflammation and oxidative stress drive vascular aging and contribute to microvascular dysfunction. The systemic immune-inflammation index (SII) is a marker used to assess immune-inflammatory and thrombotic status and has shown prognostic value in chronic heart failure, and acute myocardial infarction. However, its role in CMVD remains underexplored. DESIGN: To address this gap, we retrospectively analyzed 180 patients with angina who underwent myocardial contrast stress echocardiography between January and November 2022 at the First Affiliated Hospital of Harbin Medical University. METHODS: Based on coronary microcirculatory function, patients were divided into two groups: 91 with normal function and 89 with microcirculatory disorders. Clinical data and lab indicators were compared. RESULTS: SII was significantly higher in the CMVD group (722.96 ± 354.10 vs 618.51 ± 324.50; p < 0.05). Logistic regression identified SII, LDL cholesterol as independent CMVD predictors. Pearson correlation demonstrated an inverse relationship between SII and coronary flow reserve, supporting its link with impaired microvascular function. Receiver operating characteristic analysis further showed that the combined SII and LDL model provided improved discriminatory performance compared with either marker alone, achieving an area under the curve of 0.76 with a sensitivity of 77.5% and specificity of 69.2%. CONCLUSION: SII is independently associated with CMVD and improved discriminatory performance when combined with LDL. Can Combining Inflammation and Cholesterol Blood Markers Improve the Detection of Coronary Microvascular Disease?Why was the study done?Coronary microvascular disease (CMVD) is a heart condition that affects the small blood vessels of the heart. It can cause chest pain and other symptoms even when the major coronary arteries appear normal. Detecting CMVD can be challenging, and doctors are looking for simple blood tests that may help identify patients at risk. The Systemic Immune-Inflammation Index (SII) is a blood marker that reflects inflammation and clotting activity in the body. It has already been shown to predict outcomes in cancer, neurological diseases, heart failure, and heart attacks. However, its role in CMVD has not been well studied.What did the researchers do?In this study, we reviewed medical records from 180 patients who underwent a specialized heart ultrasound test (myocardial contrast stress echocardiography) in 2022. Based on their coronary microvascular function, patients were divided into two groups: those with normal small-vessel function and those with CMVD.What did the researchers find?We found that SII was independently associated with CMVD in patients with angina. Among the evaluated inflammatory indices, SII showed improved discriminatory performance compared with NLR, PLR, while the combined SII and LDL model further improved diagnostic performance over either biomarker alone. In addition, modest but significant negative correlation between SII, LDL, and CFR.What do the findings mean?The findings suggested a potential relationship between inflammatory and lipid-related pathways and impaired coronary microvascular function. To the best of our knowledge, this is among the first studies to evaluate the diagnostic value of SII for CMVD assessment in patients with angina. Given their low cost and routine availability in clinical practice, the combination of SII and LDL may represent a practical approach for identifying patients at risk of CMVD; however, prospective multicenter studies are needed to validate its clinical utility.