Researchers have found in a new study that hyperinsulinemia is independently associated with the development of coronary microvascular disease, establishing a critical link between elevated insulin levels and impaired coronary microvascular function. The study underlines the fact that high fasting insulin concentration significantly increases the risk of coronary microvascular disease (CMVD), independent of traditional cardiovascular risk factors such as diabetes, hypertension, and age. The study was published in the journal of Diabetes, Metabolic Syndrome and Obesity by Tan Q. and colleagues.
Coronary microvascular disease disorder, which impairs the regulation of blood flow in small heart vessels, is increasingly being recognized as a major cause of ischemic chest pain among patients without obstructive coronary artery disease. In contrast to classic coronary artery disease, CMVD affects the microvasculature, and diagnosis and management are challenging.
This clinical trial included 347 patients with symptoms of ischemic chest pain without obstructive coronary artery disease. All patients underwent noninvasive coronary flow reserve assessment by transthoracic Doppler echocardiography to evaluate coronary microvascular function. All patients with CFR values <2.0 (n = 105) were considered to be suffering from CMVD, while those patients who had a CFR ≥ 2.0 were regarded as non-CMVD (n = 245). Finally, biochemical analyses of fasting insulin (FINS), fasting blood glucose (FBS), and glycosylated hemoglobin (HbA1c) were determined for metabolic status.
Participants were also divided into three groups according to fasting insulin tertiles: low-insulin group (n = 118), medium-insulin group (n = 114), and high-insulin group (n = 115). Adjusted odds ratios (ORs) and 95% CIs were calculated using multivariate logistic regression models to identify independent risk factors for CMVD.
Results
Indeed, a strong association was evidenced between hyperinsulinemia and coronary microvascular dysfunction.
Values of FINS, FBS, HOMA-IR, and HbA1c were significantly higher in patients with CMVD compared to those without, showing a pronounced metabolic imbalance. Clinical features demonstrated that the patients in CMVD were more often female, and diabetes and hypertension were more prevalent in them, with P < 0.05.
When divided by insulin levels, CFR progressively decreased from the low-insulin to the high-insulin group, suggesting a dose-response relationship between insulin levels and coronary dysfunction.
In the multivariate regression analysis, hyperinsulinemia was confirmed as an independent predictor of CMVD, with FINS > 12.4 μIU/mL yielding an odds ratio of 2.279 (95% CI 1.046–4.967).
Other independent risk factors of significance included:
Female sex: OR 3.218 (95% CI 1.858–5.572)
Diabetes mellitus: OR 1.920 (95% CI 1.049–3.513)
Hypertension: OR 1.746 (95% CI 1.013–3.007)
Advancing age: OR 1.036 (95% CI 1.005–1.069)
This large clinical analysis has presented evidence that hyperinsulinemia independently associates with coronary microvascular disease, acting as a major metabolic driver of coronary dysfunction. Patients with FINS > 12.4 μIU/mL have a more than doubled risk of developing CMVD compared to those with lower insulin levels.
Reference:
Tan Q, Zu C, Zhang W, Hao J, Li Y, Lu Q, Li Z, Guo Y. Relationship Between Hyperinsulinemia and Coronary Microvascular Disease. Diabetes Metab Syndr Obes. 2025;18:3931-3940
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