Coronary Microvascular Dysfunction and Risk of Cardiovascular Events in Type 2 Diabetes Without Obstructive Coronary Artery Disease (CAD): A Prospective Study

BACKGROUND: Coronary microvascular dysfunction (CMD) is increasingly recognized as a contributor to adverse cardiovascular outcomes in patients with diabetes mellitus (DM), yet it remains underdiagnosed. This is largely because routine evaluation is limited by the need for complex, time-consuming, and not routinely performed diagnostic methods, which primarily focus on macrovascular disease. OBJECTIVE: To prospectively evaluate the association between CMD and major adverse cardiovascular events (MACE) - defined as myocardial infarction, hospitalization for heart failure, and cardiovascular death - in patients with type 2 diabetes without obstructive coronary artery disease (CAD). METHODOLOGY: We conducted a prospective observational study at Shifa College of Medicine, Islamabad, from August 2022 to July 2024. A total of 264 adults with type 2 DM of five or more years' duration and non-obstructive CAD (<50% stenosis on angiography/CT) were consecutively enrolled. Exclusion criteria included type 1 diabetes, left ventricular ejection fraction <50%, significant structural or valvular heart disease, prior revascularization, acute coronary syndrome at baseline, and incomplete data. CMD was diagnosed using transthoracic Doppler echocardiography, with coronary flow reserve (CFR) <2.0 considered abnormal in accordance with current consensus. CFR was measured in the left anterior descending artery by two independent operators blinded to outcomes, with reproducibility assessed in a subset. Patients were followed for 24 months; loss to follow-up (7.95%) was excluded from survival analyses. Multivariate Cox regression adjusting for age, sex, hypertension, dyslipidemia, BMI, and diabetes duration was performed, with hazard ratios (HR) and 95% confidence intervals (CI) reported. RESULTS: =0.018). Cardiovascular mortality was higher in CMD (7.8% vs. 2.6%), while non-cardiovascular mortality was similar between groups. Event-free survival was significantly shorter in CMD patients on Kaplan-Meier analysis. CONCLUSION: CMD strongly and independently predicts long-term adverse cardiovascular outcomes in patients with type 2 diabetes without obstructive CAD, even after adjusting for conventional risk factors such as hypertension and smoking. Early detection of CMD using CFR assessment may improve risk stratification and guide preventive management in this high-risk population.