Angiotensinogen and Risk of Stroke Events in Patients with Type 2 Diabetes Mellitus

Background: Activation of the renin-angiotensin system (RAS) in diabetic patients is a vital pathophysiological mechanism of cardiovascular complications. Aim: We aimed to assess whether serum and urinary angiotensinogen levels could predict the risk of stroke events in patients with type 2 diabetes. Methods: An analysis of the relationships between serum and urinary angiotensinogen levels at baseline and the risk of stroke events was performed in a study consisting of 467 patients with type 2 diabetes with a follow-up of 5 years. Multivariate Cox regression models were built by controlling for a large range of related risk factors. Results: Kaplan–Meier analysis showed that patients with low estimated glomerular filtration rate (eGFR) < 57 mL/min/1.73 m 2 had a significantly higher risk of stroke events than those with high eGFRs (≥ 57 mL/min/1.73 m 2 , P=0.040). Our results suggested that urinary angiotensinogen levels (HR=2.74, 95% CI 1.50– 5.88, P =< 0.001), but not serum angiotensinogen levels (HR=1.42, 95% CI 0.95– 2.65, P =0.071), were independent predictors of the risk of stroke events in patients with type 2 diabetes after adjusting for confounding factors. Similarly, sensitivity analysis also suggested that higher urinary angiotensinogen levels still contributed to an increased risk of stroke events (HR=2.71, 95% CI 1.48– 5.82, P< 0.001) but not serum angiotensinogen levels (HR=1.37, 95% CI 0.89– 2.21, P=0.104). Importantly, we found that significant associations only existed in patients with eGFRs< 60 mL/min/1.73 m 2 (HR=2.78, 95% CI 1.59– 6.30, P< 0.001) but not in patients with eGFRs≥ 60 mL/min/1.73 m 2 (HR=1.39, 95% CI 0.95– 3.53, P=0.054). Conclusion: The study suggested that elevated urinary angiotensinogen levels were correlated with a higher risk of stroke events in patients with type 2 diabetes mellitus.