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

Abstract

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 filtra-tion rate (eGFR) <57 mL/min/1.73 m2 had a significantly higher risk of stroke events than those with high eGFRs (≥57 mL/min/1.73 m2, 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 angiotensi-nogen 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 m2 (HR=2.78, 95% CI 1.59–6.30, P<0.001) but not in patients with eGFRs≥60 mL/min/1.73 m2 (HR=1.39, 95% CI 0.95–3.53, P=0.054). Conclusion: The study suggested that elevated urinary angiotensinogen levels were corre-lated with a higher risk of stroke events in patients with type 2 diabetes mellitus.