Progression of cardiovascular autonomic neuropathy and cardiovascular disease in type 2 diabetes

Background: To examine whether the progression rate of cardiovascular autonomic neuropathy (CAN) stage is an independent predictive factor for cardiovascular disease (CVD) in type 2 diabetes. Methods: Standardized cardiovascular autonomic reflex tests (CARTs) using traditional Ewing method were performed at baseline. The follow-up CARTs was recommended once every two years. We estimated the primary CVD endpoint, defined as coronary artery disease and ischemic stroke. The association between the progression rate of CAN stage and CVD was examined using time-dependent Cox proportional hazard models. Results: At baseline, 578 patients completed follow-up CARTs; the cohort comprised 329 women (56.9%) with a mean age of 58.3±10.3years and a mean diabetes duration of 10.1±6.2years. One hundred and seventy-six patients (30.4%) developed CAN progression between baseline and follow-up CARTs. In the multivariable Cox proportional hazards regression analysis, patients with CAN progression demonstrated a 3.32 times higher risk (95% confidence interval, CI 1.81-6.14, P<0.001) of CVD than those without CAN progression. Patients who experienced CAN progression from the normal to definite stage had the greatest risk of CVD compared to other patients (hazard ratio 4.91, 95% CI 2.05-11.77, P for trend=0.001). Conclusions: CAN stage progression was associated with an increased risk of CVD in this type 2 diabetes cohort. Patients with rapid CAN progression had the greatest risk of CVD. Thus, regular screening and risk management of CAN progression is necessary to prevent CVD.