Heterogeneous blood pressure treatment effects on cognitive decline in type 2 diabetes: A machine learning analysis of a randomized clinical trial

Aim: We aimed to identify the characteristics of patients with diabetes who can derive cognitive benefits from intensive blood pressure (BP) treatment using machine learning methods.

Materials and methods: Using data from the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes (ACCORD-MIND) study, 1349 patients with type 2 diabetes who underwent BP treatment (intensive treatment targeting a systolic BP <120 mmHg vs. standard treatment targeting <140 mmHg) were included in the machine learning analysis. Seventy-nine variables correlated with diabetes and cognitive function were used to build the causal forest and causal tree models for identifying heterogeneous BP treatment effects on cognitive decline.

Results: Our analyses identified four variables including urinary albumin-to-creatinine ratio (UACR, mg/g), Framingham 10-year cardiovascular risk score (FRS, %), triglycerides (TG, mmol/L) and diabetes duration, that categorized the participants into five subgroups with different risk benefits for cognitive decline from BP treatments. Subgroup 1 (UACR ≥65 mg/g) had an absolute risk reduction (ARR) of 15.36% (95% CI, 5.01%-25.46%) from intensive versus standard BP treatment (hazard ratio [HR], 0.36; 95% CI, 0.18-0.73). Subgroup 2 (UACR <65 mg/g, FRS ≥26%, TG <2.3 mmol/L and diabetes duration ≥9 years) had an ARR of 14.74% (95% CI, 4.56%-24.59%) from intensive versus standard BP treatment (HR, 0.34; 95% CI, 0.15-0.77). No significant benefits were found for other subgroups.

Conclusions: Patients with type 2 diabetes with high UACR, or with low UACR and low TG, but high predicted cardiovascular risk and long diabetes duration were likely to derive cognitive benefits from intensive BP treatment.