Predicting the risk of stroke among patients with type 2 diabetes: a systematic review and meta-analysis of C-statistics

Abstract

Objective: Stroke is a major cause of disability and death worldwide. People with diabetes are at a twofold to fivefold increased risk for stroke compared with people without diabetes. This study systematically reviews the literature on available stroke prediction models specifically developed or validated in patients with diabetes and assesses their predictive performance through meta-analysis.

Design: Systematic review and meta-analysis.

Data sources: A detailed search was performed in MEDLINE, PubMed and EMBASE (from inception to 22 April 2019) to identify studies describing stroke prediction models.

Eligibility criteria: All studies that developed stroke prediction models in populations with diabetes were included.

Data extraction and synthesis: Two reviewers independently identified eligible articles and extracted data. Random effects meta-analysis was used to obtain a pooled C-statistic.

Results: Our search retrieved 26 202 relevant papers and finally yielded 38 stroke prediction models, of which 34 were specifically developed for patients with diabetes and 4 were developed in general populations but validated in patients with diabetes. Among the models developed in those with diabetes, 9 reported their outcome as stroke, 23 reported their outcome as composite cardiovascular disease (CVD) where stroke was a component of the outcome and 2 did not report stroke initially as their outcome but later were validated for stroke as the outcome in other studies. C-statistics varied from 0.60 to 0.92 with a median C-statistic of 0.71 (for stroke as the outcome) and 0.70 (for stroke as part of a composite CVD outcome). Seventeen models were externally validated in diabetes populations with a pooled C-statistic of 0.68.

Conclusions: Overall, the performance of these diabetes-specific stroke prediction models was not satisfactory. Research is needed to identify and incorporate new risk factors into the model to improve models' predictive ability and further external validation of the existing models in diverse population to improve generalisability.

Keywords: meta-analysis; prediction model; risk; stroke; systematic review.

Figure 1

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) diagram for systematic review of studies presenting stroke prediction models developed or validated in individuals with diabetes.

Figure 2

Forest plot of C-statistics, with 95% CIs of risk prediction models when outcome was reported for stroke.

Figure 3

Forest plot of C-statistics, with 95% CIs of risk prediction models when stroke was reported as part of a composite cardiovascular disease outcome. AD-ON, Action in Diabetes and Vascular Disease:Preterax and Diamicron Modified Release Controlled Evaluation-Observational; EPIC-NL,European Prospective Investigation into Cancer and Nutrition-Netherlands; HWNNs,hybrid wavelet neural networks; MACE, major adverse cardiovascular event; NZDCS, New Zealand Diabetes Cohort Study; SMART, second manifestations ofarterial disease; SOMs, self-organising maps.

Figure 4

Forest plot of C-statistics, with 95% CIs, of stroke prediction models that are externally validated in two or more independent cohorts. JHS, Jackson Heart Study; MESA,Multiethnic Study of Atherosclerosis; UKPDS, United Kingdom ProspectiveDiabetes Study