Abstract
BackgroundAccumulating evidence suggests that HbA1c levels, a common clinical indicator of chronic glucose metabolism over the preceding 2-3 months, are independent risk factor for cardiovascular disease, including heart failure. The aim of this protocol is to conduct a systematic review and meta-analysis to assess the possible predictive value of HbA1c on mortality and readmission in patients with heart failure.MethodsA systematic and comprehensive search will be performed using PubMed, Embase, Central and other databases before August 2021 to identify relevant trials. All-cause mortality is the pre-specified primary endpoint. Cardiovascular death and heart failure readmission are secondary interested endpoints. We will only include prospective and retrospective cohort trials and place no restrictions on the language, race, region and publication period. The Newcastle-Ottawa Scale will be used to assess the quality of each trial included. If there are sufficient trials, we will conduct meta-analysis with pooled relative risks and corresponding 95% confidence interval to evaluate the possible predictive value of HbA1c on mortality and readmission. Otherwise, we will undertake a narrative synthesis. Heterogeneity and publication bias will be assessed. If heterogeneity is significant among included trails, a sensitivity analysis or subgroup analysis will be used to explore the source of heterogeneity, such as diverse types of heart failure or patients with diabetes and non-diabetes. Also, we will conduct meta-regression to examine the time-effect and treatment-effect modifiers on all-cause mortality compared between different quantile of HbA1c levels. Finally, a restricted cubic spline model may be used to explore the dose-response relationship between HbA1c and adverse outcomes.DiscussionThis planned analysis is anticipated to identify the predictive value of HbA1c on mortality and readmission in patients with heart failure. Improved understanding of different HbA1c levels and their specific effect on diverse types of heart failure or patients with diabetes and non-diabetes is expected to be figured out. Also, a dose-response relationship or optimal range of HbA1c will be determined to instruct clinicians and patients.PROSPERO registration detailsCRD42021276067