Research Article: Serum glycated hemoglobin level as a predictor of atrial fibrillation: A systematic review with meta-analysis and meta-regression

Date Published: March 7, 2017

Publisher: Public Library of Science

Author(s): Wenwei Qi, Nixiao Zhang, Panagiotis Korantzopoulos, Konstantinos P. Letsas, Min Cheng, Fusheng Di, Gary Tse, Tong Liu, Guangping Li, Vincenzo Lionetti.


Glycated hemoglobin (HbA1c) is a long-term measure of glucose control. Although recent studies demonstrated a potential association between HbA1c levels and the risk of atrial fibrillation (AF), the results have been inconsistent. The aim of this meta-analysis is to evaluate the utility of HbA1c level in predicting AF.

PubMed and the Cochrane Library databases were searched for relevant studies up to March 2016. Prospective cohort studies and retrospective case-control studies were included. Relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs) of AF development were determined for different HbA1c levels. The random effect model was conducted according to the test of heterogeneity among studies. Subgroup analyses and meta-regression models were carried out to identify potential sources of heterogeneity.

Eight prospective cohort studies with 102,006 participants and 6 retrospective case-control studies with 57,669 patients were finally included in the meta-analysis. In the primary meta-analysis, HbA1c levels were not associated with an increased risk of AF whether as a continuous (RR, 1.06; 95% CI, 0.96–1.18) or categorical variable (RR, 0.99; 95% CI, 0.83–1.18). Nevertheless, prospective studies showed about 10% increased risk of AF with elevated HbA1c levels both as a continuous (RR, 1.11; 95% CI, 1.06–1.16) and as a categorical variable (RR, 1.09; 95% CI, 1.00–1.18). In subgroup analyses, pooled results from studies with longer follow-up durations, published after 2012, aged < 63 years, with exclusion of cardiac surgery patients demonstrated an increased risk of AF for every 1% increase in HbA1c levels, while studies conducted in the United States with longer follow-up (more than 96 months), larger sample size and higher quality score (≥6) showed an increased risk of AF for higher HbA1c level as a categorical variable. Elevated serum HbA1c levels may be associated with an increased risk of AF, but further data are needed. Serum HbA1c levels might be considered as a potential biomarker for prediction of AF.

Partial Text

Atrial fibrillation (AF) is the most common arrhythmia occurring in 2.3–3.4% of the general population and its prevalence is estimated to be at least doubled by 2050 [1]. AF represents a major public health problem with a significant impact on cardiovascular morbidity and mortality as well as on health care cost [2,3]. Glycated hemoglobin (HbA1c) is a reliable biochemical marker of glucose control over the preceding 2–3 months and is widely used in daily clinical practice. The association between HbA1c and AF has been investigated in previous studies but the findings have been controversial [3–7]. A recent study from Japan showed that higher HbA1c is associated with a decreased risk of AF [8], while the Atherosclerosis Risk in Communities Study showed an increased risk of AF [9]. Therefore, we performed a comprehensive meta-analysis to evaluate the current evidence regarding the potential association between HbA1c and AF risk.

The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement [10] was used in this study (detailed in S1 PRISMA Checklist).

In this comprehensive meta-analysis, we demonstrated that increased HbA1c levels were associated with an increased risk of AF in prospective cohort studies but not in case-control studies. A recent study from Eastern Norway indicated a significant positive correlation between HbA1c levels and duration of AF (r = 0.408, p = 0.005), thereby implicating abnormal glucose metabolism in increasing AF burden [20]. Given that diabetes increases thromboembolic risk in AF and further promotes the arrhythmia, HbA1c levels could be a useful marker in strategies aiming to reduce AF burden and its related complications. In support of this notion, Saliba et al. recently showed that glycated hemoglobin is directly associated with stroke risk, and the use of HbA1c improved accuracy for predicting stroke events in diabetic patients with AF [21]. Based on retrospective data with the effect size of standardized mean difference (SMDs) mostly among Chinese subjects, Yang et al. demonstrated elevated HbA1c levels could increase the risk of AF in patients with diabetes mellitus (DM) [22]. We further investigated this in the general population with the effect size of RRs, both based on prospective and retrospective studies conducted globally.

This comprehensive meta-analysis suggests that elevated serum HbA1c levels were associated with an increased risk of AF in prospective studies, and therefore serum HbA1c levels may be viewed as a potential biomarker to predict AF and as a tool for AF prevention. Undoubtedly, further prospective studies with larger population sizes are needed to elucidate the exact prognostic role of HbA1c in AF development. Finally, the use of HbA1c levels as a prognostic and monitoring tool in the management of AF as well as its related complications should be evaluated carefully.




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