Subclinical thyroid dysfunction and the risk of incident atrial fibrillation: A systematic review and meta-analysis

Thyroid hormones act on the cardiovascular system directly by modulating its function and indirectly by transcriptional regulation of gene expression in the heart and the vasculature. Studies have shown associations between overt and subclinical thyroid disorders and cardiovascular outcomes. The aim of this study was to perform a systematic review and meta-analysis to assess the potential relationships between subclinical hyper- and hypothyroidism and risk of atrial fibrillation (AF), and post-operative AF.

MEDLINE and Scopus databases were searched from inception to 18th February 2023 for randomised controlled trials, case-control studies, and cohort studies which assessed the relationship between subclinical thyroid dysfunction and incident AF events. Risk of bias and the quality of evidence were assessed using the RoBANS tool and GRADE approach, respectively. Meta-analysis was conducted in Review Manager 5.4 using the Mantel-Haenszel statistical method and a random-effects model. Data are presented as risk ratios with 95% confidence intervals. Statistical heterogeneity amongst studies was assessed by the chi-squared (χ2) test and I2 statistic. p≤0.05 were considered significant.

A total of 6467 records were identified, of which 10 cohort studies met the inclusion criteria. Both subclinical hyperthyroidism and subclinical hypothyroidism were associated with an increased risk of incident AF (risk ratio (RR), 1.99; 95% confidence interval (CI), 1.43-2.77; n = 5 studies; p<0.0001 and RR, 1.19; CI, 1.03-1.39; n = 7 studies; p = 0.02, respectively). Subgroup analysis for post-operative AF revealed marked heterogeneity between studies (I2 = 84%) and association with subclinical hypothyroidism was not significant (RR, 1.41; CI, 0.89-2.22; n = 3 studies; p = 0.15).

The current evidence suggests that both subclinical hyperthyroidism and subclinical hypothyroidism are associated with increased risk of incident AF. Further investigation is required to determine potential causal links that would guide future clinical practice.