Heart Rate Variability in Hyperthyroidism: A Systematic Review and Meta-Analysis

Abstract

Objective: Cardiovascular effects of thyroid hormones may be measured through heart rate variability (HRV). We sought to determine the impact of hyperthyroidism on HRV. Design: A systematic review and meta-analysis on the impact of hyperthyroidism on HRV. Methods: PubMed, Cochrane, Embase and Google Scholar were searched until 20 August 2021 for articles reporting HRV parameters in untreated hyperthyroidism and healthy controls. Random-effects meta-analysis was stratified by degree of hyperthyroidism for each HRV parameter: RR intervals (or Normal-to-Normal intervals—NN), SDNN (standard deviation of RR intervals), RMSSD (square root of the mean difference of successive RR intervals), pNN50 (percentage of RR intervals with >50 ms of variation), total power (TP), LFnu (low-frequency normalized unit) and HFnu (high-frequency), VLF (very low-frequency), and LF/HF ratio. Results: We included 22 studies with 10,811 patients: 1002 with hyperthyroidism and 9809 healthy controls. There was a decrease in RR (effect size = −4.63, 95% CI −5.7 to −3.56), SDNN (−6.07, −7.42 to −4.71), RMSSD (−1.52, −2.18 to −0.87), pNN50 (−1.36, −1.83 to −0.88), TP (−2.05, −2.87 to −1.24), HFnu (−3.51, −4.76 to −2.26), and VLF power (−2.65, −3.74 to −1.55), and an increase in LFnu (2.66, 1.55 to 3.78) and LF/HF ratio (1.75, 1.02 to 2.48) (p < 0.01). Most parameters had ES that was twice as high in overt compared to subclinical hyperthyroidism. Increased peripheral thyroid hormones and decreased TSH levels were associated with lower RR intervals. Conclusions: Hyperthyroidism is associated with a decreased HRV, which may be explained by the deleterious effect of thyroid hormones and TSH. The increased sympathetic and decreased parasympathetic activity may have clinical implications.

Keywords: autonomic nervous activity; biomarker; prevention; public health; thyroid.

Figure 1

Flow chart. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for the search strategy. HRV: Heart rate variability.

Figure 2

Meta-analysis of HRV parameters of untreated hyperthyroid patients compared with controls. RR: RR intervals (or normal-to-normal intervals—NNs), SDNN: standard deviation of RR intervals, pNN50: percentage of adjacent NN intervals differing by more than 50 ms, RMSSD: the square root of the mean squared difference of successive RR intervals, LF: low frequency, LFnu: low frequency-normalized units, HF: high frequency, HFnu: high frequency-normalized units, LF/HF ratio: low frequency/high frequency ratio, VLF: very low frequency.

Figure 3

Meta-regressions of significant factors influencing heart rate variability in untreated hyperthyroid patients (exhaustive meta-regressions are presented in Figure S5). RR: RR intervals (or normal-to-normal intervals—NNs), BMI: body mass index, FT4: free thyroxine, FT3: free triiodothyronine, TSH: thyroid-stimulating hormone, RMSSD: the square root of the mean squared difference of successive RR intervals, SBP: systolic blood pressure, VLF: very low frequency, LF: low frequency, LFnu: low frequency-normalized units, HF: high frequency, HFnu: high frequency-normalized units, LF/HF ratio: low frequency/high frequency ratio.