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Review
. 2022 Aug 16;10(8):1982.
doi: 10.3390/biomedicines10081982.

Effect of Hyperthyroidism Treatments on Heart Rate Variability: A Systematic Review and Meta-Analysis

Valentin Brusseau  1 , Igor Tauveron  1   2 , Reza Bagheri  3 , Ukadike Chris Ugbolue  4   5 , Valentin Magnon  6 , Jean-Baptiste Bouillon-Minois  6   7 , Valentin Navel  8   9 , Frederic Dutheil  6   10
Affiliations
Review

Effect of Hyperthyroidism Treatments on Heart Rate Variability: A Systematic Review and Meta-Analysis

Valentin Brusseau et al. Biomedicines. .

Abstract

The reversibility of HRV abnormalities in hyperthyroidism remains contradictory. The design of this study involves conducting a systematic review and meta-analysis on the effect of antithyroid treatments on HRV in hyperthyroidism. PubMed, Cochrane, Embase, and Google Scholar were searched until 4 April 2022. Multiple reviewers selected articles reporting HRV parameters in treated and untreated hyperthyroidism. Independent data extraction by multiple observers was stratified by degree of hyperthyroidism for each HRV parameter: RR intervals, 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. We included 11 studies for a total of 471 treated hyperthyroid patients, 495 untreated hyperthyroid patients, and 781 healthy controls. After treatment, there was an increase in RR, SDNN, RMSSD, pNN50, TP, HFnu, and VLF and a decrease in LFnu and LF/HF ratio (p < 0.01). Overt hyperthyroidism showed similar results, in contrast to subclinical hyperthyroidism. Compared with controls, some HRV parameter abnormalities persist in treated hyperthyroid patients (p < 0.05) with lower SDNN, LFnu, and higher HFnu, without significant difference in other parameters. We showed a partial reversibility of HRV abnormalities following treatment of overt hyperthyroidism. The improvement in HRV may translate the clinical cardiovascular benefits of treatments in hyperthyroidism and may help to follow the evolution of the cardiovascular morbidity.

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

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Conflict of interest statement

The authors declare that there are no conflicts of interest that could be perceived as prejudicing the impartiality of this review.

Figures

Figure 1
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. The study protocol was registered and received INPALSY registration number: INPLASY202280062.
Figure 2
Figure 2
Meta-analysis of HRV parameters of untreated hyperthyroid patients compared with treated hyperthyroid patients. 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 milliseconds, 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. ○: effect size stratified by subclinical or overt status; ♦: effect size for all studies.
Figure 3
Figure 3
Meta-analysis of HRV parameters of treated hyperthyroid patients compared with healthy 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 milliseconds, 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, ♦: effect size for all studies.
Figure 4
Figure 4
Metaregressions of factors influencing heart rate variability: RR, SDNN, RMSSD, pNN50, VLF, and total power in (A) and LF, LFnu, HF, HFnu, and LF/HF in (B) in treated hyperthyroid patients compared with untreated hyperthyroid patients. LF: low frequency, BMI: body mass index, FT4: free thyroxine, TSH: thyroid-stimulating hormone, LFnu: low frequency normalized—units, FT3: free triiodothyronine, HF: high frequency, HFnu: high frequency—normalized units, LF/HF ratio: low frequency/high frequency ratio. RR: RR intervals (or normal-to-normal intervals-NNs), BMI: body mass index, FT4: free thyroxine, FT3: free triiodothyronine, TSH: thyroid-stimulating hormone, SDNN: standard deviation of RR intervals, RMSSD: the square root of the mean squared difference of successive RR-intervals, SBP: systolic blood pressure, DBP: diastolic blood pressure, pNN50: percentage of adjacent NN intervals differing by more than 50 milliseconds, VLF: very low frequency, ○: effect size stratified by subclinical or overt status.
Figure 4
Figure 4
Metaregressions of factors influencing heart rate variability: RR, SDNN, RMSSD, pNN50, VLF, and total power in (A) and LF, LFnu, HF, HFnu, and LF/HF in (B) in treated hyperthyroid patients compared with untreated hyperthyroid patients. LF: low frequency, BMI: body mass index, FT4: free thyroxine, TSH: thyroid-stimulating hormone, LFnu: low frequency normalized—units, FT3: free triiodothyronine, HF: high frequency, HFnu: high frequency—normalized units, LF/HF ratio: low frequency/high frequency ratio. RR: RR intervals (or normal-to-normal intervals-NNs), BMI: body mass index, FT4: free thyroxine, FT3: free triiodothyronine, TSH: thyroid-stimulating hormone, SDNN: standard deviation of RR intervals, RMSSD: the square root of the mean squared difference of successive RR-intervals, SBP: systolic blood pressure, DBP: diastolic blood pressure, pNN50: percentage of adjacent NN intervals differing by more than 50 milliseconds, VLF: very low frequency, ○: effect size stratified by subclinical or overt status.
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