Cardiovagal modulation and oxidative stress in hypothyroidism on maintenance therapy

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Kundeti Neeraja
Nivedita Nanda
Jayaprakash Sahoo
G K Pal

Abstract

 Aim: To analyze the autonomic control of heart rate variability (HRV) in subjects with peripheral hypothroidism undergoing hormone replacement
therapy with L-thyroxine (L-T4) for 5-10 years.

Methods: Thyroid profile, lipid profile, lipid-risk factors, parameters of oxidative stress [malondialdehyde (MDA)], inflammation [high-sensitive
C-reactive protein (CRP)] and Heart rate variability (HRV) was analyzed in thirty-eight hypothyroid patients on treatment for more than five
years and compared with healthy euthyroid volunteers of similar age, gender, and body composition. The link of oxidative stress with HRV
parameters was assessed by Spearman-Rho correlation and regression analyses.

Results: Hypothyroid patients on L-T4 treatment, had higher TSH (p<0.01), lipid profile (p<0.05) and lipid risk factors (p<0.05), high-sensitive
C-reactive-protein (hsCRP) (3.31 versus 4.95 mg/L; p<0.05) and MDA (2.66 versus 6.87 μm/L; p <0.001) in serum. There was gross reduction
in HRV parameters [reduced standard deviation of NN interval (SDNN), root mean square of successive differences between normal heartbeats
(RMSSD), total power (TP) and elevated ratio of low to high frequency power (LF/HF ratio)] in patients. Elevated MDA was correlated with
vagal withdrawal (decreased SDNN, RMSSD and TP) and TSH. In multiple regression analysis TSH and TP contributed to the rise in MDA.

Conclusion: Hormone replacement therapy with L-T4 for hypothyroidism alone does not resolve persistent hyperlipidemia, oxidative stress
and inflammation in primary hypothyroid patients even after five years of treatment. Association of oxidative stress with reduced cardiovagal
modulation in these patients suggests persistence of cardiovascular risk despite standard treatment which warrants further investigation.

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References

  1. Klein I, Ojama K. Thyroid hormone and the cardiovascular system. New Eng J Med. 2001;344:501-9.
  2. Unnikrishnan AG, Menon UV. Thyroid disorders in India: An epidemiological perspective. Indian J Endocrinol Metab 2011;15(Suppl2):S78–S81.
  3. Biondi B, Klein I. Hypothyroidism as a risk factor for cardiovascular disease. Endocrine. 2004;24:1-13.
  4. Plaza-Florido A, Migueles JH, Mora-Gonzalez J, et al. The Role of Heart Rate on the Associations Between Body Composition and Heart Rate Variability in Children With Overweight/Obesity: The ActiveBrains Project. Front Physiol. 2019 Jul 16;10:895.
  5. Pal GK, Adithan C, Ananthanarayanan PH, et al. Effects of gender on sympathovagal imbalance, prehypertension status, and cardiovascular risks in first-degree relatives of type 2 diabetics. Am J Hypertens 2014;27:317-24.
  6. Karthik S, Pal GK, Nanda N, et al. Sympathovagal imbalance in thyroid dysfunctions in females: correlation with thyroid profile, heart rate and blood pressure. Indian J Physiol Pharmacol 2009;5:243–52.
  7. Lakshmi V, Vaney N, Madhu SV. Effect of thyroxine therapy on autonomic status in hypothyroid patients. Indian J Physiol Pharmacol 2009;53:219–26.
  8. Celik A, Aytan P, Dursun H, et al. Heart rate variability and heart rate turbulence in hypothyroidism before and after treatment. Ann Noninvasive Electrocardiol 2011;16:344–50.
  9. Ziegler D, Sohr CG, Nourooz-Zadeh J. Oxidative stress and antioxidant defense in relation to the severity of diabetic polyneuropathy and cardiovascular autonomic neuropathy. Diabetes Care. 2004;27:2178-83.
  10. Baskol G, Atmaca H, Tanriverdi F, Baskol M, Kocer D, Bayram F. Oxidative stress and enzymatic antioxidant status in patients with hypothyroidism before and after treatment. Exp Clin Endocrinol Diabetes 2007;115:522–26.
  11. Nanda N, Bobby Z, Hamide A, Koner BC, Sridhar MG. Association between oxidative stress and coronary lipid risk factors in hypothyroid women is independent of body mass index. Metabolism 2007;56:1350–5.
  12. Udovcic M, Pena RH, Patham B, Tabatabai L, Kansara A. Hypothyroidism and the Heart. Methodist DeBakey Cardiovasc J 2017;13:55–9.
  13. Duntas LH, Brenta G. Thyroid hormones: a potential ally to LDL-cholesterol-lowering agents. Hormones (Athens) 2016;15:500-10.
  14. Nanda N, Bobby Z, Hamide A. Persistence of Oxidative Stress in Newly Diagnosed Hypothyroid Patients Despite Effective Thyroxin Therapy. Int J Clin Exp Physiol 2018;5:70-4.
  15. Chakrabarti SK, Ghosh S, Banerjee S, Mukherjee S, Chowdhury S. Oxidative stress in hypothyroid patients and the role of antioxidant supplementation. Indian J Endocrinol Metab 2016;20:674–78.
  16. Nanda N, Bobby Z, Hamide A. Oxidative stress in anti thyroperoxidase antibody positive hypothyroid patients. Asian J Biochem. 2012; 7:54-8.
  17. Pal GK, Shyma P, Habeebullah S, Shyjus P, Pal P. Spectral analysis of heart rate variability for early prediction of pregnancy-induced hypertension. Clin Exp Hypertens 2009;31:330-41.
  18. Task force of the European Society of Cardiology and the North American society of Pacing and Electrophysiology. Heart rate variability: Standard and measurement, physiological interpretation and clinical use. Circulation 1996; 93:1043–65.
  19. Yesilbursa D, Serdar Z, Serdar A, Sarac M, Coskun S, Jale C. Lipid peroxides in obese patients and effects of weight loss with orlistat on lipid peroxides levels. Int J Obes 2004;29:142–45.
  20. Indumathy J, Pal GK, Pal P. Sympathovagal imbalance in obesity: Cardiovascular perspectives. Int J Clin Exp Physiol. 2014;1:93-100.
  21. Karmisholt J, Andersen S, Laurberg P. Weight Loss after Therapy of Hypothyroidism Is Mainly Caused by Excretion of Excess Body Water Associated with Myxoedema. J Clin Endocrinol Metab 2011;96:E99–103.
  22. Stangierski A, Ruchała M, Krauze T, Moczko J, Guzik P. Treatment of severe thyroid function disorders and changes in body composition. Endokrynol Pol 2016;67:359–66.