Cardiovagal modulation and oxidative stress in hypothyroidism on maintenance therapy

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 mm/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.