Subclinical hypothyroidism (SCH) is described as elevated thyroid-stimulating hormone (TSH) combined with a normal range of free T4 and T3 levels.1 Most people with SCH have TSH levels between 4–10 mIU/L (mild SCH), and TSH levels above 10 mIU/L (severe SCH) are often an indication to start hormone replacement therapy.2,3 SCH is an early stage of thyroid gland dysfunction that is more common in females than males and is estimated to affect 5–10 % of the normal population.2,4 Additionally, SCH is more common in advanced-age people and areas with low iodine consumption.4 However, the prevalence may vary due to the population, gender, ethnicity, TSH measurements, and demographic area.5

Hypothyroidism has gradually been recognized as a cardiovascular risk factor, and in this regard, many studies have investigated the association between overt hypothyroidism and high blood pressure (BP).6, 7, 8, 9 However, SCH and its effect on BP are still under discussion, and various results on the impact of TSH on BP have been obtained.10, 11, 12, 13, 14, 15, 16 In a recent meta-analysis, middle-aged (mean age<65) females with SCH were found to be more likely to develop hypertension, but there was no significant association in older females.17 However, no association between hypertension and SCH was found in males.14,15 Another meta-analysis of observational studies could not rule out a link between SCH and BP, and these patients had higher systolic blood pressure (SBP); however, this association could be attributed to the age difference between the SCH group and the euthyroid group in the general population.18 Based on these studies, one can assume that the association between high TSH and BP is a way that can increase the possibility of hypertension in the future or is one of the risk factors for its incidence.19

Treatment of SCH is recommended in people with severe SCH or people of younger ages with mild SCH who show symptoms of hypothyroidism.1 Accordingly, the treatment of choice in this population is small doses of levothyroxine.20 In recent years, some randomized clinical trials (RCTs) and observational studies have investigated the effect of levothyroxine therapy in people with SCH, including its effect on BP.7, 21, 22, 23, 24, 25, 26, 27, 28, 29 In this regard, a systematic review and meta-analysis in 2018 summed up the results of 10 RCTs and concluded that treatment with levothyroxine could significantly reduce systolic BP.30 This study also analyzed 19 cohort studies, and the result was that levothyroxine significantly reduces both systolic and diastolic BP.30

In recent years, other prospective studies and RCTs have been published on this issue, and the results of some previous RCTs have been updated.24,28,29,31, 32, 33, 34 According to these studies and the fact that hypertension is an independent and strong risk factor in cardiovascular diseases, an update is needed. In this regard, this systematic review and meta-analysis aims to evaluate the effect of levothyroxine therapy on BP in patients with SCH.