Subclinical hypothyroidism is a condition whereby the function of the thyroid gland is slightly below normal in its ability to produce thyroid hormones. This condition has been reported to affect 5 to 10% of the population. Usually, people with subclinical hypothyroidism do not have symptoms given that the level of thyroid hormone is mildly insufficient. However, since thyroid hormone regulates body metabolism, including cholesterol and blood pressure levels, there is some concern that subclinical hypothyroidism may increase the risk of developing heart disease. This study will assess whether treatment of subclinical hypothyroidism decreases the risk of having heart disease. This study will be conducted using the Clinical Practice Research Datalink (CPRD) database from the United Kingdom (UK). The study population will include patients with subclinical hypothyroidism and compare the occurrence of heart disease and related outcomes among those who received levothyroxine treatment (the standard treatment for subclinical hypothyroidism) and among those who were not given levothyroxine treatment. The results from this study will inform clinicians whether treatment of subclinical hypothyroidism decreases the risk of heart disease or death and will be important in guiding decision makers involved in creating guidelines for management of subclinical hypothyroidism.
Mild-subclinical hypothyroidism (SCH) is defined as having an elevated thyroid-stimulating hormone (TSH) level less than 10mU/L with a normal thyroxine level and has been reported to affect 5 to 10% of the population. Mild-SCH has been shown to affect an array of metabolic parameters including lipid profile, blood pressure, and body mass index. Previous studies have shown that untreated mild-SCH may be associated with an increased risk of cardiovascular-related mortality. However, there is a paucity of studies assessing whether levothyroxine treatment decreases cardiovascular events. The goal of this study will be to determine the association between levothyroxine treatment and the risk of cardiovascular outcomes and mortality among patients with mild-SCH using a population-based cohort study.
We will use the Clinical Practice Research Database (CPRD) to conduct a population-based cohort study. We will assemble a cohort of patients with no prior history of thyroid disease who have mild-SCH, based on two consecutive TSH measurements obtained within one year of each other between January 1, 1998 and December 31, 2018, with follow-up until December 31, 2019. Mild-SCH will be defined as having a TSH level between 5 and 10mU/L. Patients will be followed until having a cardiovascular event or censored at one of the following events: end of registration with the general practice, non-cardiovascular death (for outcomes other than all-cause mortality), or end of the study period (December 31, 2019), whichever comes first. We will use time-conditional propensity scores to match patients with mild-SCH who are treated with levothyroxine to those who were not treated. We will use Cox proportional hazards model to estimate hazards ratio (HR) and corresponding 95% confidence intervals (CI) for the risk of MACE associated with levothyroxine treatment versus no treatment among propensity score matched patients with mild-SCH. We will also conduct several secondary and sensitivity analyses to confirm our findings.
The primary outcome of this study will be having a major adverse cardiovascular event (MACE) defined as a composite of MI, stroke (ischemic and hemorrhagic), and cardiovascular-related mortality. Secondary outcomes of this study will be heart failure (HF), renal outcomes and all-cause mortality.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Oriana Hoi Yun Yu - Corresponding Applicant - Sir Mortimer B Davis Jewish General Hospital
Christel Renoux - Collaborator - McGill University
Christopher Filliter - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Kristian Filion - Collaborator - McGill University
Mona Vahidi Rad - Collaborator - McGill University
pauline reynier - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Robert Platt - Collaborator - McGill University
Roland Grad - Collaborator - McGill University
Kyle Johnson - Collaborator - McGill University
Wusiman Aibibula - Collaborator - Sir Mortimer B Davis Jewish General Hospital
HES Admitted Patient Care;ONS Death Registration Data;Practice Level Index of Multiple Deprivation