Duration of over- and under-treatment of hypothyroidism is associated with increased cardiovascular risk

Objective: To investigate the association between hypothyroidism and cardiovascular disease (CVD) in both treated and untreated hypothyroid patients, and the consequences of over- and under-treatment with respect to cardiovascular risk. Design: A registry-based case-control study nested within a population-based cohort of 275 467 individuals with at least one serum thyroid stimulating hormone (TSH) measurement in the period of 1995-2011. Methods: Incident cases of CVD were matched with controls according to gender, age and year of birth. Conditional logistic regression analyses were performed to calculate CVD risks associated with exposure to hypothyroidism, with adjustment for 19 pre-existing comorbidities, including cardiovascular disease and diabetes, using the Charlson Comorbidity Index. Results: Overall, 20 487 individuals experienced CVD (9.4%, incidence rate 13.1 per 1000 person-years, 95% confidence interval (CI), 13.0-13.3). Risk of CVD was increased in untreated hypothyroidism compared to euthyroidism (odds ratio (OR): 1.83 (95% CI: 1.43-2.35; P < 0.001)). Cardiovascular risk was increased in both treated and untreated hypothyroid individuals per half year of elevated TSH (OR: 1.11 (95% CI: 1.06-1.16; P < 0.001) and OR: 1.15 (95% CI: 1.09-1.23; P = 0.001), respectively). In patients treated with levothyroxine, OR for CVD was 1.12 (95% CI: 1.06-1.18; P < 0.001) for each 6 months of decreased TSH. Conclusion: Cardiovascular risk is increased in untreated, but not in treated hypothyroid patients. Among those with treated hypothyroidism, duration of decreased TSH (overtreatment) had a similar impact on cardiovascular risk as duration of elevated TSH (under-treatment), highlighting the importance of initiating treatment and maintaining biochemical euthyroidism in hypothyroid patients in order to reduce the risk of CVD and death.