Suboptimal Levothyroxine Treatment is Associated with Increases in Mean Blood Pressure and Blood Pressure Variability

Context: Thyroid hormone homeostasis is critical to the metabolic function of cardiovascular tissues. The degree to which the suboptimal treatment of hypothyroidism with levothyroxine (LT4) impacts blood pressure (BP) and blood pressure variability (BPV) is not known. Objectives: Determine the relationship between LT4 time above range (TAR) (TSH level >4.5 mIU/L), time below range (TBR) (TSH <0.4 mIU/L), and changes in annual mean systolic (SBP) and diastolic blood pressure (DBP) and visit-to-visit BPV. Methods: Using longitudinal data from 2203 adult patients treated with LT4, we modeled within-individual changes in annual mean BP and BPV as a function of TAR and TBR (% time). Linear mixed-effect modeling was utilized to allow for differences in observation time between patients. Models were adjusted for sociodemographics, baseline comorbidities, weight, LT4 dose, time, and year of study enrollment. Sensitivity analyses were conducted with wide in-range boundaries (TSH 0.1-10 mIU/L) and stratification by hypertension at baseline. Results: In the primary modeling, a 100% increase in TAR was associated with significant increases in annual mean SBP and DBP (+1.8 mmHg, P = .011; +1.0 mmHg, P = .024, respectively). Similarly, a 100% increase in TBR was associated with increases in annual mean SBP and DBP (+2.7 mmHg, P = .004; +1.3 mmHg, P = .034, respectively). However, the expected differences in BP with TAR and TBR diminished in subsequent years. One hundred percent TAR and TBR were associated with small increases in annual visit-to-visit diastolic BPV (+0.67 mmHg, P = .009; +0.85 mmHg, P = .020, respectively). Conclusion: Suboptimal LT4 treatment was associated with increases in mean BP and BPV, representing potential mediators in the pathway between suboptimal LT4 treatment and cardiovascular disease.