Manuel R Blum1, Baris Gencer2, Luise Adam1,3, Martin Feller1,4, Tinh-Hai Collet5, Bruno R da Costa4,6, Elisavet Moutzouri1,4, Jörn Dopheide3, Michèle Depairon7, Gerasimos P Sykiotis5, Patricia Kearney8, Jacobijn Gussekloo9, Rudi Westendorp10, David J Stott11, Douglas C Bauer12, Nicolas Rodondi1,4. 1. Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 2. Cardiology Division, University Hospital of Geneva, University of Geneva, Geneva, Switzerland. 3. Clinic for Angiology, Swiss Cardiovascular Center, Inselspital, University of Bern, Bern, Switzerland. 4. Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland. 5. Service of Endocrinology, Diabetes and Metabolism, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland. 6. Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada. 7. Service of Angiology, Department of Heart and Vessels, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland. 8. University College Cork, Cork, Ireland. 9. Leiden University Medical Center, Leiden, Netherlands. 10. Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark. 11. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom. 12. University of San Francisco, San Francisco, California.
Abstract
Context: Subclinical hypothyroidism (SHypo) has been associated with atherosclerosis, but no conclusive clinical trials assessing the levothyroxine impact on carotid atherosclerosis exist. Objective: To assess the impact of treatment of SHypo with levothyroxine on carotid atherosclerosis. Design and Setting: Randomized, double-blind, placebo-controlled trial nested within the Thyroid Hormone Replacement for Subclinical Hypothyroidism trial. Participants: Participants aged ≥65 years with SHypo [thyroid-stimulating hormone (TSH), 4.60 to 19.99 mIU/L; free thyroxine level within reference range]. Intervention: Levothyroxine dose-titrated to achieve TSH normalization or placebo, including mock titrations. Main Outcome Measures: Carotid intima media thickness (CIMT), maximum plaque thickness measured with ultrasound. Results: One hundred eighty-five participants (mean age 74.1 years, 47% women, 96 randomized to levothyroxine) underwent carotid ultrasound. Overall meanTSH ± SD was 6.35 ± 1.95 mIU/L at baseline and decreased to 3.55 ± 2.14 mIU/L with levothyroxine compared with 5.29 ± 2.21 mIU/L with placebo (P < 0.001). After a median treatment of 18.4 months (interquartile range 12.2 to 30.0 months), mean CIMT was 0.85 ± 0.14 mm under levothyroxine and 0.82 ± 0.13 mm under placebo [between-group difference = 0.02 mm; 95% CI, -0.01 to 0.06; P = 0.30]. The proportion of carotid plaque was similar (n = 135; 70.8% under levothyroxine and 75.3% under placebo; P = 0.46). Maximum carotid plaque thickness was 2.38 ± 0.92 mm under levothyroxine and 2.37 ± 0.91 mm under placebo (between-group difference -0.03; 95% CI, -0.34 to 0.29; P = 0.86). There were no significant interactions between levothyroxine treatment and mean CIMT, according to sex, baseline TSH (categories 4.6 to 6.9, 7.0 to 9.9, and ≥10 mIU/L), or established cardiovascular disease (all P for interaction ≥ 0.14). Conclusion: Normalization of TSH with levothyroxine was associated with no difference in CIMT and carotid atherosclerosis in older persons with SHypo.
RCT Entities:
Context:Subclinical hypothyroidism (SHypo) has been associated with atherosclerosis, but no conclusive clinical trials assessing the levothyroxine impact on carotid atherosclerosis exist. Objective: To assess the impact of treatment of SHypo with levothyroxine on carotid atherosclerosis. Design and Setting: Randomized, double-blind, placebo-controlled trial nested within the Thyroid Hormone Replacement for Subclinical Hypothyroidism trial. Participants: Participants aged ≥65 years with SHypo [thyroid-stimulating hormone (TSH), 4.60 to 19.99 mIU/L; free thyroxine level within reference range]. Intervention: Levothyroxine dose-titrated to achieve TSH normalization or placebo, including mock titrations. Main Outcome Measures: Carotid intima media thickness (CIMT), maximum plaque thickness measured with ultrasound. Results: One hundred eighty-five participants (mean age 74.1 years, 47% women, 96 randomized to levothyroxine) underwent carotid ultrasound. Overall mean TSH ± SD was 6.35 ± 1.95 mIU/L at baseline and decreased to 3.55 ± 2.14 mIU/L with levothyroxine compared with 5.29 ± 2.21 mIU/L with placebo (P < 0.001). After a median treatment of 18.4 months (interquartile range 12.2 to 30.0 months), mean CIMT was 0.85 ± 0.14 mm under levothyroxine and 0.82 ± 0.13 mm under placebo [between-group difference = 0.02 mm; 95% CI, -0.01 to 0.06; P = 0.30]. The proportion of carotid plaque was similar (n = 135; 70.8% under levothyroxine and 75.3% under placebo; P = 0.46). Maximum carotid plaque thickness was 2.38 ± 0.92 mm under levothyroxine and 2.37 ± 0.91 mm under placebo (between-group difference -0.03; 95% CI, -0.34 to 0.29; P = 0.86). There were no significant interactions between levothyroxine treatment and mean CIMT, according to sex, baseline TSH (categories 4.6 to 6.9, 7.0 to 9.9, and ≥10 mIU/L), or established cardiovascular disease (all P for interaction ≥ 0.14). Conclusion: Normalization of TSH with levothyroxine was associated with no difference in CIMT and carotid atherosclerosis in older persons with SHypo.
Authors: Enoch J Abbey; John McGready; Luigi Ferrucci; Eleanor M Simonsick; Jennifer S R Mammen Journal: J Am Geriatr Soc Date: 2021-01-08 Impact factor: 7.538