Thyroid dysfunction associated with increased risk for incident stroke
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Both exogenous hyperthyroidism and hypothyroidism are associated with increased odds for incident stroke, with risk increasing over time, according to findings published in the Journal of Clinical Endocrinology & Metabolism.
“Our study elucidated clinically meaningful findings suggesting that thyroid hormone treatment intensity is a novel, modifiable risk factor for stroke, even after controlling for prior history of atrial fibrillation,” Maria Papaleontiou, MD, assistant professor in the division of metabolism, endocrinology and diabetes at the University of Michigan, told Healio. “Our findings have implications for both physicians and patients. Physicians should be vigilant of the possible association between thyroid hormone treatment intensity and heightened risk for acute stroke independent of major cardiovascular risk factors. Even though the reasons leading to exogenous hyperthyroidism and hypothyroidism are variable, recognizing the association between exogenous hyperthyroidism or hypothyroidism and increased incident atrial fibrillation and stroke is particularly pertinent for vulnerable populations, such as older and multimorbid adults. In view of the importance of medication safety, particularly in these vulnerable populations, efforts should be undertaken to maintain patients in the euthyroid range to avoid adverse cardiovascular effects.”
Papaleontiou and colleagues conducted an observational retrospective cohort study of thyroid hormone users aged 18 years or older followed from 2004 to 2017 at the Veterans Health Administration. The analysis included 733,208 adults with at least two outpatient thyroid-stimulating hormone measurements and 406,030 with at least two outpatient free thyroxine measurements. Separate cohorts were evaluated for incident atrial fibrillation and incident stroke. Incident events occurring after thyroid hormone initiation and through 2017 were included. Serum TSH and T4 measurements were obtained through laboratory records. Reference range was 0.5 mIU/L to 5.5 mIU/L for TSH and 0.9 ng/dL to 1.7 ng/dL for free T4.
Incident atrial fibrillation occurred in 11.08% and incident stroke in 6.32% of the cohort. People with higher TSH were less likely to have incident atrial fibrillation in multivariable analysis (OR = 0.97; 95% CI, 0.96-0.97) whereas higher free T4 was associated with increased likelihood for atrial fibrillation (OR = 1.04; 95% CI, 1.03-1.05). Higher TSH was associated with a lower likelihood for incident stroke when controlling for demographic and CV risk factors, including atrial fibrillation (OR = 0.98; 95% CI, 0.98-0.99).
Participants with a TSH of less than 0.1 mIU/L had higher odds of atrial fibrillation (OR =1.31; 95% CI, 1.24-1.38) and stroke (OR = 1.33; 95% CI, 1.24-1.43) compared with people with euthyroid. People with a free T4 of greater than 1.9 ng/dL also had a higher likelihood for atrial fibrillation (OR = 1.36; 95% CI, 1.26-1.47) and stroke (OR = 1.17; 95% CI, 1.06-1.3) compared with euthyroid. Similar associations were observed with exogenous hypothyroidism. Adults with a TSH higher than 5.5 mIU/L were more likely to have atrial fibrillation (OR = 1.13; 95% CI, 1.1-1.15) and stroke (OR = 1.29; 95% CI, 1.26-1.33) than euthyroid adults. Those with a T4 of less than 0.7 ng/dL also had higher odds for stroke (OR = 1.29; 95% CI, 1.22-1.35) than those with euthyroid.
The likelihood of atrial fibrillation and stroke increased over time for adults with exogenous hyperthyroidism and hypothyroidism. Similar associations were observed in people aged 65 years or older or those who developed ischemic stroke.
“Future studies should investigate whether thyroid hormone treatment targets need to be redefined based on clinical outcomes and identify strategies for cardiovascular disease prevention in these patients to optimize delivery of care across diverse patient populations,” Papaleontiou said.
For more information:
Maria Papaleontiou, MD, can be reached at mpapaleo@med.umich.edu.
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