Iodine-Induced Hypothyroidism and Long-Term Risks of Incident Heart Failure

Abstract

Background Although most individuals can adapt to a large iodine load and remain euthyroid, hypothyroidism can develop after iodine exposure. Hypothyroidism is associated with adverse cardiovascular consequences, including heart failure. This study was performed to investigate the relationships between iodine-induced hypothyroidism and incident heart failure. Methods and Results This cohort study of the US Veterans Health Administration (1998-2021) included adults aged ≥18 years with a serum thyroid-stimulating hormone (thyrotropin) <60 days of iodine contrast administration, and <1 year of a baseline normal serum thyroid-stimulating hormone. Cox proportional hazards regression ascertained risk of incident heart failure following iodine-induced hypothyroidism, adjusting for age, sex, race and ethnicity, body mass index, and history of coronary heart disease, dyslipidemia, diabetes, and hypertension. Of 45 470 veterans (mean±SD age, 61.1±14.1 years; 88% men), 3361 (7.4%) developed iodine-induced hypothyroidism. Heart failure developed in 5685 (12.5%) individuals over a median follow-up of 3.6 years (interquartile range, 1.9-7.2 years). Adjusted for risk factors, iodine-induced hypothyroidism was associated with increased risk of heart failure, compared with those who remained euthyroid after iodine exposure (adjusted hazard ratio [HR], 1.11 [95% CI, 1.01-1.22]). Women were at greater risk than men (adjusted HR: women, 1.65 [95% CI, 1.13-2.40]; men, 1.08 [95% CI, 0.98-1.19]; P for interaction, 0.02). Conclusions In the largest US study of this topic, hypothyroidism following iodine exposure was associated with an increased risk of incident heart failure, particularly in women. These findings support the need for further research to address the clinical significance of this issue, including the possible sex-specific risks of incident heart failure in more diverse data sets and study populations.

Keywords: heart failure; hypothyroidism; iodine; thyroid dysfunction.

Figure 1. Flow of study sample selection.

T3 indicates triiodothyronine; T4, thyroxine; TSH, thyroid‐stimulating hormone; and VHA, Veterans Health Administration.

Figure 2. Cumulative incidence of heart failure (HF) according to thyroid function (euthyroid vs hypothyroid) following iodine exposure.

The adjusted hazard ratio (aHR) was calculated by Cox proportional hazard models adjusting for age, sex, race and ethnicity, body mass index, and history of coronary heart disease, diabetes, dyslipidemia, and hypertension. Inverse probability weight obtained used these variables was applied to draw the adjusted incidence curve. Overall hypothyroidism after a previously normal baseline thyroid‐stimulating hormone and iodine administration was associated with an increased risk of heart failure (aHR, 1.11 [95% CI, 1.01–1.22]). The E‐value for the point estimate (and the lower bound of 95% CI) was 1.46 (1.11).

Figure 3. Associations between hypothyroidism and risk of heart failure by age, sex, and race and ethnicity.

Model adjusted for age, sex, race and ethnicity, body mass index, and history of coronary heart disease, diabetes, dyslipidemia, and hypertension. HR indicates hazard ratio.