Elisa Gatta, Andrea Delbarba, Enrico Vizzardi, Mario Rotondi, Carlo Cappelli
Hypothyroidism was more consistently associated with cardiovascular mortality than with incident cardiovascular events. However, the lack of a statistically significant association with cardiovascular events should not be interpreted as evidence of absence of effect. These findings are consistent with the hypothesis that thyroid dysfunction may be more closely associated with adverse cardiovascular outcomes after disease onset than with incident cardiovascular events.
PURPOSE: The cardiovascular impact of hypothyroidism remains controversial, particularly regarding the distinction between cardiovascular disease occurrence and cardiovascular prognosis. We performed a systematic review and meta-analysis to separately evaluate the association between hypothyroidism and incident cardiovascular events and cardiovascular mortality.
METHODS: PubMed/MEDLINE, Scopus, and Web of Science were systematically searched for studies published between January 2014 and April 2026 evaluating cardiovascular outcomes in adult patients with overt or subclinical hypothyroidism compared with euthyroid controls. Separate random-effects meta-analyses were performed for cardiovascular events and cardiovascular mortality using pooled odds ratios (ORs) with 95% confidence intervals (CIs). Study quality was assessed using the QUIPS tool.
RESULTS: Nine studies involving 9,662 patients were included. Six studies evaluating cardiovascular events (5,795 participants) showed no significant association between hypothyroidism and incident cardiovascular events (OR 0.92, 95% CI 0.78-1.09; p = 0.35), with low-to-moderate heterogeneity (I² = 24.6%). By contrast, eight studies evaluating cardiovascular mortality (7,526 participants) demonstrated a significantly increased mortality risk among hypothyroid patients (OR 2.73, 95% CI 2.16-3.43; p < 0.0001), with low heterogeneity (I² = 9.7%). Leave-one-out sensitivity analyses confirmed the robustness and stability of the mortality findings. Qualitative synthesis consistently showed worse outcomes in acute and high-risk cardiovascular settings, including acute coronary syndromes, acute heart failure, spontaneous coronary artery dissection, and coronary artery bypass grafting.
CONCLUSIONS: Hypothyroidism was more consistently associated with cardiovascular mortality than with incident cardiovascular events. However, the lack of a statistically significant association with cardiovascular events should not be interpreted as evidence of absence of effect. These findings are consistent with the hypothesis that thyroid dysfunction may be more closely associated with adverse cardiovascular outcomes after disease onset than with incident cardiovascular events.