Editorial: Crosstalk between thyroid and heart

The intricate interplay between the thyroid and the heart has garnered significant attention due to their essential roles in regulating metabolism and cardiovascular function, respectively. Thyroid hormones profoundly impact cardiac performance, rhythm, and vascular dynamics, while the heart's pathophysiological conditions can influence thyroid hormone levels. Furthermore, thyroid hormone can influence the response of the heart to stress such as ischemia. This bidirectional relationship highlights the need for comprehensive understanding to optimize patient care. The articles published in the focus entitled CV disease and thyroid function highlights further aspects of the complex relationship between thyroid and heart. Interestingly three of the published papers used mendelian randomization (MR) as a new approach that employes genetic variations, mainly singlenucleotide polymorphisms (SNPs), and potential risk factors aiming to evaluate the potential causal relationship among them. This method is effective to reduce biases derived from confounding and reverse causation (1). Zhang M et al used MR to assess the relationship between TH and carotid intima-media thickness (CIMT) that is an early sign of atherosclerosis (2). The authors showed that lower levels of Free Thyroxine (FT4) within the normal range and hypothyroidism were associated with increased CIMT, whereas thyroxine therapy was associated with a CIMT reduction. However, using multivariate MR, FT4 was not linked to CIMT, but only apolipoprotein (apo) A-I and B.Intriguingly, high FT4 levels were associated to high apoA-I circulating levels, as well as increased TSH was associated with high apoB levels. In the context of CV risk, Jin Z et al. confirmed, using MR approach, the causal relationship between hypothyroidism and coronary heart disease. In the same study, this relation was partially mediated by HbA1c (3). These data are a proof of the intermingled TH action with different CV risk factors potentially inducing atherosclerosis and thus increasing CV risk. In the heart failure context, Liu J et al, MR, showed a causal relationship between hyperthyroidism and all-cause heart failure, suggesting a genetic link between hyperthyroidism and development of all-cause heart failure (4). This result is a further proof of the pathophysiological role of TH in heart failure. Experimental studies showed that altered TH metabolism may induce abnormal changes in structure and function of the heart favouring the progression of heart failure (5). Clinical studies showed the negative prognostic impact of the altered TH metabolism, also considering the early and middle abnormalities, i.e. subclinical hypothyroidism and hyperthyroidism and low T3 syndrome (6). Moreover, TH treatment in the experimental context, exerts cardioprotective effects through modulation of different key cellular pathways, including preservation of mitochondrial activity and morphology, antifibrotic and proangiogenic actions, and promotion of cell regeneration and growth after the postischemic injury (7). It is noteworthy that TH dysfunction can be considered as part of the hormonal and metabolic derangement in heart failure that may induce the progression of the disease both at the level of the heart and other organs, making it a systemic disease (8).In the context of left ventricular function, Li H et al showed that patients with overt hyperthyroidism present with diastolic dysfunction only in 30% of cases and those patients had high circulating levels of connective tissue growth factor (CTGF) compared to hyperthyroid patients with normal diastolic function (9). Interestingly, CTGF is considered a type of pro-fibrotic factor and a new marker of cardiac dysfunction in patients with heart failure. Excessive CTGF can induce myocardial hypertrophy and also the proliferation of cardiac fibroblast and deposition of extracellular matrix. This is a new result showing left ventricular diastolic dysfunction, as a sign of myocardial hardness, in presence of high CTGF levels, matches the evidence of the relationship between CTGF expression and the degree of fibrosis of papillary thyroid carcinoma. In the last paper, Shen X et al showed, in a retrospective study on patients with acute aortic dissection (AAD), that an increase of one standard deviation in FT4 levels was associated with a 31,9 % increased risk of MACE and 36,1% of in-hospital mortality whereas a higher FT3/FT4 ratio was associated with a 20% reduction in MACE risk (10). Taken together, these results highlight the importance of assessing thyroid function in the context of patients with CV diseases, both with the objective to cure the disease but also in the cardiovascular prevention framework. The thyroid could be seen as a conductor presiding over the function several organs, systems, including hormonal pathways, the inflammatory system as well as the immune system. Changes in thyroid metabolism within the normal range could be viewed as homeostatic responses to preserve the functional balance of the individual organ and organs among themselves. For example, high FT4 values, within the normal range as observed by Zhang M et al. The demonstration of this fine and systemic tuning exerted by thyroid at the systemic level, and in the specific case on the CV system, is provided by the evidence that minimal alterations in thyroid metabolism can be detrimental to the CV system, either directly, through morphofunctional alterations, as shown by Li H et al but also indirectly by causing alterations in the other known CV risk factors, such as glucose and lipid metabolism, as shown by Zhang Z and Jin. From the perspective of precision medicine, it is very important to further study the close relationship between the thyroid and the cardiovascular system in order to identify the key elements for the treatment of thyroid disorders with a view to the prevention and treatment of cardiovascular disease.