Minor perturbations of thyroid homeostasis and major cardiovascular endpoints—Physiological mechanisms and clinical evidence
It is well established that thyroid dysfunction is linked to an increased risk of cardiovascular morbidity and mortality. The pleiotropic action of thyroid hormones strongly impacts the cardiovascular system and affects both the generation of the normal heart rhythm and arrhythmia. A meta-analysis o...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.942971/full |
| _version_ | 1828183198102716416 |
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| author | Patrick Müller Melvin Khee-Shing Leow Melvin Khee-Shing Leow Melvin Khee-Shing Leow Melvin Khee-Shing Leow Johannes W. Dietrich Johannes W. Dietrich Johannes W. Dietrich Johannes W. Dietrich |
| author_facet | Patrick Müller Melvin Khee-Shing Leow Melvin Khee-Shing Leow Melvin Khee-Shing Leow Melvin Khee-Shing Leow Johannes W. Dietrich Johannes W. Dietrich Johannes W. Dietrich Johannes W. Dietrich |
| author_sort | Patrick Müller |
| collection | DOAJ |
| description | It is well established that thyroid dysfunction is linked to an increased risk of cardiovascular morbidity and mortality. The pleiotropic action of thyroid hormones strongly impacts the cardiovascular system and affects both the generation of the normal heart rhythm and arrhythmia. A meta-analysis of published evidence suggests a positive association of FT4 concentration with major adverse cardiovascular end points (MACE), but this association only partially extends to TSH. The risk for cardiovascular death is increased in both subclinical hypothyroidism and subclinical thyrotoxicosis. Several published studies found associations of TSH and FT4 concentrations, respectively, with major cardiovascular endpoints. Both reduced and elevated TSH concentrations predict the cardiovascular risk, and this association extends to TSH gradients within the reference range. Likewise, increased FT4 concentrations, but high-normal FT4 within its reference range as well, herald a poor outcome. These observations translate to a monotonic and sensitive effect of FT4 and a U-shaped relationship between TSH and cardiovascular risk. Up to now, the pathophysiological mechanism of this complex pattern of association is poorly understood. Integrating the available evidence suggests a dual etiology of elevated FT4 concentration, comprising both ensuing primary hypothyroidism and a raised set point of thyroid function, e. g. in the context of psychiatric disease, chronic stress and type 2 allostatic load. Addressing the association between thyroid homeostasis and cardiovascular diseases from a systems perspective could pave the way to new directions of research and a more personalized approach to the treatment of patients with cardiovascular risk. |
| first_indexed | 2024-04-12T06:28:55Z |
| format | Article |
| id | doaj.art-31caa11ef6194e2a9e70e1180a3880c4 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-12T06:28:55Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-31caa11ef6194e2a9e70e1180a3880c42022-12-22T03:44:04ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-08-01910.3389/fcvm.2022.942971942971Minor perturbations of thyroid homeostasis and major cardiovascular endpoints—Physiological mechanisms and clinical evidencePatrick Müller0Melvin Khee-Shing Leow1Melvin Khee-Shing Leow2Melvin Khee-Shing Leow3Melvin Khee-Shing Leow4Johannes W. Dietrich5Johannes W. Dietrich6Johannes W. Dietrich7Johannes W. Dietrich8Department for Electrophysiology, Medical Hospital I, Klinikum Vest, Recklinghausen, NRW, GermanySingapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeDepartment of Endocrinology, Tan Tock Seng Hospital, Singapore, SingaporeMetabolic Disorders Research Programme, Lee Kong Chian School of Medicine, Singapore, SingaporeCardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore, SingaporeDiabetes, Endocrinology and Metabolism Section, Department of Internal Medicine I, St. Josef Hospital, Ruhr University Bochum, Bochum, NRW, GermanyDiabetes Centre Bochum/Hattingen, St. Elisabeth-Hospital Blankenstein, Hattingen, NRW, GermanyCentre for Rare Endocrine Diseases, Ruhr Centre for Rare Diseases (CeSER), Ruhr University Bochum and Witten/Herdecke University, Bochum, NRW, GermanyCentre for Diabetes Technology, Catholic Hospitals Bochum, Ruhr University Bochum, Bochum, NRW, GermanyIt is well established that thyroid dysfunction is linked to an increased risk of cardiovascular morbidity and mortality. The pleiotropic action of thyroid hormones strongly impacts the cardiovascular system and affects both the generation of the normal heart rhythm and arrhythmia. A meta-analysis of published evidence suggests a positive association of FT4 concentration with major adverse cardiovascular end points (MACE), but this association only partially extends to TSH. The risk for cardiovascular death is increased in both subclinical hypothyroidism and subclinical thyrotoxicosis. Several published studies found associations of TSH and FT4 concentrations, respectively, with major cardiovascular endpoints. Both reduced and elevated TSH concentrations predict the cardiovascular risk, and this association extends to TSH gradients within the reference range. Likewise, increased FT4 concentrations, but high-normal FT4 within its reference range as well, herald a poor outcome. These observations translate to a monotonic and sensitive effect of FT4 and a U-shaped relationship between TSH and cardiovascular risk. Up to now, the pathophysiological mechanism of this complex pattern of association is poorly understood. Integrating the available evidence suggests a dual etiology of elevated FT4 concentration, comprising both ensuing primary hypothyroidism and a raised set point of thyroid function, e. g. in the context of psychiatric disease, chronic stress and type 2 allostatic load. Addressing the association between thyroid homeostasis and cardiovascular diseases from a systems perspective could pave the way to new directions of research and a more personalized approach to the treatment of patients with cardiovascular risk.https://www.frontiersin.org/articles/10.3389/fcvm.2022.942971/fullthyroid functionsudden cardiac deathventricular arrhythmiacardiac electrophysiologyMACEhypothyroidism |
| spellingShingle | Patrick Müller Melvin Khee-Shing Leow Melvin Khee-Shing Leow Melvin Khee-Shing Leow Melvin Khee-Shing Leow Johannes W. Dietrich Johannes W. Dietrich Johannes W. Dietrich Johannes W. Dietrich Minor perturbations of thyroid homeostasis and major cardiovascular endpoints—Physiological mechanisms and clinical evidence Frontiers in Cardiovascular Medicine thyroid function sudden cardiac death ventricular arrhythmia cardiac electrophysiology MACE hypothyroidism |
| title | Minor perturbations of thyroid homeostasis and major cardiovascular endpoints—Physiological mechanisms and clinical evidence |
| title_full | Minor perturbations of thyroid homeostasis and major cardiovascular endpoints—Physiological mechanisms and clinical evidence |
| title_fullStr | Minor perturbations of thyroid homeostasis and major cardiovascular endpoints—Physiological mechanisms and clinical evidence |
| title_full_unstemmed | Minor perturbations of thyroid homeostasis and major cardiovascular endpoints—Physiological mechanisms and clinical evidence |
| title_short | Minor perturbations of thyroid homeostasis and major cardiovascular endpoints—Physiological mechanisms and clinical evidence |
| title_sort | minor perturbations of thyroid homeostasis and major cardiovascular endpoints physiological mechanisms and clinical evidence |
| topic | thyroid function sudden cardiac death ventricular arrhythmia cardiac electrophysiology MACE hypothyroidism |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.942971/full |
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