The diagnosis and possible treatment of subclinical hypothyroidism remains a controversial subject in medicine. While some doctors debate how to treat this problem, and further, if to treat it at all, some doctors are publishing research to suggest a connection between subclinical hypothyroidism and cardiovascular disease.
What is subclinical hypothyroidism and how does it affect your heart?
A good example of these controversies are demonstrated in the opening paragraphs of new and recent research.
A November 2021 paper in the journal The Medical clinics of North America (1) offered these observations on the treatment of Subclinical thyroid disease.
“Subclinical thyroid disease is frequently encountered in clinic practice. Although overt thyroid dysfunction has been associated with adverse clinical outcomes, uncertainty remains about the implications of subclinical thyroid disease. Available data suggest that subclinical hypothyroidism may be associated with increased risk of cardiovascular disease and death. Despite this finding, treatment with thyroid hormone has not been consistently demonstrated to reduce cardiovascular risk. Subclinical hyperthyroidism has been associated with increased risk of atrial fibrillation and osteoporosis, but the association with cardiovascular disease and death is uncertain. The decision to treat depends on the degree of thyroid-stimulating hormone suppression and underlying comorbidities.”
In other words, treatment depends on the individual patient’s circumstance.
A November 2019 study (2) titled: “Subclinical hypothyroidism and cardiovascular risk factors” wrote this:
“Thyroid hormones have multiple effects on lipid metabolism as well as on the cardiovascular system function. These negative cardiovascular effects have long been recognized in overt hypothyroidism but can be reversed by treatment with levothyroxine.
Subclinical hypothyroidism, defined as an elevated thyrotropin (TSH) with a normal free thyroxine (FT4), is frequent in the general population and increase with age. Subclinical hypothyroidism has been linked to cardiovascular risk factors, dyslipidemia and increased atherosclerosis. Although some studies have demonstrated that lipids are elevated in subclinical hypothyroidism, other studies did not confirm these data. Clinical trials have also demonstrated there is no clear evidence that levothyroxine therapy in subjects with milder form (TSH<10 mU/L) of subclinical hypothyroidism could improve lipid status and the other cardiovascular risk factors.
Nevertheless, TSH level seems the best predictor of cardiovascular disease, in particular when its levels are above 10 mU/L. . . until clinical recommendations (are) updated, the decision to treat or not treat patients with subclinical hypothyroidism will still base on clinical judgment, clinical practice guidelines, and expert opinion.”
Impact on cholesterol
A February 2020 (3) study from the same research team expanded on the above findings and found TSH has a direct effect on total cholesterol, triglycerides, and non-HDLc (non-HDL cholesterol is your total cholesterol value minus your HDL cholesterol.)
A 2018 study (4) published by the Academic Center for Thyroid Diseases, University Medical Center, Rotterdam, The Netherlands found that a “decrease in T3 levels is accompanied by unfavorable changes in serum lipids.”
Artery stiffness and thyroid dysfunction
A January 2021 study (5) wrote: “Thyroid hormone modulation of cardiovascular function has been associated with cardiovascular disease. Recent evidence suggests that free thyroxine (FT4) levels are associated with an increase in systemic arterial stiffness . . .” Further this study suggested that higher free thyroxine levels increase arterial stiffness at the common carotid level, consistent with a detrimental effect on elastic arteries. (A condition of “hardening of the arteries can develop).
“The last decade has seen a renewed interest on the impact of subclinical hypothyroidism on the cardiovascular system and whether or not it should be treated.”
To treat and how to treat patients with suspected subclinical hypothyroidism who may be at risk for cardiovascular disease and heart attack risk is also somewhat controversial.
A January 2020 study published in the journals Frontiers in endocrinology (6) reviewed the current literature regarding the problem of subclinical hypothyroidism and cardiovascular disease:
Thyroid hormone receptors (cells that bind with thyroid hormone) are present in the myocardium (heart muscle) and endothelium (cells of the blood vessels), and small alterations in its levels could have significant effects in cardiac function. Specifically, overt hypothyroidism is associated with an increased risk for atherosclerotic cardiovascular disease due to metabolic and hemodynamic (blood flow) effects. Several concomitant factors like impaired lipid profile (poor cholesterol metabolism), low-grade chronic inflammatory state, increased oxidative stress and increased insulin resistance enforce this relationship. The last decade has seen a renewed interest on the impact of subclinical hypothyroidism on the cardiovascular system and whether or not it should be treated.”
A problem in the medical research, as attested to by this study, is the confusion or non-understanding of the impact on even the smallest variation in thyroid hormone production on heart function
A problem in the medical research, as attested to by this study, is the confusion or non-understanding of the impact on even the smallest variation in thyroid hormone production on heart function. Let’s listen to the researchers again:
“Guidelines of American College of Cardiology/American Heart Association for the diagnosis and management for heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different TSH levels or specific T3 levels.
Several studies showed that heart failure patients with Overt Hypothyroidism or mild thyroid dysfunction had more hospitalizations and poor prognosis, compared to patients who had normal thyroid function.
Another important observation was that about 15–30% of patients with heart failure reported to have low levels of T3, called “Low T3 syndrome” and this was also associated directly with the prognosis and severity of the heart failure.
The main findings reported in heart failure associated with low T3 syndrome can be summarized as: (a) Decrease in Left ventricle diastolic and systolic function, (b) Increase in systemic vascular resistance, (c) Decrease in cardiac contractility, (d) Renal function deterioration, and finally (e) cardiac output reduction.
Subtle changes in circulating thyroid hormone levels may have a significant impact on the cardiovascular system and subclinical thyroid dysfunction has been associated with a 20–80% increase in vascular morbidity and mortality risk.
Let’s remember this study opens with the question: should subclinical hypothyroidism be treated to address heart disease risks?
High-normal TSH concentrations and cardiovascular disease
A February 2020 study (7) in the Journal of the American Medical Association examined the role of subclinical hypothyroidism and its association with an increased risk of cardiovascular disease and mortality in American adults.
The key to the study was to understand the extent to which subclinical hypothyroidism, elevated serum TSH and normal serum free thyroxine, or high-normal TSH concentrations (ie, upper normative-range TSH concentrations) are associated with mortality through cardiovascular disease.
In this study, 9020 participants were examined:
4658 (51.6%) were men; the average age of the patient was 49.4 years old. The study and follow up trailed these patients for a little more than seven years.
The study patients had routine serum thyroid function test results consistent with subclinical hypothyroidism and high-normal TSH concentrations were both associated with increased all-cause mortality when compared with another group in the middle-normal TSH range.
Cardiovascular disease mediated 14.3% and 5.9% of the associations of subclinical hypothyroidism and high-normal TSH with all-cause mortality, respectively, with the cardiovascular mediation being most pronounced in women (7.5%-13.7% of the association) and participants aged 60 years and older (6.0%-14.8% of the association).
The research concludes: “In this study, cardiovascular disease mediated (confirmed) the associations of subclinical hypothyroidism and high-normal TSH concentrations with all-cause mortality in the US general population. Further studies are needed to examine the clinical benefit of thyroid hormone replacement therapy targeted to a middle-normal TSH concentration or active cardiovascular disease screening for people with elevated TSH concentrations.”
The terrible triad – what is the role of vitamin D in subclinical hypothyroidism and cardiovascular risk?
A September 2021 (8) paper looked at how vitamin D deficiency and autoimmune thyroid diseases may play a role in cardiovascular disease.
“The role of thyroid hormones in the cardiovascular system, through several direct and indirect effects is recognized. Even very small modification in thyroid hormone levels (as those observed in subclinical hypothyroidism or hyperthyroidism, and low triiodothyronine syndrome (this is low T3, normal or slightly low T4 and normal or low TSH) may adversely affect the cardiovascular system, whereas thyroid hormones benefit the cardiovascular system and improve the prognosis.
There is also evidence of vitamin D effects on cardiometabolic disease (e.g., through modulation of endothelial and smooth muscle cell activity (flexibility of arteries), renin-angiotensin-aldosterone system (hormone system that help regulate blood pressure ), nitric oxide, oxidative stress, and inflammatory response), as well as an association between vitamin D [25(OH)D] deficiency and autoimmune thyroid diseases or cancer, and a relationship between vitamin D concentration and titers of antibodies and thyroid autoimmunity replacement.
Interestingly, experimental data indicate a direct effect of vitamin D on Type 2 deiodinase expression (simply the T4 to T3 conversion system) causing subsequential peripheral conversion of T4 into T3. However, the functional links among thyroid hormones, vitamin D and the cardiovascular system, and clinical effects of coexisting abnormalities in this new troublesome triad, have not yet been reviewed.”
Treating subclinical hypothyroidism
As shown in the research above the recommendation to treat and how to treat the subclinical hypothyroidism should be based on clinical judgment, clinical practice guidelines, and expert opinion. At the Magaziner Center for Wellness we also try to identify factors that may be adversely affecting the thyroid gland such as environment chemicals or heavy metals, and look for nutrient imbalances or food sensitivities. We then treat these areas to build up the body’s innate healing mechanisms. Since the thyroid is part of the endocrine system and many chemicals contribute to dysfunction of these glands, we educate our patients about exposure to environmental factors that may impair thyroid function. We also assess and treat for bio-energetic weaknesses that can also help to improve thyroid function.
If you would like to explore more information, please contact our office so we can start a conversation with you.
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References
1 Evron JM, Papaleontiou M. Decision Making in Subclinical Thyroid Disease. Med Clin North Am. 2021 Nov;105(6):1033-1045. doi: 10.1016/j.mcna.2021.05.014. Epub 2021 Sep 7. PMID: 34688413.
2 Delitala AP, Scuteri A, Maioli M, Mangatia P, Vilardi L, Erre GL. Subclinical hypothyroidism and cardiovascular risk factors. Minerva medica. 2019 Nov.
3 Delitala AP, Scuteri A, Maioli M, Casu G, Merella P, Fanciulli G. Effect of rhTSH on Lipids. J Clin Med. 2020 Feb 14;9(2):515. doi: 10.3390/jcm9020515. PMID: 32074945; PMCID: PMC7073530.
4 Beukhof CM, Massolt ET, Visser TJ, et al. Effects of Thyrotropin on Peripheral Thyroid Hormone Metabolism and Serum Lipids. Thyroid. 2018;28(2):168-174. doi:10.1089/thy.2017.0330
5 Stamatouli A, Bedoya P, Yavuz S. Hypothyroidism: Cardiovascular Endpoints of Thyroid Hormone Replacement. Front Endocrinol (Lausanne). 2020 Jan 9;10:888. doi: 10.3389/fendo.2019.00888. PMID: 31998229; PMCID: PMC6962138.
6 Delitala AP, Scuteri A, Fiorillo E, Orrù V, Lakatta EG, Schlessinger D, Cucca F. Carotid Beta Stiffness Association with Thyroid Function. Journal of Clinical Medicine. 2021 Jan;10(3):420.
7 Inoue K, Ritz B, Brent GA, Ebrahimi R, Rhee CM, Leung AM. Association of subclinical hypothyroidism and cardiovascular disease with mortality. JAMA network open. 2020 Feb 5;3(2):e1920745-.
8 Vassalle C, Parlanti A, Pingitore A, Berti S, Iervasi G, Sabatino L. Vitamin D, Thyroid Hormones and Cardiovascular Risk: Exploring the Components of This Novel Disease Triangle. Frontiers in Physiology. 2021;12.
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