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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 13  |  Issue : 1  |  Page : 23-27

Diastolic dysfunction in subclinical hypothyroid patients in rural India: A case–control study


1 Department of Medicine, Midnapore Medical College, Paschim Midnapore, India
2 Department of Cardiology, Calcutta National Medical College, Kolkata, West Bengal, India

Date of Web Publication13-Jan-2016

Correspondence Address:
Chiranjib Nag
Department of General Medicine, Midnapore Medical College, Paschim Midnapore - 721 101, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0189-7969.173855

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  Abstract 

Background: Thyroid dysfunction may affect the heart. Conflicting evidence exists regarding cardiac involvement in subclinical hypothyroid.
Objective: Aim of the study is to investigate left ventricular dysfunction in subclinical hypothyroidism.
Materials and Methods: This is a case–control study including 51 subclinical hypothyroid patients and 55 age, sex, and body surface area matched control. After meeting inclusion and exclusion criteria, the study population was selected and evaluated with two-dimension, M-mode, and pulse Doppler echocardiography. The following parameters were measured - left ventricular end-diastolic diameter, left ventricular end-systolic diameters, posterior wall thickness, interventricular septal thickness, fractional shortening, left ventricular ejection fraction, left ventricular mass index, diastolic transmitral peak velocity (E and A wave), E/A ratio, deceleration time of mitral E wave, and Tei index. Student's t-test for independent sample with calculation of P value (two-tailed) was applied for statistical analysis using SPSS software (version 17.0).
Results: There was significant left ventricular diastolic dysfunction as measured by increased mitral peak A velocity (66.3 ± 8.4 mm/s in case vs. 52.4 ± 4.8 mm/s in control, P < 0.001), decreased E/A ratio (0.90 ± 0.08 in case vs. 1.31 ± 0.36 in control, P < 0.001), prolonged isovolumetric relaxation time (120 ± 13 ms in case vs. 76 ± 9 ms in control, P = 0.035), increased Tei index (0.29 ± 0.13 in case vs. 0.22 ± 0.10 in control, P = 0.015). Left ventricular systolic function as measured by other parameters was similar in both groups with no significant change.
Conclusion: Subclinical hypothyroidism is significantly associated with left ventricular diastolic dysfunction.

Keywords: Cardiac dysfunction, left ventricular dysfunction, sub-.clinical hypothyroidAddress


How to cite this article:
Nag C, Seth BC, Haldar SK. Diastolic dysfunction in subclinical hypothyroid patients in rural India: A case–control study. Nig J Cardiol 2016;13:23-7

How to cite this URL:
Nag C, Seth BC, Haldar SK. Diastolic dysfunction in subclinical hypothyroid patients in rural India: A case–control study. Nig J Cardiol [serial online] 2016 [cited 2019 Aug 21];13:23-7. Available from: http://www.nigjcardiol.org/text.asp?2016/13/1/23/173855


  Introduction Top


The heart is affected by thyroid hormone, and it is could to have adverse cardiac effects in thyroid disorder.[1] Thyroid dysfunction itself exists in a wide range – from hyperthyroid state to hypothyroid with subclinical hyperthyroidism and subclinical hypothyroidism in between. Clinically, apparent illness in the extreme two disorders can easily seek medical attention. The problem exists in dealing with the subclinical dysfunctions.

A number of studies have demonstrated cardiac problems in both subclinical hyperthyroidism and subclinical hypothyroidism. There is an increased resting heart rate; supravenrticular arrhythmias, diastolic dysfunction, and increased left ventricular mass are some of the established cardiological manifestations of subclinical hyperthyroidism.[2],[3]

Subclinical hypothyroidism is defined as variable increase in serum thyroid stimulating hormone (TSH) concentration with apparently normal serum free T4 and free T3 levels.[4] Prevalence of subclinical hypothyroidism is about 10% among individuals over age 60 years, with a higher prevalence in women.[4] According to some literature, it is associated with left ventricular diastolic dysfunction and may also lead to exercise intolerance and diastolic heart failure or atherosclerosis.[5],[6],[7],[8] Doppler echocardiography has been used extensively to evaluate left ventricular systolic and diastolic function in patients with subclinical hypothyroidism. Alterations of left ventricular diastolic function, indications by a prolonged isovolumetric relaxation time (IVRT), and abnormal time-to-peak filling rate are the most common association reported.[5] On the other hand, some authors clearly deny any association of cardiac dysfunction in subclinical hypothyroidism.[9],[10] That is why, there is no established guideline regarding treatment plan of these patients. Some favor treatment with levothyroxine whereas others disagree.

Because of this dilemma, the study was conducted to find out whether cardiac function exists in subclinical hypothyroid patients and establish a clear relationship between left ventricular diastolic function and subclinical hypothyroid Indian patients.


  Materials and Methods Top


This was a case-control study involving 51 subclinical hypothyroid patients and 55 normal control subjects. The study was conducted at a rural-based medical college situated in the Eastern part of India. Patients were selected at the outpatient clinic of the hospital among those with no other co-morbidity who came for routine health check-up at the hospital. They, however, had subclinical thyroid dysfunction after their blood samples were tested.

Inclusion criteria were (1) elevation of TSH level higher than the upper limit range (4.2 mU/L) but below 10 mU/L on two separate occasions at least 6 week apart (TSH level of 10 mU/L or greater was not included, because of established diastolic dysfunction and heart failure in these patients);[11] (2) normal free thyroxine (FT4) levels (9–16 pmol/L) and normal free triiodothyronine (FT3) level (3.7–6.5 pmol/L); (3) no other co-morbidity including diabetes, hypertension, lipid disorder, and known heart disease; and (4) age more than 18 years.

The following patients were excluded from the study: (1) Patients with diabetes, hypertension, dyslipidemia, known thyroid disorder, known cardiac disorder. (2) Patients receiving drugs that may interfere with thyroid function. (3) Known alcoholic. (4) Age more than 60 years (The last two were exclusion criteria because there may be the presence of established diastolic dysfunction).

Age, sex, and body surface area matched healthy control subjects were selected from the relatives of the patients attending the clinics. Same exclusion criteria were applied to the control subjects also. Cardiovascular, respiratory diseases, and other major illness were excluded in both the patients and controls by a complete clinical workup.

Assessment of thyroid status

After a period of overnight fasting, venous blood samples were taken from each case and control. TSH was estimated by the automated third generation chemiluminescent immunometric assay (Immulite; Siemens); FT3 and FT4 were done by competitive analog-based immunoassay (Immulite; Siemens).

Doppler-echocardiography

All cases and controls were evaluated using a GE VingMed Vivid 5 Echocardiography System (General Electric Health Care pvt. ltd.) with 2.0 MHz probe by a single cardiologist who was blinded to the patient's status. Examinations were performed putting the patients in left lateral decubitus position using standard parasternal long axis, parasternal short axis, and apical two-, four- and five- chamber views. M-mode images were obtained from the parasternal long-axis views for assessment of left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameters (LVESD), posterior wall thickness (PWT), interventricular septal thickness (IVST), fractional shortening (FS), and left ventricular ejection fraction (LVEF). According to Teicholtz method, LVEF was calculated.[12] Left ventricular mass index (LVMI) was calculated using Devereux's formula.[13] At apical four chamber view, pulsed-wave Doppler was used to measure transmitral flow velocity. Diastolic transmitral peak velocity (E and A wave), E/A ratio, and deceleration time (DT) of mitral E wave was measured. At apical five-chamber view, continuous-wave Doppler was used to obtain isovolumetric contraction time, IVRT, and aortic ejection time (ET). Left ventricular Tei index was calculated by formula (ICT + IVRT)/ET.[14] The final value of each index was the mean of measurement of three consecutive beats. Tei index can evaluate both systolic and diastolic function as a composite index, independent of preload and afterload.[15] If any one of the following parameters were present, diastolic dysfunction was said to be present. They were (a) E/A ≤1.0, (b) IVRT ≥ 100 ms, and (c) DT ≥220 ms.[15]

Statistical analysis

For comparison of the baseline characteristics, thyroid status, and echocardiography findings of the cases (subclinical hypothyroid) and control subjects, Student's t-test for independent sample with calculation of P value (two-tailed) was applied. All data were presented as mean ± standard deviation. P < 0.05 was considered significant statistically. The calculation was performed using SPSS software version 17.0 for Windows (IBM corporation).


  Results Top


Among the 51 cases of subclinical hypothyroidism, 40 (78.4%) were female, and 11 (21.6%) were male. The mean age for the patients was 39.5 (±8.4) years. Comparison of patients with age, sex, and body surface area matched healthy control subjects are shown in [Table 1]. Thyroid profile of the study population is shown in [Table 2]. Both case and control groups had normal mean FT4 and FT3 level. Obviously due to selection criteria, subclinical hypothyroid patients had higher level of TSH than the control group. This difference is statistically significant with P = 0.025.
Table 1: Baseline characteristics of the study population

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Table 2: Thyroid profile of study group

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M mode and two-dimension echocardiographic measurements are summarized in [Table 3]. There was no significant difference in LVEDD (47.5 ± 3.8 mm in case vs. 48.2 ± 4.2 mm in control, P = 0.821), LVESD (28.5 ± 2.6 mm in case vs. 29.6 ± 3.1 mm in control, P = 0.722), PWT (8.4 ± 0.8 mm in case vs. 8.2 ± 0.9 mm in control, P = 0.363), IVST (8.6 ± 1.3 in case vs. 8.1 ± 1.6 mm in control, P = 0.091), and LVMI (78.4 ± 13.4 g/m 2 in case vs. 76.7 ± 16.6 g/m 2 in control, P = 0.486). All patients had normal left ventricular systolic function. When compared to the control group, there is no significant difference in systolic function among subclinical hypothyroid group as evidenced by LVEF and FS. Mean LVEF among case was 70.1 ± 5.1% and among control was 71.2 ± 4.4%, P = 0.287. FS among subclinical hypothyroid patients was 41.5 ± 3.8% and among healthy control was 42.6 ± 4.8% with P = 0.954.
Table 3: Echocardiographic systolic function in all subjects

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Doppler echocardiographic parameters are summarized in [Table 4]. There is clear evidence of diastolic dysfunction of left ventricle among patients with subclinical hypothyroidism. They had normal mitral peak E velocity 60.1 ± 6.5 mm/s in case and 70.6 ± 11.2 mm/s in control group with no significant difference (P = 0.084). However, mitral peak A velocity was increased significantly with reference to control group (66.3 ± 8.4 mm/s in case vs. 52.4 ± 4.8 mm/s in control, P < 0.001). Diastolic dysfunction was evidenced by decreased E/A ratio (0.90 ± 0.08 in case vs. 1.31 ± 0.36 in control, P < 0.001) and prolonged IVRT (120 ± 13 in case vs. 76 ± 9 in control, P = 0.035). However, there was no significant difference in DT among cases in compare to control group. Tei index was 0.29 ± 0.13 in subclinical hypothyroid patients and 0.22 ± 0.10 in healthy control group. This difference was statistically significant (P = 0.015). As normal value of Tei index is <0.40, values in both groups were in normal range. However, as Tei index among subclinical hypothyroid was significantly higher than control, it can be said that there is some degree of ventricular dysfunction in subclinical hypothyroidism in compare to normal subject.
Table 4: Doppler echocardiographic measurement

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  Discussion Top


There are some conflicting evidence in regards to subclinical hypothyroidism. A study published by Cappola et al., stated that unrecognized subclinical hypothyroidism is not a cardiovascular risk factor.[16] The cardiovascular health study found no increased cardiovascular risk in subjects with TSH <10.0 mU/l.[9] Again, in another study, Rodondi et al. said that there may be increased risk of heart failure in patients with TSH level >7 mIU/L, but no other cardiovascular events.[10] Based on the reviewed data, recommendation was made against routine treatment of subclinical hypothyroid disease with TSH level 4.5–10.0 mIU/L.[6]

Contrary to that, Biondi et al., found subclinical hypothyroidism to be associated with left ventricular systolic and diastolic dysfunction and enhanced risk for atherosclerosis and myocardial infarction based on the fact that heart responds to minimal, but persistent changes in blood level of thyroid hormone that is typical for subclinical hypothyroidism.[5] Hak et al., had similar observation that it is a strong indicator of risk for atherosclerosis and myocardial infarction in elderly woman.[6] There is also evidence regarding increased arterial stiffness in this disorder.[7] A number of studies demonstrated diastolic dysfunction in subclinical hypothyroidism, and, based on their observation, they recommended to treating these patient as levothyroxine may reverse this diastolic dysfunction over the period of time.[17],[18],[19]

Our study found significant diastolic dysfunction of left ventricle in patients with subclinical hypothyroidism though systolic function remains unaffected. We found significant increase in mitral peak A velocity, reduced E/A ratio, and prolongation of IVRT in Doppler echocardiography. Mitral peak E velocity is unaltered. There is also higher Tei index among subclinical hypothyroidism compared to normal subjects. This is similar to the findings stated by Biondi et al., though they had not measured Tei index.[20] Our study also supports data from Kosar et al. where they found significant lower E/A ratio and prolongation of IVRT in both the left and right ventricle, though we have not included right ventricular dysfunction in our study.[21] In contrast to their study, we found no decrease in mitral E velocity. A study on 42 patients with subclinical hypothyroidism by Franzoni et al. found decreased E velocity increased A velocity and decreased E/A ratio, whereas Vitale et al., did not found any change in these parameters.[17],[18] Vitale et al., demonstrated diastolic dysfunction in the form of prolonged precontraction time and prolonged myocardial relaxation time. None of them used Tei index as a parameter.

Our study found no alteration in left ventricular morphology and systolic function. LVMI was also not changed. This is supportive of the findings of the cardiovascular health study.[9] In contrast to the findings by Erkan et al., mean left ventricular PWT and interventricular septum thickness remained unaffected in our study.[19] They also found no difference in pulsed-wave Doppler-derived diastolic indices (such as E and A velocities, E/A ratio) between case and control group stating that conventional indices may not be sensitive to detect mild degree of diastolic dysfunction in subclinical hypothyroid patients. In this regard, they recommend using tissue Doppler echocardiography to measure mitral annular E' velocities in septal and anterior localizations, which was also done by Franzoni et al.[18] A step forward, Brenta et al. demonstrated diastolic dysfunction in subclinical hypothyroid by radionuclide ventriculography.[8]

We followed strict exclusion criteria in patient selection. Other potential causes of diastolic dysfunction (such as diabetes, hypertension, and coronary artery disease) were not included in this study. We also excluded alcoholics and person aged over 60 years in fear of presence of preexisting diastolic dysfunction. Hence, diastolic dysfunction in the study group is mainly attributed by the disease entity itself that is, subclinical hypothyroidism. Based on results from our study, we can say that diastolic dysfunction is a recognized threat to subclinical hypothyroidism. Pulse wave Doppler echocardiography is sufficient to detect this diastolic dysfunction. It should be applied to all patients with subclinical hypothyroidism who is a potential candidate of suffering from diastolic dysfunction.

Limitation of our study is small number of the study population. Furthermore, we have not seen the effect of levothyroxin treatment and its impact on reversibility of diastolic dysfunction in subclinical hypothyroidism. Hence, any recommendation about treatment protocol of these patients cannot be made.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med 2001;344:501-9.  Back to cited text no. 1
    
2.
Smit JW, Eustatia-Rutten CF, Corssmit EP, Pereira AM, Frölich M, Bleeker GB, et al. Reversible diastolic dysfunction after long-term exogenous subclinical hyperthyroidism: A randomized, placebo-controlled study. J Clin Endocrinol Metab 2005;90:6041-7.  Back to cited text no. 2
    
3.
Kahaly GJ, Dillmann WH. Thyroid hormone action in the heart. Endocr Rev 2005;26:704-28.  Back to cited text no. 3
    
4.
Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, et al. Subclinical thyroid disease: Scientific review and guidelines for diagnosis and management. JAMA 2004;291:228-38.  Back to cited text no. 4
    
5.
Biondi B, Palmieri EA, Lombardi G, Fazio S. Effects of subclinical thyroid dysfunction on the heart. Ann Intern Med 2002;137:904-14.  Back to cited text no. 5
    
6.
Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: The Rotterdam Study. Ann Intern Med 2000;132:270-8.  Back to cited text no. 6
    
7.
Owen PJ, Rajiv C, Vinereanu D, Mathew T, Fraser AG, Lazarus JH. Subclinical hypothyroidism, arterial stiffness, and myocardial reserve. J Clin Endocrinol Metab 2006;91:2126-32.  Back to cited text no. 7
    
8.
Brenta G, Mutti LA, Schnitman M, Fretes O, Perrone A, Matute ML. Assessment of left ventricular diastolic function by radionuclide ventriculography at rest and exercise in subclinical hypothyroidism, and its response to L-thyroxine therapy. Am J Cardiol 2003;91:1327-30.  Back to cited text no. 8
    
9.
Rodondi N, Bauer DC, Cappola AR, Cornuz J, Robbins J, Fried LP, et al. Subclinical thyroid dysfunction, cardiac function, and the risk of heart failure. The cardiovascular health study. J Am Coll Cardiol 2008;52:1152-9.  Back to cited text no. 9
    
10.
Rodondi N, Newman AB, Vittinghoff E, de Rekeneire N, Satterfield S, Harris TB, et al. Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch Intern Med 2005;165:2460-6.  Back to cited text no. 10
    
11.
Razvi S, Weaver JU, Vanderpump MP, Pearce SH. The incidence of ischemic heart disease and mortality in people with subclinical hypothyroidism: Reanalysis of the Whickham Survey cohort. J Clin Endocrinol Metab 2010;95:1734-40.  Back to cited text no. 11
    
12.
Teichholz LE, Kreulen T, Herman MV, Gorlin R. Problems in echocardiographic volume determinations: Echocardiographic-angiographic correlations in the presence of absence of asynergy. Am J Cardiol 1976;37:7-11.  Back to cited text no. 12
    
13.
Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, et al. Echocardiographic assessment of left ventricular hypertrophy: Comparison to necropsy findings. Am J Cardiol 1986;57:450-8.  Back to cited text no. 13
    
14.
Karatzis EN, Giannakopoulou AT, Papadakis JE, Karazachos AV, Nearchou NS. Myocardial performance index (Tei index): Evaluating its application to myocardial infarction. Hellenic J Cardiol 2009;50:60-5.  Back to cited text no. 14
    
15.
Rakowski H, Appleton C, Chan KL, Dumesnil JG, Honos G, Jue J, et al. Canadian consensus recommendations for the measurement and reporting of diastolic dysfunction by echocardiography: From the investigators of consensus on diastolic dysfunction by echocardiography. J Am Soc Echocardiogr 1996;9:736-60.  Back to cited text no. 15
    
16.
Cappola AR, Fried LP, Arnold AM, Danese MD, Kuller LH, Burke GL, et al. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA 2006;295:1033-41.  Back to cited text no. 16
    
17.
Vitale G, Galderisi M, Lupoli GA, Celentano A, Pietropaolo I, Parenti N, et al. Left ventricular myocardial impairment in subclinical hypothyroidism assessed by a new ultrasound tool: Pulsed tissue Doppler. J Clin Endocrinol Metab 2002;87:4350-5.  Back to cited text no. 17
    
18.
Franzoni F, Galetta F, Fallahi P, Tocchini L, Merico G, Braccini L, et al. Effect of L-thyroxine treatment on left ventricular function in subclinical hypothyroidism. Biomed Pharmacother 2006;60:431-6.  Back to cited text no. 18
    
19.
Erkan G, Erkan AF, Cemri M, Karaahmetoglu S, Cesur M, Cengel A. The evaluation of diastolic dysfunction with tissue Doppler echocardiography in women with subclinical hypothyroidism and the effect of L-thyroxine treatment on diastolic dysfunction: A pilot study. J Thyroid Res 2011;2011:654304.  Back to cited text no. 19
    
20.
Biondi B, Fazio S, Palmieri EA, Carella C, Panza N, Cittadini A, et al. Left ventricular diastolic dysfunction in patients with subclinical hypothyroidism. J Clin Endocrinol Metab 1999;84:2064-7.  Back to cited text no. 20
    
21.
Kosar F, Sahin I, Turan N, Topal E, Aksoy Y, Taskapan C. Evaluation of right and left ventricular function using pulsed-wave tissue Doppler echocardiography in patients with subclinical hypothyroidism. J Endocrinol Invest 2005;28:704-10.  Back to cited text no. 21
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]


This article has been cited by
1 Echocardiographic evaluation of left ventricular diastolic dysfunction in subclinical hypothyroidism: A case–control study
Yuthika Malhotra,Rajeev Mohan Kaushik,Reshma Kaushik
Endocrine Research. 2017; : 1
[Pubmed] | [DOI]



 

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