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Table of Contents
Year : 2022  |  Volume : 12  |  Issue : 2  |  Page : 66-70

Elevated thyroid-stimulating hormone is a risk factor in coronary artery bypass grafting

1 Department of Cardiovascular and Thoracic Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
2 Department of Anaethesia, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
3 Department of Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

Date of Submission07-Jul-2021
Date of Decision01-Aug-2021
Date of Acceptance02-Aug-2021
Date of Web Publication21-May-2022

Correspondence Address:
Dr. Shantanu Pande
Department of Cardiovascular and Thoracic Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jicc.jicc_42_21

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Introduction: Asymptomatic hypothyroidism is endemic in most regions of our country. We planned a study to observe the effect of thyroid-stimulating hormone (TSH) in otherwise asymptomatic for hypothyroidism patients, on outcome after coronary artery bypass grafting (CABG). Materials and Methods: This is a retrospective cohort study conducted between January 2017 and December 2019. A total of 449 patients undergoing CABG were included in the study. Patients with redo operations, combined procedures, and emergency operations were excluded from the study. The groups were formed on the level of TSH (normal, subclinical elevation, and clinical elevation) as follows: TSH normal (Group 1, n = 309), TSH subclinical elevation (Group 2, n = 122), and TSH clinical elevation (Group 3, n = 12). One-way ANOVA was used to analyze the groups. Results: There was an increase in the use of inotrope, appearance of atrial fibrillation, and use of intra-aortic balloon pump in Group 3 when compared to that in Groups 1 and 2, P = 0.0001. Higher mortality was observed in group 3 (25%) when compared to group 1 (2.91%) and group 2 (2.45%). There was no difference in the level of free T4, between groups. T3 was similar in TSH normal, TSH subclinical elevation, and clinical elevation group. TSH level of >10 mIU/l predicted mortality with a sensitivity of 91.7% and a specificity of 99.8% in predicting mortality. Conclusion: About 2.67% of the patients undergoing CABG had asymptomatic but clinical elevation of TSH, and it is associated with higher mortality.

Keywords: Coronary artery bypass grafting, hypothyroidism, subclinical hypothyroidism

How to cite this article:
Thukral A, Kotwal AS, Gupta RP, Rastogi A, Pande S, Agarwal SK, Tewari S. Elevated thyroid-stimulating hormone is a risk factor in coronary artery bypass grafting. J Indian coll cardiol 2022;12:66-70

How to cite this URL:
Thukral A, Kotwal AS, Gupta RP, Rastogi A, Pande S, Agarwal SK, Tewari S. Elevated thyroid-stimulating hormone is a risk factor in coronary artery bypass grafting. J Indian coll cardiol [serial online] 2022 [cited 2022 Jun 30];12:66-70. Available from: https://www.joicc.org/text.asp?2022/12/2/66/345625

  Introduction Top

Hypothyroid state exists as endemic disease in geographical regions of India.[1] Thus, there exists a broad clinical spectrum of this disease.[2] At one end is the asymptomatic but clinically diagnosed variant of the disease, while at the extreme end is severely symptomatic hypothyroidism.[3] Because of these factors, there exist a huge group of patients who are diagnosed as asymptomatic subclinical hypothyroidism. Hypothyroidism is associated with cardiac diseases and aggravates the symptoms of existing cardiac disorder.[4] It also affects the cardiac function directly, thus adversely affecting the outcome. It has been associated with hypertension, lipid abnormalities, and depressed cardiac contractility, all of which have been an independent risk factors for cardiac disease.[5] Hypothyroidism has also been implicated in aggravating the symptoms arising from coronary artery disease.[6],[7] Presence of hypothyroidism has been associated with complications after surgical procedures, especially wound healing and even increase in mortality.[8] It is thus advised to treat hypothyroid state before any surgical procedure. Because of the endemic nature of this disease and a huge clinical spectrum, subclinical and clinical but asymptomatic hypothyroid state exists undetected.[9] Assessment of thyroid function has not been a routine in preoperative evaluation before cardiac procedure. Hence, these potentially risky subset of asymptomatic but subclinical or clinical hypothyroidism may be operated undetected, exposing them to increased postoperative risk. This study was designed to observe the effect of asymptomatic from thyroid status but with raised thyroid stimulating hormone (TSH) level on the outcome of coronary artery bypass grafting (CABG).

  Materials and Methods Top

This retrospective cohort study was performed between January 2017 and December 2019. The study recruited patients undergoing CABG. The study was approved by the Institute's Ethics Committee (PGI/BE/620/2018), which granted waiver of consent from the patients included in it.

Inclusion criteria were patients with chronic stable angina, patients with chronic stable angina normal sinus rhythm, and hemodynamic stability in patients with severe coronary artery disease.

Exclusion criteria were unstable angina, acute coronary syndrome, hemodynamic instability atrial fibrillation, and urgent or semi-emergency operation in patients of severe coronary artery disease who underwent CABG.

A total of 443 patients were included in the study. These patients were then divided into three groups based on their thyroid status preoperatively decided by thyroid function test. The level of TSH in the blood of the patient was the criterion for categorizing the function of thyroid gland. These values are representative of TSH levels just before the operation. A value of TSH of <3.9 mIU/lwas considered normal (Group 1, n = 309), a value of >4 and <9.9 was considered as subclinical elevation of TSH (Group 2, n = 122), and a value of >10 mIU/l was labeled as clinical elevation of THS (Group 3, n = 12). This definition of TSH levels in various hypothyroidism has been suggested by the American Thyroid Association.[5] However, it also mentions other criteria such as symptoms and derangement of other thyroid function parameters. Because none of the patients had symptoms of hypothyroidism, they were not treated with thyroid hormone in any of the groups. All these patients had no manifestation of hypothyroid symptoms. Patient data were accessed from digital record using hospital information symptoms. Clinical status, risk factors, preoperative investigations, and echocardiography were retrieved.

The primary end point of this study was mortality. Secondary end points were chosen from factors that could affect mortality and morbidity in these patients, namely intensive care unit stay, ventilation time, and use of inotropes. Inotropes are used for improving the contractility and manipulating systemic vascular resistance in the postoperative period. It is difficult to compare the variety of inotropes used, hence we used a scoring system (Wenowsky's score) to compare the various groups involved. The score was calculated from the maximum dose of inotrope that was required during the intensive care unit stay duration. The score was extended to use of norepinephrine.[10] The power of study was calculated by eliminating the confounding variables by using case–control matching which reduces the sample size of 10 in each group to eliminate the difference in sample size in groups. The primary end point for the study was considered as mortality. Mortality for Group 3 was 20%, while it was 0% for combined Groups 1 and 2. Power was calculated using Z test with pooled variance. N1 and N2 were 10 each with N of 20. P1 is 0.20 and P2 0.001 with a difference of 0.199. Target α is 0.05 with actual α being 0.000. The power of study is 12%. Though, the difference in mortality is clinically extremely significant, the study is statistically underpowered. It would require 35 patients in each group with case control 1:1 matching to power the study to 80%. The power is 12% and thus underpowered. Though it is clinically extremely significant difference, it is underpowered statistically. It would require 35 patients in each group with case–control 1:1 matching to power the study to 80%.

Different techniques of performing CABG were applied by surgeons based on their preference. Off-pump CABG (n = 422) was the most common procedure used in these patients, followed by on-pump CABG (n = 14) and minimally invasive CABG (n = 13). Similarly, different configurations and grafts were used by surgeon according to their preference. Conventional grafting using one internal mammary artery to left anterior descending artery and vein conduits from aorta to lateral and inferior grafts were used in 383 patients. Total arterial revascularization using bilateral internal mammary artery was used in 66 patients.

Statistical analysis

The number of patients in Group 3 was much lower than that of the other two groups, hence variables were expressed in mean and standard deviation. Comparison between groups was done using one-way ANOVA method. Intergroup comparison was done using post hoc analysis. Bonferroni method was used when the equivalence of variance was achieved and Tamhane method where equivalence of variance was not achieved between variables in the groups. Pearson's method was used to observe correlation between variables. Case–control matching was done to eliminate the bias of confounding variables such as age, sex, diabetes mellitus, hypertension, left ventricular function, and either on- or off-pump CABG. This matching was done between Group 3 and Groups 1 and 2 combined to eliminate the inequality of the numbers between groups, and comparison was done using Mann–Whitney U-test. Receiver operator characteristics curve was calculated for mortality and TSH level. A P < 0.05 was considered significant. Statistics was performed using SPSS 20 version for Windows (SPSS, Inc. Chicago, IL, USA).

  Results Top

Patients in this study had a similar age and gender distribution among the groups. The preoperative risk factors for development of coronary artery disease were also similar in between groups [Table 1]. All the patients were in chronic stable angina class 2 and were prescribed adequate antianginal treatment. Patients were on prescription of an antiplatelet, a betablocker, lipid-controlling drug, ACE inhibitor, and an anti-anginal drug. Thyroid assessment done just before the operation [Table 2]. Free T4 was not significantly different within groups. Patients in Group 3 (n = 12) had TSH value of >10 mIU/l and had maximum mortality (n = 3). Echocardiographic assessment revealed no significant difference between groups. Left ventricle end diastolic diameter presented as median (minimum – maximum) was 46 mm (32 – 86), 45 mm (35 – 76) and 46 mm (30 -58) respectively from group 1-3. Left ventricle end-systolic diameter was 27 mm (22–50), 29 mm (19–55), 26.5 mm (20 – 40) respectively, in Groups 1-3. Left ventricle ejection fraction was 55% (20–60), 58 (32–66), 55% (40 – 60) respectively, in groups 1-3. The operative and postoperative details are represented in [Table 3]. Intra-aortic balloon pump (IABP) was used in 25 patients and significantly more in Group 3 [Table 3]. Significantly higher mortality was observed in clinical hypothyroid group when compared to euthyroid and subclinical hypothyroid groups. However, there was no difference in mortality between euthyroid and subclinical hypothyroid groups [Table 3]. While ventilation time and intensive care unit stay were not statistically significant among the groups, there was a significant difference in the use of inotropes in clinical hypothyroid patients when compared to that of euthyroid or subclinical hypothyroid group [Table 3]. The case–control matching which had ten cases each in Group 3 and combined Groups 1 and 2 is presented in [Table 4]. The factors that showed statistically significant difference were the intensive care unit stay and use of IABP. However, clinically significant difference was observed in mortality. All mortalities were within 30 days and in the intensive care unit. The value of TSH, >10 μIU/l, was associated with mortality with 91.7% sensitivity and 99.8% specificity. The receiver operative characteristic curve revealed area under curve of 0.916 with P = 0.001, [Figure 1].
Table 1: Preoperative risk factors

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Table 2: Thyroid function assessment

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Table 3: Operative and postoperative parameters

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Table 4: Comparison of variables for endpoint after case–control matching

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Figure 1: Receiver operator characteristic curve of mortality with the level of thyroid-stimulating hormone (IU/ml) in the serum of patients

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  Discussion Top

In this study, patients with overt has shown increased requirement of inotropes, IABP usage, and development of new-onset atrial fibrillation after CABG. It has been reported that hypothyroidism is a risk factor for development of atrial fibrillation in coronary artery disease patients.[11] Mortality has been well-established in patients with hypothyroidism undergoing cardiac surgery and especially in patients operated for coronary artery disease.[12],[13] It was witnessed in this study as significantly higher use of inotropes and IABP, indicative of impaired cardiac output as witnessed in hypothyroidism.[14] These factors are also the independent markers of mortality after CABG.[15]

Though the use of inotropes was higher in clinical elevation in TSH group, its contribution to increased mortality cannot be established. William et al. evaluated inotrope usage in different hospitals after CABG and found that though it may vary from 30% to 100%, it does not affect the mortality, the incidence of atrial fibrillation, renal failure, or acute limb ischemia.[16] Intensive care unit stay and ventilation time in our study were comparable to those of other investigators.[17] Kotfis et al. studied the effect of ventilation time after CABG. They found that 44% had ventilation between 12 and 24 h, as observed in our study. Ventilation time was also dependent on age, gender, postoperative risk, and smoking.[18] In our study, we found that value of TSH in excess of 10 mIU/l is associated with mortality with 91.7% sensitivity and 99.8% specificity. All these patients had asymptomatic thyroid status at the time of admission. Hence, no treatment was initiated based on mere TSH levels. Operation was performed as the required free T4 levels were present in all cases. It was observed that there was no difference in free T4 levels in all the groups. T3 and T4 hormone level in blood was significantly less in the clinical elevation of TSH level group as compared to normal TSH status and subclinical elevation in TSH group, but they were within safe range before operation.[19] Free T4 level was considered for adequacy to proceed for operation as observed in other studies. The European Thyroid Association has recommended the use of TSH, free T4, and free T3 levels as the markers of effective therapy. Euthyroid should be considered when all these estimations are normal.[20],[21] In our study, patients presented with symptomatic coronary artery disease, hence presence of adequate free T4 levels was considered appropriate for surgery. It is important to note that despite adequacy of thyroid hormones in the body, higher TSH level remained a marker for mortality after CABG as discussed by Vacante et al.[22]

Subclinical hypothyroidism, generally asymptomatic, has been associated with increased cardiovascular risk. Rodondi et al. reported subclinical hypothyroidism in 6.2% with increased mortality in patients with coronary heart disease. They also found an increased mortality in patients with TSH of more than 10 μIU/l, as witnessed in our study.[23] However, it has not been a risk in our study, when compared with normal TSH level patients. Though subclinical hypothyroidism is associated with increased mortality, it has not been observed in our study. The subclinical hypothyroid group had no significant difference in mortality or morbidity when compared with euthyroid group in this study. This difference may have risen due to the off-pump technique of operation that was followed in majority of patients in our study as compared to other studies. There is evidence that cardiopulmonary bypass use decreases the concentration of thyroid hormone in the postoperative period.[24],[25] Another factor that may have resulted in no significant difference in euthyroid and subclinical hypothyroid group has been a comparable and normal range of T3 and T4 levels in subclinical hypothyroid group. The only difference was higher TSH level in the subclinical elevation of TSH group patients, but its value was <10 μIU/l. This may have resulted from the endemic nature of the disease, with these subclinical hypothyroid patients being in the early spectrum of the disease.[26] Walsh et al. discussed that increased level of TSH >10 μIU/l has been associated with increased mortality in coronary heart disease.[27] This study has implicated these levels with high sensitivity and specificity with mortality in CABG patients.

The study is limited by the nature of this study that is retrospective. The thyroid functions were available immediately preoperative and the patients had no history or previously available investigations. Similarly, the length of thyroid status preoperatively is also not available. Though significant and strong result, still the number of asymptomatic and clinical elevation of TSH level patients is small in number.

  Conclusion Top

Asymptomatic clinical elevation of TSH level also had normal levels of free T4 in the blood, but low normal T3 and T4 levels. TSH levels were different in all the groups and a value of >10 mIU/l was associated with higher mortality after CABG. This may suggest that a treatment for a longer duration in such asymptomatic but clinical elevation till the TSH level fall to a lesser value is required.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1]

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


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