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Research Article | Volume 14 Issue 5 (Sept - Oct, 2024) | Pages 495 - 500
“Association of Thyroid Profile with severity of Acute Coronary Syndrome in Elderly Patients”
 ,
1
Post Graduate in Department of General Medicine in Blde (Du) Shri Bm Patil Medical College Hospital and Research Centre, India
2
Professor In Department of General Medicine in Blde (Du) Shri Bm Patil Medical College Hospital and Research Centre, India
Under a Creative Commons license
Open Access
Received
July 30, 2024
Revised
Aug. 31, 2024
Accepted
Sept. 10, 2024
Published
Oct. 12, 2024
Abstract

Background: Acute Coronary Syndrome (ACS) is a predominant cause of mortality, particularly in the elderly population (>60 years). This study aimed to evaluate the correlation between thyroid hormone profiles and the severity of ACS  in old  patients, using Killip classification and TIMI flow grade. Material and Method: This hospital-based cross-sectional study involved 95 patients aged over 60 years, presenting with ACS at Shri B M Patil Medical College. Exclusion criteria included known coronary artery disease, thyroid disorders, use of medications affecting thyroid function, and other conditions impacting thyroid tests. Thyroid profiles were measured within 72 hours of admission using the Electrochemiluminescence method. ACS severity was assessed using the Killip classification and TIMI flow grade. Statistical analysis was performed using JMP SAS 16 Software, with significance set at p<0.05. Results: The mean age of patients was 66.2 years, with 64.2% being male. Chest pain (91.5%) was the most common symptom. Hypertension (50.5%) and diabetes (46.3%) were prevalent comorbidities. ECG indicated STEMI in 64.2% of patients, with positive Troponin I in 85.3%. Single, double, and triple vessel diseases were observed in 31.6%, 42.1%, and 26.3% of cases, respectively. TIMI flow grade 2 was most common (48.4%), and Killip class 2 was the most frequent clinical severity (32.6%). Lower T3 and T4 levels were significantly associated with higher Killip classes, indicating severe ACS, while higher T3 levels correlated with higher TIMI grades, indicating better perfusion. Conclusion: The study found a strong relationship between thyroid hormone levels and the severity of ACS in older people. Lower thyroid hormone levels are related with more severe ACS, implying that thyroid profiling might be an important tool in the risk assessment and treatment of older ACS patients. More study is needed to investigate the underlying processes and corroborate these findings across a variety of clinical contexts.

Keywords
INTRODUCTION

Acute coronary syndrome, or ACS, is the leading cause of mortality, particularly among people over the age of 60. According to the ICMR, the death rate from ischemic heart disease in India in 2016 was 21.97% for those over 70 and 22.06% for persons aged 50 to 69 combined.1–3 The elderly (over 60) are eight times more likely to have an acute myocardial infarction than younger people. Subjects over the age of 60 account for nearly half of all acute myocardial infarction-related in-hospital deaths.4

 

Thyroid function test abnormalities are prevalent in acute illness and have been associated to disease severity and fatality in extreme cases. Thyroid issues have a considerable influence on cardiac function. Hyperthyroidism is associated with high BP and pulmonary artery hypertension, whereas hypothyroidism is usually associated with diastolic hypertension, dyslipidemia, atherosclerotic arterial plaque instability, and endothelial dysfunction.5 Hyperthyroidism and thyrotoxicosis can also cause chest discomfort and an irregular ECG. Thyroid hormone alterations reported in ACS are defined as "Low T3 Syndrome," consisting of low total T3, normal TSH, and T4, with the pathophysiological cause being decreased activity of the 5' mono-deiodinase, which converts T4 to T3 .5

 

The acute action of cytokines contributes significantly to the pathophysiology of low T3 syndrome. According to research, an aberrant thyroid profile is identified in ACS and corresponds with its severity, which necessitates the objective of this investigation. In this study, we will examine the severity of the ACS and connect it with the thyroid hormone profile. We prefer to incorporate the following parameters when determining the severity of acute coronary syndrome: 1) Killip Classification: Clinical Severity.6 2) Coronary Angiography -Timi Flow Grade.7

 

The Killip category was suggested in 1967 by “Thomas Killip III and John T. Kimball”. To establish which patients were most likely to die, a physical examination of those who may have suffered an acute myocardial infarction served as the foundation for this classification. It is used to determine the degree of heart failure clinically, thereby showing the severity of ACS (Acute MI). Coronary Angiography -Timi Flow Grade is used to establish a method of measuring penetration & perfusion of dye in coronary angiography. Because it measures perfusion, it may be used to identify the degree of ischemia and so ACS.8

 

There is limited literature available among Indian population, hence this study was designed with aim to correlate the parameters of thyroid profile with the severity of acute coronary syndrome using Killip classification and Timi flow grade in the elderly. Present study aimed to assess the correlation of thyroid profile with the severity of acute coronary syndrome using Killip classification and Timi flow grade in the elderly.

MATERIAL & METHOD

Present hospital based cross-sectional study was conducted among the patients above 60years who are admitted in the medicine ward/ICCU due to newly diagnosed acute coronary syndrome(ACS) being diagnosed on basis of clinical features  (typical OR atypical features), ECG  (STEMI OR Non-STEMI according to ACCF & AHA guidelines), raised biomarkers and who undergo coronary angiography admitted in in Shri B M Patil medical college and research center Vijaypura were included. Patients who are known case of coronary artery disease, case of thyroid disorder, patients on corticosteroids, amiodarone, levothyroxine, and drugs used in hyperthyroidism and patients with established diseases, such as chronic renal failure, chronic obstructive pulmonary disease, liver cirrhosis, and diabetic ketoacidosis and conditions that are known to affect thyroid function tests were excluded. The study was conducted after obtaining the institutional Ethics clearance and patients were enrolled after collecting the written informed consent.

 

ACS severity assessment.

  • KILLIP CLASSIFICATION -The classification was given by Thomas-Killip and John  Kimball in 1967 patients. 

 

It is being used to assess the severity of heart failure clinically hence indicating the severity of ACS (Acute MI)6

 

  • Killip I: clinical features of heart failure are not present.
  • Killip II: crepitations in the lung fields, S3, and elevated JVP.
  • Killip III: acute cardiogenic pulmonary edema.
  • Killip IV: cardiogenic shock or hypotension (defined as SBP < 90 mmHg), and evidence of peripheral vasoconstriction (oliguria, cyanosis, and sweating).

 

2) Coronary Angiography -Timi Flow Grade

  TIMI Coronary Grade Flow is used to ensure a uniform and consistent method of recording perfusion on coronary arteriography.7

  • Grade 0 (absent perfusion): There is absent forward flow beyond occlusion.
  • Grade 1 (penetration without no perfusion): The contrast material goes beyond the obstruction but dye fails to opacify coronary arteries distal to the obstruction for duration of the cine angiographic filming sequence.
  • Grade 2 : The contrast dye goes beyond the occlusion  and dye  opacifies the coronary artery  distal to the obstruction.  The rate of entry of dye  material into the artery  distal to obstruction or the rate of clearance from the distal artery  is very  slower than its entry into or clearance from  other comparable arteries which are not perfused occluded artery —
  • Grade 3(complete perfusion): Forward  flow into the bed distal to the obstruction occurs as good  as forward flow into the artery  proximal to obstruction , and clearance of dye  material from the involved artery  is as fast  as clearance of dye  from an uninvolved artery  in the same artery  or the opposite artery.

 

Thyroid hormones were measured by the Electrochemiluminescence method by Jeffrey’s reaction in the fully automated autoanalyzer Vitros 250 in the hospital laboratory. Thyroid hormone profile was measured in patients of acute coronary syndrome within 72hrs of admission. For thyroid hormone profile, 2 ml blood is collected in a plain red vacutainer.

 

Statistical analysis: The information got were entered into the Microsoft Excel, and statistical analysis was done with JMP SAS 16 Software. Results were expressed as Mean (Median) ±SD, counts and percentages, and diagrams. Normally distributed continuous variables between 2 groups were compared using ANOVA test, and for not normally distributed variables, Kruskal walli's test was used. Categorical variables were compared using the Chi-square test.  (If necessary) P<0.05 was considered as statistically significant. 

RESULT

The present study included total of 95 patients fulfilling inclusion criteria, with mean age of 66.2yrs, among them 64.2% were male and 35.8% were female patients.

 

 

Table 3: Showing the characteristics of the patients

 

Frequency

Percent

Chief complaints

Chest pain

87

91.5%

Breathlessness

37

38.9%

Sweating

15

15.7%

Vomiting

10

10.5%

Comorbid condition

Hypertension

48

50.5%

Diabetes mellitus

44

46.3%

IHD

2

2.1%

None

29

30.5%

Habits

Smoking

42

44.2%

Tobacco

48

50.5%

Alcohol

22

23.2%

Jugular venous pressure

Elevated

64

67.4%

Normal

31

32.6%

ECG

NSTEMI

21

22.1%

STEMI

61

64.2%

Unstable Angina

13

13.7%

Troponin-I

Negative

14

14.7%

Positive

81

85.3%

Ejection fraction

<40

30

31.6%

>50

21

22.1%

40-50

44

46.3%

Regional wall motion abnormalities

Anterior wall

54

56.8%

Inferio-lateral wall

40

42.1%

Posterior wall

1

1.1%

Coronary angiography

DVD

40

42.1%

SVD

30

31.6%

TVD

25

26.3%

 

Majority of the patients presented with chest pain (91.5%), 38.9% with breathlessness, 15.7% with sweating and 10.5% with vomiting. Among the comorbidities, 50.5% were hypertensive and 46.3% were diabetic. Among the habits, 44.5% were smokers, 50.5% with tobacco chewing and 23.2% were alcoholic. Majority of the patients presented with chest pain (91.5%), 38.9% with breathlessness, 15.7% with sweating and 10.5% with vomiting. Jugular venous pressure was elevated in 67.4% of the cases and normal in 32.6%. On ECG, 64.2% were with STEMI, 22.1% with NSTEMI and 13.7% with unstable angina. Among the patients, Troponin I was positive in 85.3% cases and negative in 14.7%. Coronary angiography showing the single vessel disease in 31.6%, double vessel disease in 42.1% and triple vessel disease in 26.3%.

 

Table 11: Showing the severity based on TIMI flow grade and KILLIP classification

 

Count

N %

TIMI Flow grade

1.0

22

23.2%

2.0

46

48.4%

3.0

27

28.4%

KILLIP Classification

Class 1

27

28.4%

Class 2

31

32.6%

Class 3

18

18.9%

Class 4

19

20.0%

 

TIMI glow grade showing majority in grade 2 (48.4%) followed by 28.4% in grade 3 and 23.2% in grade 1. Also according to KILLIP classification, majority were in class 2 (32.6%) followed by 28.4% in class 1, 20% in class 4 and 18.9% on class 3.

 

Table 12: Comparison of the TIMI flow grade and KILLIP classification with mean level of thyroid hormone

 

T3

T4

TSH

Mean

SD

Mean

SD

Mean

SD

Timi Flow Grade

1.0

.55

.41

9.24

3.02

2.46

1.61

2.0

.73

.08

9.24

2.51

2.49

1.62

3.0

1.01

.26

9.29

2.64

3.17

1.50

p-value

0.01*

0.24

0.01*

KILLIP classification

Class 1

1.09

.31

9.61

2.99

2.94

1.51

Class 2

.78

.07

9.30

2.22

2.57

1.51

Class 3

.64

.07

9.69

3.38

2.43

1.90

Class 4

.42

.07

8.25

1.79

2.71

1.63

p-value

0.01*

0.01*

0.51

 

Table showing the mean level of thyroid hormones with TIMI flow grade in the study. There is significant higher T3 level with increase in grade of TIMI glow and also the TSH levels. There is significant lower mean level of the T3 and T4 levels with increase in class if KILLIP classification. The mean level of T3 and T4 is significantly lower in class 4 compared to the class 1, 2 and class3 patients. There is no significant difference in the mean level of TSH,

DISCUSSION

The relationship between thyroid function and the severity of acute coronary syndrome (ACS) in the elderly is becoming increasingly interesting and clinically relevant. Thyroid hormones have an important role in cardiovascular physiology by affecting cardiac contractility, heart rate, and vascular function. Thyroid function changes in senior people can have a major influence on cardiovascular health, potentially worsening the severity of ACS presentations. Understanding how thyroid profiles, such as T3, T4, and TSH levels, correspond with ACS severity might give important insights into the pathogenesis of cardiovascular disease in the elderly, as well as possible targets for therapeutic therapies. This talk will look at current research results and their implications for clinical practice in terms of the relationship between thyroid function and ACS outcomes in older patients.

 

Based on the findings of the present study correlating thyroid profile with the severity of acute coronary syndrome (ACS) in elderly patients. The study encompassed 95 elderly patients with a mean age of 66.2 years, predominantly male (64.2%), presenting primarily with chest pain (91.5%) and various associated symptoms including breathlessness, sweating, and vomiting. Comorbidities such as hypertension (50.5%) and diabetes (46.3%) were prevalent, while smoking (44.5%), tobacco chewing (50.5%), and alcohol consumption (23.2%) were notable habits among the participants. In study by Shreewastay RK et al., ACS was predominantly seen in males, with subclinical hypothyroidism being the most common thyroid dysfunction. Hypertension, dyslipidemia, diabetes mellitus, and smoking were commonly associated with ACS patients. Out of 186 ACS patients, 127 (68.28%) belonged to  male, with a mean age group  of 60 ± 13.70 yrs. Factors such as hypertension(HTN), diabetes , smoking, family history of CAD , and dyslipidemia were noted in 80 (43.01%), 42 (22.58%), 83 (44.62%), 11 (5.91%), and 79 (42.47%) patients, respectively. 9 In a research by Rahman S et al., patients had an average age of 59.23 ± 11.30 years and 64.0% (127) were male. 58% of them experienced an ST-segment elevation myocardial infarction (STEMI), whereas 42% had unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI).10 Gurdogan M et al. reported similar findings with patients aged 63.42 ± 12.5 years, with 73.9% being male.11

 

Clinical evaluations revealed high rates of jugular venous pressure elevation (67.4%) and a spectrum of ACS presentations on ECG, with STEMI being the most common (64.2%). Troponin I was elevated in 85.3% of cases, indicating myocardial injury. Coronary angiography demonstrated significant coronary artery disease, with varying degrees of vessel involvement. In similar terms with the current study Kumar R et al. have documented with In comparison, the STEMI group patients  had a significantly higher  prevalence of abnormal  thyroid hormone than the NSTEMI and unstable angina  groups (p=0.02).Total  9 ACS patients had died, each with low fT3 and TSH levels and increased rT3 levels (p<0.05).Abnormalities  in thyroid status have been associated to an elevated risk of coronary artery disease development and cardiovascular cause of death. These variations might affect ventricular function, serum cholesterol levels, heart rate, and rhythm. Thus, recognizing this link may lead to improved treatment options for ACS patients, potentially lowering significant cardiovascular consequences.12

 

Hlilcevic M et al. shown that altered thyroid status in acute myocardial infarction is associated with the severity of coronary artery lesions, LVEF, and the inflammatory response.13 According to Rahman S et al., patients with aberrant TFTs had greater rates of heart failure (p=0.001 & 0.003 in STEMI & UA/NSTEMI, respectively), longer hospital admissions (3+0.17 days), and more than four times the death rate compared to those with normal TFTs. Conclusion: Abnormal thyroid hormone levels are common in ACS patients, contributing to high morbidity and death.10

 

Thyroid hormone levels exhibited significant correlations with the severity of ACS as assessed by TIMI flow grade and KILLIP classification. Specifically, higher TIMI flow grades were associated with elevated T3 and TSH levels, whereas lower KILLIP classes correlated with higher T3 and T4 levels. Patients in KILLIP class 4 consistently showed significantly lower levels of T3 and T4 compared to classes 1, 2, and 3. In accordance with the current study, Arambam P et al. found that the thyroid dysfunction group had a greater risk of major adverse cardiovascular events (MACE) than the euthyroid group. Furthermore, the frequency of rehospitalization for cardiovascular reasons was substantially greater in the thyroid dysfunction group (32.2%) compared to the euthyroid group (19.7%, p=0.0374). Hypothyroidism is a significant risk factor in ACS patients, particularly in older females, and is linked to a greater incidence of MACE.14 Gurdogan M et al. shown that elevated TSH levels within the normal range at hospital admission are an independent predictor of overall mortality in euthyroid ACS patients throughout a 6-month follow-up period after hospitalization and release.11

 

Qan FA et al. reported a 9.8% death rate and found that all died patients had low triiodothyronine (T3) syndrome, which was substantially linked with lower free triiodothyronine (FT3) levels (P > 0.001). Based on our profile data, there were no significant differences in free thyroxine (FT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) levels during coronary care unit hospitalization among patients undergoing cardiac catheterization, those with ST-segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI), unstable angina, and atrial fibrillation.15

 

This relationship can be attributed to the essential roles that thyroid hormones play in cardiovascular health. Thyroid hormones influence myocardial contractility, heart rate, and vascular tone, all of which are critical in maintaining adequate cardiac output and perfusion. In elderly patients, who often have a diminished physiological reserve, alterations in thyroid function can exacerbate the clinical severity of ACS. Hypothyroidism, characterized by low T3 and T4 levels, can contribute to decreased myocardial efficiency, impaired diastolic function, and increased vascular resistance, thereby worsening the clinical course of ACS. These insights highlight the potential utility of thyroid profiling as a valuable tool in the risk stratification of elderly patients presenting with ACS. Identifying thyroid dysfunction can aid in tailoring personalized management strategies, such as optimizing thyroid hormone levels or addressing underlying cardiovascular issues that may be exacerbated by thyroid abnormalities. Furthermore, incorporating thyroid function assessment into routine clinical evaluation for elderly ACS patients may enhance prognostic accuracy and guide more effective therapeutic interventions.

CONCLUSION

These findings underscore the intricate relationship between thyroid function and the severity of ACS in elderly patients. Elevated thyroid hormone levels appear to correlate with less severe ACS presentations, while lower levels may indicate more advanced disease and poorer clinical outcomes. These insights highlight the potential role of thyroid profiling in risk stratification and personalized management strategies for elderly patients presenting with acute coronary syndromes. Further research is warranted to elucidate the underlying mechanisms and validate these findings in broader clinical settings.

 

Funding: Nil

Conflict of interest: Nil

REFERENCE
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  2. Banerjee A. Coronary artery disease and its problems in management. Vol. 99, Journal of the Indian Medical Association. India; 2001. p. 474–5.
  3. Organization WH. The world health report: 1999: making a difference. World Health Organization; 1999.
  4. Ambali AP, Bomman JV. Clinical profile of 150 elderly patients with acute myocardial infarction. 2018;
  5. Lamprou V, Varvarousis D, Polytarchou K, Varvarousi G, Xanthos T. The role of thyroid hormones in acute coronary syndromes: Prognostic value of alterations in thyroid hormones. Clin Cardiol. 2017;40(8):528–33.
  6. Hashmi KA, Adnan F, Ahmed O, Yaqeen SR, Ali J, Irfan M, et al. Risk Assessment of Patients After ST-Segment Elevation Myocardial Infarction by Killip Classification: An Institutional Experience. Cureus. 2020;12(12):e12209.
  7. Sarkar A, Grigg WS, Lee JJ. TIMI Grade Flow. StatPearls. 2023. p. 1–9.
  8. Mello BHG de, Oliveira GBF, Ramos RF, Lopes BBC, Barros CBS, Carvalho E de O, et al. Validation of the Killip-Kimball classification and late mortality after acute myocardial infarction. Arq Bras Cardiol. 2014 Aug;103(2):107–17.
  9. Shreewastav RK, Dhungana SP, Pokhrel S, Jayshwal R, Pandey H. Thyroid Hormone Abnormalities and Associated Risk Factors among Acute Coronary Syndrome Patients at a Tertiary Care Hospital. Kathmandu Univ Med J. 2023;83(3):309–14.
  10. Rahman SO, Halder KC, Anam MA, Akand S, Aslam MM, Rashid MM. Thyroid Profile in Patients with Acute Coronary Syndrome. Sch J App Med Sci. 2022;8:1351–5.
  11. Gürdoğan M, Altay S, Korkmaz S, Kaya Ç, Zeybey U, Ebik M, et al. The effect of thyroid stimulating hormone level within the reference range on in-hospital and short-term prognosis in acute coronary syndrome patients. Medicina (B Aires). 2019;55(5):175.
  12. Kumar R, Sinha R, Gunjan G, Singh SK. A Cross-Sectional Study of Acute Coronary Syndrome and Thyroid Profile: Dissecting the Relationship to Improve Patient Care. Cureus. 2024;16(3):1–9.
  13. Halilčević M, Begić E, Džubur A, Džubur A, Aziri B, Durak-Nalbantić A, et al. Relation between thyroid hormonal status, neutrophillymphocyte ratio and left ventricular systolic function in patients with acute coronary syndrome. Med Glas. 2023;20(1).
  14. Arambam P, Kaul U, Gupta S, Alok A, Kumar S, Janardhanan R. Thyroid Dysfunction in Acute Coronary Syndrome and its Prognostic Implications. Indian Heart J. 2022;74:S45.
  15. Abdulaziz Qari F. Thyroid Hormone Profile in Patients With Acute Coronary Syndrome. Iran Red Crescent Med J. 2015;17(7):e26919. 
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