Thyroid-stimulating hormones in geriatric population and cardiac markers

INTRODUCTION

Subclinical hypothyroidism (SCH) is mainly diagnosed through biochemical evaluation, characterized by elevated thyroid-stimulating hormone (TSH) levels while thyroid hormone levels remain within the normal range.^[1] SCH has been linked with an amplified possibility of developing coronary heart disease and a higher death rate.^[2] The prevalence of cardiovascular ailment, along with rising TSH levels, tends to increase with age, making SCH a common condition in the elderly that can significantly affect cardiovascular health.^[1,3]

Due to the limited sensitivity and specificity of electrocardiography (ECG) in diagnosing acute myocardial infarction (AMI), the European Society of Cardiology and the American College of Cardiology have outlined standardized diagnostic criteria. According to these guidelines, an AMI diagnosis requires at least two of the following: Classic symptoms (such as chest pain, dyspnea, or sweating), a typical rise in cardiac biomarkers – preferably troponins (cardiac troponin [cTn] I or cardiac troponin T [cTnT]) or creatine kinase-myocardial band (CK-MB) isoenzymes – or new ischemic changes on ECG, such as ST-segment elevation or depression, new onset of left bundle branch block (LBBB), or the appearance of pathological Q waves.^[4]

This research was conducted to investigate the link between TSH and cardiac biomarkers in elderly individuals with SCH who presented with chest pain and myocardial infarction (MI).

MATERIAL AND METHODS

RESULTS

There was no statistically significant difference in age or gender across the study groups. The study found a higher, though not statistically significant, average TSH level in the case groups (Groups 1 and 3) at 91.8 ± 6.6 uIU/mL, compared to the control groups (Groups 2 and 4), which had an average of 1.6 ± 0.6 uIU/mL (correlation coefficient r = 0.29, P = 0.04). The mean age of participants was 69 ± 7 years. In Group 1, a significant positive correlation was observed between TSH and CPK-MB (r = 0.69, P = 0.001), TnT (r = 0.21, P = 0.03), and B-type natriuretic peptide (BNP) (r = 0.66, P = 0.001). In contrast, Group 2 showed no significant correlation between TSH and CPKMB (r = 0.08, P = 0.70), TnT (r = 0.17, P = 0.59), and BNP (r = 0.03, P = 0.65). In Group 3, TSH showed a significant correlation with CPK-MB (r = 0.71, P = 0.03), a strong and significant correlation with TnT (r = 0.86, P = 0.001), and a non-significant correlation with BNP (r = 0.14, P = 0.60). Group 4 demonstrated no significant correlation between TSH and any of the cardiac markers: CPK-MB (r = 0.13, P = 0.70), TnT (r = 0.002, P = 0.99), and BNP (r = 0.08, P = 0.57) [Tables 1 and 2 and Figure 1].

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Figure 1:

Correlation of CPK-MB and TnT with Thyroid Stimulating Hormone in Group 1, 2, 3 and 4. CPK-MB: Creatine phosphokinase myocardial band, TNT: Troponin T

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DISCUSSION

There was no statistically significant difference in the distribution of age or gender between the case and control groups. The study revealed a slight but non-significant elevation in TSH levels among patients with SCH (7.8 ± 1.8 uIU/mL) when compared to euthyroid individuals (1.9 ± 0.9 uIU/mL), with a correlation coefficient of r = 0.05 and a P = 0.66. These results align with the findings of Baumgartner et al.^[6] Notably, a significant correlation was observed in Group 1 between TSH and the cardiac markers CPK-MB (r = 0.69, P = 0.001), TnT (r = 0.21, P = 0.03), and BNP (r = 0.66, P = 0.001). In contrast, Group 2 exhibited no significant correlation for CPK-MB (r = 0.08, P = 0.70), TnT (r = 0.17, P = 0.59), or BNP (r = 0.03, P = 0.65). These results imply that even modest increases of TSH levels may significantly elevate cardiac markers in patients with SCH compared to euthyroid individuals.

While a considerable body of literature supports the connection between cardiac function and SCH,^[1,5,7,8] our study offers an alternative insight: Despite the lack of significant differences in TSH levels between Groups 1 and 2 and Groups 3 and 4, cardiac markers were notably higher. This suggests a possible need to reevaluate age-adjusted reference ranges for cardiac biomarkers in elderly patients presenting with chest pain or suspected MI and to prevent overdiagnosis based solely on elevated markers.

Creatine kinase (CK) is an enzyme made up of two subunits – M and B – and exists in three isoenzyme forms: CK-BB (CK1), CK-MB (CK2), and CK-MM (CK3). CK-MB is found in various tissues such as the heart, skeletal muscles, small intestine, diaphragm, and uterus. Consequently, its levels can be elevated in non-cardiac conditions involving trauma or inflammation, limiting its specificity for cardiac damage. Furthermore, due to its relatively high molecular weight, CKMB is not as effective in detecting subtle myocardial injury.^[4]

Hypothyroidism is one of the conditions that can cause falsely elevated CK-MB levels, potentially leading to incorrect diagnoses of AMI. Since hypothyroidism can independently raise CK-MB levels, it is important to consider thyroid function when interpreting CK-MB as a biomarker for AMI.^[9]

The heart releases several proteins into circulation, such as myoglobin, BNP, troponin I, which blocks the interaction between actin and myosin, and TnT, which binds to tropomyosin. cTns have multiple isoforms that are highly specific to cardiac tissue.^[4]

While the cytosolic levels of troponin C and CK-MB are relatively similar, a substantial amount of cTn is embedded within the heart muscle’s contractile structure. Consequently, the overall cTn content per gram of myocardium is 13–15 times greater than that of CK-MB. This higher concentration explains the superior sensitivity of cTn in detecting early myocardial injury and why cTn levels can remain elevated in blood even when CK-MB levels appear normal. The extended elevation of cTn is attributed to its gradual release from the contractile apparatus over time.^[10,11]

Increased cardiac troponin levels, signaling genuine myocardial injury, may also occur in various cardiac and non-cardiac conditions unrelated to AMI. A notable cause of falsely elevated troponin results, despite no actual heart damage, is the presence of heterophile antibodies. These antibodies are known to interfere in troponin assays and can also disrupt the accuracy of thyroid function tests, hormonal assessments, and tumor marker measurements.^[12,13]

CONCLUSION

This study underscores the importance of recognizing the influence of elevated TSH in elderly patients with SCH on cardiac biomarkers.