European Journal of Cardiovascular Medicine

Subclinical hypothyroidism (SCH), defined biochemically as elevated serum thyroid-stimulating hormone (TSH) with normal free thyroxine (FT4) levels, has garnered increasing clinical interest due to its subtle yet significant impact on systemic physiology, particularly the cardiovascular system (1). While often asymptomatic, SCH is associated with alterations in lipid metabolism, endothelial dysfunction, and systemic vascular resistance, all of which may contribute to atherosclerosis and cardiac dysfunction (2,3).

Ischemic heart disease (IHD), a leading cause of morbidity and mortality worldwide, is primarily driven by coronary artery atherosclerosis and compromised myocardial perfusion (4). Emerging evidence suggests a possible association between thyroid dysfunction and the pathogenesis and progression of IHD. SCH has been implicated in elevating cardiovascular risk by increasing serum low-density lipoprotein (LDL) cholesterol, promoting diastolic hypertension, and impairing cardiac contractility (5,6). These effects are particularly concerning in patients already burdened with established coronary artery disease, as they may further compromise myocardial function.

Despite growing awareness, the true prevalence of SCH among IHD patients remains under-explored, especially in South Asian populations where both thyroid disorders and cardiovascular diseases are highly prevalent. Moreover, the clinical significance of detecting SCH in patients with IHD—whether it alters therapeutic decisions or prognostic outcomes—remains a matter of ongoing debate (7,8). Given these considerations, this study aims to assess the prevalence of SCH in individuals diagnosed with ischemic heart disease and to evaluate its potential impact on cardiovascular risk parameters and functional outcomes.

A total of 150 adult patients aged between 40 and 75 years, diagnosed with ischemic heart disease (IHD) based on clinical history, electrocardiography (ECG), and echocardiographic findings, were recruited. Exclusion criteria included patients with known thyroid disorders, those on thyroid medications, individuals with recent acute myocardial infarction (<6 weeks), and patients with severe systemic illnesses such as chronic kidney disease, liver dysfunction, or malignancy.

Data Collection and Investigations
A detailed clinical history including age, gender, smoking status, history of hypertension, diabetes mellitus, and hyperlipidemia was recorded. A thorough physical examination was conducted, and relevant cardiovascular parameters were assessed.

Fasting blood samples were collected from all participants for biochemical analysis. Thyroid function tests, including serum TSH and free thyroxine (FT4), were measured using chemiluminescence immunoassay (CLIA). Based on TSH values, patients were classified into two groups:

• Euthyroid: TSH within the reference range (0.4–4.0 µIU/mL)
• Subclinical Hypothyroid: TSH >4.0 µIU/mL with normal FT4 levels

Lipid profile, fasting blood glucose, and HbA1c were also evaluated. Cardiac function was assessed using 2D echocardiography to determine left ventricular ejection fraction (LVEF).

Statistical Analysis
Data were analyzed using SPSS version 26.0. Continuous variables were expressed as mean ± standard deviation (SD), and categorical variables were expressed as frequencies and percentages. The chi-square test was used for comparing proportions, while independent t-tests were applied for comparing means between groups. Logistic regression analysis was performed to determine the association between SCH and cardiovascular risk factors. A p-value of less than 0.05 was considered statistically significant.

A total of 150 patients with ischemic heart disease (IHD) were included in the study, out of which 38 patients (25.3%) were diagnosed with subclinical hypothyroidism (SCH), while the remaining 112 (74.7%) were euthyroid.

Demographic and Clinical Characteristics
The mean age of the study population was 59.4 ± 10.2 years, with males comprising 61.3% of the participants. There was no statistically significant difference in mean age between the SCH and euthyroid groups (60.2 ± 9.8 years vs. 58.9 ± 10.4 years, p=0.42). Hypertension and diabetes mellitus were more prevalent in the SCH group (68.4% and 57.9%, respectively) compared to the euthyroid group (51.2% and 39.3%, respectively), with the difference being statistically significant for hypertension (p=0.03) (Table 1).

Table 1. Demographic and clinical characteristics of study participants

Thyroid and Lipid Profile Findings
The mean serum TSH level in the SCH group was significantly higher (6.9 ± 0.5 µIU/mL) compared to the euthyroid group (2.8 ± 0.7 µIU/mL, p<0.001), while FT4 levels remained within the normal range in both groups. Patients with SCH had a higher mean LDL cholesterol (137 ± 20 mg/dL) than euthyroid individuals (120 ± 15 mg/dL, p=0.02), along with elevated total cholesterol and triglycerides (Table 2).

Table 2. Thyroid function and lipid profile comparison between groups

Cardiac Function Analysis
Echocardiographic evaluation revealed that patients in the SCH group had a significantly lower mean left ventricular ejection fraction (LVEF) of 48.3% ± 6.2 compared to 55.1% ± 5.8 in the euthyroid group (p=0.004), suggesting a notable decline in cardiac function associated with SCH (Table 3).

Table 3. Comparison of cardiac function between SCH and euthyroid patients

These findings suggest a potential relationship between subclinical hypothyroidism and adverse cardiovascular parameters in patients with ischemic heart disease (Tables 1–3).

This study highlights a notable prevalence of subclinical hypothyroidism (SCH) among patients with ischemic heart disease (IHD), aligning with the hypothesis that thyroid dysfunction may influence cardiovascular outcomes. In our sample, 25.3% of patients with IHD were found to have SCH, consistent with earlier reports ranging from 15% to 30% in similar cardiac cohorts (1,2).

The elevated prevalence observed may be attributed to the pathophysiological influence of thyroid hormones on the cardiovascular system. Thyroid hormones play a crucial role in modulating myocardial contractility, vascular tone, and lipid metabolism (3,4). Even in the absence of overt hypothyroidism, SCH has been associated with impaired left ventricular function and increased vascular resistance, as seen in our study where patients with SCH had significantly lower ejection fractions (5,6). This finding is corroborated by Rodondi et al., who demonstrated an increased risk of heart failure and coronary events in individuals with elevated TSH levels but normal FT4 (7).

Increased levels of LDL cholesterol and total cholesterol in the SCH group reinforce the evidence linking thyroid dysfunction with dyslipidemia, a major risk factor for atherosclerosis and coronary artery disease (8,9). Thyroid hormones enhance hepatic LDL receptor activity, and a deficiency can lead to lipid accumulation, thereby promoting plaque formation (10). Our findings also support those of Cappola et al., who reported worsened lipid profiles in patients with SCH, even in the absence of clinical symptoms (11).

The association between SCH and hypertension observed in our study further supports the cardiovascular implications of thyroid dysfunction. Hypothyroid states are known to increase systemic vascular resistance, contributing to elevated diastolic blood pressure and impaired ventricular relaxation (12,13). These hemodynamic changes could explain the higher rates of hypertension in the SCH group.

Another critical observation in this study was the reduced cardiac output, reflected by lower LVEF values in SCH patients. This may be explained by reduced myocardial sensitivity to catecholamines and altered calcium handling in cardiac myocytes under hypothyroid states (14). Moreover, studies have reported that SCH may worsen endothelial dysfunction and increase arterial stiffness, both of which negatively impact cardiac performance (15).

Despite these associations, the clinical management of SCH in patients with IHD remains controversial. While some studies suggest that levothyroxine therapy may improve lipid profile and cardiac function, others argue against routine treatment in asymptomatic patients, especially in elderly populations where overtreatment may increase the risk of atrial fibrillation or osteoporosis (6,7). The American Thyroid Association recommends individualized treatment decisions, particularly for TSH values above 10 µIU/mL or in younger patients with underlying cardiovascular disease (8).

The strength of this study lies in its focus on a clinically relevant yet often overlooked endocrine abnormality in cardiac patients. However, limitations include its cross-sectional design, which precludes establishing causality, and the single-center setting, which may limit generalizability. Furthermore, we did not follow patients longitudinally to assess outcomes or the effect of initiating thyroid hormone replacement.

Future prospective studies are warranted to explore whether early identification and management of SCH in IHD patients could lead to improved cardiovascular outcomes. Additionally, randomized controlled trials assessing the benefits and risks of levothyroxine therapy in this subgroup could provide clearer guidance for clinicians.

Subclinical hypothyroidism is prevalent among patients with ischemic heart disease and is associated with adverse cardiovascular parameters such as hypertension, dyslipidemia, and reduced left ventricular function. Early identification and appropriate monitoring of thyroid function in IHD patients may help in risk stratification and management, potentially improving clinical outcomes.

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