European Journal of Cardiovascular Medicine

Hypothyroidism, characterized by an underactive thyroid gland, is a common endocrine disorder with significant systemic implications. One of the notable manifestations of hypothyroidism is its impact on cardiovascular function, which has become a growing area of interest in recent research. Studies have highlighted the complex interplay between hypothyroidism, cardiac function, and pulmonary health ¹. Hypothyroidism is known to influence various aspects of cardiovascular health, including heart rate, blood pressure, and cardiac contractility. The condition is often associated with an increased risk of cardiovascular diseases, including heart failure and coronary artery disease ¹. One of the specific cardiac complications seen in hypothyroid patients is left ventricular diastolic dysfunction (LVDD), which refers to impaired relaxation and filling of the left ventricle during diastole ². This condition is a precursor to heart failure with preserved ejection fraction (HFpEF), which is increasingly recognized in patients with thyroid dysfunction ³.Diastolic dysfunction in hypothyroidism can be attributed to several pathophysiological mechanisms. These include alterations in myocardial stiffness, impaired myocardial relaxation, and increased left ventricular mass ⁴. The accumulation of extracellular matrix proteins and increased collagen deposition contribute to myocardial stiffness, which in turn impairs diastolic filling and relaxation ⁵. Additionally, hypothyroidism-induced changes in endothelial function and reduced cardiac output can exacerbate diastolic dysfunction, leading to symptomatic heart failure ⁶. Spirometry is a common pulmonary function test used to assess lung function by measuring parameters such as forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF) ⁷. While primarily used to diagnose and manage respiratory conditions, spirometric parameters can also provide insights into cardiovascular health. Restrictive spirometric patterns are characterized by reduced FVC and FEV1, have been associated with various forms of cardiac dysfunction ⁸.In the context of hypothyroidism, spirometric abnormalities can reflect underlying cardiac issues. Studies have shown that restrictive lung patterns are often seen in patients with LVDD, suggesting a potential link between reduced lung volumes and impaired cardiac function ⁹. The restrictive pattern may result from increased pressure in the pulmonary circulation or reduced lung compliance secondary to cardiovascular changes ¹⁰. This association highlights the need for a comprehensive evaluation of both pulmonary and cardiac function in patients with hypothyroidism.Research into the relationship between hypothyroidism, spirometric parameters, and LVDD is still evolving. Some studies have indicated that hypothyroid patients with LVDD exhibit significant reductions in spirometric parameters, such as FVC and FEV1, compared to those without diastolic dysfunction ¹¹. These findings suggest that diastolic dysfunction might influence pulmonary function, potentially due to the impact of impaired cardiac filling on respiratory mechanics ¹².Additionally, the restrictive lung pattern observed in hypothyroid patients with LVDD could be attributed to several factors. Increased left ventricular mass and altered myocardial compliance can lead to elevated pressures in the pulmonary circulation, thereby affecting lung function ¹³. The presence of restrictive lung disease may further exacerbate the cardiovascular burden by limiting overall pulmonary capacity and impacting gas exchange ¹⁴.Furthermore, the interplay between thyroid hormones and lung function is complex. Thyroid hormones play a critical role in regulating metabolism, cardiovascular function, and respiratory mechanics ¹⁵. An imbalance in thyroid hormone levels can lead to alterations in respiratory muscle strength, lung compliance, and overall pulmonary function. These changes may be compounded in patients with concurrent cardiac dysfunction, such as LVDD, resulting in more pronounced spirometric abnormalities ¹⁶.The association between spirometric parameters and LVDD in hypothyroid patients has important clinical implications. Early detection of restrictive lung patterns in patients with hypothyroidism may provide valuable insights into their cardiac health and the potential presence of LVDD ¹⁷. Comprehensive management strategies should include regular assessment of both pulmonary and cardiac function to address the multifaceted nature of hypothyroidism-related complications.Spirometry can serve as a useful tool in monitoring hypothyroid patients for signs of diastolic dysfunction. Identifying restrictive lung patterns may prompt further evaluation of cardiac function, potentially leading to early intervention and improved outcomes. Management of hypothyroidism should be tailored to address both thyroid hormone levels and associated cardiovascular and respiratory issues. This may include optimizing thyroid hormone replacement therapy, monitoring for signs of LVDD, and implementing strategies to improve pulmonary function ¹⁸. Thus, the relationship between spirometric parameters and LVDD in hypothyroid patients underscores the importance of a holistic approach to patient management. Understanding how hypothyroidism affects both cardiac and pulmonary function can enhance clinical practice and improve patient outcomes. Further research is needed to explore the mechanisms underlying these associations and to develop targeted interventions for managing both hypothyroidism and its associated complications.In the Kashmiri population, unique genetic and environmental factors, such as high-altitude living, cold climate, and specific dietary habits, may influence the prevalence and manifestation of cardiovascular and pulmonary diseases. However, there is a paucity of data on the relationship between spirometry parameters and left ventricular diastolic dysfunction in patients with hypothyroidism. This study aimed to fill the gap by investigating the association between lung function, as measured by spirometry, and LVDD in a hypothyroid patients on treatment.

Study Design

This study was designed as a Hospital based cross-sectional study.

Study Subjects and Settings

The study was conducted at Post Graduate Department of Physiology in collaboration with Post graduate Department of Medicine, GMC Srinagar and Associated SMHS/SSH Hospitals during year 2023 to 2024. This hospital based study was conducted to evaluate the association between spirometric parameters and left ventricular diastolic dysfunction (LVDD) in patients with hypothyroidism. The study was approved by the institutional ethics committee, and informed consent was obtained from all subjects. A total of 100 hypothyroid patients on treatment were recruited from the Medicine/Endocrinology OPD/IPD of Govt SMHS Hospital Srinagar. The sample was divided into two groups:

• Group 1: 50 hypothyroid patients with LVDD .
• Group 2: 50 hypothyroid patients without diastolic dysfunction.

Inclusion criteria were:

• Age between 25 and 70 years.
• Diagnosed hypothyroid patients confirmed by thyroid function tests.
• Stable on thyroid hormone replacement therapy for at least six months.

Exclusion criteria included:

• Presence of other significant cardiac conditions (systolic heart failure, valvular heart disease).
• Chronic respiratory diseases (asthma, chronic obstructive pulmonary disease).
• Recent acute illness or exacerbation of existing conditions.

Sample Size Calculation:

The sample size was calculated by including factors like, type of test, the expected effect size, the desired power, and the significance level. Since we studied the association between spirometric parameters and left ventricular diastolic dysfunction (LVDD) in hypothyroid patients, we used the following formula for estimating sample size for comparing two independent means:

Where:

• n = Sample size required per group
• Zα/2​ = Z-score for the desired significance level (95% confidence level)
• Zβ​ = Z-score for the desired power (80% power)
• σ ²₁^​ and σ²₂= Variances of the two groups
• M1​−M2​ = Expected difference in means between the two groups

Spirometry Analysis

Spirometry was performed using a computerized spirometer HELIOS 401 of recorders and Medicare systems private limited (RMS). The procedure followed the guidelines of the American Thoracic Society/European Respiratory Society (ATS/ERS). The following parameters were recorded:

• Forced Vital Capacity (FVC)
• Forced Expiratory Volume in 1 second (FEV1)
• FEV1/FVC ratio
• Peak Expiratory Flow (PEF)

Echo Cardiography Measurements

In subjects echocardiogram was done by experienced cardiologists on Aloka IPF –1503 ultrasound imaging system. Cardiac 2D-Mode, M-mode and Doppler. Key measurements recorded:

• Left ventricular ejection fraction (LVEF)
• Left ventricular mass index (LVMI)
• E/A ratio (ratio of early to late diastolic filling velocities)
• Deceleration time (DT) and isovolumetric relaxation time (IVRT)

Patients were categorized into LVDD and non-LVDD groups based on echocardiographic findings and clinical criteria for diastolic dysfunction.

Sample Collection.

5 ml blood was collected by phlebotomists by venipuncture from patients and healthy controls at common collection center facility of Government Shri-Maharaja Hari Singh Hospital (SMHS), which was immediately transferred into 3ml heparin vial. Heparinized 5ml blood was centrifuged at 4000 RPM for 2 minute and plasma/serum was analyzed for Biochemical parameters (Thyroid Profile and Lipid profile). Biochemical parameters were analyzed at diagnostic laboratories of Biochemistry SMHS Hospital Srinagar on Abbott Alinity (USA).

Data Collection

Demographic information, medical history, and spirometry results were collected from all participants. Echocardiographic data were reviewed to confirm the diagnosis of LVDD in the patient group.

Statistical Analysis

Descriptive statistics were used to summarize the sociodemographic, biochemical, and spirometric parameters. Comparisons between groups were made using independent t-tests for continuous variables and chi-square tests for categorical variables. Pearson’s correlation coefficients were calculated to assess the relationships between spirometric parameters and echocardiographic measures. Multiple regression analysis was performed to evaluate the impact of spirometric parameters on LVDD, adjusting for potential confounders. Statistical significance was considered at p < 0.05. All analyses were conducted using SPSS 18.1 (Chicago, IL).

Sociodemographic and baseline Characteristics

Table 1: Sociodemographic and Baseline Characteristics of the Study Subjects (n=100)

The Sociodemographic and baseline characteristics of the study participants are summarized in Table 1. The average age of patients with LVDD is significantly higher compared to those without dysfunction, suggesting that older age might be associated with the presence of diastolic dysfunction in hypothyroidism. There is no significant gender difference between the two groups, indicating that LVDD is not associated with gender among hypothyroid patients. Although there are slightly more patients with higher education in the group without dysfunction, the differences in educational attainment between the groups are not statistically significant. A higher percentage of patients with LVDD belong to the low socioeconomic status group compared to those without dysfunction, though the difference is not statistically significant. Patients with LVDD have significantly higher systolic and diastolic blood pressure compared to those without dysfunction, highlighting the association of elevated blood pressure with diastolic dysfunction in hypothyroidism.

Table 2: Biochemical Parameters of the Study Subjects (n=100)

Table 2 described that the, TSH levels are significantly higher in patients with LVDD compared to those without dysfunction, indicating that higher TSH may be associated with diastolic dysfunction even in treated hypothyroid patients. FT4 and FT3 levels are not significantly different between the two groups, suggesting that diastolic dysfunction in these patients may be more related to TSH levels rather than free thyroid hormone concentrations. Total Cholesterol and LDL levels are significantly elevated in patients with LVDD, suggesting that dyslipidemia is a key factor associated with diastolic dysfunction in hypothyroidism.HDL levels are slightly lower in LVDD patients, though not reaching statistical significance, indicating that higher HDL levels might be protective. Triglycerides are significantly higher in LVDD patients, further supporting the role of lipid abnormalities in the development of diastolic dysfunction.

Table 3: Echocardiographic Findings in the Study Subjects (n=100)

Table -3 summarizes that the Patients with LVDD have significantly larger left atrial diameters compared to those without dysfunction, suggesting left atrial enlargement as a common finding in diastolic dysfunction. Both left ventricular end-diastolic diameter (LVEDD) and left ventricular mass index (LVMI) are significantly higher in LVDD patients, indicating increased left ventricular size and mass, which are typical features of diastolic dysfunction. The ejection fraction is notably lower in LVDD patients, although still within the normal range, suggesting that while systolic function is preserved, it is slightly reduced compared to those without dysfunction. A markedly lower E/A ratio in LVDD patients indicates impaired diastolic filling. An E/A ratio less than 1 is characteristic of diastolic dysfunction. Both deceleration time and is ovolumetric relaxation time (IVRT) are significantly prolonged in LVDD patients, reflecting delayed ventricular relaxation, a hallmark of diastolic dysfunction. Mitral E-wave velocity is significantly reduced, and mitral A-wave velocity is higher in LVDD patients. These findings support the presence of abnormal diastolic filling patterns, as seen in patients with diastolic dysfunction.

Table 4: Comparison of Spirometric Parameters between Hypothyroid Patients with LVDD and Without Dysfunction (n=100)

Table-4 describes here that in patients with LVDD and a restrictive pattern of lung function have significantly lower FVC compared to those without dysfunction. This suggests a restrictive lung pattern, commonly associated with diastolic dysfunction, possibly due to the impact of ventricular stiffness and increased cardiac mass on lung function. FEV1 is also significantly reduced in LVDD patients compared to those without dysfunction. This further indicates a restrictive pattern where both lung volumes and airflow are compromised. Although FEV1 and FVC are reduced, the FEV1/FVC ratio remains within normal limits in both groups, which is characteristic of restrictive lung disease rather than obstructive disease. PEF is significantly lower in LVDD patients, reflecting diminished overall lung capacity and strength, which might be influenced by increased cardiac load and impaired relaxation of the heart. The reduction in mid-range expiratory flow (FEF25-75%) in LVDD patients suggests a decline in small airway function, which may be associated with reduced lung volumes seen in restrictive lung patterns. MVV is significantly lower in LVDD patients, indicating decreased overall respiratory muscle endurance and lung capacity, further supporting the restrictive nature of the pulmonary impairment in patients with diastolic dysfunction.

Table 5: Association of Spirometric Parameters with Anthropometric Parameters in Hypothyroid Patients with LVDD and Without Dysfunction.

In Table-5, BMI and waist circumference are significantly higher in LVDD patients, indicating an association between increased body weight and central obesity with reduced lung function and LVDD. The waist-to-hip ratio shows a non-significant trend towards a higher value in the LVDD group.

Table 6: Association of Spirometric Parameters with Biochemical Parameters in Hypothyroid Patients with LVDD and Without Dysfunction

Table-6 describes that, Cholesterol levels (total, LDL) and triglycerides are significantly higher in LVDD patients, indicating a lipid metabolism disturbance associated with both hypothyroidism and diastolic dysfunction. HDL cholesterol is lower in LVDD patients, though not reaching statistical significance.

Table 7: Correlation of Spirometric Parameters with Echocardiographic Parameters (n=100)

Table-7 summarizes that the FVC and FEV1: Both forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) are significantly lower in patients with LVDD and a restrictive spirometric pattern compared to those with no dysfunction and normal spirometry. This suggests that restrictive lung disease is more prevalent in patients with LVDD, reflecting a possible relationship between compromised lung function and diastolic dysfunction. There is no significant difference in the FEV1/FVC ratio between the two groups, as both values remain in the normal range, consistent with restrictive lung impairment rather than obstructive disease. The PEF is significantly reduced in the LVDD group, indicating reduced pulmonary function associated with diastolic dysfunction. The ejection fraction is slightly reduced in LVDD patients, supporting the evidence of mild systolic dysfunction in the context of diastolic impairment. The left ventricular mass index (LVMI) is significantly higher in LVDD patients, suggesting that increased left ventricular mass is associated with both diastolic dysfunction and restrictive lung patterns. The echocardiographic parameters like E/A Ratio, Deceleration Time, IVRT shows significant differences between the two groups, with LVDD patients showing typical signs of diastolic dysfunction (lower E/A ratio, prolonged deceleration time, and IVRT). These parameters also correlate with the presence of restrictive spirometric patterns, highlighting the relationship between heart and lung dysfunction in hypothyroid patients.

Table 8: Post-Hoc Analysis of Spirometric Parameters between Hypothyroid Patients with LVDD and Without Dysfunction (n=100)

Table-8 summarizes that the post-hoc analysis confirms significant differences between hypothyroid patients with LVDD and those without dysfunction. FVC, FEV1, PEF, FEF25-75%, and MVV all show significant reductions in the LVDD group, with p-values < 0.001 across parameters. These findings indicate a strong association between diastolic dysfunction and impaired pulmonary function, particularly related to restrictive lung patterns. The FEV1/FVC ratio remains within the normal range and does not show significant differences between the two groups, reinforcing that the observed reductions are consistent with restrictive, not obstructive, lung disease.

Table 9: Regression Analysis of Spirometric Parameters and LVDD in Hypothyroid Patients (n=100)

Table-9, summarizes that the regression analysis, spirometric parameters (FVC, FEV1, PEF, FEF25-75%, and MVV) show strong negative associations with LVDD in hypothyroid patients. The β-coefficients are all negative and statistically significant (p < 0.001), indicating that reductions in lung function are predictive of the presence of LVDD. For example, for every unit decrease in FVC (% Predicted), the likelihood of having LVDD increases by 0.45 units. The high β-coefficients, particularly for FEV1 (-0.48) and MVV (-0.47), suggest that these measures are particularly sensitive predictors of diastolic dysfunction in hypothyroid patients with restrictive lung patterns.

This study explored the association between spirometric parameters and left ventricular diastolic dysfunction (LVDD) in hypothyroid patients, revealing significant correlations between restrictive pulmonary patterns and impaired cardiac function. The results underscore the complex interplay between thyroid function, cardiac health, and respiratory mechanics. Our study findings found that hypothyroid patients with LVDD exhibited markedly reduced values for forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF) compared to those without diastolic dysfunction. The mean differences were significant, indicating a robust association between restrictive spirometric patterns and LVDD. This finding aligns with previous research suggesting that restrictive lung patterns are often observed in patients with cardiac dysfunction ^19,20. The restrictive nature of the lung impairment in these patients likely reflects underlying cardiac changes, such as increased left ventricular stiffness and impaired myocardial relaxation, which are characteristic of diastolic dysfunction ²¹.The significant reductions in spirometric parameters in our study suggest that LVDD may contribute to impaired pulmonary function, possibly due to elevated pressures in the pulmonary circulation or reduced lung compliance resulting from cardiovascular changes ²². These findings are consistent with other studies, who reported similar associations between decreased lung volumes and cardiac dysfunction in hypothyroid patients ²³. Increased left ventricular mass and elevated pulmonary pressures can lead to decreased lung volumes and impaired respiratory mechanics, further exacerbating pulmonary function in patients with diastolic dysfunction ²⁴.The observed restrictive spirometric pattern in patients with LVDD can be attributed to several mechanisms. Hypothyroidism itself can lead to decreased respiratory muscle strength and reduced lung compliance ²⁵. Our study's findings of lower maximal voluntary ventilation (MVV) in patients with LVDD support this, reflecting diminished respiratory muscle performance and endurance ²⁶. Additionally, diastolic dysfunction can contribute to pulmonary congestion, leading to further impairment of lung function ²⁷. The elevated left ventricular mass index (LVMI) and prolonged deceleration times observed in patients with LVDD in our study suggest that increased myocardial stiffness and elevated left atrial pressure may be responsible for the restrictive lung patterns ²⁸.The complex interaction between thyroid hormones and lung function also plays a role. Thyroid hormones regulate various physiological processes, including metabolism, cardiovascular function, and respiratory mechanics ²⁹. Imbalances in thyroid hormone levels can adversely affect lung function, particularly in the presence of cardiac dysfunction. The restrictive lung patterns observed in hypothyroid patients with LVDD may reflect compounded effects of thyroid hormone deficiency and impaired cardiac function ³⁰.Our findings are consistent with observations in other patient populations. For instance, Lam et al. (2011) found that restrictive lung disease is common in patients with heart failure and preserved ejection fraction (HFpEF), a condition related to LVDD ³¹. Restrictive lung patterns in these patients were associated with increased left atrial pressure and impaired myocardial relaxation, similar to the findings in our study. This study suggests that the mechanisms underlying restrictive lung disease in hypothyroid patients with LVDD are akin to those observed in other populations with diastolic dysfunction ³².The association between spirometric parameters and LVDD has significant clinical implications. Recognizing restrictive lung patterns in hypothyroid patients can provide early indications of worsening cardiac function. Regular assessment of pulmonary function through spirometry could help identify patients at risk for LVDD, allowing for timely intervention and management ³³. Comprehensive care for hypothyroid patients should include monitoring both thyroid hormone levels and cardiac function, with particular attention to potential pulmonary implications ³⁴.Optimizing thyroid hormone replacement therapy remains a cornerstone of treatment, but addressing concurrent cardiovascular and respiratory issues is also crucial. Regular evaluation of spirometric parameters and cardiac function can help mitigate complications and improve patient outcomes ³⁵. Future research need to focus on exploring the potential benefits of combined therapies and interventions aimed at improving both pulmonary and cardiac health in hypothyroid patients. While this study provides valuable insights, it has limitations. The sample size, although adequate for detecting significant differences, was relatively small, and larger studies are needed to validate these findings.

This study highlights the significant association between spirometric parameters and left ventricular diastolic dysfunction (LVDD) in hypothyroid patients. Our findings reveal that hypothyroid patients with LVDD exhibit markedly reduced spirometric measures, including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF), compared to those without diastolic dysfunction. These results suggest that restrictive lung patterns observed in hypothyroid patients may reflect underlying cardiac dysfunction, likely due to increased left ventricular stiffness and impaired myocardial relaxation. The implications of these findings are notable for clinical practice. Regular assessment of spirometric parameters in hypothyroid patients can aid in the early detection of LVDD, potentially leading to timely interventions and improved patient outcomes. Comprehensive management should include both thyroid hormone optimization and monitoring of cardiovascular and respiratory health. Future research should further explore the mechanisms underlying these associations and evaluate the effectiveness of integrated therapeutic approaches in improving both cardiac and pulmonary function in hypothyroid patients. Overall, this study underscores the importance of a holistic approach in managing hypothyroidism, addressing both endocrine and cardiovascular components to enhance patient care.

Conflict of Interest: Nil

Financial Support: Nil

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