European Journal of Cardiovascular Medicine

Hypothyroidism is a prevalent endocrine disorder caused by a deficiency of thyroid hormones (THs), typically due to inadequate hormone production or, less commonly, insufficient hormone action in target tissues. This condition disrupts normal metabolic and physiological functions.1 Thyroid hormones are crucial for regulating the body's metabolism and significantly impact the cardiovascular system. Hypothyroidism, characterized by low thyroid hormone levels, leads to several cardiometabolic changes. These include impaired diastolic function, reduced cardiac contractility, endothelial dysfunction, decreased nitric oxide production, reduced arterial compliance, and diminished vascular smooth muscle relaxation. These alterations contribute to a low metabolic state, increasing the risk of heart failure, diastolic hypertension, atherosclerosis, and potentially coronary artery disease (CAD).

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, accounting for 17.9 million deaths (32% of all global deaths) in 2019. The majority of these deaths (85%) were caused by heart attacks and strokes. Over 75% of CVD deaths occur in low- and middle-income countries, highlighting a significant health disparity. Additionally, CVDs were responsible for 38% of the 17 million premature deaths (under age 70) from noncommunicable diseases in 2019, underscoring their substantial impact on global mortality.3

Thyroid hormone significantly impacts the cardiovascular system and is linked to adverse cardiovascular outcomes. Both overt and subclinical hypothyroidism, often accompanied by hypercholesterolemia and hypertension, are associated with cardiovascular disease. Variations in free T3 levels have been connected to coronary artery disease (CAD), and studies suggest a link between thyroid function abnormalities (both overt and subtle) and atherosclerosis. Additionally, even variations in thyroid function within the normal range may potentially contribute to adverse outcomes related to CAD, though this remains speculative.4-6 Studies have identified hypothyroidism as a risk factor for CAD, with a clear association between elevated TSH levels and increased CAD risk.7,8 However, some studies have found no link between TSH levels and cardiovascular diseases or mortality.9 A meta-analysis suggests that higher TSH levels are associated with a modest increase in CAD risk, though the relationship remains inconsistent across different research findings.

Coronary angiography (CAG) is the gold standard for diagnosing CAD but is invasive and carries risks such as blood vessel injury, bleeding, and heart attacks.9As an alternative, the non-invasive treadmill exercise test (TET) was developed, which avoids catheter insertion and contrast agents. However, TET results can be influenced by factors like physical fitness, age, and gender, and the lack of a quantitative absolute standard for CAD diagnosis, along with individual patient differences, makes interpreting TET results challenging for clinicians.10.

All patients who are newly diagnosed with hypothyroidism and admitted or visited OPD in the Department of General Medicine.One Year from Date of Approval from the Ethical Committee.

Study Design: Observational Study.

Inclusion Criteria:

1. Newly diagnosed hypothyroidism patient. Patients age >18yrs.
2. Patients consenting for study.

Exclusion Criteria:

1. Hypothyroidism patients already on treatment.
2. Significant history of drug intake like Beta blocker, OCPs (oral contraceptive pills), Amiodarone. Glucocorticoid and Antineoplastic drugs.
3. Pregnancy, lactating mother.
4. Known patient of Coronary artery disease, Cerebrovascular accident, Peripheral arterial disease, hypertension.
5. Patient Recruitment & Consent

-               Consecutive sampling of eligible patients from Endocrinology OPD/IPD.

-               Informed written consent obtained.

2. Treadmill Test (TMT) Execution

-               Standard Bruce protocol or modified protocol as per patient tolerance.

-               Continuous ECG monitoring, BP recording at each stage.

-               Test endpoints: Symptom-limited (chest pain, fatigue), significant ST changes, arrhythmias, or target heart rate achievement.

Statistical Analysis

Kolmogorov Smirnov test was used to test the normality of the data. Categorical variables are expressed in terms of frequency (n) and percentage (%) Continuous variables are expressed in terms of mean, standard deviation (SD), median and interquartile range (IQR). Pearson correlation test was used. P<0.05 was considered as statistically significant. Analysis will be performed using IBM SPSS version 27.0 statistical software.

Table 1: Age group distribution

The age group distribution reveals that the majority of participants (63.3%) fall within the 21–40 age range, with the highest proportion (33.3%) in the 21–30 group, followed closely by 30.0% in the 31–40 group. The frequency declines with increasing age, as only 24.4% are aged 41–50, and older age groups (51–70) constitute a smaller share (12.2% combined). This skew toward younger participants suggests that the sample is relatively young, with a gradual decrease in representation among middle-aged and older individuals.

Table2: Thyroid profile

The descriptive statistics for thyroid function tests (T3, T4, and TSH) reveal distinct patterns in the sample of 90 individuals. T3 levels range from 0.10 to 1.00, with a mean of 0.4354 and a median of 0.395, indicating a slightly right-skewed distribution (mean > median). The IQR (0.31–0.502) suggests moderate variability around the median. For T4, the range is much wider (1.20–40.10), with a mean (4.8939) significantly higher than the median (3.150), indicating strong right skewness likely due to outliers or extreme high values. The IQR (2.675–3.825) shows that the middle 50% of values cluster in a relatively narrow range, but the maximum (40.10) suggests possible anomalies or severe hyperthyroid cases. TSH levels range from 9.3 to 70.0, with a mean (19.812) close to the median (17.95), implying a near-symmetric distribution. The IQR (13.925–22.925) indicates that most values are concentrated within this range, consistent with expected variability in thyroid dysfunction (e.g., hypothyroidism, given elevated TSH).

Table 3: Lipid profile

Triglycerides range from 56.9 to 240.7 mg/dL, with a mean of 140.76 and median of 152.10, indicating a slight left skew (mean < median). The IQR(98.6–171.4) shows that 50% of values fall near or above the borderline-high threshold(>150mg/dL),suggestingamoderatecardiovascularriskinthisgroup.

TotalCholesterollevelsspanfrom78.3to265.4mg/dL,withamean of 195.90 and median of 214.55. The median exceeds the desirable range (<200 mg/dL), and the left-skewed distribution (mean < median) implies some individuals have very low values pulling the mean down. The IQR (164.48–228.65) indicates that half the sample is in the border line-high to high risk category.

Table4: 2DEcho

The 2D echocardiography results revealed that all 90 participants (100%) had normal findings, with no abnormal cases detected in the study population.

The rising incidence of coronary artery disease underscores the critical need for early prediction and timely intervention to reduce associated morbidity and mortality. Rather than solely focusing on treatment after onset, proactive risk assessment and preventive strategies are essential to identify high-risk individuals in the initial stages, enabling early therapeutic measures to mitigate disease progression and improve outcomes.11

In our study the sample of 90 individuals has an age range of 21–65 years, with a mean age of 37.20 (SD = 11.16), indicating moderate-to-high variability. Most participants (63.3%) are between 21–40 years old, with the largest subgroup being 21–30 (33.3%), followed by 31–40 (30.0%). Representation declines with age, with only 24.4% in the 41–50 group and 12.2% in the 51–70 range, reflecting a younger-skewed sample.12 Additionally, there is a notable gender imbalance, with males comprising 63.3% (n=57) and females 36.7% (n=33).

The thyroid function tests in the sample of 90 individuals show distinct patterns: T3 levels (mean 0.4354, median 0.395) exhibit slight right skewness, while T4 levels (mean 4.8939, median 3.150) display strong right skewness due to potential outliers, with one extreme value reaching 40.10. TSH levels (mean 19.812, median 17.95) are near-symmetrically distributed, with most values falling within 13.925–22.925, consistent with hypothyroid tendencies. Lipid profiles indicate cardiovascular risk trends—triglycerides (mean 140.76, median152.10) show slight left skewness, with half the sample in borderline-high ranges (>150 mg/dL). Total cholesterol (median 214.55) exceeds desirable levels (<200 mg/dL), with left skewness suggesting some very low values. LDL cholesterol (median 125.10) places many in near-optimal/above-optimal ranges, though some approach high-risk levels (>130 mg/dL).13

In a study by Patil C et al,14 study revealed that 31% of participants tested positive on the TMT (indicating possible myocardial ischemia), while 69% were negative. Age distribution among positive TMT cases showed 29.03% in the 40-50 group, 45.16% in the 51-60 group, and 25.81% in those over 60, though no significant correlation was found between age and TMT results (p=0.30). Similarly, diabetes duration did not significantly influence TMT outcomes (p=0.75), with positive cases distributed as 25.80% (<5 years), 54.84% (5-10 years), and 19.35% (>10 years). Hypertension prevalence was higher in males (69.23%) than females (30.77%), but no significant gender-based correlation was observed (p=0.40). However, a strong association was found between hypertension and TMT results (p<0.0001)—93.55% of positive TMT cases had hypertension, compared to only 18.84% in the negative group.15

Conversely, 81.16% of negative TMT cases were non-hypertensive, suggesting that hypertension is a key predictor of abnormal TMT findings, independent of age, diabetes duration, or gender.

Our study uniquely identifies thyroid dysfunction (low T3/T4, elevated TSH) as a driver of atherogenic lipid profiles (↑TG, ↑cholesterol), even without overt CAD. This expands beyond traditional risk factors (hypertension, diabetes) emphasized in other studies. For example:

• Patil linked hypertension (93.55% of TMT+ cases) to ischemia.
• Chaurasia highlighted diabetes (38.7% TMT+).
• Kim MK associated male gender with silent CAD in diabetics.

Our findings suggest thyroid status may modulate lipid risks independently, necessitating its inclusion in CAD screening protocols, especially in younger cohorts.16.

Our study challenges traditional CAD risk frameworks by highlighting thyroid dysfunction as a critical, underrecognized factor in lipid metabolism and subclinical CVD. While contrasting with older cohorts in TMT outcomes, it aligns with broader metabolic risk trends (obesity, dyslipidemia) and underscores the need for age- and comorbidity-adjusted risk models.

This study highlights thyroid dysfunction as a key modulator of lipid metabolism in a young, predominantly male cohort. While no overt cardiac abnormalities were detected, the observed lipid imbalances - linked to hypothyroidism - emphasize the need for early intervention to prevent future cardiovascular disease. Further research should explore the LDL paradox and longitudinal CAD progression in similar populations.

1. Almandoz JP, Gharib H.Hypothyroidism: etiology, diagnosis, and management. Med Clin North Am. 2012;96(2):203–21.
2. Klein I,             Danzi                  Thyroid disease    and         the          heart. Circulation.2007;116(15):1725–35.
3. World Health Organization. Cardiovascular diseases (CVDs. 2021 [cited 2025 Apr         14]. Available from: https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)
4. Braverman LE, Cooper D. Werner &Ingbar’s the thyroid: a fundamental and clinical text. 7th ed. Philadelphia: Wolters Kluwer Health; 2012.
5. Cappola AR, Ladenson PW. Hypothyroidism and atherosclerosis.J ClinEndocrinolMetab. 2003;88(6):2438–44.
6. Taylor PN, Razvi S, Pearce SH, Dayan CM. Clinical review: a review of the clinical consequences of variation in thyroid function within the reference range. J ClinEndocrinolMetab. 2013;98(9):3562–7.
7. Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010;304(12):1365–74.
8. Asvold BO, Bjøro T, Nilsen TI, Vatten LJ. Association between blood pressure and serum thyroid-stimulating hormone concentration within the reference range: a population-based study. J ClinEndocrinolMetab. 2007;92(3):841–5.
9. Ittermann T, Haring R, Sauer S, Wallaschofski H, Dörr M, Nauck M, et al. Decreased serum TSH levels are not associated with mortality in the adult northeast German population. Eur J Endocrinol. 2010;162(4):579–85.
10. Ochs N, Auer R, Bauer DC, Nanchen D, Gussekloo J, Cornuz J, et al. Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med. 2008;148(11):832–45.
11. Nigam P, Baghel PK. Treadmill test in hypothyroidism. Int J Med Res Rev. 2016;4(3):338-346. doi: 10.17511/ijmrr.2016.i03.09.
12. Nagrani S, Patil P, Barsode SS, Momale N, Mehta P. Study of exercise treadmill test in type 2 diabetes mellitus patients. Int J Adv Med. 2021 Apr;8(4):557.
13. Kim MK, Baek KH, Song KH, Kwon HS, Lee JM, Kang MI, Yoon KH, Cha BY, Son HY, Lee KW. Exercise treadmill test in detecting asymptomatic coronary artery disease in type 2 diabetes mellitus. Diabetes Metab J. 2011 Feb 28;35(1):34.
14. Patil C. A Study of Screening of Asymptomatic Coronary Artery Disease In Type 2 Diabetes Mellitus Patients By Treadmill Test And Its Correlation With High Sensitivity C-Reactive Protein. Shinde S, editor. JETIR. 2024 Jul 1;11(7).
15. Chaurasia AS, Uddhav Mali A, Kadu S, Kashyap P, Dake R. Clinical study of risk stratification of coronary artery disease in high-risk patients by Treadmill stress test. J Cardiovasc Dis Res. 2023 Oct 28;14(9).
16. Lopez DM, Divakaran S, Gupta A, Bajaj NS, Osborne MT, Zhou W, et al. Role of exercise treadmill            testing    in        the assessment     of coronary microvascular disease. Cardiovasc Imaging. 2022 Feb 1;15(2):312-21.