Background: Thyroid dysfunction has been associated with cardiovascular disease. Subclinical hypothyroidism (SH), which is characterized by elevated thyroid stimulating hormone (TSH) levels and normal circulating free thyroid hormones is an independent risk factors for the pathogenesis of atherosclerosis and cardiovascular disease, affecting adversely the endothelial function. AIM: The aim of the study is to evaluate association between subclinical Hypothyroidism (SCH) and atherosclerosis as measured by CIMT. Methodology: A Cross Sectional Study conducted at Mahatma Gandhi Medical College & Hospital Jaipur Patients who are Diagnosed as Cases of Subclinical Hypothyroidism in Mahatma Gandhi Hospital on 130 patients who are divided into two groups-65 patients in Euthyroid group and 65 patients in Subclinical Hypothyroidism group. Result: Subclinical hypothyroidism was associated with significant dyslipidemia, elevated CRP, and increased CIMT, suggesting early atherosclerotic changes. However, conflicting findings in literature and the study's cross-sectional design limit causal inference. Conclusion: Subclinical hypothyroidism is associated with atherogenic dyslipidemia, elevated CRP, and increased CIMT, indicating a potential link to early atherosclerosis.
Thyroid disorders are among the most common endocrine problems worldwide, with an estimated 41 million people affected in India alone1. These disorders encompass a spectrum ranging from overt and subclinical hypothyroidism to overt and subclinical hyperthyroidism. Thyroid hormones play a critical role in regulating metabolism, including lipid metabolism, energy balance, and cardiovascular function. Hypothyroidism, especially in its subclinical form, is the most prevalent type, particularly among aging women. The metabolic disturbances associated with thyroid dysfunction, particularly subclinical hypothyroidism (SCH), have been increasingly linked to the development of atherosclerosis (AS), a leading cause of cardiovascular morbidity and mortality globally. Atherosclerosis is a chronic inflammatory disease of medium and large-sized arteries, characterized by lipid accumulation, thickening of the arterial wall, and plaque formation. The underlying mechanisms include oxidative stress, endothelial dysfunction, vascular remodeling, and immune cell infiltration2. Early in its course, AS may remain asymptomatic, but over time it can lead to significant complications such as myocardial infarction, stroke, and peripheral vascular disease. One of the early detectable changes associated with AS is the thickening of the arterial wall, best measured non-invasively using carotid intima-media thickness (CIMT)3. This marker is a widely accepted surrogate for early atherosclerosis and cardiovascular risk. Dyslipidemia is a primary driver of atherosclerosis. Elevated levels of total cholesterol, LDL cholesterol, and triglycerides, along with decreased HDL cholesterol4, are known to disrupt endothelial integrity and promote plaque formation. LDL particles, particularly when oxidized (ox-LDL), play a central role by attracting monocytes and transforming them into macrophages, which in turn become foam cells—hallmarks of early atherosclerotic plaques. Oxidative stress, often enhanced in hypothyroid states, promotes further inflammation and accelerates plaque instability. HDL, generally protective due to its role in reverse cholesterol transport, loses its anti-atherogenic properties when oxidized (ox-HDL), thus becoming pro-inflammatory and contributing to plaque rupture and thrombosis. Subclinical hypothyroidism, defined by elevated TSH with normal circulating thyroid hormones5, has been associated with an unfavorable lipid profile. Studies have consistently shown that individuals with SCH have higher levels of total cholesterol, LDL, and triglycerides, with lower levels of HDL. Moreover, inflammatory markers such as C-reactive protein (CRP) are elevated in SCH, indicating a low-grade inflammatory state that further contributes to vascular injury6,7. These metabolic and inflammatory alterations contribute to endothelial dysfunction, vascular stiffness, and increased CIMT—factors that collectively enhance cardiovascular risk. Several studies support the association between SCH and increased CIMT, reinforcing the hypothesis that SCH may promote early atherosclerosis. Therapeutic intervention with levothyroxine has demonstrated improvements in lipid profiles and reductions in CIMT, suggesting a potential benefit in treating SCH to prevent cardiovascular events8. However, not all studies agree, with some showing no significant relationship between TSH levels and CIMT, highlighting the complexity of the condition and the need for individualized treatment decisions9.
AIM
The aim of the study is to evaluate association between subclinical Hypothyroidism (SCH) and atherosclerosis as measured by CIMT.
Thyroid disorders are among the most common endocrine problems worldwide, with an estimated 41 million people affected in India alone1. These disorders encompass a spectrum ranging from overt and subclinical hypothyroidism to overt and subclinical hyperthyroidism. Thyroid hormones play a critical role in regulating metabolism, including lipid metabolism, energy balance, and cardiovascular function. Hypothyroidism, especially in its subclinical form, is the most prevalent type, particularly among aging women. The metabolic disturbances associated with thyroid dysfunction, particularly subclinical hypothyroidism (SCH), have been increasingly linked to the development of atherosclerosis (AS), a leading cause of cardiovascular morbidity and mortality globally. Atherosclerosis is a chronic inflammatory disease of medium and large-sized arteries, characterized by lipid accumulation, thickening of the arterial wall, and plaque formation. The underlying mechanisms include oxidative stress, endothelial dysfunction, vascular remodeling, and immune cell infiltration2. Early in its course, AS may remain asymptomatic, but over time it can lead to significant complications such as myocardial infarction, stroke, and peripheral vascular disease. One of the early detectable changes associated with AS is the thickening of the arterial wall, best measured non-invasively using carotid intima-media thickness (CIMT)3. This marker is a widely accepted surrogate for early atherosclerosis and cardiovascular risk. Dyslipidemia is a primary driver of atherosclerosis. Elevated levels of total cholesterol, LDL cholesterol, and triglycerides, along with decreased HDL cholesterol4, are known to disrupt endothelial integrity and promote plaque formation. LDL particles, particularly when oxidized (ox-LDL), play a central role by attracting monocytes and transforming them into macrophages, which in turn become foam cells—hallmarks of early atherosclerotic plaques. Oxidative stress, often enhanced in hypothyroid states, promotes further inflammation and accelerates plaque instability. HDL, generally protective due to its role in reverse cholesterol transport, loses its anti-atherogenic properties when oxidized (ox-HDL), thus becoming pro-inflammatory and contributing to plaque rupture and thrombosis. Subclinical hypothyroidism, defined by elevated TSH with normal circulating thyroid hormones5, has been associated with an unfavorable lipid profile. Studies have consistently shown that individuals with SCH have higher levels of total cholesterol, LDL, and triglycerides, with lower levels of HDL. Moreover, inflammatory markers such as C-reactive protein (CRP) are elevated in SCH, indicating a low-grade inflammatory state that further contributes to vascular injury6,7. These metabolic and inflammatory alterations contribute to endothelial dysfunction, vascular stiffness, and increased CIMT—factors that collectively enhance cardiovascular risk. Several studies support the association between SCH and increased CIMT, reinforcing the hypothesis that SCH may promote early atherosclerosis. Therapeutic intervention with levothyroxine has demonstrated improvements in lipid profiles and reductions in CIMT, suggesting a potential benefit in treating SCH to prevent cardiovascular events8. However, not all studies agree, with some showing no significant relationship between TSH levels and CIMT, highlighting the complexity of the condition and the need for individualized treatment decisions9.
AIM
The aim of the study is to evaluate association between subclinical Hypothyroidism (SCH) and atherosclerosis as measured by CIMT.
A Cross Sectional Study conducted at Mahatma Gandhi Medical College & Hospital Jaipur Patients who are Diagnosed as Cases of Subclinical Hypothyroidism in Mahatma Gandhi Hospital on 130 patients who are divided into two groups-65 patients in Euthyroid group and 65 patients in Subclinical Hypothyroidism group. This study was conducted in MG Medical College & Hospital, Jaipur from July 2023 to December 2024 for a period of 1.5 years. It is an observational case control study and 130 cases of newly diagnosed subclinical hypothyroidism from the medical and endocrine OPD were selected which were divided in two groups based on TSH range: SCH (5.5-10μIU/ml) & Euthyroid subjects(TSH -Normal) to compare the findings. All the patients of age >18 years were included in the study. Those patients were excluded from the study who were having thyroid disease, diabetes, hypertension and any cardiovascularrisk and patients on thyroxine, hypolipidemic drugs or drugs causing dyslipidemia were also excluded. Thyroid profile, lipid profile and qualitative CRP (positive and negative) were estimated in all the participants of study group by taking fasting samples. Thyroid stimulating hormone (TSH), T3 & T4 were measured by using enzyme linked immunosorbant assay (ELISA) technique and the patients with TSH range(>5.5μIU/ml), T3 & T4 within reference range were said to having SCH. CIMT was measured by recording ultra sonographic images of both the left and right common carotid artery with a 12MHz linear array transducer. Patients were examined in the supine position, with the head turned 45° from the side during the scanning procedure. The reference point for the measurement of IMT was the beginning of the dilatation of the carotid bulb, with loss of the parallel configuration of the near and far walls of the common carotid artery. The mean IMT of the four measurements was calculated in each patient. Total cholesterol (<200 mg/dl), Triglycerides (<150 mg/dl) and High-density lipoprotein cholesterol (40-60 mg/dl) were measured by using CHOD/POD method, GPO-PAP method, and CHODPOD/ Phospho tungustate method respectively. LDL cholesterol (<130 mg/dl) was estimated by Friedewald formula. Total cholesterol/ HDL-C and LDL-C/HDL-C ratio were also calculated by dividing TC and LDL-C with HDL-C respectively.
Table 1: Profile of categorical parameters with respect to Thyroid status
Parameter |
Thyroid Status |
P Value |
||||||
Euthyroid |
Subclinical Hypothyroid |
Total |
||||||
No. |
% |
No. |
% |
No. |
% |
|||
Age Category |
<=30 Years |
10 |
41.7% |
14 |
58.3% |
24 |
18.5% |
.380 |
31-40 Years |
6 |
40.0% |
9 |
60.0% |
15 |
11.5% |
||
41-50 Years |
34 |
49.3% |
35 |
50.7% |
69 |
53.1% |
||
51-60 Years |
11 |
68.8% |
5 |
31.3% |
16 |
12.3% |
||
>60 Years |
4 |
66.7% |
2 |
33.3% |
6 |
4.6% |
||
Total |
65 |
50.0% |
65 |
50.0% |
130 |
100.0% |
||
Smoking |
No |
39 |
50.0% |
39 |
50.0% |
78 |
60.0% |
1.00 |
Yes |
26 |
50.0% |
26 |
50.0% |
52 |
40.0% |
||
Total |
65 |
50.0% |
65 |
50.0% |
130 |
100.0% |
||
Sex |
Female |
36 |
50.7% |
35 |
49.3% |
71 |
54.6% |
.860 |
Male |
29 |
49.2% |
30 |
50.8% |
59 |
45.4% |
||
Total |
65 |
50.0% |
65 |
50.0% |
130 |
100.0% |
||
Residence |
Rural |
40 |
50.6% |
39 |
49.4% |
79 |
60.8% |
.857 |
Urban |
25 |
49.0% |
26 |
51.0% |
51 |
39.2% |
||
Total |
65 |
50.0% |
65 |
50.0% |
130 |
100.0% |
The study shows an equal distribution of euthyroid and subclinical hypothyroid cases (50% each) among 130 participants. No statistically significant association was found between thyroid status and age, smoking, sex, or residence (p > 0.05 for all variables).Above table shows that the SCH group and Euthyroid group was comparable on parameter of age distribution, smoking, sex and residential status
Table 2: Profile of continuous parameters with respect to Thyroid Status
Parameter |
Thyroid Status |
P Value |
||
Euthyroid |
Subclinical Hypothyroid |
Total |
||
Mean (SD) |
Mean (SD) |
Mean (SD) |
||
Age (years) |
45.55±10.35 |
42.22±9.63 |
43.88±10.10 |
.062 |
BMI |
23.24±1.77 |
24.36±1.58 |
23.80±1.77 |
.001 |
Total Cholesterol (mg/dl) |
186.48±16.50 |
243.55±19.05 |
215.02±33.70 |
<.001 |
Triglyceride (mg/dl) |
144.43±8.05 |
154.05±7.59 |
149.24±9.17 |
<.001 |
LDL (mg/dl) |
125.23±6.63 |
145.23±9.39 |
135.23±12.90 |
<.001 |
HDL (mg/dl) |
49.71±3.67 |
41.29±3.37 |
45.50±5.49 |
<.001 |
VLDL (mg/dl) |
19.40±2.24 |
25.38±3.80 |
22.39±4.32 |
<.001 |
TC/HDL |
3.78±.47 |
5.94±.73 |
4.86±1.25 |
<.001 |
LDL/HDL |
2.53±.24 |
3.54±.41 |
3.04±.61 |
<.001 |
CIMT (mm) |
0.49±0.07 |
0.83±0.05 |
0.66±0.18 |
<.001 |
T3 (ng/ml) |
1.37±.37 |
1.40±.37 |
1.38±.37 |
.637 |
T4 (mcg/ml) |
9.89±2.58 |
10.05±2.81 |
9.97±2.69 |
.694 |
TSH (μIU/ml) |
3.74±.63 |
7.35±.92 |
5.54±1.97 |
<.001 |
CRP (mg/dl) |
0.88±0.66 |
2.02±0.89 |
1.45±0.97 |
<.001 |
Subclinical hypothyroid patients showed significantly higher BMI, lipid profile (TC, LDL, TG, VLDL), TC/HDL, LDL/HDL ratios, CIMT, TSH, and CRP levels compared to euthyroid individuals (p < 0.001 for most parameters). No significant difference was observed in age, T3, or T4 levels between the groups (p > 0.05).Above table shows that mean age, T3 ,T4 was comparable in SCH group and Euthyroid group whereas mean BMI, TC,TG,LDL,VLDL, TC/HDL, LDL/HDL, CIMT, and CRP was significantly higher in SCH group as compared to Euthyroid group.
Table 3: Correlation of various parameters with TSH
Parameter |
Correlation coefficient |
P Value |
BMI |
.360 |
<.001 |
Total Cholesterol (mg/dl) |
.750 |
<.001 |
Triglyceride (mg/dl) |
.420 |
<.001 |
LDL (mg/dl) |
.696 |
<.001 |
HDL (mg/dl) |
-.711 |
<.001 |
VLDL (mg/dl) |
.617 |
<.001 |
TC/HDL |
.784 |
<.001 |
LDL/HDL |
.761 |
<.001 |
CIMT (mm) |
.857 |
<.001 |
T3 (ng/ml) |
-.026 |
.773 |
T4 (mcg/ml) |
-.019 |
.832 |
CRP (mg/dl) |
.542 |
<.001 |
The data shows significant positive correlations between BMI, lipid profile components, and CIMT, with the strongest correlation observed for CIMT (r = .857, *p* < .001). T3 and T4 levels showed no significant correlation, indicating minimal association with the measured parameters. Above table shows that TSH level was significantly associated with TC,TG, LDL, HDL,VLDL, TC/HDL, LDL/HDL, CRP and CIMT.
Hypothyroidism is one of the significant common causes of hyperlipidemia which is linked to atherosclerosis. Nature and degree of dyslipidemia in overt hypothyroidism has been demonstrated in many studies and there is no doubt about the beneficial effects of thyroid substitution on serum lipids and on the risk for cardiovascular diseases10. Although the relationship between SCH and an atherogenic lipoprotein profile is still under debate, a meta-analysis of 13 intervention studies showed that levothyroxine therapy led to a significant reduction in both serum total cholesterol and LDL cholesterol levels11.
The study assessed thyroid status distribution across various demographic factors among 130 individuals, equally divided between euthyroid and subclinical hypothyroid groups. Age-wise, the highest proportion of participants (53.1%) were in the 41–50 years category, with no significant association between age and thyroid status (p = .380). Smoking status also showed no association with thyroid condition (p = 1.00), as both smokers and non-smokers were evenly split. Gender and residence type similarly demonstrated no significant relationship with thyroid status, with p values of .860 and .857, respectively. Overall, thyroid status was independent of age, sex, smoking, and rural-urban distribution in this cohort. In present study the CIMT was significantly higher in SCH group as compared to Euthyroid dysfunction. Unal E et al.(2016)12, Rastgooye Haghi A et al.(2017)13 and Tan M et al.(201914]in their study found that CIMT was significantly higher in SCH group as compared to Euthyroid dysfunction which is consistent with results of present study.
The comparison of biochemical and clinical parameters between euthyroid and subclinical hypothyroid individuals revealed significant differences across most markers. Subclinical hypothyroid individuals had higher BMI (24.36 vs. 23.24, p = .001), lipid levels, and atherogenic ratios, including total cholesterol, LDL, VLDL, and TC/HDL, all with p < .001. HDL levels were significantly lower in the subclinical hypothyroid group (41.29 vs. 49.71, p < .001). CIMT was notably elevated in subclinical hypothyroid individuals (0.83 mm vs. 0.49 mm, p < .001), indicating a higher cardiovascular risk. T3 and T4 levels showed no significant differences between groups, while TSH was markedly higher in the subclinical group (p < .001). Additionally, CRP, a marker of inflammation, was significantly elevated in subclinical hypothyroid individuals (2.02 vs. 0.88, p < .001).Subclinical hypothyroidism has a major influence on derangement of lipid profile leading to early atherosclerosis. One of the largest study, the Colorado study conducted on thyroid dysfunction also showed that there is derangement of lipid profile with increasing TSH values15. Tanis et al also concluded that SCH is independently associated with atherosclerosis and cardiovascular morbidity which can be attributed to dyslipidemia and substitution with exogenous thyroid replacement reverses the lipid changes16.Monzani et al also showed that the SCH group had higher CIMT values as compared to Euthyroid group17. Nagasaki et al18 and Kim et al (2009)19 also found the similar association in their study and found significantly higher CIMT values in hypothyroid and SCH group as compared to control group and replacement with thyroxine decreased the CIMT values on follow up.
However, not all researches showed an association between TSH and CIMT. In the study of Chiche et al.20among a population of hyperlipidemic patient’s investigators found that neither prevalence nor severity of carotid plaques nor CIMT were significantly different between hypothyroid patients and controls. Similarly Chiche F et al. in their study found that subclinical hypothyroid patients have normal CIMT20.
LIMITATIONS
The present study have concluded that subclinical hypothyroidism is associated with an atherogenic lipid. Subclinical hypothyroidism is characterized by an increase in concentration of total cholesterol, LDL and triglycerides and by decrease in HDL levels. There might be a potential link between subclinical hypothyroidism and atherosclerosis which was further strengthened by the fact that this study also found a positive significant association of increased CIMT and CRP
Chiche F, Jublanc C, Coudert M, Carreau V, Kahn JF, Bruckert E. Hypothyroidism is not associated with increased carotid atherosclerosis when cardiovascular risk factors are accounted for in hyperlipidemic patients. Atherosclerosis. 2009; 203:269–276