European Journal of Cardiovascular Medicine

Elevated blood thyroid-stimulating hormone (TSH) levels with normal free thyroxine (T4) concentrations, frequently without any clinical symptoms, are the biochemical hallmark of subclinical hypothyroidism (SCH). It is a common endocrine condition that is more common in women and increases in frequency as people age. Interestingly, postmenopausal women are a group that is more vulnerable to SCH because of hormonal changes and age-related physiological alterations. Biondi B ET AL. (2019)^[1]

A decrease in oestrogen levels during the postmenopausal period causes a number of metabolic changes, such as insulin resistance, elevated central adiposity, and undesirable lipid profiles. All of these alterations raise this population's risk of cardiovascular diseases (CVD). Due to the possible cumulative effect on cardiovascular risk, the interaction between SCH and various metabolic disorders has attracted a lot of study interest. Motlani V et al. (2023)^[2]

The relationship between SCH and metabolic syndrome (MetS), a group of disorders that includes central obesity, dyslipidaemia, hypertension, and poor glucose tolerance, has been the subject of several investigations. According to a thorough meta-analysis of 19 trials with a total of 79,000 participants, those with SCH were 28% more likely than their euthyroid counterparts to acquire MetS. This correlation was especially strong among Asian adults and groups, highlighting possible age- and ethnic-related vulnerabilities. Ding X et al. (2021)^[3]

Further analysing the components of MetS, SCH has been connected to higher probabilities of central obesity, hypertension, raised triglyceride levels, and lowered high-density lipoprotein cholesterol (HDL-C) levels. These results imply that SCH may increase cardiovascular risk by playing a role in the pathophysiology of MetS components. Rochlani Y et al. (2017)^[4]

Beyond metabolic abnormalities, SCH has cardiovascular ramifications. According to a meta-analysis of prospective cohort studies with more than half a million individuals, SCH is linked to a 20% increase in all-cause mortality and a 33% higher risk of CVD. Interestingly, this risk increase was more pronounced in those who already had cardiovascular risk factors, underscoring the compounding effect of SCH in susceptible groups. Moon S et al. (2018)^[5]

Studies conducted in India have shown that women with MetS had a significant frequency of SCH. For example, 18.8% of patients with MetS had SCH, according to a cross-sectional research done in Gujarat. In order to enable early identification and management, our data highlight the significance of routine thyroid function monitoring in people with MetS, particularly postmenopausal women. Deshmukh V et al. (2013)^[6]

There is still a dearth of information specifically addressing postmenopausal women in the Indian subcontinent, despite mounting evidence that SCH is associated with metabolic and cardiovascular disorders. Clarifying the connection between SCH and cardiovascular risk in this group is crucial because of the distinct genetic, nutritional, and lifestyle variables that affect them. Suh S et al. (2015)^[7]

Objectives of the Study:

1. To assess the prevalence of subclinical hypothyroidism in postmenopausal women.
2. To evaluate the association between SCH and metabolic syndrome in this population.
3. To compare the prevalence of cardiovascular risk factors between postmenopausal women with SCH and those with normal thyroid function.

Study Design

This was a case-control study conducted over a one-year period at the Mysore Medical College and Research Institute (MMCRI), Mysore.

Sample Size

A total of 100 postmenopausal women were recruited: 50 diagnosed with SCH and 50 euthyroid controls.

Inclusion Criteria

• Women who are postmenopausal (defined as the cessation of menstruation for at least 12 consecutive months).

Exclusion Criteria

• Women with a known history of cardiovascular disease.
• Known cases of hypothyroidism on treatment or previously diagnosed.

Sources of Data

• Primary: Outpatient and inpatient services at KR Hospital.
• Secondary: Published articles, journals, textbooks, and internet sources.

Method of Data Collection

A structured questionnaire was used to record sociodemographic data, clinical history, and symptoms. Clinical examination and laboratory investigations were carried out, including:

• Serum TSH and free T4 levels
• Lipid profile (Total cholesterol, LDL, HDL, Triglycerides)
• Fasting blood glucose
• Blood pressure
• Waist circumference

Definition of SCH

• TSH > 4.5 mIU/L and normal free T4

Statistical Methods

Data were analyzed using SPSS trial version.

• Descriptive statistics: Mean, standard deviation, frequency, and proportion.
• Inferential statistics: Chi-square test and independent t-test to compare the case and control groups.

Visualization: Bar and pie charts for categorical data representation.

Table 1: Demographic and Clinical Characteristics of Study Participants

There was no discernible age difference between the groups, as Table 1 shows that the mean age of individuals in the SCH group was 58.6 ± 6.3 years, whereas that of the control group was 57.2 ± 5.9 years (p = 0.25). However, SCH participants had a substantially higher body mass index (BMI) (27.8 ± 3.5 kg/m2) than controls (25.4 ± 3.1 kg/m2; p = 0.01). Likewise, the SCH group had a significantly larger waist circumference (92.5 ± 5.2 cm vs. 85.3 ± 4.8 cm; p < 0.001), indicating more central adiposity. Both systolic blood pressure (138 ± 14 mmHg vs 126 ± 10 mmHg) and diastolic blood pressure (88 ± 8 mmHg vs 80 ± 7 mmHg) were also significantly elevated in the SCH group (p < 0.001), reflecting greater cardiovascular strain.

Table 2: Biochemical Parameters

Thyroid function and metabolic biochemical marker comparisons are shown in Table 2. The diagnosis was confirmed by the SCH group's significantly higher TSH levels (7.5 ± 2.1 mIU/L) compared to controls (2.2 ± 0.8 mIU/L; p < 0.001). Free T4 levels were similar between the groups (p = 0.08), as expected in subclinical hypothyroidism. Notably, SCH participants had significantly worse lipid profiles, including elevated total cholesterol (210 ± 32 mg/dL vs 186 ± 28 mg/dL; p = 0.01), LDL cholesterol (138 ± 21 mg/dL vs 112 ± 19 mg/dL; p < 0.001), and triglycerides (168 ± 34 mg/dL vs 132 ± 30 mg/dL; p < 0.001). HDL cholesterol was significantly lower in the SCH group (40 ± 7 mg/dL vs 49 ± 8 mg/dL; p < 0.001). Additionally, fasting blood glucose was modestly elevated in the SCH group (102 ± 12 mg/dL vs 96 ± 10 mg/dL; p = 0.02), reflecting early metabolic dysregulation.

Table 3: Prevalence of Metabolic Syndrome Components

The prevalence of each component of the metabolic syndrome is shown in Table 3. Notably greater percentages of SCH participants possessed: Obesity in the centre (76% versus 42%; p < 0.001), Triglycerides were higher (68% vs. 36%; p < 0.001), HDL cholesterol was lower (62% vs. 28%; p < 0.001), Blood pressure was higher (70% vs. 40%; p < 0.001), Reduced glucose while fasting (34% vs. 18%; p = 0.04), The correlation between subclinical hypothyroidism and metabolic risk clusters was further supported by the fact that the SCH group had a considerably higher prevalence of metabolic syndrome, which is defined as the presence of three or more of the aforementioned components, at 72%, compared to 36% for controls (p < 0.001).

Table 4: Cardiovascular Risk Assessment

As illustrated in Table 4, multiple markers of cardiovascular risk were elevated among SCH subjects. A significantly greater proportion of SCH participants had an atherogenic index (TG/HDL) > 0.21 (60% vs 30%; p < 0.001), indicating increased atherogenic potential. Furthermore, a Framingham Risk Score ≥10% was more common in the SCH group (48% vs 22%; p = 0.002), suggesting higher 10-year cardiovascular event risk. Finally, high-sensitivity C-reactive protein (hs-CRP), an inflammatory marker of cardiovascular risk, was elevated (>3 mg/L) in 58% of SCH participants compared to only 26% of controls (p < 0.001), indicating an increased inflammatory burden.

By contrasting important anthropometric, biochemical, and cardiovascular risk indicators with euthyroid controls, this study examined the association between postmenopausal women's subclinical hypothyroidism (SCH) and cardiovascular risk. The results support the clinical importance of SCH in this group by indicating that it is linked to a number of metabolic and cardiovascular disorders.

Anthropometric and Blood Pressure Changes

In line with earlier findings that connected thyroid disease to central obesity, postmenopausal women with SCH had noticeably higher BMIs and waist circumferences than controls (Singh et al., 2020)^[8]. Even a minor thyroid hormone shortage, as shown in SCH, might encourage fat formation and weight gain because thyroid hormones affect lipid mobilisation and basal metabolic rate (Razvi et al., 2018).^[9]. The observed increase in SCH participants' systolic and diastolic blood pressure is consistent with earlier research that suggests elevated TSH may result in impaired endothelial function and increased systemic vascular resistance (Zhou et al., 2019).^[10]

Lipid and Glucose Profile Abnormalities

Patients with SCH had significant dyslipidaemia, which was defined by decreased HDL levels and increased levels of total cholesterol, LDL, and triglycerides. These anomalies are known to contribute to atherogenesis and are well-documented outcomes of hypothyroid conditions (Pearce et al., 2017; Zhang et al., 2021).^[11,12] Lipid buildup is encouraged by elevated TSH levels because they decrease LDL clearance and impede hepatic LDL receptor activation (Biondi & Cooper, 2019).^[1] Cardiovascular risk is further increased by triglyceride rise and HDL lowering, which both contribute to an unfavourable atherogenic index (Zhao et al., 2020). ^[13] Early insulin resistance is suggested by a slight but statistically significant rise in fasting glucose in the SCH group. This confirms results from earlier cross-sectional studies that link SCH to poor glucose metabolism, which is most likely caused by systemic inflammation and increased adiposity (Duntas & Wartofsky, 2016). ^[14]

Increased Prevalence of Metabolic Syndrome

The study's startling discovery was that SCH patients had a far greater frequency of metabolic syndrome (72% vs. 36%). In line with previous research, the SCH group had higher rates of central obesity, dyslipidaemia, hypertension, and impaired fasting glucose (Tzotzas et al., 2017; Asvold et al., 2019).^[15,16] The risk of cardiovascular disease, type 2 diabetes, and stroke is increased by the clustering of these metabolic abnormalities, underscoring the necessity of early screening and lifestyle modifications for SCH patients, especially postmenopausal women.

Cardiovascular Risk Indicators

The Framingham risk score, hs-CRP, and atherogenic index were used to objectively evaluate cardiovascular risk. Profiles for all three measures were substantially poorer for SCH individuals. A strong indicator of atherosclerosis, the atherogenic index, was doubled in 60% of SCH participants compared to controls. Additionally, the SCH group had a considerably higher Framingham risk score, which calculates the 10-year risk for cardiovascular events. More than half of the SCH participants had elevated hs-CRP levels (>3 mg/L), which is indicative of increased systemic inflammation and is linked to cardiovascular morbidity on its own (Ridker et al., 2016).^[17]  These results lend credence to the increasing body of evidence suggesting that SCH is not a benign biochemical anomaly but rather may put people at risk for poor cardiovascular outcomes, especially in high-risk groups such as postmenopausal women (Biondi, 2019; Rodondi et al., 2021).^[1,18]

Clinical Implications

Routine thyroid monitoring may be warranted in SCH patients due to the higher frequency of metabolic syndrome and cardiovascular risk factors, especially in postmenopausal women. Interventions aimed at blood pressure, weight, lipids, and glucose management may be made easier with early diagnosis. Although there is still disagreement about whether thyroid hormone replacement in SCH improves these metrics, tailored risk factor management is clearly necessary (Taylor et al., 2017).^[9]

This study shows that central obesity, dyslipidaemia, high blood pressure, and poor glucose metabolism are all substantially correlated with subclinical hypothyroidism in postmenopausal women. As a result, metabolic syndrome and cardiovascular risk scores are much greater in SCH patients. These results highlight the potential advantages of early metabolic and cardiovascular risk assessment in postmenopausal women as well as the significance of screening for thyroid dysfunction in this population.

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