Risk factors of ischemic heart disease among hypothyroid patients in Bangladesh

*Corresponding author: Barua S Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution License 4.0. Risk factors of ischemic heart disease among hypothyroid patients in Bangladesh Rezwana I 1, Pathan M F 2, Amin F 3, Rahman M. A 4, Hasan M.M 5, Roy NC 6, Dutta M 7, Bhowmik GC 8, Roy H 9 and Barua S 10, * 1 Dr. Israt Rezwana, Registrar, Department of Endocrinology, Sir Salimullah Medical College & Hospital, Dhaka. 2 Prof. Dr. Md. Faruque Pathan, Director of BIRDEM Academy, Department of Endocrinology, Dhaka. 3 Prof. Dr. Feroz Amin, Head of the Dept. Department of Endocrinology BIRDEM General Hospital, Dhaka. 4 Dr. Md. Arifur Rahman, Registrar, Department of Gastroenterology, Dhaka Medical College Hospital,Dhaka 5 Dr. Md. Mehdi Hasan, Assistant Registrar, Department of Cardiology, National Institute of Cardiovascular Diseases & Hospital, Dhaka. 6 Dr. Nikhil Chandra Roy, Assistant Professor, Department of Gastroenterology, Bangladesh Medical College & Hospital, Dhaka. 7 Dr. Mita Dutta, Medical Officer, Dept. of Endrocrinology, Bangabandhu Sheikh Mujib Medical University, Shahbagh, Dhaka. 8 Dr. Goutom Chandra Bhowmik Assistant Registrar, Department of Cardiology, National Institute of Cardiovascular Diseases & Hospital, Dhaka. 9 Dr. Haripada Roy, Junior Consultant, Department of Cardiology, Kotalipara Upzilla Health Complex, Kotalipara, Gopalgonj, Bangladesh. 10 Dr Sushanta Barua, Assistant Registrar, Department of Cardiology, National Institute of Cardiovascular Diseases & Hospital, Dhaka. World Journal of Biology Pharmacy and Health Sciences, 2025, 22(01), 356-371 Publication history: Received on 16 February 2025; revised on 24 March 2025; accepted on 27 March 2025 Article DOI: https://doi.org/10.30574/wjbphs.2025.22.1.0336 Abstract Background: Hypothyroidism in patients with cardiac diseases is associated with worse outcomes. However, this has not yet been adequately investigated in Bangladeshi people. Objective: To find out the Risk Factors of Ischemic Heart Disease Patients Among Hypothyroid Patients Materials and methods: This cross-sectional observational study, conducted at the Department of Endocrinology and Allied Medicine, BIRDEM General Hospital, recruited 90 consecutive patients with ischemic heart disease but no prior history of hypothyroidism. Serum levels of TSH, FT4, and anti-thyroid peroxidase (TPO) antibodies were measured using an automated analyzer with a chemiluminescent immunoassay method. Subclinical hypothyroidism (SCH) was defined as a TSH level between 4.12 mIU/L and 10 mIU/L, while overt hypothyroidism was defined as a TSH level above 10 mIU/L. We used chi-square tests, the independent sample t-test, One-way ANOVA, The significance level was set at p < 0.05. Results: Of the 90 enrolled participants, 68 (75.6%) were euthyroid, 15 (16.7%) had subclinical hypothyroidism (SCH), and 7 (7.8%) had overt hypothyroidism. Of the patients with hypothyroidism, 7(31.8%) were anti-TPO antibody positive. Hypothyroidism was significantly more prevalent in females, non-smokers, obese individuals, those with HbA1c ≥ 10%, and patients with LVEF < 50%. In the hypothyroid group, mean ± SD systolic blood pressure, diastolic blood pressure, BMI, and HbA1c were also significantly higher. Although 95.5% of hypothyroid patients had dyslipidemia, there were no significant differences observed in specific lipid profiles between hypothyroid and euthyroid patients. Heart failure patients showed significantly more hypothyroidism and lower mean ± SD FT4 World Journal of Biology Pharmacy and Health Sciences, 2025, 22(01), 356-371 357 compared to patients without heart failure. Interestingly, mean ± SD TSH was significantly lower in females and the hypothyroid group. Predictors for hypothyroidism in IHD patients were female gender, non-smoker, higher BMI, higher SBP, and HbA1c ≥10%. Among these, the strongest predictor was BMI with an odds ratio of 7.920. Conclusion: This study highlights the association between hypothyroidism and IHD, particularly in patients with the identified risk factors. It emphasizes the importance of screening for thyroid function in IHD patients, especially those with the mentioned characteristics. Keywords: Antithyroid peroxidase; Cardiovascular disease; Hypothyroidism; Ischemic heart disease; Left ventricular ejection fraction & non-communicable diseases 1. Introduction Ischemic heart disease (IHD), also known as coronary artery disease (CAD) and atherosclerotic cardiovascular disease (ACD), is the leading global cause of death, disability and suffering1. It is acknowledged as a significant threat to sustainable development in the 21st century2. An increasing number of individuals with non-fatal IHD experience chronic disabilities and impaired quality of life3.The primary culprit behind IHD is atherosclerosis, an inflammatory arterial disease linked to lipid deposition and metabolic alterations triggered by multiple risk factors in over 70% of susceptible individuals4. IHD manifests clinically as myocardial infarction and ischemic cardiomyopathy1.Globally, IHD affects an estimated 126 million people, representing approximately 1.72% of the world's population. In 2017 alone, IHD caused nine million deaths1. The current prevalence rate of 1,655 per 100,000 population is projected to exceed 1,845 by 2030, with Eastern European countries experiencing the highest burden. Notably, individuals of South Asian descent have a substantially increased risk of CAD compared to most other ethnicities. Cultural and environmental factors unique to South Asian populations may influence the impact of genetic variations on CAD risk5.Like other countries, Bangladesh is experiencing a shift in disease burden from communicable to non-communicable diseases (NCDs) 6. A 2011 report by the Department of Public Health and Primary Care at the University of Cambridge highlighted that Bangladesh likely has the highest rates of cardiovascular disease (CVD) among South Asian nations yet receives the least research attention. In the global fight against CVD, Bangladesh remains a 'missing in action' country7.Obesity, diabetes mellitus, hypertension, tobacco consumption, dyslipidemia, globalization are the leading risk factors of IHD8. Despite substantial progress in prevention and control, the etiology of CVD is not completely understood9, as evidenced by failures of new treatments10. Moreover, men have substantially higher rates of ischemic heart disease (IHD) than women at the same level of established risk factors9, generating the possibility of discovering new potentially modifiable risk factors 11. The hypothalamic–pituitary-thyroid axis interacts with the hypothalamic–pituitary–gonadal axis 12. In humans, both overt and subclinical thyroid dysfunction, especially the former, are associated with higher risk of CVD events 13, 14, 15. As such, thyroid function might play a role in CVD11 . Observationally, higher TSH, even within the normal range, is associated with higher risk of CVD events16. In some, but not all observational studies, hypothyroidism is associated with unhealthier lipids and glucose metabolism, such as an association of higher TSH with higher total cholesterol17, higher low-density lipoprotein (LDL)-cholesterol17, lower high-density lipoprotein (HDL)-cholesterol 18, and higher HbA1c, and of higher FT4 with lower LDL-cholesterol19 , higher HDL-cholesterol20, and lower fasting glucose19. Observationally, people who are TPOAb-positive have higher TSH and faster carotid intima media thickness (cIMT) progression 21. A meta-analysis of cohort studies has shown that higher and lower TSH are both associated with higher risk of CVD events 22. Subclinical hypothyroidism has been associated with increased incidence of atherosclerosis and myocardial infarction in several studies23. Some prospective studies also indicate that treatment of subclinical hypothyroidism, including groups with minimally elevated TSH levels, results in improvement in surrogate markers for ASCVD (Atherosclerotic cardiovascular disease) such as atherogenic lipids and carotid intima media thickness 24. Presence of antithyroid peroxidase (TPO) antibody in subclinical hypothyroidism indicates heightened risk25. However, in another study, cardiovascular risk associated with subclinical hypothyroidism did not differ by TPO-Ab status26.In our country (Bangladesh), there is paucity of information, especially in recent time regarding this association between overt and subclinical hypothyroidism and IHD. One study 27 has been conducted in the Department of Physiology, Dhaka Medical College, to see the thyroid hormone status in IHD. It showed that serum FT3 and FT4 were significantly lower and serum TSH was significantly higher in IHD patients than that of healthy subjects. Another study 28 was done at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from November 2012 to April 2013 to see effect of hypothyroidism on the echocardiographic changes of the heart and also on the effect of therapy on the cardiac changes. They found lower left ventricular ejection fraction in hypothyroid group, which was significantly improve after treatment. However, the prevalence of hypothyroidism in IHD has not yet been investigated adequately in Bangladesh. As a result the burden of the problem is not that much addressed. So the current study is conducted to observe the risk factors of IHD among hypothyroidism in patient. World Journal of Biology Pharmacy and Health Sciences, 2025, 22(01), 356-371 358 2. Material and Methods This study employed a cross-sectional design to assess the risk factors for Ischemic Heart Disease (IHD) among hypothyroidism patients in Bangladesh. The research was conducted over two phases: Phase 1: March 2018 to November 2019 Phase 2: March 2022 to March 2023 Setting: Department of Endocrinology and Metabolism and Allied Medicine Department, BIRDEM General Hospital, Shah Bagh, Dhaka. 2.1. Participants 2.1.1. Inclusion criteria • Diagnosed and documented IHD (chronic coronary syndrome) • No prior history of hypothyroidism • Attending outpatient or inpatient departments at BIRDEM General Hospital 2.1.2. Exclusion criteria • Pregnant women • Women taking oral contraceptives • Patients on medications affecting thyroid function (thyroid replacement, anti-thyroid drugs, Amiodarone, Corticosteroids, Lithium) • Recent iodine contrast media exposure • Severely ill patients (sepsis, predominant systemic disease) • Acute coronary syndrome • Other structural heart disease 2.2. Ethical Considerations Formal ethical approval was obtained from the Institutional Review Board (IRB) of BIRDEM Academy. 2.3. Sample Size A total of 90 patients were recruited based on the defined inclusion and exclusion criteria. 2.4. Data Collection • Sociodemographic and Clinical Data: A structured questionnaire collected information on demographics, medical history, and current medications. Written informed consent was obtained before participation. • Anthropometric Measurements: Height, weight, waist circumference, hip circumference, and waist-hip ratio were measured following standardized protocols. Body Mass Index (BMI) was calculated. • Blood Pressure Measurement: Blood pressure was measured using a calibrated sphygmomanometer. • Laboratory Investigations: Fasting blood samples were collected to measure TSH and FT4 levels. Anti-TPO antibodies were tested in patients diagnosed with overt or subclinical hypothyroidism. Assays were performed in BIRDEM Laboratory following standard protocols. 2.5. Data Management and Analysis Data were collected using a pre-designed questionnaire and entered SPSS version 25. Descriptive statistics were used to summarize participant characteristics. Independent sample t-tests were employed to compare continuous variables between groups. One-way ANOVA tests were used for comparisons across more than two groups. Categorical data were analyzed using Chi-square tests or Fisher's exact tests, as appropriate. Binary logistic regression analysis was performed to identify independent predictors of hypothyroidism. Statistical significance was set at p < 0.05. 3. Results A total of 90 responders with clinically manifest IHD, were analyzed in the present study to measure thyroid function test. The demographic characteristics of the study population are depicted in Table 1. Mean (±SD) age of the study population was 61.88±11.85 years. A good number 42.2 % (38/90) of participants were more than 65 years. It appears World Journal of Biology Pharmacy and Health Sciences, 2025, 22(01), 356-371 359 that females were more dominant in the study than males. About 51.1% (46/90) of the participants were female. Table 2 represents the clinical condition of the studied patients. Mean (±SD) duration of patients experiencing IHD, HTN and DM was 6.82 ± 4.61 years, 9.44±5.60 years and 12.77±6.66 years respectively. 30 (33.3%) participants were ex-smoker, all of them were male. In addition to this, 22.2% study population had history of intervention for IHD, among them 75.0% had PCI. Family history of hypothyroidism was revealed in 10.0% participants. A good number of participants that is 61.1% was taking lipid lowering agent. On examination arrhythmia was found in only 1(1.1%) patient. Cutaneous marker of cardiovascular disease i.e. xanthelasma was present in 5(5.6%). Mean (±SD) systolic blood pressure and diastolic blood pressure was 127.44±14.63 mmHg and 76.22±9.34 mmHg. Anthropometric measurements of the participant’s shows mean (±SD) BMI of studied population were 25.12±3.89 Kg/m2, among them 47.8% were obese and 26.7% were overweight. 90.9% male participants had waist circumference >90 cm, whereas 100% female had waist circumference >80 cm. Mean (±SD) waist circumference and waist hip ratio was 102.82±7.41 cm and 0.97±0.05 respectively. The results of the participants' laboratory measurements are presented in Table 3. From the table, it appears that mean (±SD) TSH was 4.20 ± 6.31 mIU/L. Other than that, mean (±SD) FT4 in the studied patients was 13.96 ± 2.74 pmol/L. In addition, mean (±SD) fasting plasma glucose was 9.67±3.41 mmol/L, mean (±SD) HbA1C was 10.45 ± 2.79 % and 53.3% had HbA1C ≥10%. The lipid profile shows mean (±SD) serum cholesterol level among the studied patients was 156.30 ± 47.01 mg/dl, mean (±SD) HDL 30.53±8.89 mg/dl, mean (±SD) LDL 86.85±40.29 mg/dl and mean (±SD) TG 211.64±150.05 mg/dl. In echocardiography mean (±SD) LVEF was 50.24±9.46 % and 45.6% patients were suffering from mild to moderate LV dysfunction. Table 4 is the display of frequency of hypothyroidism in IHD patient. Here 22(24.4%) patient was detected to have hypothyroidism, among them 7.8 % had overt hypothyroidism and 16.7% had subclinical hypothyroidism. Figure 1 shows that among the hypothyroid group 31.8 % patient was anti TPO (thyroid peroxidase) antibody positive and 68.2% patient was anti TPO antibody negative. Table 5 shows in overt hypothyroid group more participants ( 42.9%) were anti TPO antibody positive in comparison to subclinical hypothyroid (26.7%) group, though the difference was not significant (p>0.05). The table 6 shows that gender, history of intervention for IHD, presence of heart failure was statistically different in stable angina and old MI group(p<0.05). The table 7 shows that age, HbA1C and LVEF was statistically different in with or without heart failure groups (p<0.05). The above table8 shows the thyroid function categories and mean (± SD) FT4 was statistically different in with and without HF groups (p<0.05). Table-9 shows no parameters were significantly different between types of heart failure (p>0.05). Table 11 shows that female gender, nonsmoker, obese, HbA1C≥ 10% and LVEF <50 % has significant p value (<0.05) and was associated with hypothyroidism. In hypothyroid group mean (±SD) SBP, DBP, BMI and HbA1C was also significantly (p<0.05) more. Table 12 shows that mean TSH was significantly (p<0.05) more in female gender and hypothyroid patients, on the other hand FT4 was significantly less in female gender and hypothyroid patient. Table 13 shows the Odds ratio of risk factors of hypothyroid individuals of studied population. It appears from the table that univariate binary logistic regression analysis was conducted to find out any association of hypothyroidism with patient’s age, gender, smoking status, duration of IHD, family history of hypothyroidism, systolic blood pressure, diastolic blood pressure, BMI, HbA1C, Total cholesterol and LDL. A significant association was found for hypothyroidism of IHD patients with female gender, nonsmoker, obesity, higher SBP and HbA1C≥10 (p<0.05). Among them the strongest predictor of hypothyroidism was BMI with a odds ratio of 7.920. Table 1 Demographic characteristics of the study population (n=90) Variables Frequency (%) Age (years) ≤35 2(2.2) 36-44 4(4.4) 45-54 14(15.6) 55-64 32(35.6) ≥65 38(42.2) Mean ± SD 61.88±11.85 Gender Male 44 (48.9) Female 46 (51.1) Within parentheses are percentages over total. World Journal of Biology Pharmacy and Health Sciences, 2025, 22(01), 356-371 360 Table 2 Clinical characteristics of the study population (n=90) Variables Mean ± SD Frequency (%) Duration of IHD (years) 6.82±4.61 Duration of HTN (years) 9.44±5.60 Duration of DM (years) 12.77±6.66 Smoking status Never 60(66.7) Ex smoker 30(33.3) Current 0(0) Family H/O hypothyroidism Absent 81(90.0) Present 9(10.0) H/O intervention for IHD Absent 70(77.8) Present 20(22.2) Type of Intervention CABG 5(25.0) PCI 15(75.0) H/O taking Anti lipid drug Yes 55(61.1) No 35(38.9) Arrhythmia Absent 89(98.9) Present 1 (1.1) Xanthelasma Absent 85(94.4) Present 5(5.6) BMI (Kg/m2) 25.12±3.89 Underweight(<18.4) 3(3.3) Normal (18.5-22.9) 20(22.2) Over weight (23-24.9) 24(26.7) Obese (≥25) 43(47.8) WC (cm) 102.82±7.41 Male (> 90 cm) 40(90.9) (<90 cm) 4(9.1) Female (> 80 cm) 100(100.0) (<80 cm) 0(0.0) World Journal of Biology Pharmacy and Health Sciences, 2025, 22(01), 356-371 361 HC (cm) 104.61±7.43 WHR 0.97± .05 Systolic blood pressure (mmHg) 127.44±14.63 Diastolic blood pressure (mmHg) 76.22±9.34 Within parentheses are percentages over total; IHD= Ischemic heart disease, HTN=Hypertension, DM= Diabetes mellitus, CABG=Coronary artery bypass grafting, PCI=Per cutaneous coronary intervention, BMI=Body mass index, WC= Waist circumference, HC = Hip circumference, WHR= Waist hip ratio. Table 3 Laboratory parameters of the study population (n=90) Variables Mean ± SD Frequency (%) FPG (mmol/L ) HbA1C ( %) <10% ≥ 10% 9.67±3.41 10.45 ±2.79 2 (46.7) 48 (53.3) TSH (mIU/L) 4.20±6.31 FT4 ( pmol/L) 13.96±2.74 Total Cholesterol (mg/dl) 156.30±47.01 LDL (mg/dl) 86.85± 40.29 HDL (mg/dl) 30.53±8.89 TG (mg/dl) 211.64±150.05 Within parentheses are percentages over total; FPG=Fasting blood glucose, TSH= Thyroid stimulating hormone, FT4=Free T4, LDL =Low-density lipoprotein , HDL=High-density lipoprotein , TG=Triglyceride, LVEF= Left ventricular ejection fraction. Table 4 Thyroid status in patients with IHD (n=90) Frequency Percentage (%) Total patients 90 100.0 Euthyroid1 68 75.6 Hypothyroid 22 24.4 Overt hypothyroid2 7 7.8 Subclinical hypothyroid3 15 16.7 1Euthyroid = TSH 0.45 – 4.12 mIU/L, 2Overt hypothyroid= TSH> 10 mIU/L , 3Subclinical hypothyroid= TSH> 4.12 – up to 10 mIU/L World Journal of Biology Pharmacy and Health Sciences, 2025, 22(01), 356-371 362 3.1. Anti thyroid antibody in hypothyroid group (n=22) Figure 1 Distribution of hypothyroid patients according to Anti thyroid peroxidase antibody (n=22) Table 5 Anti TPO antibody in subclinical and overt hypothyroidism (n=22) Anti TPO antibody Subclinical hypothyroidism Frequency (%) Overt hypothyroidism Frequency (%) p value Negative 11(73.3) 4(57.1) 0.630a Positive 4(26.7) 3(42.9) Mean ± SD(U/ml) 61.92± 46.49 61.99±35.25 0.945b Within parentheses are percentage over total. P value calculated by a= Fisher exact test and b=Mann - Whitney U test. 3.2. Type of IHD in study population(n=90) Figure 2 Distribution of the study participants according to the type of IHD (n=90) The figure 2 is showing that 72.2% participants had stable angina and 27.8% had old MI (Myocardial infarction). World Journal of Biology Pharmacy and Health Sciences, 2025, 22(01), 356-371 363 Table 6 Comparison of demographic, clinical and laboratory variables in different IHD groups (n=90) Variables Stable angina(n=65) Old MI(n=25) p value Frequency (%) Frequency (%) Gender Male Female 26(40.0) 39(60.0) 18(72.0) 7(28.0) 0.007a H/O intervention for IHD Absent Present 55(84.5) 10(15.4) 15(60.0) 10(40.0) 0.012a Family H/O hypothyroidism Absent Present 59(90.8) 6(9.2) 22(88.0) 3(12.0) 0.704b Presence of HF Yes No 11(16.9) 54(83.1) 14(56.0) 11(44.0) 0.000a SBP(mmHg) Mean ± SD 128.69±14.03 124.20±15.92 0.312c DBP(mmHg) Mean ± SD 76.77±9.57 74.80±8.71 0.400c T cholesterol(mg/dl) Mean ± SD 156.27±49.25 156.36±41.56 0.725c LDL(mg/dl) Mean ± SD 86.98±40.19 86.52±41.36 0.968c HbA1C(%) <10 ≥10 32(49.2) 33(50.8) 10(40.0) 15(60.0) 0.432a Within parentheses are percentages over total; HF=Heart failure, SBP=Systolic blood pressure, DBP=Diastolic blood pressure; p values were calculated by using a=chi square test, b=Fisher exact test , Table 7 Comparison of demographic, clinical and laboratory variables in with or without heart failure group (n=90) Variables With HF(n=25) WithoutHF(n=65) p value Frequency (%) Frequency (%) Age (years) <65 ≥65 9(36.0) 16(64.0) 43(66.2) 22(33.8) 0.009a Gender Male Female 13(52.0) 12(48.0) 31(47.7) 34(52.3) 0.714a World Journal of Biology Pharmacy and Health Sciences, 2025, 22(01), 356-371 364 Family H/O hypothyroidism Absent Present 23(92.0) 2(8.0) 58(89.2) 7(10.8) 1.00b SBP(mmHg) Mean ± SD 129.80±15.17 126.54±14.44 0.145c DBP(mmHg) Mean ± SD 73.40±8.50 77.31±9.48 0.084c T cholesterol(mg/dl) Mean ± SD 156.84±45.05 156.09±48.09 0.935c LDL(mg/dl) Mean ± SD 85.72±45.18 87.29±38.61 0.742c HbA1C(%) <10 ≥10 7(28.0) 18(72.0) 35(53.8) 30(46.2) 0.028a LVEF(%) <50 ≥50 23(92.0) 2(8.0) 19(29.2) 45(70.8) 0.000a Within parentheses are percentages over total; p values were calculated by using a=chi square test ,b=Fisher exact test , c= Mannwhitney Utest. Table 8 Thyroid function categories, anti TPO Ab, FT4 and TSH level in with or without HF groups Parameters With HF (n=25) Without HF (n=65) p value Frequency (%) Frequency (%) Thyroid function categories(n=90) Euthyroid Hypothyroid 13(52.0) 12(38.0) 55(84.6) 10(15.4) 0.001a Anti TPO Ab(n=22) Positive Negative 5(41.7) 7(58.3) 2(20.0) 8(80.0) 0.381b FT4 (pmol/L) 12.46±2.90 14.54±2.47 0.001c (n=90) Mean ± SD TSH (mIU/L) 7.25±10.76 3.02±2.72 0.180d (n=90) Mean ± SD Within parentheses are percentage over total; p values were calculated by using a= Chi square test, b=Fisher exact test,c= Independent sample ttest, World Journal of Biology Pharmacy and Health Sciences, 2025, 22(01), 356-371 371 [33] Mayer Jr, O., Šimon, J., Filipovský, J., Plášková, M. and Pikner, R., 2006. Hypothyroidism in coronary heart disease and its relation to selected risk factors. Vascular health and risk management, 2(4), p.499. [34] Santhoshakumari, T.M.J. and Sneha, M., 2019. 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