|Year : 2017 | Volume
| Issue : 1 | Page : 1-9
Impact and predictors of thyroid dysfunction among patients with stenotic coronary artery lesion during late postacute coronary syndrome
Sahar H Elhini1, Ragaa A Matta1, Nossa N Eledawi1, Lamia Hamdi2
1 Department of Internal Medicine, School of Medicine, Minia University Hospital, Minia, Egypt
2 Department of Clinical Pathology, School of Medicine, Minia University Hospital, Minia, Egypt
|Date of Submission||19-Nov-2016|
|Date of Acceptance||26-Jan-2017|
|Date of Web Publication||27-Apr-2017|
Ragaa A Matta
Department of Internal Medicine, School of Medicine, Minia University Hospital, Minia, 61111
Source of Support: None, Conflict of Interest: None
Thyroid dysfunction (TD) is a risk factor for coronary heart disease (CHD) events. We study the prevalence and predictors of TD and its impact on characteristics, cardiac function, and ischemic severity of patients with manifest CHD.
Patients and methods
A total of 200 patients 6–12 months after acute coronary syndrome had at least one vessel − significant stenotic coronary artery lesion. Before elective angiography, patients underwent anthropometric measurement, routine biochemical assay, thyroid hormones, and thyroid peroxidase antibody.
The prevalence of TD was 17.5%: 12% for hypothyroidism (9.5% subclinical, 2.5% overt) and 5.5% for hyperthyroidism (2.5% subclinical, 3% overt). Compared with the euthyroid group, the hypothyroid group had a significantly higher age, BMI, diastolic blood pressure (BP), atherogic lipid profile, and impaired cardiac functions and higher pulmonary artery systolic pressure (PASP), and the hyperthyroid group had significantly higher systolic BP, ejection fraction (EF), and PASP and significantly lower diastolic BP and lipid profile. Independent predictors for hypothyroidism were age, bradycardia, increased BMI, lower EF, diastolic dysfunction, and atherogenic lipid profile, whereas increased PASP was an independent predictor for hyperthyroidism. Thyroid-stimulating hormone (TSH) was positively correlated and both free triiodothyronine and free thyroxine were negatively correlated to BP, BMI, lipid profile, impaired EF, and coronary atherosclerosis severity. TSH and free thyroxine were positively correlated to PASP, which increased significantly through hypothyroidism to hyperthyroidism. TSH and free triiodothyronine were independent predictors of severity of CHD.
Age, obesity, impaired cardiac function, and atherogenic lipid profile are predictors of hypothyroidism, and PASP is the predictor of hyperthyroidism among manifest CHD. Thyroid hormones are predictors of severity of coronary atherosclerosis and correlated to cardiac functions and PASP.
Keywords: late postacute coronary syndrome, severity of coronary atherosclerosis, thyroid dysfunction
|How to cite this article:|
Elhini SH, Matta RA, Eledawi NN, Hamdi L. Impact and predictors of thyroid dysfunction among patients with stenotic coronary artery lesion during late postacute coronary syndrome. Egypt J Obes Diabetes Endocrinol 2017;3:1-9
|How to cite this URL:|
Elhini SH, Matta RA, Eledawi NN, Hamdi L. Impact and predictors of thyroid dysfunction among patients with stenotic coronary artery lesion during late postacute coronary syndrome. Egypt J Obes Diabetes Endocrinol [serial online] 2017 [cited 2018 Dec 17];3:1-9. Available from: http://www.ejode.eg.net/text.asp?2017/3/1/1/205206
| Introduction|| |
Thyroid hormones have many effects on the cardiovascular system . The relationship between abnormal thyroid function and coronary heart disease (CHD) has been recognized for a long time, especially in hypothyroidism status . Even subclinical hypothyroidism and subclinical hyperthyroidism , have been related to increased risk of CHD events and mortality, although still controversial ,. Similar to severe systemic conditions, myocardial infarction or severe heart failure may affect thyroid hormone secretion and their peripheral conversion, leading to low T3 syndrome. Although the recovery stage of altered thyroid hormone concentration takes place as the illness resolves and is characterized by elevated thyroid-stimulating hormone (TSH) levels, full recovery may be prolonged to several months ,. Previous studied to detect primary thyroid disorders during acute coronary syndrome (ACS) may be biased. Others were retrospective and rare in our locality ,,,.
In animal studies, thyroid hormones, particularly free triiodothyronine (FT3), influence cardiomyocyte phenotype and morphology, and they have cardioprotective effects: they inhibit inflammation, apoptosis, and pathological cardiac remodeling after myocardial infarction . Clinical trials have highlighted on influences of low T3 syndrome rather than primary thyroid disorder on cardiac functions and prognosis ,.
Cross-sectional studies among patients undergoing coronary angiography showed conflicting data about the relation of thyroid hormones with severity of coronary atherosclerosis ,,,. However, all these studies were conducted in euthyroid patients with small samples and without previous ACS. From a clinical point of view, the effect of thyroid dysfunction (TD) on prevalent CHD may be more important than the effect of the thyroid function in the reference range.
Little data about thyroid autoimmunity are available among CHD patients despite its association with many coronary risk factors namely hyperlipidemia, abdominal obesity, and endothelium-dependent arterial dilation in euthyroid patients ,.
Our study aimed to identify the prevalence and predictors of primary thyroid disorders, and their interplay with conventional coronary risk factors, cardiac function, and severity of coronary atherosclerosis among patients with manifest CHD with significant stenotic coronary lesion in late post-ACS.
| Patients and methods|| |
This prospective observational cross-sectional study, among 200 manifest CHD patients, was carried out in Internal Medicine Department, Minia University Hospital, between December 2012 and December 2014. Patients were selected from consecutive adults aged older than 30 years undergoing coronary angiography for diagnostic and revascularization purposes in Cardiac Catheterization Unit, Minia University Hospital. Patients were recruited into the study if they fulfilled two criteria: (i) clinically stable at the time of the study with minimum 6 months and maximum 12 months after hospitalization for acute coronary events to allow full recovery of altered thyroid hormones during acute illness (sick euthyroid syndrome), and (ii) significant coronary artery stenosis more than 70 obstruction of the lumen in one vessel or more. Patients having any one of the following criteria were excluded: (a) euthyroid sick syndrome (excluding critically ill patients, acute cardiac injury, or severe heart failure) or low serum T3 syndrome; (b) recent acute myocardial infarction, previous revascularization, or rheumatic valvular heart disease; (c) hypothalamus and/or pituitary gland diseases; (d) intake of drugs that influence thyroid function within the past 3 months including amiodarone; (e) recent infections, a malignant tumor, serious liver dysfunction, renal dysfunctions, or chest disease; and (f) pregnancy.
The study protocol was approved by the Institutional Ethics Committee, and all patients gave informed consents to participate in this study. The study was conducted in accordance with the ethical guidelines of the Declaration of Helsinki and International Conference on Harmonization Guidelines for Good Clinical Practice.
Patients were first evaluated for CHD at the outpatient department. All patients answered a standardized questionnaire and underwent thorough clinical examination, blood sampling, ECG, and echocardiography before coronary angiography. Personal history, demographic characteristics, conventional risk factors for CHD, and current pharmacotherapy were obtained at interview. Anthropometric measurements were taken in a standardized manner. Height and weight were measured to calculate BMI by dividing body weight (kg) by square of height (m2) . Systemic arterial blood pressure (BP) was measured after 15 min of rest. Systemic arterial hypertension was defined by diagnosis of hypertension made previously by a physician or systolic BP more than or equal to 140 mmHg or diastolic BP more than or equal to 90 mmHg or treatment with antihypertensive medications according to European Society of Hypertension and the European Society of Cardiology guidelines . Diabetes mellitus (DM) was defined by diagnosis of diabetes made previously by a physician, fasting plasma glucose (FPG) more than or equal to 126, either 2-h postprandial glucose or random blood glucose more than or equal to 200 mg/dl, classic symptoms in previously untreated patients, or use of insulin or oral hypoglycemic agents according to the American Diabetes Association guidelines .
Before coronary angiography, venous blood samples were collected from all patients between 8:00 and 10:00 a.m. after an overnight fast for at least 12 h. All samples were collected and processed according to standard biochemistry assay in the clinical laboratory at Minia University hospital. FPG, 2-h postprandial glucose, serum creatinine, triglyceride (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) were determined by enzymatic methods using automated chemistry analyzer system Konelab 201 (Thermo Electron Corporation, Vantaa, Finland). Low-density lipoprotein cholesterol (LDL-C) was calculated according to the Friedewald formula . Estimated glomerular filtration rate was calculated using the Cockcroft–Gault formula :
Assessment of thyroid hormones
Stored serum at −20°C was used to assess thyroid function. Automated chemiluminescent procedures (Mini-VIDAS; BioMérieux, Marcy-l’Étoile, France) were used for quantitative measurement of TSH, FT3, and free thyroxin (FT4) by available kits from Biomerieux Deutschland GmbH (Nürtingen, Germany). The laboratory reference ranges were 0.3–4.5 μIU/ml for TSH, 1.4–4.2 pg/ml for FT3, and 0.65–1.97 ng/dl for FT4.
Patients were classified according to thyroid function into three groups:
- Group I: the euthyroid group included patients with FT3, FT4, and TSH levels within the reference ranges.
- Group II: the hypothyroid group included patients with TSH levels above 4.5 μIU/ml and subdivided into subclinical or overt hypothyroidism when both FT3and FT4 levels were within or less than the reference ranges, respectively.
- Group III: the hyperthyroid group included patients with TSH levels below 0.3 μIU/ml and subdivided into subclinical or overt hyperthyroidism when both FT3 and FT4 levels were within or more than the reference ranges, respectively.
Anti-thyroid peroxidase (TPO): The architect anti-TPO assay is a two-step immunoassay for the quantitative measurement of anti-TPO using Chemiflex technology (Accubind ELISA micro wells; Monobind Inc., Lake Forest, California, USA). Normal value ranges up to 5.6 IU/ml .
After undergoing routine ECG to detect ischemic changes or old myocardial infarction , echocardiography was performed by using Vivid-3 echocardiography device (General Electric Inc., USA) with probe frequency of 7.5 MHz. According to recommendations of the American Society of Cardiology, ejection fraction (EF), a marker of systolic function, was assessed using M-mode by parasternal long axis while the patient in the left lateral position. Resting wall motion abnormalities were assessed using calculative method by e-ball assessment. Diastolic dysfunction was assessed by tracing of mitral flow Doppler. Pulmonary artery systolic pressure (PASP) was assessed using the modified Bernoulli equation .
All patients were subjected to coronary angiography, which was performed using standard Judkins technique . Angiographic findings were reviewed by two experienced cardiologists who were blinded to the study protocol. CHD was defined as a greater than 50% stenosis by visual assessment in at least one major vessel or principal side branch (Judkins technique). The affected artery was determined from angiographic characteristics of occlusion (occlusion due to thrombus formation or ulceration with decreased contrast density). Coronary artery stenosis of more than 70% is defined as significant or obstructive. Multivessel coronary artery disease is defined as having two or more coronary arteries with obstructive lesions .
It was performed and evaluated by radiology specialists using TOSHIBA SSA-340 machine (Toshiba Co., Tokyo, Japan), with superficial probe of 7 MHz frequency following standard ultrasonography techniques .
| Results|| |
In the present study, 17.5% of CHD patients had primary thyroid disorders (35/200). Group I, the euthyroid group, represented 82.5% (165/200), with a mean age±SD of 58.76±8.98 years and male/female ratio of 109 : 56. Group II, the hypothyroid group, corresponded to 12% (24/200), with a mean age of 64.70±5.74 years and a male/female ratio of 15 : 9, of which 9.5% (19/200) and 2.5% (5/200) had subclinical and overt hypothyroidism, respectively. Group III, the hyperthyroid group, corresponded to 5.5% (11/200), with a mean age of 56.90±7.73 years and a male/female ratio of 5 : 6, of which 2.5% (5/200) and 3% (6/200) had subclinical and overt hyperthyroidism. Owing to the small number of subgroups, the statistical study involved the three main groups.
Thyroid studied parameters among different coronary heart disease groups
In [Table 1], as expected compared with group I, TSH levels and positive anti-TPO were statistically significantly higher but FT3 and FT4 were statistically significantly lower in group II. Group III had statistically significant higher FT3, FT4, positive anti-TPO, and thyroid gland morphological changes (diffuse enlargement, thyroid nodule, multinodular goiter) and significantly lower TSH level than group I.
Comparison of studied conventional cardiovascular risk factors by thyroid status among coronary heart disease patients
As shown in [Table 2], groups II and III were comparable to group I as regards sex, smoking, presence of DM and hypertension, 2-h pp blood glucose level, and estimated glomerular filtration rate. Group II had a significantly higher age, BMI, diastolic BP, TC and LDL-C, and TG, and significantly lower HDL-C and FPG than group 1 (P=0.002, 0.003, <0.001, <0.001, 0.001, 0.003, 0.003, 0.028, respectively). Group III had significantly higher systolic BP and significantly lower diastolic BP, TC, and LDL-C than group I (P=0.035, 0.009, 0.008, 0.006, respectively), but no significant difference as regards age, BMI, TG, and HDL-C between both groups was detected.
|Table 2 Comparative study of conventional cardiovascular risk factors among different coronary heart disease groups|
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Comparison of studied cardiac parameters among different coronary heart disease patient groups
As shown in [Table 3], groups II and III were comparable to group I as regards the presence of dyspnea and ECG ischemic changes. Group II had significantly impaired systolic and diastolic functions and higher PASP pressure than group I (P=0.03, 0.04, <0.001, respectively), with no significant difference of SWMA between the two groups. Group III had significantly higher EF and PASP and lower SWMA than Group (P<0.001, <0.001, 0.015, respectively).
|Table 3 Comparison of studied cardiac parameters among different coronary heart disease patients groups|
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Correlation of thyroid hormones levels and studied conventional cardiovascular risk factors
On one hand, TSH level had significant positive but FT3 and FT4 had significant negative correlations with diastolic BP, BMI, TC ([Figure 1]), LDL-C ([Figure 2]), and TG ([Figure 3]) (P<0.001 for all except for correlation of FT3 with diastolic BP and LDL-C, P=0.02 for both). In addition, TSH had significant positive correlation with age and negative correlations with HDL-C (P<0.001 for both, [Figure 4]), and FT4 had a significant positive correlation with systolic BP (P<0.001). No significant correlation was found between TSHs levels and DM, hypertension, smoking, and plasma glucose level ([Figure 1]).
|Figure 1 Correlation of TSH with TC among patients with CHD. CHD, coronary heart disease; TC, total cholesterol; TSH, thyroid-stimulating hormone|
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|Figure 2 Correlation of TSH with LDL among patients with CHD. CHD, coronary heart disease; LDL, low-density lipoprotein; TSH, thyroid-stimulating hormone|
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|Figure 3 Correlation of TSH with serum TG among patients with CHD. CHD, coronary heart disease; TG, triglyceride; TSH, thyroid-stimulating hormone|
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|Figure 4 Correlation of TSH with HDL cholesterol among patients with CHD. CHD, coronary heart disease; HDL, high-density lipoprotein; TSH, thyroid-stimulating hormone|
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Correlation of thyroid hormones levels previously mentioned cardiac parameters (clinically, by ECG, echocardiography, and angiography)
TSH had significant positive and FT3 had significant negative correlations with the presence of orthopnea, right-side heart failure, diastolic dysfunction, and number of coronary vessel occluded angiographic assessed (P<0.001 for all except for correlation of FT3 with angiographic data and diastolic dysfunction; P=0.002 for both). As regards other echocardiographic data, EF had a significant negative correlation with TSH level and positive correlations with FT3 and FT4 (P=0.001 for all); PASP had a significant positive correlation with TSH level and FT4 (P=0.02, <0.001, respectively); and resting wall motion abnormalities had a significant negative correlation with TSH level and FT3 (P=0.02, 0.03, respectively). FT4 had a significant negative correlation with angiographic data (P=0.001).
To evaluate the independent role of studied conventional risk factors and cardiac parameters in addition to thyroid hormones for prediction of hypothyroidism and hyperthyroidism among CHD patients, multiple logistic regression analyses were performed using all parameters that were significant in the university analyses as independent factors in [Table 4]; as expected, TSH levels were predictors for both disorders. Older age, higher pulse and BMI, the presence of orthopnea, impaired EF, diastolic dysfunction, and elevated LDL-C and TG levels were independent predictors for hypothyroidism (P=0.040, 0.037, 0.021, 0.026, 0.008, 0.044, 0.013, respectively); higher PASP was an independent predictor for hyperthyroidism (P<0.001, respectively).
|Table 4 Multiple logistic regression analysis of some risk factors for prediction of hypothyroidism and hyperthyroidism in ischemic patients|
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When the following risk factors − hypertension, DM, smoking, dyspnea, orthopnea, diastolic BP, BMI, EF, LDL-C, TC, TG, TSH, and FT3–were subjected to multiple logistic regression analysis as independent factors for prediction of severe ischemia hypertension, DM, smoking, dyspnea, orthopnea, BMI, EF, LDL-C, TC, and TSH were positive independent predictors of severe ischemia (P=0.042, 0.009, 0.008, 0.002, 0.029, 0.0388, 0.042, 0,001, 0.034, 0.004, respectively). Only free T3 was a negative predictor (P=0.001).
| Discussion|| |
To ensure that our study had considerable strength, we included the large study sample (200 CHD patients) and used coronary angiography to evaluate coronary atherosclerosis. We used more stringent exclusion criteria and the impact of potential confounders was minimized. First, we ruled out the individuals with euthyroid sick syndrome, which has a higher prevalence up to 25% in CHD patients . Second, the patients enrolled in our study were clinically stable. Acute myocardial infarction and any other acute or serious diseases were not included. Third, individuals using drugs that influence thyroid function were excluded.
Studies on the prevalence and distribution of TD have primarily been carried out in the general population and to a lesser extent in ACS ,,. Studies have rarely investigated clinically stable CHD patients with obstructive coronary lesion −to our knowledge, one small study among 81 elderly Egyptian and another large retrospective study among 568 CHD patients in China ,. Among CHD patients in our study, the prevalence of TD was 17.5 versus 23.5 and 18.5% in the previous two studies, respectively. Interestingly, the prevalence of hypothyroidism in our study was 12%, of which the prevalence was 2.5% for overt and 9.5% for subclinical forms versus 17.3, 14.8, and 2.5% among elderly Egyptians and 15.3, 5.28, and 10.05% among Chinese with CHD, respectively. In our study, the prevalence of hyperthyroidism was 5.5%, of which the prevalence was 2.5% for overt and 3% for subclinical forms versus 6.2, 2.5, and 3.7% among elderly Egyptians, respectively, and 3.3% for hyperthyroidism (overt and subclinical) among Chinese with CHD. These studies were partly matched to our result. The difference may be explained by different study design and races, and the cutoff value of TSH level may be different to identify subclinical hypothyroidism.
Despite lower prevalence of autoimmune thyroid disorder in our study (5%, 10/200) compared with the general population (8.4–11.35%) ,, its prevalence was about 37.5% of hypothyroidism and 9.1% of hyperthyroidism groups versus 0% in euthyroid. Anti TPO antibody level was positively correlated to TSH, but not to FT3 or FT4. Therefore, the presence of anti-TPO was necessitating a compensatory increase in levels of TSH and the presence of TD in CHD patients. This was supported by the study of Roos and colleagues. In contrast, it was not a predictor of severity of ischemia or of TD in our study among CHD patients. Supporting our results, positive anti-TPO was neither associated with cardiovascular risk factor nor with severity of coronary ischemia in previous studies among CHD patients ,.
Thyroid hormones affect lipid metabolism and BP . Population-based studies reported association of thyroid function even within normal range with cardiovascular risk factors ,,,,,. Similarly in CHD, we found an inverse association of both T3 and T4, and a positive association of TSH with BP, BMI, and lipid profile levels (TC, LDL-C, and TG levels); TSH was positively associated with age and inversely with HDL-C. Moreover, we studied the association of some coronary risk factors by thyroid status. In comparison with euthyroid, older age, higher diastolic BP, obesity, and atherogenic lipid profile were associated with hypothyroidism, whereas inverse lipid profile level was associated with hyperthyroidism. However, similar to Ling et al. , among patients undergoing coronary angiography, we found no association of thyroid status with the presence of DM, hypertension, smoking, and sex. The lipid abnormalities of hypothyiod and hyperthyiod groups were matched with Peppa et al. .
Some authors consider increased TSH with advanced age a normal process and consider different TSH reference ranges for different age groups . Association of obesity with hypothyroid state is explained by abolishing catabolic effect of thyroid hormones on body fats. Both T3 and T4 are vasodilators. Contributors to dystolicdysfunction in hypothyroidism even in subclinical hypothyroidism are increased peripheral vascular resistance, increased arterial stiffness and endothelial dysfunction. Thyroid hormones modulate lipid metabolism including enzyme activity, receptor expression, lipid breakdown, and clearance, thereby contributing to the expression of the lipid phenotype. Thyroid hormone deficiency and subclinical hypothyroidism were accompanied by a reduced number and activity of hepatic LDL receptor . TSH has direct action on lipid metabolism, endothelial function, and adipose tissues via binding to its own receptor. It could upregulate 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, and it may reduce hepatic LDL receptor ,. It attenuates endothelial nitric oxide and prostaglandin production and enhances adipogenesis ,.
As expected, we noticed increased prevalence of arrhythmias, especially atrial fibrillation, in hyperthyroid patients. Increased sensitivity toward circulating catecholamines, direct action of thyroid hormones on atrial ion channels, and atrial enlargement as a result of the expanded blood volume are the underlying causes .
Previous studies have reported an impaired left ventricular function among patients with overt and subclinical hypothyroidism ,, but the impact of thyroid hormone pattern on cardiac function in late post-ACS is not clear. Low thyroid hormone level is associated with increased oxidative stress, which in turn induces apoptosis . Low FT3 levels change the expression of cardiac genes and cause pathological cardiac remodeling after myocardial infarction. These lead to decreased contractility, impaired diastolic function, and reperfusion injury . In accordance with aforementioned data, a novel finding in the present study, clinical (orthopnea and right-sided heart failure) and echocardiographic (impaired EF and diastolic dysfunction) parameters of heart failure among CHD patients are more pronounced in the hypothyroid group compared with both euthyriod and hyperthyroid groups. Interestingly, these parameters were inversely correlated mainly with FT3 and to a lesser extent with FT4 (only with EF). Moreover, impaired left ventricular function was an independent predictor of hypothyroidism among CHD patients − an aspect not evaluated before. Previous studies focus on the impact of low T3 level or syndrome among patients with ACS. It was an indicator of severe cardiac injury and left ventricular functions, and a strong predictor of short-term and long-term poor prognoses. Moreover, 6-month echocardiographic left ventricular mechanics were specific and sensitive for prediction of low FT3 levels ,,,.
TD, but primarily with hyperthyroidism, may be associated with pulmonary hypertension because of increased pulmonary vascular resistance, endothelial dysfunction, endothelial and smooth muscle cell proliferation, and autoimmunity. These changes are reversible with treatment of underlying thyroid disorder . In accordance, novel findings in our study were higher PASP among CHD patients with TD predominantly among those with hyperthyroidism; also, PASP was positively correlated with TSH level and FT4 not FT3, and it was an independent predictor of hyperthyroidism among CHD patients − an aspect not mentioned before.
Association of thyroid hormones and subclinical hypothyroidism with carotid atherosclerosis is still under debate ,. We found that FT3 and FT4 levels were inversely associated and TSH concentration was positively associated with the severity of coronary atherosclerosis angiography assessed. In addition, both FT3 and TSH were independent predictors to it. Results of previous cross-sectional studies among patients undergoing coronary angiography were conflicting. Although Erta et al. , reported FT3 (neither FT4 nor TSH) was both inversely correlated with and independent predictor for severity of coronary atherosclerosis in euthyroid CHD, Linga et al. , reported that FT4 was inversely and TSH was positively, on one hand, correlated to severity of coronary atherosclerosis in the entire wide spectrum range of thyroid hormones not in the euthyroid range. In contrast, Jung et al. , reported positive associations of FT4 and coronary atherosclerosis.
The proportion of TD among patients with late post-ACS in our study was higher than the prevalence reported in the epidemiological survey (3.8–6.7%) ,.
| Conclusion|| |
The proportion of TD among patients with late post-ACS is 17.5%. Age, obesity, impaired cardiac function, and atherogenic lipid profile are predictors of hypothyroidism, and PASP is a predictor of hyperthyroidism among manifest CHD. Thyroid hormones are predictors to severity of coronary atherosclerosis and correlated to cardiac functions and PASP. These findings suggested that thyroid function screening may facilitate risk stratification in individuals with symptoms of CHD and could provide additional information for selecting the individuals who would benefit from coronary angiography.
Limitations of our study
This study has a cross-sectional design, and it is impossible to consider the causality of TD in CHD. Despite the large sample size, the small number of participants with subclinical and overt hyperthyroidism precluded precise estimates for those subgroups.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]