{"id":59332,"date":"2024-06-25T10:34:37","date_gmt":"2024-06-25T10:34:37","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=59332"},"modified":"2024-07-03T17:46:19","modified_gmt":"2024-07-03T17:46:19","slug":"lipoprotein-associated-phospholipase-a2-and-hs-crp-are-correlated-with-anti-tpo-antibodies-in-jordanian-non-pregnant-women-with-hashimotos-thyroiditis","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no2\/lipoprotein-associated-phospholipase-a2-and-hs-crp-are-correlated-with-anti-tpo-antibodies-in-jordanian-non-pregnant-women-with-hashimotos-thyroiditis\/","title":{"rendered":"Lipoprotein-Associated Phospholipase A2 and hs-CRP are Correlated with Anti-TPO Antibodies in Jordanian Non-Pregnant Women with Hashimoto\u2019s Thyroiditis"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

The thyroid gland, a vital endocrine organ, plays a central role in\nregulating metabolic, growth, and developmental processes in humans 1<\/sup>.\nServing as a major target of autoimmune disorders, the thyroid continuously\nreleases hormones, including thyroxine, triiodothyronine, and calcitonin,\ncrucial for physiological homeostasis 2<\/sup>. Notably, thyroid hormones\nexert a profound influence on the cardiovascular system, and imbalances can\nlead to a spectrum of disorders from goiter to life-threatening conditions 3,4<\/sup>. Thyroid\ndysfunction, encompassing hyper- and hypothyroidism, can precipitate heart\nfailure, fibrillation, and hypertension by impacting cardiac output,\ncontractility, vascular resistance, and rhythm 4<\/sup>. Among women of\nreproductive age, thyroid diseases are particularly prevalent, with\nhypothyroidism, hyperthyroidism, and thyroid nodules\/cancer being common\nmanifestations 1,5,6<\/sup>.\nHypothyroidism, characterized by reduced thyroid gland activity, has\nfar-reaching effects on various physiological systems, including neuromuscular,\ngastrointestinal, and cardiovascular functions, as well as lipid metabolism\nassociated with heart disease 7,8<\/sup>. Autoimmune thyroid disease\n(AITD), the most frequent thyroid dysfunction, encompasses disorders such as\nHashimoto’s thyroiditis and Graves’ disease, manifesting through the production\nof thyroid autoantibodies like Anti-TPO and thyroglobulin antibodies (Tg) 9,10<\/sup>.\nIn AITD, cardiovascular risks associated with thyroid hormone imbalance may\nresult in hemodynamic, hormonal, and metabolic changes, influencing factors\nsuch as hs-CRP and PLA2 11<\/sup>. C-reactive protein, an acute-phase\nprotein linked to inflammation, and lipoprotein-associated phospholipase A2\n(Lp-PLA2), associated with subclinical cardiovascular disease, emerge as\nsignificant markers in understanding the cardiovascular implications of thyroid\ndisorders 12,13<\/sup>. This comprehensive overview underscores the intricate\nrelationship between thyroid function, autoimmune thyroid diseases, and\ncardiovascular health.<\/p>\n\n\n\n

Methodology <\/strong><\/p>\n\n\n\n

Ethical approval<\/strong><\/p>\n\n\n\n

The institutional review board (IRB) of Faculty of\nAllied Medical Sciences at Al-Ahliyya Amman University approved this study.(IRB:\nAAU\/3\/9\/2021-2022). Data and samples were collected after written consent was\nobtained from each participant before the start of data collection.<\/p>\n\n\n\n

Sample Collection and\nHandling<\/strong><\/p>\n\n\n\n

Three to 4 ml of human blood samples were meticulously collected by standard venipuncture procedure from Talyah Medical Labs. To ensure standardization, samples were gathered after 8-12 hours of overnight fasting, with fasting times duly verified before specimen collection. The blood specimens underwent careful management in the dedicated blood withdrawal room before being promptly transported to the clinical laboratories at Talyah Medical Labs. The inclusion criteria encompass individuals aged between 20 and 50 years old, non-pregnant females, non-alcoholics, and individuals diagnosed with hypothyroidism. Conversely, the exclusion criteria involve diabetic patients, individuals with kidney or liver-related issues, as well as lactating women and those in menopause. Additionally, individuals with polycystic ovary syndrome are also excluded from the study.<\/p>\n\n\n\n

Processing and Storage<\/strong><\/p>\n\n\n\n

Upon collection in\nplain tubes, whole blood was allowed to clot at room temperature for 5 minutes.\nThe subsequent removal of the clot was achieved through centrifugation at\n3,000-3500 rpm for 5 minutes. All serum samples were judiciously stored at\n\u221220\u00b0C to maintain sample integrity, ensuring optimal conditions for subsequent\nanalyses.<\/p>\n\n\n\n

Biochemical analysis<\/strong><\/p>\n\n\n\n

Total cholesterol (TC), high-density lipoprotein\ncholesterol (HDL-C), and triglycerides (TG) were measured using enzymatic\ncolorimetric assays. In contrast, low-density lipoprotein cholesterol (LDL-C)\nlevels were calculated using Friedewald’s formula, ensuring a comprehensive\nlipid profile assessment.<\/p>\n\n\n\n

Diagnostic Biomarkers  <\/strong><\/p>\n\n\n\n

Serum thyroid-stimulating hormone <\/strong><\/p>\n\n\n\n

Thyroid-stimulating hormone ELISA Kit from Italy company (Diametra-Catalogue number: DKO013) with a reference rang from (0.27-4.2 mIU\/L) was used. This kit is used to measure TSH levels in different types of samples including: human serum and plasma. This kit is based on Direct ELISA which measures antibody concentrations using antigen-coated bounded in the microELISA (Alhajj & farhana, 2021). The micro-ELISA plate provided in this kit has been pre-coated with conjugated antibody specific to TSH. Standards or samples were added to the appropriate Micro-ELISA plate wells were combined with specific antibody. Then, a Horseradish Peroxidase (HRP)-conjugated antibody was added to each micro-ELISA plate well and incubated for 90 minutes at room temperature. After incubation, the free components were washed away. <\/p>\n\n\n\n

Tetramethylbenzidine (TMB) substrate\nsolution was added to each well followed by incubation for 20 minutes at room\ntemperature. Only those wells that contain TSH and HRP conjugated-TSH antibody\nappeared as blue color and then turned into yellow after the addition of the\nstop solution. The optical density (OD) was measured spectrophotometrically\nusing ELISA reader at a wavelength of 450 nm. The OD value is proportional to\nthe concentration of TSH. Concentration of TSH in the samples was calculated by\ncomparing the OD of the samples to the standard curve. The sensitivity of the\ntest is 0.01 mIU\/L.<\/p>\n\n\n\n

Serum thyroid hormone<\/strong><\/p>\n\n\n\n

Free thyroxin hormone ELISA Kit was obtained from Italy company (Diametra- catalogue number: DKO038) with a reference rang from (12-22 pmol\/l)  and used for analysis. This kit is used to measure FT4 levels in different types of samples including: human serum, plasma. This kit is based on Direct enzyme-linked immunosorbent assay ELISA type. The micro-ELISA plate provided in this kit has been pre-coated with an antibody specific to FT4. Standards or samples were added to the appropriate Micro-ELISA plate wells were combined.  A HRP-conjugated antibody specific for FT4 was added to each micro-ELISA plate well and incubated for 1 Hour at room temperature. After incubation, the free components were washed away. <\/p>\n\n\n\n

TMB substrate\nsolution was added to each well and incubate for 15 minutes at room\ntemperature. Only those wells that contain FT4 and HRP conjugated-FT4 antibody\nappeared as blue color and then turned into yellow after the addition of the\nstop solution. The OD was measured spectrophotometrically using ELISA reader at\na wavelength of 450 nm. The OD value is proportional to the concentration of\nFT4. Concentration of FT4 in the samples was calculated by comparing the OD of\nthe samples to the standard curve. The sensitivity of the test is 0.11 pmol\/L <\/p>\n\n\n\n

Serum Phospholipase A2, Lipoprotein Associated<\/strong><\/p>\n\n\n\n

Serum PLA2, from USA company (MyBioSource-catalogue number: MBS035611) was used. This kit is based on Sandwich ELISA type which measures antigen concentrations using antibody-coated bounded in the microELISA (Alhajj & farhana, 2021). MicroELISA plate was pre-coated with an antibody specific to PLA2. Standards or samples are added to the appropriate microELISA plate wells and combined to the specific antibody. Horseradish Peroxidase-conjugated antibody specific for PLA2 was added to microELISA plate well and incubated for 60 minutes at 37\u00b0C and then the free components were washed away. Chromogen solution A&B was added to each well, then, was incubated for 15 minutes at 37\u00b0C. Only those wells that contain PLA2 and HRP conjugated PLA2 antibody appeared as blue color and then turned into yellow after the addition of the stop solution. The OD, was measured spectrophotometrically at a wavelength of 450 nm, was proportional to the PLA2 levels in the serum samples. The levels of PLA2 ranged from 6.25- 200 ng\/ml for serum. The sensitivity of the test was 1.0 ng\/ml. <\/p>\n\n\n\n

Serum anti-thyroid peroxidase<\/strong><\/p>\n\n\n\n

Serum anti-TPO levels were measured using the human anti-TPO ELISA Kit for Germany company (Aesku- catalogue number: 3401) with a reference rang from (40 IU\/ml)  using Sandwich enzyme immunoassay-ELISA method. The Microelisa strip plate provided in this kit has been pre-coated with an antibody specific to anti-TPO. Standards or samples are added to the appropriate Microelisa strip plate wells and combined to the specific antibody. Then, a Horseradish Peroxidase-conjugated antibody specific for anti-TPO was added to Microelisa strip plate well and incubated for 30 minutes at room temperature and then the free components were washed away. The Conjugate was added to each well and incubated for 30 minutes at room temperature then the free components were washed away.<\/p>\n\n\n\n

The TMB substrate solution was added\nto each well incubate for 30 minutes at room temperature. Only those wells that\ncontain anti-TPO and HRP conjugated anti-TPO antibody appeared blue in color\nand then turned yellow after the addition of the stop solution Incubate 5\nminutes minimum. The OD, was measured spectrophotometrically at a wavelength of\n450 nm, was proportional to the anti-TPO levels in the serum samples. The\nlevels of anti-TPO ranged from 0-3000 IU\/ml for serum. The sensitivity of the\ntest was 10 IU\/ml.<\/p>\n\n\n\n

Serum high sensitivity C-Reactive Protein       <\/strong><\/p>\n\n\n\n

Serum High Sensitivity C-Reactive\nprotein ELISA Kit for USA company (Monobind – catalogue number:3125-300) with a\nreference rang from (< 3 \u03bcg\/ml) was used. This kit is used to measure hs-CRP\nlevels in different types of samples including: human serum, and plasma. This\nkit is based on Sandwich assay ELISA type. MicroELISA plate provided in this\nkit has been pre-coated with an antibody specific to hs-CRP. Standards or\nsamples were added to the appropriate wells of microELISA plate and combined\nwith the specific antibody. A Horseradish Peroxidase (HRP)-conjugated antibody\nspecific for hs-CRP was added to each microELISA plate well and incubated for\n15 minutes at room temperature. After incubation, the free components were\nwashed away. <\/p>\n\n\n\n

TMB and hydrogen peroxide (H2O2) solution substrate was added to each well and incubated for 15 minutes at room temperature. Only those wells that contain hs-CRP and HRP conjugated-hs-CRP antibodies were appeared as blue in color and then turned into yellow after the addition of the stop solution. The OD was measured spectrophotometrically using ELISA reader at a wavelength of 450 nm. The OD value is proportional to the concentration of hs-CRP. The concentration of hs-CRP in the samples was calculated by comparing the OD of the samples to the standard curve. The sensitivity of the test is 0.014 \u03bcg\/ml.<\/p>\n\n\n\n

Statistical analysis<\/strong><\/p>\n\n\n\n

SPSS V.22 was used for\ndata analysis, including Chi-square tests for demographic and clinical parameters,\nand independent t-tests for quantitative data with significance at p < 0.05.\nThe study also investigated correlations between thyroid markers and\ncardiovascular risk factors using Pearson\u2019s correlations in univariate linear\nregression analysis.<\/p>\n\n\n\n

Results <\/strong><\/p>\n\n\n\n

Frequency of abnormal\nvalues of clinical parameters in patients and healthy subjects.<\/strong><\/p>\n\n\n\n

The study included 90\nfemale participants aged 20 to 50, divided into a patient group (n = 50) and a healthy subjects group (n = 40) matched for age and inclusion criteria\n(table 1). Hypothyroidism patients exhibited a significantly higher frequency\nof decreased FT4 levels (***p=0.0001) and increased anti-TPO levels (***p=0.0001)\ncompared to healthy\nindividuals (figure 1). Additionally,\nhypothyroidism patients showed a higher prevalence of abnormal LDL cholesterol\n(***p=0.001), HDL levels (**p=0.040), and elevated hs-CRP (**p=0.005),\nindicating an association with cardiovascular and hypothyroidism risk factors\n(figure 2).<\/p>\n\n\n\n

Table 1: Frequency of high-risk levels of thyroid gland abnormalities in the two groups of study hypothyroidism patients and healthy individuals.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Parameter<\/strong><\/p>\n<\/td>\n

\n

Healthy subjects<\/strong><\/p>\n<\/td>\n

\n

Hypothyroidism patients<\/strong><\/p>\n<\/td>\n

\n

P.value<\/strong><\/p>\n<\/td>\n

\n

Chi-Square<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

FT4 (pmol\/L)<\/p>\n<\/td>\n

\n

Normal<\/p>\n<\/td>\n

\n

39 (97.5%)<\/p>\n<\/td>\n

\n

17 (34.0%)<\/p>\n<\/td>\n

\n

0.0001***<\/p>\n<\/td>\n

\n

38.120<\/p>\n<\/td>\n<\/tr>\n

\n

High risk, < 12<\/p>\n<\/td>\n

\n

1 (2.5%)<\/p>\n<\/td>\n

\n

33 (66.0%)<\/p>\n<\/td>\n<\/tr>\n

\n

Anti-TPO (IU\/ml)<\/p>\n<\/td>\n

\n

Normal<\/p>\n<\/td>\n

\n

33 (82.5%)<\/p>\n<\/td>\n

\n

14 (28.0%)<\/p>\n<\/td>\n

\n

0.0001***<\/p>\n<\/td>\n

\n

26.454<\/p>\n<\/td>\n<\/tr>\n

\n

High risk, > 40<\/p>\n<\/td>\n

\n

7 (17.5%)<\/p>\n<\/td>\n

\n

36 (72.0%)<\/p>\n<\/td>\n<\/tr>\n

\n

hs-CRP (\u03bcg\/ml)<\/p>\n<\/td>\n

\n

Low risk, \u2264 3<\/p>\n<\/td>\n

\n

38 (95.0%)<\/p>\n<\/td>\n

\n

36 (72.0%)<\/p>\n<\/td>\n

\n

0.005**<\/p>\n<\/td>\n

\n

8.042<\/p>\n<\/td>\n<\/tr>\n

\n

High risk, > 3<\/p>\n<\/td>\n

\n

2 (5.0%)<\/p>\n<\/td>\n

\n

14 (28.0%)<\/p>\n<\/td>\n<\/tr>\n

\n

LDL (mg\/dl)<\/p>\n<\/td>\n

\n

Normal<\/p>\n<\/td>\n

\n

25 (62.5%)<\/p>\n<\/td>\n

\n

14 (28.0%)<\/p>\n<\/td>\n

\n

0.001***<\/p>\n<\/td>\n

\n

10.771<\/p>\n<\/td>\n<\/tr>\n

\n

High risk,>100<\/p>\n<\/td>\n

\n

15 (37.5%)<\/p>\n<\/td>\n

\n

36 (72.0%)<\/p>\n<\/td>\n<\/tr>\n

\n

HDL (mg\/dl)<\/p>\n<\/td>\n

\n

Normal<\/p>\n<\/td>\n

\n

30 (75.0%)<\/p>\n<\/td>\n

\n

27 (54.0%)<\/p>\n<\/td>\n

\n

  0.040**<\/p>\n<\/td>\n

\n

4.220<\/p>\n<\/td>\n<\/tr>\n

\n

High risk, < 45<\/p>\n<\/td>\n

\n

10 (25.0%)<\/p>\n<\/td>\n

\n

     23 (46.0%)<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

*For Significant P-values<\/p>\n\n\n\n
\"\"<\/td>\n\n

Figure 1: Frequency of normal and increased anti-TPO levels in both healthy subjects and hypothyroidism patients.<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 2: Frequency of normal and increased hs-CRP levels in <\/strong>both healthy subjects and hypothyroidism patients.<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Clinical and laboratory characteristics<\/strong><\/p>\n\n\n\n

Table 2 summarizes the clinical and\nlaboratory characteristics of both hypothyroidism patients and healthy individuals.\nThe mean age showed no significant difference between the two groups. However,\nhypothyroidism patients exhibited significantly higher levels of hs-CRP (1.27 \u00b1\n0.94 vs. 0.04 \u00b1 0.02, p<0.0001), phospholipase-A2 (57.28 \u00b1 21.96 vs. 47.15 \u00b1\n12.92, p=0.012), and anti-TPO (103.51 \u00b1 91.80 vs. 30.32 \u00b1 15.14, p<0.001)\ncompared to the healthy\nsubjects.<\/p>\n\n\n\n

Furthermore, hypothyroidism patients\ndisplayed significantly elevated TSH levels (7.09 \u00b1 2.81 vs. 2.06 \u00b1 0.81,\np<0.001) and lower FT4 levels (9.41 \u00b1 4.68 vs. 16.19 \u00b1 2.52, p<0.001)\ncompared to the healthy group.<\/p>\n\n\n\n

Regarding lipid profiles, hypothyroidism\npatients had higher mean levels of serum total cholesterol (207.84 \u00b1 49.78 vs.\n168.11 \u00b1 47.27, p=0.0001) and LDL (137.51 \u00b1 49.52 vs. 94.05 \u00b1 41.62, p=0.0001)\ncompared to the healthy group. However, there were no statistical differences\nin serum HDL and triglyceride concentrations between the two groups (p=0.26 and\np=0.183, respectively).<\/p>\n\n\n\n

Table 2: Comparison of laboratory data between Hypothyroidism patients and healthy subjects.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

    parameter<\/strong><\/p>\n<\/td>\n

\n

Healthy subjects<\/strong><\/p>\n

(No=36)<\/strong><\/p>\n<\/td>\n

\n

Hypothyroidism patients (No=44)<\/strong><\/p>\n<\/td>\n

\n

P-value<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Anti-TPO (IU\/ml)<\/p>\n<\/td>\n

\n

30.32 \u00b1 15.14<\/p>\n<\/td>\n

\n

103.51 \u00b1 91.80<\/p>\n<\/td>\n

\n

<0.001\u066d**<\/p>\n<\/td>\n<\/tr>\n

\n

TSH (mIU\/L)<\/p>\n<\/td>\n

\n

2.06 \u00b1 0.81<\/p>\n<\/td>\n

\n

7.09 \u00b1 2.81<\/p>\n<\/td>\n

\n

<0.001\u066d**<\/p>\n<\/td>\n<\/tr>\n

\n

 FT4 (pmol\/L)<\/p>\n<\/td>\n

\n

16.19 \u00b1 2.52<\/p>\n<\/td>\n

\n

9.41 \u00b1 4.68<\/p>\n<\/td>\n

\n

<0.001\u066d**<\/p>\n<\/td>\n<\/tr>\n

\n

PLA2 (ng\/ml)<\/p>\n<\/td>\n

\n

47.15 \u00b112.92<\/p>\n<\/td>\n

\n

57.28 \u00b1 21.96<\/p>\n<\/td>\n

\n

0.012\u066d<\/p>\n<\/td>\n<\/tr>\n

\n

Hs-CRP (\u03bcg\/ml)<\/p>\n<\/td>\n

\n

0.04 \u00b1 0.02<\/p>\n<\/td>\n

\n

1.27 \u00b1 0.94<\/p>\n<\/td>\n

\n

<0.001\u066d**<\/p>\n<\/td>\n<\/tr>\n

\n

LDL (mg\/dl)<\/p>\n<\/td>\n

\n

94.05 \u00b1 41.62<\/p>\n<\/td>\n

\n

137.51 \u00b1 49.52<\/p>\n<\/td>\n

\n

<0.001**\u066d<\/p>\n<\/td>\n<\/tr>\n

\n

HDL (mg\/dl)<\/p>\n<\/td>\n

\n

52.77 \u00b1 12.16<\/p>\n<\/td>\n

\n

49.15 \u00b1 16.67<\/p>\n<\/td>\n

\n

0.26<\/p>\n<\/td>\n<\/tr>\n

\n

TG (mg\/dl)<\/p>\n<\/td>\n

\n

98.36 \u00b1 41.70<\/p>\n<\/td>\n

\n

113.90 \u00b1 61.25<\/p>\n<\/td>\n

\n

0.18<\/p>\n<\/td>\n<\/tr>\n

\n

TC (mg\/dl)<\/p>\n<\/td>\n

\n

168.11\u00b1 47.27<\/p>\n<\/td>\n

\n

207.84 \u00b1 49.78<\/p>\n<\/td>\n

\n

<0.001\u066d<\/p>\n<\/td>\n<\/tr>\n

\n

LDL-HDL<\/p>\n<\/td>\n

\n

1.90 \u00b1 0.97<\/p>\n<\/td>\n

\n

3.13 \u00b1 1.62<\/p>\n<\/td>\n

\n

< 0.001\u066d<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

TC; total cholesterol, TG; triglycerides, PLA2; phospholipase A2, TSH; thyroid stimulating hormone, HDL; high-density lipoprotein cholesterol, LDL; low-density lipoprotein cholesterol, hs-CRP; high sensitivity C-reactive protein, anti-TPO; anti-thyroid peroxidase, T4; thyroxine, *; significantly p-value.<\/p>\n\n\n

Correlations of age with different parameters in hypothyroidism patients and healthy subjects.<\/strong><\/p>\n\n\n\n

Table 3 illustrates the correlation between\nage and various health parameters in both healthy subjects and\nhypothyroidism patients. Among healthy subjects, age showed no significant\ncorrelation with thyroid parameters (TSH, anti-TPO) and cardiovascular markers (PLA2,\nLDL, HDL). However, a significant positive correlation was observed between age\nand hs-CRP (r = -0.307, P = 0.030), while a significant negative correlation\nwas found with FT4 (r = -0.335, P = 0.017).<\/p>\n\n\n\n

In contrast, among hypothyroidism patients,\nthere was no statistical correlation between age and TSH, PLA2, LDL, HDL, and\nanti-TPO.<\/p>\n\n\n\n

Table 3: Correlations of age with different parameters in non-pregnant women with hypothyroidism and healthy subjects.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

 <\/strong>Parameters<\/strong><\/p>\n<\/td>\n

\n

Healthy subjects<\/strong><\/p>\n<\/td>\n

\n

Hypothyroidism patients<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Correlation<\/strong><\/p>\n

Coefficient (r)<\/strong><\/p>\n<\/td>\n

\n

P value<\/strong><\/p>\n<\/td>\n

\n

Correlation<\/strong><\/p>\n

Coefficient (r)<\/strong><\/p>\n<\/td>\n

\n

P value<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Age vs FT4<\/strong><\/p>\n<\/td>\n

\n

0.109<\/p>\n<\/td>\n

\n

0.504<\/p>\n<\/td>\n

\n

-0.335<\/p>\n<\/td>\n

\n

0.017<\/p>\n<\/td>\n<\/tr>\n

\n

Age vs TSH<\/strong><\/p>\n<\/td>\n

\n

0.184<\/p>\n<\/td>\n

\n

0.256<\/p>\n<\/td>\n

\n

0.145<\/p>\n<\/td>\n

\n

0.314<\/p>\n<\/td>\n<\/tr>\n

\n

Age vs Anti-TPO<\/strong><\/p>\n<\/td>\n

\n

0.100<\/p>\n<\/td>\n

\n

0.541<\/p>\n<\/td>\n

\n

-0.017<\/p>\n<\/td>\n

\n

0.906<\/p>\n<\/td>\n<\/tr>\n

\n

Age vs Phospholipase A2<\/strong><\/p>\n<\/td>\n

\n

0.175<\/p>\n<\/td>\n

\n

0.280<\/p>\n<\/td>\n

\n

0.009<\/p>\n<\/td>\n

\n

0.950<\/p>\n<\/td>\n<\/tr>\n

\n

Age vs Hs-CRP<\/strong><\/p>\n<\/td>\n

\n

-0.146<\/p>\n<\/td>\n

\n

0.370<\/p>\n<\/td>\n

\n

0.307<\/p>\n<\/td>\n

\n

0.030<\/p>\n<\/td>\n<\/tr>\n

\n

Age vs LDL<\/strong><\/p>\n<\/td>\n

\n

0.017<\/p>\n<\/td>\n

\n

0.919<\/p>\n<\/td>\n

\n

-0.044<\/p>\n<\/td>\n

\n

0.762<\/p>\n<\/td>\n<\/tr>\n

\n

Age vs HDL<\/strong><\/p>\n<\/td>\n

\n

-0.271<\/p>\n<\/td>\n

\n

0.091<\/p>\n<\/td>\n

\n

-0.060<\/p>\n<\/td>\n

\n

0.678<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Correlation between thyroid function\nbiomarkers and cardiovascular risk factors in Hashimoto\u2019s patients<\/strong><\/p>\n\n\n\n

Table 4 presents the correlation analysis\nresults for various parameters. PLA2 demonstrates a moderate positive and\nsignificant correlation with TSH (r = 0.461, p=0.001), but no significant\ncorrelation is observed with FT4 and anti-TPO. Both LDL and HDL do not show\nsignificant correlations with thyroid gland function tests (FT4, TSH,\nanti-TPO).<\/p>\n\n\n\n

Furthermore, hs-CRP exhibits a positive and\nsignificant correlation with anti-TPO (r= 0.352, p=0.012), while hs-CRP shows a\nnegative and significant correlation with FT4. However, no significant\ncorrelation is observed between hs-CRP and TSH.<\/p>\n\n\n\n

Table 4: Correlation analysis between thyroid function biomarkers and cardiovascular risk factors.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
\n

Cardiovascular parameter <\/strong><\/p>\n<\/td>\n

\n

                                Thyroid markers<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

  FT4<\/strong><\/p>\n<\/td>\n

\n

TSH<\/strong><\/p>\n<\/td>\n

\n

Anti-TPO<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Correlation<\/strong><\/p>\n

Coefficient (r)<\/strong><\/p>\n<\/td>\n

\n

P-value<\/strong><\/p>\n<\/td>\n

\n

Correlation<\/strong><\/p>\n

Coefficient (r)<\/strong><\/p>\n<\/td>\n

\n

P-value<\/strong><\/p>\n<\/td>\n

\n

Correlation<\/strong><\/p>\n

Coefficient (r)<\/strong><\/p>\n<\/td>\n

\n

P-value<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

PLA2<\/strong><\/p>\n<\/td>\n

\n

-0.032<\/p>\n<\/td>\n

\n

0.823<\/p>\n<\/td>\n

\n

0.461<\/p>\n<\/td>\n

\n

0.001<\/p>\n<\/td>\n

\n

0.147<\/p>\n<\/td>\n

\n

0.308<\/p>\n<\/td>\n<\/tr>\n

\n

hs-CRP<\/strong><\/p>\n<\/td>\n

\n

-0.304<\/p>\n<\/td>\n

\n

0.032<\/p>\n<\/td>\n

\n

0.242<\/p>\n<\/td>\n

\n

0.090<\/p>\n<\/td>\n

\n

0.352<\/p>\n<\/td>\n

\n

0.012<\/p>\n<\/td>\n<\/tr>\n

\n

LDL<\/strong><\/p>\n<\/td>\n

\n

-0.168<\/p>\n<\/td>\n

\n

0.244<\/p>\n<\/td>\n

\n

0.190<\/p>\n<\/td>\n

\n

0.186<\/p>\n<\/td>\n

\n

0.176<\/p>\n<\/td>\n

\n

0.223<\/p>\n<\/td>\n<\/tr>\n

\n

HDL<\/strong><\/p>\n<\/td>\n

\n

0.084<\/p>\n<\/td>\n

\n

0.564<\/p>\n<\/td>\n

\n

0.214<\/p>\n<\/td>\n

\n

0.136<\/p>\n<\/td>\n

\n

-0.047<\/p>\n<\/td>\n

\n

0.745<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Discussion <\/strong><\/p>\n\n\n\n

Hashimoto’s thyroiditis, an autoimmune\nthyroid disease characterized by thyroid volume increase, parenchymal\nlymphocyte infiltration, and antibodies against thyroid antigens, has become\nthe most prevalent disorder in thyroid gland dysfunction. Patients with\nHashimoto’s thyroiditis (HT) are more prone to cardiovascular disease and\nmalignant neoplasms. Our unique\nstudy, focusing specifically on non-pregnant women with hypothyroidism (mean\nage 32.1 years), aligns with demographic data from the HT community, emphasizing\nthe distinctiveness of our study group. Notably, the prevalence of Hashimoto’s\nthyroiditis is higher in women than in males 14<\/sup>, and females are\nmore likely to experience autoimmune thyroid disease (AITD) and hypothyroidism 15,16<\/sup>.<\/p>\n\n\n\n

Diagnosis\nof Hashimoto’s thyroiditis involves clinical symptoms and laboratory results,\nincluding high TSH levels with normal to low thyroxine levels. Despite limited\nevidence that anti-thyroid peroxidase antibodies (anti-TPO) contribute to\nautoimmune thyroid disease onset, anti-TPO antibody treatments aid in\ncomplement function recovery. Our study underscores the importance of using\nanti-TPO as a first-tier test in conjunction with TSH and FT4 to prevent\noverlooking individuals with normal TSH but increased autoantibodies.\nAdditionally, we explore the association between Hashimoto’s and cardiac\nmarkers such as PLA2, hs-CRP, and lipid profile, aiming to identify potential\ncost-effective strategies for long-term conditions like thyroid cancer and\ncardiovascular disease prevalent in women of childbearing age. Our findings\nreveal increased TSH levels and low thyroxine levels in Hashimoto\u2019s disease,\nconsistent with prior research 17<\/sup>, emphasizing the endothelium’s\nsensitivity to thyroid hormone action 18<\/sup>.<\/p>\n\n\n\n

TSH levels\nserve as useful indicators of cardiovascular disease (CVD) in hypothyroid\npatients 19<\/sup>. Our study aligns with others, showing an increased\ncardiovascular risk in hypothyroidism with higher TSH levels 20<\/sup>.\nNotably, our research supports the significant increase in anti-TPO levels in\nHashimoto\u2019s patients, consistent with prior studies 9<\/sup>.<\/p>\n\n\n\n

Demographic\nvariations include higher TSH levels and antithyroid antibodies in females,\ninfluenced by age and higher in whites and Mexican Americans compared to blacks\n21<\/sup>. Increased\ncirculating thyroid autoantibodies are linked to an atherogenic lipid profile,\nwith the potential link between autoimmune thyroiditis and dyslipidemia leading\nto heart disease 22,23<\/sup>.<\/p>\n\n\n\n

Lipoprotein-associated\nphospholipase A2 (PLA2) is implicated in atherosclerosis progression by\npromoting cholesterol migration into arterial plaques. Clinical studies confirm\nincreased PLA2 activity as a risk factor for cardiovascular disease 24<\/sup>.\nOur study identifies PLA2 as a potential predictor of cardiovascular disease\nrisk. Elevated PLA2 levels, produced by inflammatory cells and linked to\ncardiovascular disease risk 25<\/sup>, theoretically induce atherogenesis\nby impairing endothelial function through inflammation, lipid abnormalities,\noxidative stress, and blood pressure 26<\/sup>.<\/p>\n\n\n\n

Increased\nhs-CRP levels, consistent with previous reports 27<\/sup>, highlight the\nimportance of assessing inflammatory status in cardiovascular risk\nstratification. However, our study found no significant difference in hs-CRP\nlevels between subclinical hypothyroidism patients and the healthy\nsubjects group.<\/p>\n\n\n\n

The study\nsupports the link between hypothyroidism and dyslipidemia, with patients\nexhibiting hyperlipidemia and high cholesterol levels 28<\/sup>. However,\nconflicting evidence exists regarding the association between hypothyroidism\nand atherosclerosis risk 29<\/sup>. HDL reduction in Hashimoto’s disease,\nconsistent with earlier findings, and its negative correlation with anti-TPO\nlevels underscore the link between autoimmunity and lipid profile 12<\/sup>.<\/p>\n\n\n\n

Positive\ncorrelations between TSH and cardiovascular risk markers, including PLA2-IIA\nand TG, support the concept that hypothyroidism increases the risk of\natherosclerosis 30<\/sup>. The study confirms the link between\nhypothyroidism and inflammation, with significantly higher levels of PLA2-IIA\nand hs-CRP in the hypothyroidism group compared to the healthy subjects group.\nPrevious research supports the correlation between Lp-PLA2, hs-CRP levels, and\ncardiovascular risk 24<\/sup>.<\/p>\n\n\n\n

Strong\nevidence indicates that hypothyroidism raises cardiovascular disease and\natherosclerosis risk by increasing LDL levels 31<\/sup>. Premenopausal\nwomen with hypothyroidism are more susceptible to cardiovascular disease than\nthose with normal thyroid function 32<\/sup>. The study emphasizes the\nimpact of autoimmune disease on the lipid profile, supporting the positive\nassociation between PLA2 and TSH, higher levels of LDL, cholesterol, and hs-CRP\nin Hashimoto\u2019s disease patients, suggesting an increased risk of heart disease 33<\/sup>.<\/p>\n\n\n\n

In conclusion, our findings in Hashimoto\u2019s\npatients reveal significant correlations between thyroid disease, thyroid\nautoimmunity, PLA2, lipid profile, and hs-CRP, suggesting an elevated\ncardiovascular risk in adult non-pregnant women with Hashimoto\u2019s thyroiditis.\nAnti-thyroid peroxidase antibody positivity is more common in this population\ncompared to healthy\nsubjects. The study establishes an association between Hashimoto\u2019s\ndisease and increased cardiovascular risk markers, specifically PLA2 and hs-CRP\nlevels. This research contributes to the understanding of biochemical\nparameters in Hashimoto’s disease, especially in the context of Jordan,\nemphasizing the importance of comprehensive assessments for cardiovascular risk\nin this patient population.<\/p>\n\n\n\n

Acknowledgment<\/strong> <\/p>\n\n\n\n

The authors would like to thank all staff\nat the lab staff of Talyah Medical Laboratory, for their cooperation.<\/p>\n\n\n\n

Funding source<\/strong><\/p>\n\n\n\n

This research was supported by Al-Ahliyya\nAmman University, Jordan with grant No.2023\/17-5.<\/p>\n\n\n\n

Conflicts of Interest<\/strong><\/p>\n\n\n\n

The authors declare no conflict of\ninterest.<\/p>\n\n\n\n

References <\/strong><\/p>\n\n\n\n

  1. Beynon ME, Pinneri K. An overview of the thyroid gland and thyroid-related deaths for the forensic pathologist. Acad Forensic Pathol<\/em>. 2016;6(2):217-236. doi:10.23907\/2016.036
    CrossRef<\/a><\/li>
  2. Barbieri A, Prasad ML, Gilani SM. Thyroid tissue outside the thyroid gland: Differential diagnosis and associated diagnostic challenges. Ann Diagn Pathol<\/em>. 2020;48:151584.
     CrossRef <\/a><\/li>
  3. Yamakawa H, Kato TS, Noh JY, Yuasa S, Kawamura A, Fukuda K, Aizawa Y. Thyroid Hormone Plays an Important Role in Cardiac Function: From Bench to Bedside. Front Physiol.<\/em> 2021;12:606931.
     CrossRef <\/a><\/li>
  4. Awad SAS, Ashraf EM, Khaled AS, Salih BS, Yousef S, Abeer et al. The epidemiology of thyroid diseases in the Arab world: A systematic review. J Public Health Epidemiol<\/em>. 2016;8(2):17-26. doi:10.5897\/JPHE2015.0770
     CrossRef <\/a><\/li>
  5. Brown EDL, Obeng-Gyasi B, Hall JE, Shekhar S. The Thyroid Hormone Axis and Female Reproduction. Int J Mol Sci.<\/em> 2023;24(12):9815.
     CrossRef <\/a><\/li>
  6. Burnett M. Injury Prevention Strategies for Pre-Professional and Professional Ballet Dancers [doctoral dissertation]. Am Univ<\/em>. 2021.
     CrossRef <\/a><\/li>
  7. Sharma A, Arya R, Mehta R, Sharma R, K Sharma A. Hypothyroidism and cardiovascular disease: factors, mechanism and future perspectives. Curr Med Chem<\/em>. 2013;20(35):4411-4421. doi:10.2174\/09298673113209990190<\/li>
  8. Udovocic M, Pena RH, Patham B, Tabatabai L, Kansara A. Hypothyroidism and the Heart. Methodist DeBakey Cardiovasc J<\/em>. 2017;13(2):55. doi:10.14797\/mdcj-13-2-55
     CrossRef <\/a><\/li>
  9. Siriwardhane T, Krishna K, Ranganathan V, Jayaraman V, Wang T, Bei K, et al. Significance of anti-TPO as an early predictive marker in thyroid disease. Autoimmune Dis<\/em>. 2019;2019:1684074.
    CrossRef <\/a><\/li>
  10. Liontiris MI, Mazokopakis EE. A concise review of Hashimoto thyroiditis (HT) and the importance of iodine, selenium, vitamin D and gluten on the autoimmunity and dietary management of HT patients. Hell J Nucl Med<\/em>. 2017;20(1):51-56.
    CrossRef <\/li>
  11. Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet<\/em>. 2017;390(10101):1550-1562.
     CrossRef <\/a><\/li>
  12. Nik MHS, Darabi M, Ziaee A, Hajmanoochehri F. Serum phospholipase A2-IIA, hs-CRP, and lipids in women with subclinical hypothyroidism. Int J Endocrinol Metab<\/em>. 2014;12(3):e17652. doi:10.5812\/ijem.17652.
     CrossRef <\/a><\/li>
  13. Younus A, Humayun C, Ahmad R, Ogunmoroti O, Kandimalla Y, Aziz M, et al. Lipoprotein-associated phospholipase A2 and its relationship with markers of subclinical cardiovascular disease: A systematic review. J Clin Lipidol<\/em>. 2017;11(2):328-337. doi:10.1016\/j.jacl.2016.12.016
     CrossRef<\/a> <\/li>
  14. Gabrielson AT, Sartor RA, Hellstrom WJ. The impact of thyroid disease on sexual dysfunction in men and women. Sex Med Rev<\/em>. 2019;7(1):57-70. doi:10.1016\/j.sxmr.2018.06.003
     CrossRef <\/a><\/li>
  15. Mammen JSR, Cappola AR. Autoimmune Thyroid Disease in Women. JAMA. 2021;325(23):2392-2393.
     CrossRef <\/a><\/li>
  16. Hussein TA, Othman RA, Oudah MK. The prevalence of thyroid stimulating blocking antibodies TSBAbs in newly diagnosed patients with AITD. Prevalence<\/em>. 2022;140(01).<\/li>
  17. Mincer DL, Jialal I. Hashimoto Thyroiditis. 2023 Jul 29. In: StatPearls [Internet]. Treasure Island (FL): StatPearls.<\/li>
  18. Jankauskas SS, Morelli MB, Gambardella J, Lombardi A, Santulli G. Thyroid hormones regulate both cardiovascular and renal mechanisms underlying hypertension. J Clin Hypertens (Greenwich). 2021;23(2):373-381.
     CrossRef <\/a><\/li>
  19. Delitala AP, Fanciulli G, Maioli M, Delitala G. Subclinical hypothyroidism, lipid metabolism and cardiovascular disease. 2017;28040402.
     CrossRef <\/a><\/li>
  20. Rodondi N, Den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh J et al; Thyroid Studies Collaboration. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA<\/em>. 2010;304(12):1365-1374. doi:10.1001\/jama.2010.1361
     CrossRef <\/a><\/li>
  21. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer et al. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab<\/em>. 2002;87(2):489-499.
     CrossRef <\/a><\/li>
  22. Diab N, Daya NR, Juraschek SP, Martin SS, McEvoy JW, Schulthei\u00df UT, K\u00f6ttgen A, Selvin E. Prevalence and Risk Factors of Thyroid Dysfunction in Older Adults in the Community. Sci Rep. 2019;9(1):13156.
    CrossRef<\/a><\/li>
  23. Tipu SAA, Fantazy K. Exploring the relationships of strategic entrepreneurship and social capital to sustainable supply chain management and organizational performance. Int J Product Perform Manage<\/em>. 2018.
     CrossRef <\/a><\/li>
  24. Cengiz H, Demirci T, Varim C, Tamer A. The effect of Thyroid Autoimmunity on Dyslipidemia in patients with Euthyroid Hashimoto Thyroiditis. Pak J Med Sci<\/em>. 2021;37(5):1365. doi:10.12669\/pjms.37.5.3447591
     CrossRef <\/a><\/li>
  25. Zhang L, Li Z, Li N. Serum IMA and LP-PLA2 Levels in Patients with Coronary Heart Disease and Their Correlation with the Degree of Myocardial Ischaemia and Their Diagnostic Value. Emerg Med Int<\/em>. 2022;2022:35726302.
    CrossRef <\/a><\/li>
  26. Clark K, Sharp S, Womack CJ, Kurti SP, Hargens TA. Increased sedentary time and decreased physical activity increases lipoprotein associated phospholipase A2 in obese individuals. Nutr Metab Cardiovasc Dis<\/em>. 2022;1703-1710. doi:10.1016\/j.numecd.2022.02.002
     CrossRef <\/a><\/li>
  27. Kvetny J, Heldgaard PE, Bladbjerg EM, Gram J. Subclinical hypothyroidism is associated with a low\u2010grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years. Clin Endocrinol (Oxf)<\/em>. 2004;61(2):232-238. doi:10.1111\/j.1365-2265.2004.02062.x
     CrossRef <\/a><\/li>
  28. Dey A, Kanneganti V, Das D. A study of the cardiac risk factors emerging out of subclinical hypothyroidism. J Family Med Prim Care<\/em>. 2019;8(7):2439. doi:10.4103\/jfmpc.jfmpc_482_19
    CrossRef <\/a><\/li>
  29. Liu H, Peng D. Update on dyslipidemia in hypothyroidism: the mechanism of dyslipidemia in hypothyroidism. Endocr Connect<\/em>. 2022;11(2):e210002.
     CrossRef <\/a><\/li>
  30. 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<\/em>. 2009;203(1):269-276. doi:10.1016\/j.atherosclerosis.2008.07.023
     CrossRef <\/a><\/li>
  31. Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med<\/em>. 2000;132(4):270-278. doi:10.7326\/0003-4819-132-4-200002150-00004
     CrossRef <\/a><\/li>
  32. Stamatouli A, Bedoya P, Yavuz S. Hypothyroidism: Cardiovascular endpoints of thyroid hormone replacement. Front Endocrinol (Lausanne)<\/em>. 2020;10:888. doi:10.3389\/fendo.2019.00888
     CrossRef <\/a><\/li>
  33. Joshi V. The Dyslipidemia and Inflammatory markers as the risk predictors for cardiovascular disease in newly diagnosed premenopausal hypothyroid women. J Med Biochem<\/em>. 2022. doi:10.5937<\/li>
  34. Hak AE, Pols HA, Visser TJ, Drexhage HA, Hofman A, Witteman JC. Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med<\/em>. 2000;132(4):270-278. doi:10.7326\/0003-4819-132-4-200002150-00004.
     CrossRef <\/a><\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"

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