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View of Cardiovascular Disease and its Correlation with Fibroblast Growth Factor-23: (Clinical Study for Babylon Patients Province)

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Cardiovascular Disease and its Correlation with Fibroblast Growth Factor- 23: (Clinical Study for Babylon Patients Province)

Dunia Abbas Khudair*, Suhayr Aesa AL-Qaysi, Alaa J. Mahrath Chemistry Department College of Medicine University of Babylon-Iraq

*Corresponding Author email address:[email protected]

Abstract

This paper is try to study the relation of fibroblast growth factor with developments of cardiovascular disease (VCD) under certain conditions. It’s well-known that CVD is a disease that affects the heart or blood vessels.

Cardiovascular diseases include atherosclerosis, coronary artery disease, heart valve disease, arrhythmia, heart failure, hypertension , orthostatic hypotension, shock, endocarditis, diseases of the aorta and its branches, disorders of the peripheral vascular system, and Congenital heart disease.

Aims: To determine if Fgf 23 is a useful biomarker for detecting of cardio vascular disease for Babylon province patients.

Method: The study included sample (blood) collection from g 88 patient ( 49male , 39 female) aged 40 to 60 years (mean age, 45.54 ±0.71665 divided into two groups (44)healthy and (44)patients. The experimental research work was conducted during the period (from 20th of Oct.2020 till 30th Jan.2021) in the labs of Biochemistry Department –Collage of Medicine –University of Babylon. The investigation of these parameters were measure by Enzyme Linked Immunosorbent Assay (ELISA) techniques.

Result:For the experiment data analysis the g study shows a significant increase in the concentration of Fgf23,where(p˂0.05)was with the control group ,the elevated levels of FGF- 23 in patients indicate a good sign for patients that needed cardiovascular therapy. On the other hand the levels of vit.D in controls was within normal value as compared with the patient reduce than normal. also result of FGF23g Roc the percent of area under the curve was 68%

Conclusion:.the study shows Fgf 23 played a crucial role in cardiovascular disease development ,and further investigation must be added about particle materials (PM) intensity with it’s effects on CVD population

Keywords : Cardiovascular disease , Fibroblast growth factor ,ELISA

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Introduction:

Cardiovascular disease (CVD) is literally disease of the heart and blood vessels, and covers all diseases that affect the heart and circulatory system of the body, including coronary heart disease (angina and heart attack), hypertension (high blood pressure), stroke and peripheral vascular disease (PVD - any disease or disorder of the circulatory system outside of the brain and heart) [1]

When cardiovascular disease affects the heart, it can trigger angina attacks (chest pain) or a more serious heart attack. If CVD affects the brain, the result may be a stroke - either a major stroke, or a mini-stroke (also known as a TIA or transient ischemic attack). Peripheral vascular disease (PVD) most commonly affects the legs but it can also affect the arms and kidneys.[2]

Also it’s well known that Fibroblast growth factor 23 or FGF23 is a protein that in humans is encoded by the FGF23 gene. FGF23 is a member of the fibroblast growth factor (FGF) family which participates in phosphate and vitamin D metabolism and regulation [3][4]

is mainly produced in bone cells, osteoblasts, and osteocytes. the kidney is the main target organ of hormone fgf23 acts on proximal and distal convoluted renal tubules. depend upon its interaction with fgf23 receptors and its obligate renal co-receptor alpha-klotho [5]in renal tubular cells, upon binding to the fgf-receptor and alpha-klotho—fgf23 stimulates the excretion of phosphate, reduces the activation of calcidiol to calcitriol, [6] hypothetical non- canonical renal effects of fgf23 include the stimulation of distal tubular sodium and calcium absorption. as well as suppression of angiotensin converting enzyme 2 transcription in the kidney [7].

fgf-23 concentrations may also rise because of accumulation in the serum secondary to decreased glomerular filtration. fgf-23 is a small molecular weight molecule, similar to that of cystatinC (CysC), which also accumulates in serum in patients with decreased renal

clearance. elevated fgf-23 levels have been reported to suppress 1-alpha hydroxylase [8]

fgf23 serum levels have been found to be associated with cardiovascular risk factors such as Apo lipoprotein a1 and high-density lipoprotein (HDL) in subjects with and without chronic kidney disease [9].elevated serum levels of fgf23 are also associated with the progression and development of left ventricular hypertrophy in patients with chronic kidney disease but are also independently associated with heart disease as well as the severity and extent of coronary artery disease in patients undergoing coronary angiography [10,11] this is supported by evidence that fgf23, except for binding to FGFR and the co-receptor klotho in the kidney and parathyroid gland, acts directly to the heart via a klotho-independent signaling pathway.). the

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link of fgf23 with direct cardiac effects and the potential association of serum levels with cardiovascular risk factors [12]

Elevated levels of fibroblast growth factor 23 (FGF23) and phosphate are highly associated with increased cardiovascular disease and mortality in patients suffering from chronic kidney disease (CKD). As the kidney function declines, serum phosphate levels rise and subsequently induce the secretion of the phosphaturic hormone FGF23. In early stages of CKD, FGF23 prevents the increase of serum phosphate levels and thereby attenuates phosphate-induced vascular calcification, whereas in end-stage kidney disease[13], FGF23 fails to maintain phosphate homeostasis. Both hyperphosphatemia and elevated FGF23 levels promote the development of hypertension, vascular calcification, and left ventricular hypertrophy by distinct mechanisms. Therefore, FGF23 and phosphate are considered promising therapeutic targets to improve the cardiovascular outcome in CKD patients[14].As a result of the aforementioned, studying the FGF-23 factor as an indicator of the development of vascular disease is a matter deserve the investigation .

*Method:

This study was performed at the laboratory of Chemistry and Biochemistry Department, College of Medicine, University of Babylon. The subjects in this prospective case-control study, included a total of 88 subjects, 44 these subjects suffering from cardio vascular disease (females 9 with 35 males ) and 44 apparently healthy control subjects (females 17with 27 males). All samples were collected during the period from.the 20st of Oct.2020 till 20th Jan.2021 Samples were collected from Marjan and Imam Al-Sadiq teaching Hospitals.

*Inclusion Criteria

The inclusion criteria for the selection of the studysubjects include:

1. cardiovascular patients group (according to the decision of the cardiovascular disease specialist)

2- Accepted to take part in the present study 3-Age of all subjects was 40-60 years old

*Exclusion Criteria

Smokers and Any one suffered from the below were excluded from this study:

Subjects less than 40years.

Subjects with diabetes, hypertension, ,liver ,kidney ,obesity and any chronic disease.

*Body Mass Index (BMI):

Body mass index (BMI) is a ratio of a person weight to a height; it commonly used to classify weight as healthy or unhealthy. BMI calculated by below equation [15] as follow:

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* Statistical Analysis :

The data analysis of this study is analyzed through using the Statistical Package of Social Sciences (SPSS) version (24). The following statistical data analysis approaches were used in order to analyze data and assess the results of the study. The researchers used descriptive and inferential data analysis to obtain results.

*Determination of human Serum Fibroblast Growth Factor-23Concentration by Enzyme Linked ImmunosorbentAssay(ELISA)

Serum fgf23 levels were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits according to manufacturers' instructions (Bioassay Technology Laboratory, respectively. Fgf23 levels ranged from 5pg/ml - 1500pg/ml).

*Results and Discussion:

* Demographic characteristics of the subject of study:

The results of the current comparative study of the patient and control groups were calculated statistically using the t-test to determine the difference in mean between the control and cardiovascular groups as well as the correlation between the different parameters of all patients. The total number of study groups was 88 adults divided into two control groups (44). Results of the( 44) patient group from demographic data are shown in Table (1-3) Table 3-1: Demographic characteristics of the study groups

P-Value: Significant level less than 0.05 SE: Stander Error

BMI(body mass index)

* Age:

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The results were expressed as means and standard error (SE). There is (no significant)(p˃

0.05)changes in age (as means) between control and CVD patients, means ±SE for the case is (47.9667± 1.0017)and for control as shown (45.5476±0.71665) as shown in Table( 3-1).

This age matching helps to eliminate differences in parameters result that may originate due to the big variation in age. [16]

*Body Mass index (BMI)

There was a significant difference (p < 0.05) in Body mass index (BMI) (as means) between control groups and cardiovascular disease patients, mean ±SE for the case are (0.2567±25.5114 ) and for control (26.4305±.24177) as shown in table 3-1.

So these results support some of the studies indicated a relationship in the interaction between obesity and Cardio vascular disease[17]

It is well known that obesity is an independent risk factor for cardiovascular disease (CVD) and one of the main causes of the increased risk of diseases such as dyslipidemia, insulin resistance, high blood pressure (HBP) or hypertension, and atherosclerosis both in adults and children[18]

So, the difference in BMI between patients and controls consider acceptable in this study that agreement with others [19]

*Gender

The other factor effect on the cardio vascular disease it is gender.

Figure( 3-1) Gender distribution of control and patient group

The Figure above indicates a slight difference betweenmale and femaleSome studies indicate that female usually have a lower rate of cardiovascular disease. Than male, a number of clinical evidence has shown that women They have a higher mortality rate and poor prognosis after acute Cardiovascular disease (CVD)[20]

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*Estimation of Fibroblast growth Factor 23 (FgF23)

One of the purpose of this study attempt to use more and valid techniques in medical college labs/ of Babylon university /chemistry and biochemistry /to gate accurate result with low cost and decrease losing of time. actually Fgf23 measured by ELISA technique .

*Mean differences of Fgf23 level according to studied groups:

As shown in table(3-2) the no significant difference (p ˂0.05) in Fgf23(as means) between control and cardiovascular patients, means ±SE for case is (618.72±69.61 ) and for control(450.92±29.026).

Table(3-2) Clinical variables data of Fgf23Groups

Associations of FGF23 serum level have been found with vascular impairment, vascular calcification, and an increased risk of cardiovascular disease[21].

many studies have shown significant and independent associations between increased FGF23 and dismal outcomes in humans. Remarkably, this association is not limited to CKD patients[22 ], but also detectable in patients without CKD [23] in whom no primary significant FGF23 excess is to be expected. Otherwise increase FGF23 levels and increased mortality as well as atherosclerosis and heart failure[24]. Others, demonstrated that occlusive atherosclerotic disease may not be the primary link between increased FGF23 levels and mortality[25]. Numerous additional explanations have been proposed as basis for the prognostic impact of FGF23 on (cardiovascular) mortality, which comprise a contribution of raised FGF23 to endothelial dysfunction [26], stimulation of the renin-angiotensin system [27], arterial stiffness, vascular calcification, inflammation ,and left-ventricular hypertrophy[26]

Negishi, et al[28].andGrunwald JE ,et al [29]reported that FGF23 was significantly associated with LVH, and they suggested that FGF23 could be a novel biomarker of left ventricular overload.

From all explained facts that mentioned above, present results consider logical results because cases that involved in this study were newly diagnosed without any complication

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such as hypertension, DM, and renal disease that have a strong effect on FGF23 level that mainly appear in last state as in heart failure.

Receiver Operating Characteristic (ROC) analysis of the FGF23.

Also to determine the role of FGF23 as a biomarker for indictor of heart disease or as predictor for new onset of disease ROC analysis was done as figure (3-2).

Present result was shown 68% that indicate there was no significant specificity and sensitivity present for FGF23 in this study.

Many factors may interfere with this result in general that differ in previous one such as number of patients. Type of technique that used in addition to effect of environmental factors.

Figure(3-2)Receiver Operating Characteristic (ROC) curve of Fgf23 of patient group Conclusion

The study shows Fgf 23g played a crucial role in cardiovascular disease development, and further investigation must be added about particle materials (PM) intensity with it’s effects on CVD population.

References:

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