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ORIGINAL ARTICLE
Year : 2019  |  Volume : 22  |  Issue : 5  |  Page : 713-717

The relationship between the atherosclerotic cardiovascular disease risk score used in the prediction of cardiovascular disease risk and endocan


Department of Internal Medicine Clinic, Faculty of Medicine, Bezmialem Vakif University, Fatih, Istanbul, Turkey

Date of Acceptance05-Feb-2019
Date of Web Publication15-May-2019

Correspondence Address:
Dr. C Karatoprak
Internal Medicine Clinic, Bezmialem Vakif University, Faculty of Medicine, 34093 Fatih, Istanbul
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_616_18

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   Abstract 


Objective: To date, there have been no studies investigating whether or not there is a correlation between the serum endocan level and the atherosclerotic cardiovascular disease (ASCVD) risk score that is frequently used in the determination of the risk of cardiovascular disease. If a single parameter such as endocan can provide reliable results which could be used in the prediction of the cardiovascular disease risk, the workload of the clinician would be lightened. The aim of this study was to investigate whether or not there is an association between the serum endocan level and the ASVCD risk score. Materials and Methods: This prospective, cross-sectional study included individuals age 40–79 years with risk factors calculated using the ASVCD score and individuals without any of those risk factors. In accordance with ASCVD risk calculation, each participant was questioned with respect to age, gender, height, weight, and lifestyle habits such as smoking, diseases, and medications. Systolic blood pressure, diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and serum endocan levels were measured and recorded. The serum endocan levels and ASCVD scores were compared. Results: The study included 205 individuals, comprising 92 (44.9%) males and 113 (55.1%) females with a mean age of 50.7 ± 7.6 years. The 10-year atherosclerosis risk was determined as mean 6.32% ± 5.9% (range, 0.3%–27.3%). The mean serum endocan level was calculated as 1109.6 ± 1479.7 ng/mL. As the ASCVD risk score increased, no increase was detected in the serum endocan level. Conclusion: The results of the study suggested that the serum endocan level is not suitable for use in place of the ASCVD risk score as a predictor of cardiovascular disease risk.

Keywords: Atherosclerotic cardiovascular disease risk score, atherosclerosis, cardiovascular disease, endocan


How to cite this article:
Cakirca M, Dae S A, Zorlu M, Kiskac M, Tunc M, Karatoprak C. The relationship between the atherosclerotic cardiovascular disease risk score used in the prediction of cardiovascular disease risk and endocan. Niger J Clin Pract 2019;22:713-7

How to cite this URL:
Cakirca M, Dae S A, Zorlu M, Kiskac M, Tunc M, Karatoprak C. The relationship between the atherosclerotic cardiovascular disease risk score used in the prediction of cardiovascular disease risk and endocan. Niger J Clin Pract [serial online] 2019 [cited 2019 May 23];22:713-7. Available from: http://www.njcponline.com/text.asp?2019/22/5/713/258284




   Objective Top


Atherosclerotic cardiovascular diseases (ASCVDs) are the leading cause of mortality worldwide.[1] Although the pathogenesis is not known, there is probably a multifactorial pathology that emerges with the interaction of genetic and environmental factors in the etiology. One of these risk factors is endothelial dysfunction. The vascular endothelium plays a basic role in processes such as inflammation, coagulation, and angiogenesis, and these roles are related to several mediators and receptors/ligands expressed from the endothelium.[2] Endocan (endothelial cell specific molecule-1) is a molecule expressed by endothelial cells and is a marker of increased tissue expression, endothelial activation (inflammation), and neovascularization.[3] Scientific data have shown that endocan is seen within the pathophysological mechanisms that are active at the start of atherosclerosis.[4]

Intervention and the treatment of atherosclerosis are based on modifying atherosclerosis risk factors.[1] There are many risk factors for atherosclerosis, and difficulties may be encountered with respect to knowing the treatment limit of risk factors that can be corrected. To overcome these difficulties, various risk score determinants have been defined to predict cardiovascular system diseases. With the use of these risk score calculators, patients determined as high risk can be administered intensive treatment and protected against a future atherosclerotic event.[5] Of these scales developed to predict the risk of atherosclerosis, the ASCVD risk score is widely used.[5]

To date, there have been no studies investigating whether or not there is a correlation between the serum endocan level and the ASCVD risk score that is frequently used in the determination of the risk of cardiovascular disease. If a single parameter such as endocan can provide reliable results which could be used in the prediction of the cardiovascular disease risk, the workload of the clinician would be lightened. The aim of this study was to investigate whether or not there is an association between the serum endocan level and the ASVCD risk score.


   Materials and Methods Top


This prospective, cross-sectional study included patients age 40–79 years who presented at our polyclinic between May 2016 and December 2016 with risk factors calculated using the ASVCD score only and individuals without any of those risk factors. Participants were excluded if they had a clinical diagnosis of cerebrovascular event, ischemic heart disease, peripheral artery disease, venous thrombosis, chronic venous failure, or heart failure or low-density lipoprotein (LDL) cholesterol >190 mg/dL.

Risk calculation and atherosclerosis risk factors

For each individual in the study group, the risk of experiencing an atherosclerotic event was calculated online using ASCVD risk calculator prepared according to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines.[6] In this way, the 10-year and the lifetime risk of an atherosclerotic event (fatal or nonfatal myocardial infarction and fatal or nonfatal ischemic stroke) was calculated. This risk score calculator was designed for use on individuals with no cardiac disease and LDL cholesterol of <190 mg/dL.

Therefore, those with LDL cholesterol >190 mg/dL were excluded from this study. While the 10-year risk can be calculated for all individuals age 40–79 years with this method, it is only suitable for lifetime risk calculation of those age 20–59 years. In accordance with ASCVD risk calculation, each participant was questioned with respect to age, gender, height, weight, and lifestyle habits such as smoking, diseases, and medications. Systolic blood pressure, diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, LDL cholesterol, and serum endocan levels were measured and recorded. The serum endocan levels and the ASCVD scores were compared.

Venous blood sampling

Venous blood samples for biochemical analysis and serum endocan level assay were taken in the early morning after 10–12 h of fasting.

Blood analyses

Biochemical analyses were made using a cobas 8000 device (2007; Roche, Tokyo, Japan) and the cobas c system kits. Thyroid hormone levels were determined using ADVIA Centaur kits (2013; ADVIA, Tarrytown, NY, USA), and the parathyroid level was tested using parathormone kits (2014; Bayswater, Victoria, Australia).

Endocan analysis

The venous blood samples were collected into gel tubes after overnight fasting. A period of 20 min was allowed for coagulation, and then the samples were centrifuged at 1500g for 15 min. The serum was stored at −80°C. Serum endocan concentration was measured using the enzyme linked immunosorbent assay method according to the protocols provided by the manufacturer (Human Endocan Elisa Kit; No. 201506; Sunred Biological Technology; Shanghai, China). To read the results at 450 nm, Multiscan FC® Microplate Photometry (Thermo Scientific, USA) was used, and the results were stated as ng/mL.

Statistical analyses

Data obtained in the study were analyzed statistically using SPSS (Statistical Package for Social Sciences, SPSS Inc., Chicago, USA) for Windows 14.0 software. Numerical variables were stated as mean ± standard deviation. The conformity to normal distribution of numerical variables was tested using one-sample Kolmogorov–Smirnov test and this was stated in the tables. Paired correlations were examined. The serum endocan level was made a dependent variable, and the risk factors in the ASVCD risk calculator were made independant variables. Linear regression analysis was applied with parametric and nonparametric methods. Paired correlations were examined between the serum endocan levels and the 10-year and lifetime risk of an atherosclerotic event scores which were calculated separately for each patient online with the AVSCD risk calculator. A two-tailed P value of <0.05 was accepted as statistically significant.

Ethical approval

The study protocol was approved by the Ethics Committee of Bezmialem Vakıf University. Informed consent was obtained from all the study participants. All the procedures of the study were in accordance with the 2009 Declaration of Helsinki.


   Results Top


The study included 205 individuals, comprising 92 (44.9%) males and 113 (55.1%) females with a mean age of 50.7 ± 7.6 years and a mean body mass index (BMI) of 28.9 ± 4.8 kg/m2. The mean systolic blood pressure of the participants was calculated as 122.4 ± 16 mmHg. The frequencies of the risk factors in the study population are shown in [Table 1].
Table 1: The study population according to the risk factors

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The mean serum endocan level was calculated as 1109.6 ± 1479.7 ng/mL (minumum: 36.97; maximum: 8489.24). The results of the biochemical parameter tests are shown in [Table 2].
Table 2: Biochemical analysis results

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The data of all the participants were input to the ASVCD risk calculator system and the risk was calculated online. The lifetime risk related to atherosclerosis could only be calculated for those age 20–59 years (n = 173), while the 10-year risk was calculated for all the participants (n = 205). The 10-year atherosclerosis risk was determined as mean 6.32 ± 5.9% (range, 0.3%–27.3%). In the 173 subjects where the lifetime risk of an atherosclerosis event could be calculated, the mean value was 45.4% ± 12.4% (range, 5%–69%).

No statistically significant correlation was determined between the serum endocan level and risk factors calculated with the ASVCD risk calculator [Table 3]. In this analysis, the serum endocan parameter was accepted as dependent, and linear regression analysis was applied using the backward method.
Table 3: The relationship between the serum endocan level and the ASCVD calculator parameters of the subjects

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No statistically significant correlation was determined between the serum endocan level and the 10-year risk rate or the lifetime risk rate [Table 4].
Table 4: The relationship between the serum endocan level and the 10-year and lifetime risk rates determined with the ASCVD risk calculator

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   Discussion Top


ASCVDs currently constitute the most common cause of morbidity and mortality. Evaluation of the risk of this process starting at an early age is of great importance with respect to protection and treatment.[1] Therefore, different risk calculation methods have been developed based on the evaluation of the basic risk factors of atherosclerosis. The Framingham, systematic coronary risk evaluation (SCORE), prospective cardiovascular münster (PROCAM), World Health Organization/International Society of Hypertension (WHO/ISH), Reynolds Risk Score, and various other national risk calculation systems are among the most well-known and widely used systems.[6],[7],[8] The ASCVD risk calculator was developed according to the AHA/ACA guidelines published in 2013.[6]

This risk score is seen as the most up-to-date cardiovascular risk calculation method and is widely used in the United States and around the world.[9] In the ASCVD risk calculator, risk estimations are made using nine parameters, two of which are laboratory tests, and the results are classsified as >7.5% high risk, 5%–7.5% moderate risk, and <5% low risk.[4] In thsi study, there were individuals at very low 10-year risk (0.3%) and at high risk (27%). The mean 10-year risk was calculated as 6.3% in the moderate risk range.

Several diseases that lead to atherosclerosis and some risk factors cause an increase in the serum endocan level. Of the risk factors in the ASCVD risk calculator that was used in this study to calculate the risk of experiencing an atherosclerotic event, there are studies that have reported that serum endocan levels are affected by systolic blood pressure, the presence of diabetes mellitus, and the use of antihypertensive agents.[10] In this study, the serum endocan level was determined as mean 1109 ng/mL, ranging from 36 to 8500 ng/mL. This very broad range of values did not show normal distribution and it was seen that an extremely wide distribution has been reported in some other studies.[10],[11] It was thought that this could have been associated with the kits used. As the normal distribution range of serum endocan has not been clarified as yet, this makes standardization and control of studies more difficult.

It was hypothesized that a correlation could be found between the serum endocan level and the ASCVD risk calculator used in the prediction of the risk of the development of atherosclerosis. However, no correlation was determined between the serum endocan level and the presence of risk factors that are in the ASCVD risk calculator. Furthermore, no significant relationship was determined between the serum endocan level and the 10-year and lifetime risk rates calculated using the ASCVD risk calculator.

In a recent study by Kose et al., it was reported that serum endocan levels were high in patients with acute coronary syndrome, but no correlation was seen between the endocan levels of the coronary artery disease burden in patients with acute coronary syndrome.[12] Wang et al. evaluated the serum endocan levels in 164 patients with hypertension and reported that a correlation was shown with endocan levels in these patients independently of the presence and severity of coronary artery disease.[13] The studies that are available in literature can be seen to have reached conflicting results. That no relationship was found between endocan and the ASCVD score in this study could be due to the tests used not being standardized or the characteristics of the selected patient groups.

When the literature was examined in terms of a relationship between endocan and dyslipidemia, there were seen to be conflicting studies. In a study that compared heart transplantation patients with a control group, a significant relationship was determined between the serum endocan level and dyslipidemia.[14] In contrast, Efe et al. compared metabolic syndrome patients with a control group, and although the serum endocan level of the metabolic syndrome patients was determined to be higher than that of the control group, no correlation was found between the serum endocan level and the metabolic syndrome parameters of age, gender, hypertension, diabetes, cholesterol. and smoking status.[10] In another study by Lv Y et al., diabetic patients were separated into two groups as those with and without atherosclerosis, and a control group was formed of nondiabetics. The serum endocan level was found to be significantly higher in diabetic patients both with and without subclinical atherosclerosis compared with the control group. In the same study, a significantly positive correlation was determined between fasting blood glucose and HbA1c.[15] As can be understood from the above-mentioned studies in literature, great differences are seen in serum endocan levels. Due to these surprising results, many conflicting conclusions have been reached. Although the results of some studies support the findings of this study, there are also studies that have obtained significant results.

As it is known from previous studies that endothelial dysfunction such as atherosclerotic events, hypertension, and diabetes affect the serum endocan level, these could be the reasons that a significant correlation was not determined between the risk factors in the ASCVD risk calculator and the risk scores calculated in this risk calculator.

Some conditions with currently unknown effects on the serum endocan level (emotional state, regular sleep, climate, BMI, genetic variations) could affect the serum endocan level. In this study, the serum endocan level values showed a very heterogeneous distribution and there were great differences between the values. This suggests that the serum endocan level is affected by several unknown factors.

In addition to some negative risk factors related to atherosclerosis, positive factors in an individual may create a balancing effect on the serum endocan level (the presence of conditions simultaneously increasing and decreasing the serum endocan level in the same person).

Limitations

The very broad range of endocan values and that no correlation was seen with the risk values suggests that there could be errors in the test techniques. However, despite two checks of the test technique analyses, no error could be discerned.


   Conclusion Top


The results of this study suggest that the serum endocan level is not suitable for use instead of the ASCVD risk score used as a predictor of cardiovascular disease risk. To be able to make more definitive conclusions, there is a need for further, large-scale, prospective studies applying techniques that could be more sensitive in the measurements of serum endocan.

Disclosures

The authors have no conflict of interests to declare.

Author contribution statement

MC, CK, and SAD wrote the main manuscript text, and MC, MZ, MK, and MT collected data. All authors reviewed the manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Barquera S, Pedroza-Tobias A, Medina C, Hernandez-Barrera L, Bibbins-Domingo K, Lozano R, et al. Global overview of the epidemiology of atherosclerotic cardiovascular disease. Arch Med Res 2015;46:328-38.  Back to cited text no. 1
    
2.
Lee HG, Choi HY, Bae JS. Endocan as a potential diagnostic or prognostic biomarker for chronic kidney disease. Kidney Int 2014;86:1079-81.  Back to cited text no. 2
    
3.
Kali A, Shetty KS. Endocan: A novel circulating proteoglycan. Indian J Pharmacol 2014;46:579-83.  Back to cited text no. 3
[PUBMED]  [Full text]  
4.
Cimen T, Akyel A, Efe TH. Reply to the Letter to the Editor entitled “Role of endothelial dysfunction and endocan in atherosclerosis: Point of origin or end point?” Angiology 2016. doi: 10.1177/0003319716664285.  Back to cited text no. 4
    
5.
Gluckman TJ, Kovacs RJ, Stone NJ, Damalas D, Mullen JB, Oetgen WJ. The ASCVD risk estimator app: From concept to the current state. J Am Coll Cardiol 2016;67:350-2.  Back to cited text no. 5
    
6.
Goff DC, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: A report of the American college of cardiology/American heart association task force on practice guidelines. Circulation 2014;129:S49-73.  Back to cited text no. 6
    
7.
D'Agostino RB1, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: The framingham heart study. Circulation 2008;117:743-53.  Back to cited text no. 7
    
8.
Garg N, Muduli SK, Kapoor A, Tewari S, Kumar S, Khanna R, et al. Comparison of different cardiovascular risk score calculators for cardiovascular risk prediction and guideline recommended statin uses. Indian Heart J 2017;69:458-63.  Back to cited text no. 8
    
9.
Cifu AS, Davis AM. Prevention, detection, evaluation, and management of high blood pressure in adults. JAMA 2017;318:2132-4.  Back to cited text no. 9
    
10.
Efe SC, Demirci K, Ozturk S, Gurbuz AS, Poci N, Kilicgedik A, et al. Serum endocan levels in patients with cardiac syndrome X. Herz 2018;43:359-63.  Back to cited text no. 10
    
11.
Celik T, Balta S, Karaman M, Ahmet Ay S, Demirkol S, Ozturk C, et al. Endocan, a novel marker of endothelial dysfunction in patients with essential hypertension: Comparative effects of amlodipine and valsartan. Blood Press 2015;24:55-60.  Back to cited text no. 11
    
12.
Kose M, Emet S, Akpinar TS, Kocaaga M, Cakmak R, Akarsu M, et al. Serum endocan level and the severity of coronary artery disease: A pilot study. Angiology 2015;66:727-31.  Back to cited text no. 12
    
13.
Wang XS, Yang W, Luo T, Wang JM, Jing YY. Serum endocan levels are correlated with the presence and severity of coronary artery disease in patients with hypertension. Genet Test Mol Biomarkers 2015;19:124-7.  Back to cited text no. 13
    
14.
Przybylowski P, Wasilewski G, Koc-Zorawska E, Malyszko J. Endocan concentration and chronic inflammatory process among heart transplant recipients. Transplant Proc 2016;48:1781-5.  Back to cited text no. 14
    
15.
Lv Y, Zhang Y, Shi W, Liu J, Li Y, Zhou Z, et al. The association between endocan levels and subclinical atherosclerosis in patients with type 2 diabetes mellitus. Am J Med Sci 2017;353:433-8.  Back to cited text no. 15
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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