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ORIGINAL ARTICLE
Year : 2018  |  Volume : 31  |  Issue : 3  |  Page : 882-886

Correlation between the serum alkaline phosphatase level and the severity of coronary artery disease


Department of Cardiovascular, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission24-Feb-2017
Date of Acceptance30-Apr-2017
Date of Web Publication31-Dec-2018

Correspondence Address:
Islam I Hegazy
Department of Cardiovascular, Faculty of Medicine, Menoufia University, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_145_17

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  Abstract 


Objective
The aim of this study was to investigate the correlation between serum alkaline phosphatase (ALP) levels and the severity of coronary artery disease (CAD) by assessing the Gensini score.
Background
The serum ALP level has been shown to be a prognostic factor in myocardial infarction and peripheral vascular disease by its promoting effect on vascular calcification.
Patients and methods
A total of 200 patients with stable angina pectoris were evaluated retrospectively. Upon admission, their ALP levels were measured with automated AU480 analyzer using kinetic rate method, and were evaluated according to Gensini score.
Results
The mean ALP level was 60 ± 21.858, ranging from 29 to 110 U/l, and there were 95 (47.50%) patients with low normal level (<63 IU/l), 75 (37.50%) patients with midrange level (63–78 IU/l), and 30 (15%) patients with high normal level (>78 IU/l). The mean Gensini score was 20.7 ± 21.8; 31 (15.50%) patients had a score of 0, 64 (32%) patients had mild CAD with a score ranging from 1 to 15, 75 (37.5%) patients had moderate CAD with a score ranging from 16 to 30, and 30 (15%) patients had severe CAD with a score more than 30. The advanced CAD group included more patients with diabetes mellitus and hypertension. Regression analysis showed a significant correlation between increased levels of serum ALP and advanced CAD in the multivariate model (χ2 = 372.434) (P < 0.001).
Conclusion
There was a significant correlation between serum ALP and severity of CAD according to Gensini score.

Keywords: alkaline phosphatase, coronary artery disease, Gensini score


How to cite this article:
Soltan GM, Elkersh AM, Farid W, Hegazy II. Correlation between the serum alkaline phosphatase level and the severity of coronary artery disease. Menoufia Med J 2018;31:882-6

How to cite this URL:
Soltan GM, Elkersh AM, Farid W, Hegazy II. Correlation between the serum alkaline phosphatase level and the severity of coronary artery disease. Menoufia Med J [serial online] 2018 [cited 2019 Jan 20];31:882-6. Available from: http://www.mmj.eg.net/text.asp?2018/31/3/882/248722




  Introduction Top


Intense attention has been focused on the search of a biomarker with an effective predictor value in patients with coronary artery disease (CAD). Recent data demonstrated that the measurement of high-sensitive C-reactive protein, a representative inflammatory marker, could not predict 41% of ST-elevation myocardial infarction (MI) patients, which suggested the need to identify the additional relevant markers based on the novel pathophysiological mechanisms[1].

As vascular calcification contributes to cardiovascular risk in various population subsets, markers of vascular calcification can be an attractive option. Several studies showed that markers of mineral metabolism such as phosphate are linked with an adverse cardiovascular outcome[2],[3].

Recently, it was suggested that alkaline phosphatase (ALP) has a pivotal role in mineral metabolism and might be a molecular marker of vascular calcification[4].

Indeed, ALP is a membrane-bound metalloenzyme that catalyzes the hydrolysis of organic pyrophosphate, an inhibitor of vascular calcification[5].

Accordingly, the role of ALP has been highlighted in terms of its effects on vascular disease. Recently, several studies reported a significant link between ALP and adverse outcome in patients with chronic kidney disease or those under hemodialysis[6].

Furthermore, two recent papers showed that higher ALP levels are associated with an excess risk of death among survivors of stroke or MI[7],[8].

Considering that vascular calcification contributes to atherosclerosis, vascular hardening, and aging, serum ALP levels may also be linked with poor vascular fate in overall patients with CAD, as well as MI survivors[9].

The aim of this study is to assess the correlation between the serum ALP level and the severity of CAD.


  Patients and Methods Top


Our study included 200 patients who presented to Menoufia University hospital, Dar Alshefaa, and The Italian Hospital for elective coronary angiography within the time period from November 2015 to August 2016.

Upon admission, their ALP levels were measured with an automated AU480 analyzer using the kinetic rate method (Beckman Coulter (UK) Ltd, High Wycombe, United Kingdom), and the severity of CAD was documented for each patient according to their Gensini score[10].

Exclusion criteria

The exclusion criteria were as follows:

  1. Patients with hepatic diseases
  2. Patients diagnosed with bone malignancies
  3. Patients with chronic renal disease
  4. Patients with active lymphomas and blood malignancies
  5. Patients with congestive heart failure
  6. Pregnant female patients
  7. Patients with evidence of active infection.


Methods

Approval of Menoufia University Ethical Committee was obtained. Informed consent was obtained for all patients.

Patients were subjected to the following:

  1. History taking: Patient history was taken with particular stress on age, risk factors for CAD, history of hepatic or renal diseases, and history of active bone or blood malignancy
  2. Complete physical examination: Complete physical examination was performed with particular stress on blood pressure, heart rate, presence of S3 gallop, and pulmonary venous congestion
  3. 12-lead ECG
  4. Standard transthoracic echocardiography.
  5. Laboratory tests: The serum ALP level was measured with an automated AU480 analyzer using the kinetic rate method (Beckman Coulter (UK) Ltd, High Wycombe, United Kingdom). Normal values in our laboratory were 30–115 IU/l. All patients in our study were subdivided according to ALP levels into three tertiles (lowest <63 IU/l, middle 63–78 IU/l, and highest >78 IU/l)
  6. Coronary angiography: Coronary angiography was performed using Seldinger technique and by visualizing coronary arteries in ordinary views with at least two perpendicular views to assess the site, type, and the severity of the lesions; the severity of CAD was documented for each patient according to their Gensini score.


Gensini scoring system

It is a scoring system that allocates a numerical value for the degree of stenosis in a coronary artery and a multiplication factor that depends on which coronary artery is involved and where the stenosis is located in the coronary artery.

This scoring system has been used in several studies to establish a correlation between the severity of CAD and other factors.

It grades narrowing of the lumen of the coronary artery and scores it as follows:

1 for 1–25%, narrowing

2 for 26–50%, narrowing

4 for 51–75%, narrowing

8 for 76–90%, narrowing

16 for 91–99%, narrowing

32 for a completely occluded artery.

The score is then multiplied by a factor according to the importance of the coronary artery as follows:

  1. Left main system lesion score is 5
  2. Proximal left anterior descending (LAD) and proximal left circumflex score is 2.5
  3. Mid LAD lesion score is 1.5
  4. The score for distal LAD, mid and distal left circumflex, and right coronary artery lesion is Any branch is 0.5.


In the Gensini score method, the coronary arteries were divided into 11 segments and their scores range from 0 to 72 based on the intensity of stenosis, which includes (i) normal coronary arteries (0 score), (ii) mild CAD (0–15 scores), (iii) moderate CAD (16–30 scores), and (iv) severe CAD (31–72 scores).

Statistical analysis

All collected data were tabulated and analyzed by the appropriate statistical tests using statistical package for the social sciences (SPSS, version 17; SPSS Inc., Chicago, Illinois, USA). Categorical data were described on numbers (percentage) and analyzed by χ2-test. Continuous data were described as mean ± SD and analyzed using standard t-test. Significance was defined as P value less than 0.05.


  Results Top


While analyzing the collected data from our study group, we found that there was no difference regarding patient gender and patient age, but there was a significant correlation between serum ALP and hypertension (P < 0.001), diabetes mellitus (DM) (P < 0.001), and smoking (P < 0.001) [Table 1].
Table 1: Correlation between alkaline phosphatase level and hypertension, diabetes mellitus, and smoking

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There was a significant relation between serum ALP level and positive ECG findings (P < 0.001) and left ventricular ejection fraction (LVEF) (P < 0.001), the presence of segmental wall motion abnormality (P < 0.001), left ventricular end diastolic diameter (LVEDD) (P < 0.001), left ventricular end systolic diameter (LVESD) (P < 0.001), and patient Canadian angina score (P < 0.001) [Table 2].
Table 2: Correlation between alkaline phosphatase level and positive electrocardiography finding, ejection fraction, Canadian angina score

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There was a significant correlation between Gensini score and hypertension (P < 0.001), DM (P < 0.001), and smoking (P < 0.001). There was a significant relation between serum Gensini score and positive ECG findings (P < 0.001). There was a significant relation between Gensini score and LVEF (P < 0.001), the presence of segmental wall motion abnormality (P < 0.001), LVEDD (P < 0.001), and LVESD (P < 0.001). There was a significant relation between Gensini score and patient Canadian angina score (P < 0.001) [Table 3].
Table 3: Correlation between Gensini score and hypertension, diabetes mellitus, smoking, positive electrocardiography findings, segmental wall motion abnormality, ejection fraction, and Canadian angina score in our study group

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There was a significant relation between serum ALP level and Gensini score [Table 4].
Table 4: Correlation between alkaline phosphatase and Gensini score

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  Discussion Top


In our study, patients with high serum ALP level were more likely to have severe CAD. A study was conducted by Sahin et al.[11] to assess the correlation between the serum ALP level and the severity of CAD. This study included 470 patients with stable angina pectoris who were evaluated retrospectively. Upon admission, their ALP levels were measured with an automated analyzer by the enzymatic method, and the severity of CAD was documented for each patient according to their Gensini score. The study revealed that elevated ALP levels are associated with higher Gensini scores and a more severe form of CAD (odds ratio = 1.015, 95% confidence interval = 1.008–1.1291, P < 0.001). This result is concordant with our study results.

A study was conducted by Webber et al.[12] to assess the association between serum ALP and C-reactive protein in the United States National Health and Nutrition Examination Survey 2005–2006. This study included 4155 men and nonpregnant women over the age of 20 years. The relationship between log-transformed ALP and plasma C-reactive protein was analyzed using univariate and multivariate models. The study revealed that ALP activity was significantly correlated with BMI and blood pressure, after adjusting for age, gender, and ethnicity (P = 0.001). ALP was significantly associated with a higher frequency of cardiovascular disease (P = 0.02), hypertension (P = 0.01), hypercholesterolemia (P = 0.04), and diabetes (P = 0.02). This result is concordant with our study results.

Park et al.[13] conducted a study to assess whether serum ALP is a predictor of mortality, MI, or stent thrombosis after implantation of coronary drug-eluting stent. This study included 1636 patients who underwent percutaneous coronary intervention with drug-eluting stent. After exclusion of patients with liver disease and cancer, the study revealed a positive correlation between ALP levels and patient Canadian angina score (P = 0.039), kidney function test (P = 0.001), left main disease as an indicator of the severity of CAD (P = 0.033), and history of nonfatal MI (P = 0.005). This result is concordant with our study results.

Waked et al.[14] conducted a study to assess bone-specific ALP and cardiovascular morbidity among patients on maintenance hemodialysis. This study included 70 uremic patients from the dialysis unit of Theodor Bilharz Research Institute. Exclusion criteria included liver diseases, ethanol or drug abuse, active malignancy, and pregnancy. Upon admission, their ALP levels were measured with an automated analyzer by the enzymatic method. The study revealed a positive correlation between ALP and LVEDD (P < 0.001), LVESD (P < 0.001), and LVEF (P < 0.001). This result is concordant with our study results.

Wannamethee et al.[15] conducted a study to assess ALP and incident cardiovascular disease and total mortality in older men. This study included 3381 patients with stable angina pectoris who were evaluated retrospectively. Upon admission, their ALP levels were measured with an automated analyzer by the enzymatic method. The study revealed a positive correlation between ALP levels and systolic blood pressure (P = 0.008), DM (P = 0.002). This result is concordant with our study results.


  Conclusion Top


There was a significant relation between serum ALP level and Gensini score and severity of CAD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Cristell N, Cianflone D, Durante A, Ammirati E, Vanuzzo D, Banfi M, et al. High-sensitivity C-reactive protein is within normal levels at the very onset of first ST-segment elevation acute myocardial infarction in 41% of cases: a multiethnic case-control study. J Am Coll Cardiol 2011; 58:2654–2661.  Back to cited text no. 1
    
2.
Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR, et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med 2008; 358:1336–1345.  Back to cited text no. 2
    
3.
Dhingra R, Sullivan LM, Fox CS, Wang TJ, D'Agostino RB Sr, Gaziano JM, et al. Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med 2007; 167:879–885.  Back to cited text no. 3
    
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Shao JS, Cali J, Towler DA. Molecular mechanism of vascular calcification: lessons learned from the aorta. Arterioscler Thromb Vasc Biol 2006; 26:1423–1430.  Back to cited text no. 4
    
5.
Johnson RC, Leopold JA, Loscalzo J. Vascular calcification: pathobiological mechanisms and clinical implications. Circ Res 2006; 99:1044–1059.  Back to cited text no. 5
    
6.
Regidor DL, Kovesdy CP, Mehrotra R, Rambod M, Jing J, McAllister CJ, et al. Serum alkaline phosphatase predicts mortality among maintenance hemodialysis patients. J Am Soc Nephrol 2008; 19:2193–2203.  Back to cited text no. 6
    
7.
Ryu WS, Lee SH, Kim CK, Kim BJ, Yoon BW Increased serum alkaline phosphatase as a predictor of long-term mortality after stroke. Neurology 2010; 75:1995–2002.  Back to cited text no. 7
    
8.
Tonelli M, Curhan G, Pfeffer M, Sacks F, Thadhani R, Melamed ML, et al. Relation between alkaline phosphatase, serum phosphate, and all cause or cardiovascular mortality. Circulation 2009; 120:1784–1792.  Back to cited text no. 8
    
9.
O'Neill WC. Pyrophosphate, alkaline phosphatase, and vascular calcification. Circ Res 2006; 99:e2.  Back to cited text no. 9
    
10.
Morito N, Inoue Y, Urata M, Yahiro E, Kodama S, Fukuda N, et al. Increased carotid artery plaque score is an independent predictor of the presence and severity of coronary artery disease. J Cardiol 2008; 51:25–32.  Back to cited text no. 10
    
11.
Sahin I, Karabulut A, Gungor B, Avci II, Okuyan E, Kizkapan F, et al. Correlation between the serum alkaline phosphatase level and the severity of coronary artery disease. Coron Artery Dis 2014; 25:349–352.  Back to cited text no. 11
    
12.
Webber M, Krishnan A, Thomas NG, Cheung BM. Association between serum alkaline phosphatase and C-reactive protein in the United States National Health and Nutrition Examination Survey 2005-2006. Clin Chem Lab Med 2010; 48:167–173.  Back to cited text no. 12
    
13.
Park JB, Kang DY, Yang HM, Cho HJ, Park KW, Lee HY, et al. Serum alkaline phosphatase is a predictor of mortality, myocardial infarction, or stent thrombosis after implantation of coronary drug-eluting stent. Eur Heart J 2013; 34:920–931.  Back to cited text no. 13
    
14.
Waked E, El Shanawani F, Raafat M, Metwally A, Abdel-Khalek A, Hassan M, et al. Bone specific alkaline phosphatase and cardiovascular morbidity among patients on maintenance hemodialysis. Life Sci J 2011; 8:1078–1087.  Back to cited text no. 14
    
15.
Wannamethee SG, Sattar N, Papcosta O, Lennon L, Whincup PH. Alkaline phosphatase, serum phosphate, and incident cardiovascular disease and total mortality in older men. Arterioscler Thromb Vasc Biol 2013; 33:1070–1076.  Back to cited text no. 15
    



 
 
    Tables

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



 

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