Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

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Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : August | Volume : 16 | Issue : 8 | Page : BC01 - BC05 Full Version

Role of Lipoprotein Associated Phospholipase A2 in Diagnosis of Coronary Artery Disease


Published: August 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/55726.16681
V Veena, M Ganesh, Santhi Silambanan

1. Assistant Professor, Department of Biochemistry, Saveetha Medical College, Thandalam, Kanchipuram, Tamil Nadu, India. 2. Head, Department of Biochemistry, Sri Ramachandra Medical College, Chennai, Tamil Nadu, India. 3. Professor, Department of Biochemistry, Sri Ramachandra Medical College, Chennai, Tamil Nadu, India.

Correspondence Address :
Dr. V Veena,
Assistant Professor, Department of Biochemistry, Saveetha Medical College, Thandalam, Kanchipuram, Tamil Nadu, India.
E-mail: drveenanobel@gmail.com

Abstract

Introduction: Cardiovascular Diseases (CVD) are a major cause of significant morbidity and mortality in industrialized countries, of which Coronary Artery Disease (CAD) is the commonest. The diagnostic workup of CAD has improved over the years starting from conventional investigations like ECG to invasive procedures like coronary angiogram. Moving forward, numerous novel inflammatory biomarkers are coming up to diagnose CAD.

Aim: To assess the role of Lipoprotein associated Phospholipase A2 (LpPLA2) as an independent predictor of CAD.

Materials and Methods: This case-control study was conducted in the Inpatient Department of Cardiology at Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India, from September 2014 to November 2014. Participants without significant blockage in the coronary arteries and without detectable atheroma served as controls and those with detectable atheroma and significant blockage in coronary arteries served as cases. Peripheral blood samples of 80 male patients aged over 40 years undergoing Coronary Angiography were processed for LpPLA2 levels. Mean and Standard deviation were calculated for the parameters included in the study. All statistical analyses were performed using Statistical Package for Social Sciences (SPSS) version 15.0.

Results: Mean age of the participants in the controls group was 51.75±8.74 years and that of the cases group was 59.15±11.31 years. The mean LpPLA2 level in the cases was found to be higher than that in the controls and the difference was statistically significant (p-value <0.05). No correlation was noted between the age and BMI of both the groups with their respective LpPLA2 levels.

Conclusion: The current study showed that LpPLA2 can be used as a potential independent predictor of CAD, thus minimising the usage of invasive investigations and favouring the psychosocial and economic welfare of the patients.

Keywords

Age, Biomarkers, Body mass index, Cardiovascular diseases, Inflammation

Cardiovascular Diseases (CVD) rank first among the causes of significant morbidity and mortality in industrialized countries, of which Coronary Artery Disease (CAD) is the commonest (1). Coronary artery disease presents with a characteristic set of symptoms such as chest pain or discomfort which starts in the centre or left side of the chest, radiating to the shoulders and sometimes to the upper limbs, dyspnoea, nausea, giddiness etc. Sometimes, this pain mimics indigestion or heartburn and goes unnoticed. In a smaller fraction of people, it is asymptomatic and is called a silent CAD (2). The diagnostic workup of CAD includes a complete and extensive elicitation of history to exclude the anticipated risk factors, a thorough clinical examination, risk scoring systems, blood investigations such as lipid profile and certain biomarkers, chest X-ray, electrocardiogram, echocardiogram, ultrasound imaging of coronary vasculature, coronary angiogram and nuclear imaging (3).

Traditional risk factors for CVD include dyslipidemia, diabetes mellitus, hypertension, smoking, alcoholism, obesity, sedentary lifestyle and unhealthy dietary habits (4). In addition, psychosocial stress also plays a major role in the causation of the disease (5). A parental family history of death due to CAD is associated with a higher risk in both men and women (6). All these risk factors have an independent tendency to predispose to the pathogenesis of CAD by promoting inflammatory processes in the coronary vasculature. A number of risk scoring systems such as Framingham risk score, Prospective Cardiovascular Munster (PROCAM) scores and Systematic Coronary Risk Evaluation (SCORE) scores are being followed to stratify the future risk of coronary events (7). Since inflammation and atherosclerosis play a central role in causation of CAD, many inflammatory markers such as C-Reactive Protein (CRP), Interleukin-1(IL-1), fibrinogen, homocysteine etc have come up which are being routinely used for Cardiovascular (CV) risk stratification (8). There are a few novel biomarkers like Lipoprotein-associated Phospholipase A2 (LpPLA2), Placental growth factor etc which are under the process of research for screening and diagnosis of CAD (4),(9). The LpPLA2, also known as Platelet Activating Factor Acetyl Hydrolase (PAF-AH) is a recently discovered, potentially useful biomarker for CVD. LpPLA2 has an active site made up of Serine, Histidine and Aspartic acid triad (10), unlike the other phospholipases which have dyads. The C-terminal of this enzyme is found to be required for its binding to High Density Lipoprotein (HDL) and Low Density Lipoprotein (LDL). LpPLA2 circulates in the blood mainly in association with LDL, HDL and also with Lipoprotein-a (Lp-a). Majority of the LDL- bound LpPLA2 is bound to the atherogenic small dense LDL. It has two prominent biological activities viz., it inactivates the potent proinflammatory mediator, Platelet Activating Factor (PAF) and it hydrolyses the oxidatively modified polyunsaturated fatty acids, to produce Lysophosphatidyl choline (LysoPC) and oxidized Non Eesterified Fatty Acids (ox NEFA) (10). The LysoPC upregulates certain proinflammatory cytokines, adhesion molecules and Monocyte Chemoattractant Protein1 (MCP-1) and ox NEFA has potent monocyte chemoattractant property, thus, promoting inflammation.

It has been proved that the factor which determines the role of LpPLA2 in atherosclerosis, proatherogenic or antiatherogenic, is the type of lipoprotein with which it is associated. While it is found that LDL-associated- LpPLA2 has a positive relationship with the risk of future cardiac events, HDL associated LpPLA2 and Lp-a associated LpPLA2 are found to be anti- atherogenic (11). However, there is no adequate literature that established a relation between LpPLA2 and subclinical atherosclerosis (12). Thus, the inclusion of patients with normal coronary arteries on angiography had an advantage over population-based controls, as it ruled out the presence of subclinical coronary disease. The aim of this study is to assess the role of LpPLA2 as an independent predictor of CAD.

Objectives:

• To estimate the serum level of LpPLA2 in the controls as well as cases of CAD who had undergone coronary angiography.
• To find whether there is any statistically significant difference in LpPLA2 levels between the controls and cases and to assess the correlation between the age and BMI of both the groups with their respective LpPLA2 levels.

Material and Methods

This case-control study was conducted in the Inpatient Department of Cardiology at Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India, from September 2014 to November 2014. The study was performed in agreement with specifications as recommended by The Institutional Ethics Committee, Sri Ramachandra Medical College and Research Institute (Ref: CSP-MED/ 14/SEP/18/165). A written informed consent was obtained from each participant before commencement of the study. The study included 80 males undergoing coronary angiography. Subjects were chosen based on convenient sampling. Out of 110 selected study participants (after including 40 as cases and 40 as controls), 20 cases and 10 controls were excluded.

Control group (n=40): All participants without significant blockage in the coronary arteries and without detectable atheroma.
Cases group (n=40): All participants with detectable atheroma and significant blockage in coronary arteries.

Inclusion criteria: Male patients, age >40 years having hypertension and hyperlipidaemia. The reason for choosing male was the higher levels of LpPLA2 (more than 200 ng/mL) and thus a greater correlation found in male compared to female in the previous studies (4). Inadequate number of female patients admitted for coronary angiogram during that particular period was another reason for the same.

Exclusion criteria: Female patients and patients with diabetes mellitus, renal disease, chronic inflammation or infection, previous history of coronary artery intervention, malignancy or thyroid disorders were excluded from the study.

Procedure

The patient data were collected through case reports. All patients were interviewed for a full medical history including age (years), family history of diabetes, hypertension and dyslipidemia. A thorough elicitation of clinical history was done which revealed history of symptoms like profuse sweating, left sided chest pain, vague chest discomfort, left shoulder pain, back pain, and palpitations. The general physical examination included measurement of height, weight and vital signs including pulse rate and blood pressure. BMI was calculated using the formula,

BMI = Weight in kilograms/ (Height in metres)2.

The controls and cases were divided into two groups based on BMI (BMI <25 kg/m2 and BMI >25 kg/m2).

Peripheral venous blood samples of about 3 mL were collected under strict aseptic conditions, from all the 80 participants. The samples were collected in yellow-topped serum separator tubes and incubated for 30 minutes for clot formation at 28° to 30°C and centrifuged at 3500 rpm for 5 minutes. Serum samples of 0.5 to 1 mL were taken in eppendorfs, labeled appropriately and stored at -20 ºC. Human serum LpPLA2 was measured using R&D systems Human PLA2G7/PAF-AH/Lp-PLA2 Quantikine ELISA Kit, catalogue number DPLG70 following the kit instructions. This assay employs the quantitative sandwich enzyme immunoassay technique.

Statistical Analysis

Mean and standard deviation were calculated for the parameters included in the study. Independent student unpaired t test was performed to determine whether there is a statistically significant difference between parameters among the two groups, with a p-value <0.05 being considered to be significant. Pearson’s correlation coefficient was used to assess the relationship between the variables and a p-value <0.05 was considered statistically significant. Pearson’s correlation coefficient was also used to assess the strength and direction of association between two variables. All statistical analyses were performed using Statistical Package for Social Sciences (SPSS) version 15.0 (SPSS Inc., Chicago. IL, USA).

Results

The clinical and demographic characteristics of both cases and controls were tabulated in (Table/Fig 1). Mean age of the participants in the controls group was 51.75±8.74 years and that of the cases group was 59.15±11.31 years. The distribution of the study participants based on their presenting symptoms is shown in (Table/Fig 2). Majority (42.5%) of controls was in the age group of 40-50 years and 40% of cases were above 60 years of age. Mean height of cases and controls were 162.28±7.96cm and 158±7.67cm (p-value=0.86) and mean weight were 74.72±13.53 kg and 64.63±9.95 kg (p-value=0.003). About 47.5% of controls had a BMI <25 kg/m2 and 92.5% of cases had a BMI >25 kg/m2 (Table/Fig 3). The mean age as well as BMI of cases was found to be higher when compared to those of controls. The mean LpPLA2 level in the cases was found to be higher than that in the controls and the difference was statistically significant (p-value <0.05) (Table/Fig 1).

Correlation between LpPLA2 levels with age and BMI in both the groups as well as in the overall subjects was assessed and was not found to be statistically correlated (Table/Fig 4), (Table/Fig 5), (Table/Fig 6).

Discussion

Coronary artery disease has been recognized as the commonest of the cardiovascular diseases, which account for majority of the morbidity and mortality in developed as well as developing countries. There is extensive evidence available linking the aetiopathogenesis of CAD to inflammation and atherosclerosis (13). The initial trigger for inflammation and thus atherosclerosis is vascular endothelial injury. This leads to an imbalance between vasodilator and vasoconstrictor substances and endothelial cell activation, thus promoting atherosclerosis (14). CAD presents with a typical set of symptoms such as pain in left side or centre of the chest, radiating to left shoulder and back, dyspnea etc. At times, these symptoms are subclinical, mimicking heartburn or indigestion, leading to a missed diagnosis (15).

As stated earlier, inflammation and atherosclerosis are the key factors in the causation of CAD and many inflammatory markers like hs-CRP, homocysteine, Interlukin-1, are being used as markers for cardiovascular risk stratification (8). However, all these conventional markers used are not specific for cardiac disease and have their own limitations. Hence, they cannot be adapted for routine clinical use. Thus, there is a need for a cardiac-specific marker which can aid in the early diagnosis and risk stratification of CAD. Lipoprotein-associated Phospholipase A2 (LpPLA2) is one such novel biomarker of CAD.

LpPLA2, also known as PAF-AH is a phospholipase enzyme, which, in humans is encoded by PLA2 G7 gene. Its synthesis is regulated by various inflammatory cytokines such as Interferon-γ and lipopolysaccharides at the transcriptional level (16). The LpPLA2 has limited expression in leukocytes and unstimulated monocytes, whereas, it is induced during differentiation to macrophages and in foam cells (17). It has two prominent biological activities like, inactivation of the potent proinflammatory mediator PAF (antiatherogenic), and hydrolysis of the oxdatively modified polyunsaturated fatty acids, to produce proinflammatory mediators such as LysoPC and ox NEFA (proatherogenic). However, a large body of evidence favours the proatherogenic property of LpPLA2 (18),(19).

The present study was primarily aimed at determining the ability of LpPLA2 to detect the presence of CAD, thus negating the need for invasive diagnostic procedures like Coronary Angiogram. Sabatine et al in his study have found LpPLA2 as a superior marker of CAD, when compared to other traditional markers such as high sensitivity C-reactive protein (hsCRP) and homocysteine (HCY) (20). Packard CJ et al., in their study has found LpPLA2 associated with the risk of CAD and not being confounded by factors like age, systolic blood pressure (18). Bhatti S et al., have found that the latest evidence are in favour of LpPLA2 in determination of cardiovascular risk over the conventional risk factors and biomarkers (19). Thus, several previous studies have established the potential of LpPLA2 as a marker of CAD, which kindled the interest and curiosity to assess its levels in the CAD patients admitted in our hospital (18),(19),(20).

Brilakis ES et al., has shown an association between LpPLA2 levels and severe angiographic CAD along with many other authors (4),(21). Moreover, Rotterdam study, which was done in an attempt to assess the relationship of LpPLA2 with subclinical atherosclerosis, had failed to establish the same (12). Thus, the inclusion of patients with normal coronary arteries on angiography had an advantage over population-based controls, as it ruled out the presence of subclinical coronary disease.

The present study population included 80 participants (male), of which 40 were controls and 40 were cases. The reason for choosing male, is the higher levels of LpPLA2 and thus a greater correlation were found in men compared to women in the previous studies (4),(22). Brilakis ES et al., showed a significant difference between males and females in his studies (p-value <0.003 and p-value <0.001 respectively) (4),(22). The reason for the lower levels in women is believed to be due to the negative regulatory effect of their high oestrogen levels on LpPLA2 mass and activity (23). West of Scotland Coronary Prevention Study (WOSCOPS) which was similarly done exclusively in males, had found LpPLA2 as an independent predictor of cardiovascular risk, which was not associated with other traditional risk factors like CRP, fibrinogen, white blood cell count, age, triglycerides, LDL, HDL and hypertension (18).

Several lines of evidence showing elevated LpPLA2 levels due to the presence of Rheumatoid Arthritis (RA) (24) and Non Alcoholic Fatty Liver Disease (NAFLD) are available (25). Though the present study population did not include patients with such conditions, there is always a possibility for the presence of subclinical manifestations of these disorders.

The mean and standard deviation of LpPLA2 level in the controls group was 114.34±76.47 ng/mL and in cases was 252.13±94.61 ng/mL (Table/Fig 1). A statistically significant difference was observed in the LpPLA2 levels of controls and cases groups (p-value <0.05). This is in agreement with the results of several other previous studies done with the aim of determining the potential of LpPLA2 to be a biomarker of CAD (Table/Fig 7).

In the current study, a statistically significant difference was noted between the age and BMI of controls and cases (p-value=0.002 and p-value=0.02 respectively). However, the correlation between age as well as BMI with LpPLA2 levels in both the controls group (p-value=0.830, p-value=0.406) and the cases group (p-value=0.584, p-value=0.237) was not statistically significant. Similar results were obtained by other authors in their study (p-value was 0.92 and 0.91 for the correlation between age and BMI with LpPLA2 levels respectively) (4). Thus, age and BMI are not associated with LpPLA2 levels in controls as well as cases.

The advantage of LpPLA2 over other inflammatory markers such as CRP, fibrinogen is that it is not influenced by factors like chronic inflammation, obesity and insulin resistance and can be used as a potentially independent marker which is directly involved in atherogenesis (18). Elevated LpPLA2 levels are also found to independently predict adverse cardiovascular outcomes (20).

Thus, the advent of such a novel, independent, less biovariable, cardiac specific marker can be effectively used in early detection and risk stratification of CAD, thus leading to a significant reduction in the associated morbidity and mortality rates.

Limitation(s)

Female study participants were not included and The correlation of parameters like diabetes, hypertension and dyslipidemia with LpPLA2 levels was not studied.

Conclusion

In view of the statistically significant difference between the LpPLA2 levels in the controls and cases groups and due to the lack of association of LpPLA2 levels with age and BMI, LpPLA2 may be useful as a potential independent predictor of CAD and thus, reduced usage of invasive procedures like coronary angiogram might eventually have a positive effect on the psychosocial and economic welfare of the patients. This study may be done with a larger sample size and correlation with severity of CAD may be studied in future studies.

Acknowledgement

Authors are thankful to all the staff of the tertiary care hospital, all the patients who participated in the study, R&D Diagnostics.

References

1.
Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global burden of cardiovascular diseases and risk factors, 1990-2019: Update from the GBD 2019 study. Journal of the American College of Cardiology. 2020;76(25):2982-3021. [crossref] [PubMed]
2.
Cohn PF, Fox KM, Daly C. Silent myocardial ischemia. Circulation. 2003;108(10):1263-77. [crossref] [PubMed]
3.
Cassar A, Holmes Jr DR, Rihal CS, Gersh BJ. Chronic coronary artery disease: Diagnosis and management. In Mayo Clinic Proceedings. Elsevier. 2009;84(12):1130-46. [crossref] [PubMed]
4.
Brilakis ES, McConnell JP, Lennon RJ, Elesber AA, Meyer JG, Berger PB, et al. Association of lipoprotein - associated phospholipase A2 levels with coronary artery disease risk factors, angiographic coronary artery disease, and major adverse events at follow-up. Eur Heart J. 2005;26(2):137-44. Available from http://www.ncbi.nlm.nih.gov/pubmed/15618069. [crossref] [PubMed]
5.
Rozanski A, Blumenthal JA, Davidson KW, Saab PG, Kubzansky L. The epidemiology, pathophysiology, and management of psychosocial risk facto rs in cardiac practice: The emerging field of behavioural cardiology. J Am Coll Cardiol. 2005;45(5):637-51. [crossref] [PubMed]
6.
Schildkraut JM, Myers RH, Cupples LA, Kiely DK, Kannel WB. Coronary risk associated with age and sex of parental heart disease in the Framingham Study. Am J Cardiol. 1989;64(10):555-59. Available from: http://linkinghub.elsevier. com/retrieve/ pii/0002914989904773. [crossref]
7.
Tolunay H, Kurmus O. Comparison of coronary risk scoring systems to predict the severity of coronary artery disease using the SYNTAX score. Cardiol J. 2016;23(1):51-56. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26503075. [crossref] [PubMed]
8.
Madjid M, Willerson JT. Inflammatory markers in coronary artery disease. British Medical Bulletin. 2011;100(1):23-28. [crossref] [PubMed]
9.
Marković M, Ignjatović S, Majkić-Singh N, Dajak M. Placental growth factor in acute coronary syndrome patients with non ST-elevation. Laboratory Medicine. 2009;40(11):675-78. [crossref]
10.
Kyoung-Rok Do, Kim AC, Chang AB, Seong SA, Shin JM, Sang-Jun Yea, et al. Darapladib binds to lipoprotein-associated phospholipase A2 with meaningful interactions. Bulletin of the Korean Chemical Society. 2014;35(1):250-52. [crossref]
11.
Tellis CC, Tselepis AD. The role of lipoprotein - associated phospholipase A2 in atherosclerosis may depend on its lipoprotein carrier in plasma. Biochem Biophys Acta. 2009;1791(5):327-38. Available from: http:// www.ncbi.nlm. nih. gov/ pubmed/ 19272461. [crossref] [PubMed]
12.
Oei HS, van der Meer IM, Hofman A, Koudstaal PJ, Stijnen T, Breteler MMB, et al. Lipoprotein-associated phospholipase A2 activity is associated with risk of coronary heart disease and ischemic stroke: The Rotterdam Study. Circulation. 2005;111(5):570-75. Available from: http://www.ncbi.nlm. nih.gov/pubmed/15699277. [crossref] [PubMed]
13.
Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352(16):1685-95. [crossref] [PubMed]
14.
Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004;109(23 Suppl 1):III27-32. [crossref]
15.
Kuller LH, Shemanski L, Psaty BM, Borhani NO, Gardin J, Haan MN, et al. Subclinical disease as an independent risk factor for cardiovascular disease. Circulation. 1995;92:720-26. [crossref] [PubMed]
16.
Cao Y, Stafforini DM, Zimmerman GA, McIntyre TM, Prescott SM. Expression of plasma platelet-activating factor acetyl hydrolase is transcriptionally regulated by mediators of inflammation. J Biol Chem. 1998;273(7):4012-20. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9461591. [crossref] [PubMed]
17.
Ferguson JF, Hinkle CC, Mehta NN, Bagheri R, Der Ohannessian SL, Shah R, et al. Translational studies of lipoprotein- Associated phospholipase A2 in inflammation and atherosclerosis. J Am Coll Cardiol. 2012;59(8):764-72. [crossref] [PubMed]
18.
Packard CJ, O’Reilly DS, Caslake MJ, McMahon AD, Ford I, Cooney J, et al. Lipoprotein- associated phospholipase A2 as an independent predictor of coronary heart disease. N Engl J Medicine. 2000;343(16):1148-55. [crossref] [PubMed]
19.
Bhatti S, Hakeem A, Cilingiroglu M. Lp- PLA2 as a marker of cardiovascular diseases. Curr Atheroscler Rep. 2010;12(2):140-44. Available from: http://link.springer.com/10.1007/s11883-010-0095-6. [crossref] [PubMed]
20.
Sabatine MS, Morrow DA, O’Donoghue M, Jablonksi KA, Rice MM, Solomon S, et al. Prognostic utility of lipoprotein- associated phospholipase A2 for cardiovascular outcomes in patients with stable coronary artery disease. Arteriosclerotic hromb Vasc Biol. 2007;27(11):2463-69. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17766330. [crossref] [PubMed]
21.
Caslake MJ, Packard CJ, Suckling KE, Holmes SD, Chamberlain P, Macphee CH, et al. Lipoprotein-associated phospholipase A(2), platelet- activating factor acetyl hydrolase: A potential new risk factor for coronary artery disease. Atherosclerosis. 2000;150(2):413-19. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10856534. [crossref]
22.
Brilakis ES, Khera A, McGuire DK, See R, Banerjee S, Murphy SA, et al. Influence of race and sex on lipoprotein- associated phospholipase A2 levels: Observations from the Dallas Heart Study. Atherosclerosis. 2008;199(1):110-15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18061193. [crossref] [PubMed]
23.
Miyaura S, Maki N, Byrd W, Johnston JM. The hormonal regulation of platelet-activating factor acetyl hydrolase activity in plasma. Lipids. 1991;26(12):1015-20. [crossref] [PubMed]
24.
Södergren A, Karp K, Bengtsson C, Möller B, Dahlqvistand SR, Jonsson SW. Is lipoprotein-associated phospholipase A2 a Link between inflammation and subclinical atherosclerosis in rheumatoid arthritis? Bio Med Research International. 2015. Article ID 673018. http://dx.doi.org/10.1155/2015/673018. [crossref] [PubMed]
25.
Colak Y, Senates E, Ozturk O, Doganay HL, Coskunpinar E, Oltulu YM, et al. Association of serum lipoprotein- associated phospholipase A2 level with non-alcoholic fatty liver disease. Metab Syndr Relat Disord. 2012;10(2):103-09. Doi: 10.1089/met.2011.0111. Epub 2011. [crossref] [PubMed]
26.
Daniels LB, Laughlin GA, Sarno MJ, Bettencourt R, Wolfert RL, Barrett-Connor E, et al. Lipoprotein- associated phospholipase A2 is an independent predictor of incident coronary heart disease in an apparently healthy older population: The Rancho Bernardo Study. J Am Coll Cardiol. 2008;51(9):913-19. Available from: http:// www. ncbi. nlm.nih. gov/pubmed/ 18308160. [crossref] [PubMed]
27.
Nambi V, Ballantyne CM. Lipoprotein- associated phospholipase A2: Pathogenic mechanisms and clinical utility for predicting cardiovascular events. Curr Atheroscler Rep. 2006;8(5):374-81. Available from: http://link.springer. com/ 10.1007/s11883-006-0034-8. [crossref] [PubMed]
28.
Jenny NS, Solomon C, Cushman M, Tracy RP, Nelson JJ, Psaty BM, et al. Lipoprotein- associated phospholipase A2 (Lp-PLA2) and risk of cardiovascular disease in older adults: Results from the Cardiovascular Health Study. Atherosclerosis. 2010;209(2):528-32. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19804. [crossref] [PubMed]
29.
Mourouzis K, Siasos G, Oikonomou E, Zaromitidou M, Tsigkou V, Antonopoulos A. Lipoprotein associated Phospholipase A2 levels, endothelial dysfunction and arterial stiffness in patients with stable coronary artery disease. Lipids Health Dis. 2021;20:12. [crossref] [PubMed]
30.
Kumar D, Mishra AK, Siddiqui MS, Qureshi A. Study of lipoprotein-associated phospholipase A2 and carotid intima media thickness as markers of increase cardiovascular risk. International Journal of Contemporary Medical Research. 2017;4 (5):1083-85.

DOI and Others

DOI: 10.7860/JCDR/2022/55726.16681

Date of Submission: Feb 23, 2022
Date of Peer Review: Mar 10, 2022
Date of Acceptance: May 09, 2022
Date of Publishing: Aug 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Mar 05, 2022
• Manual Googling: May 07, 2022
• iThenticate Software: May 17, 2022 (9%)

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