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

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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."



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Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
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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.
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Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




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




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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 : January | Volume : 16 | Issue : 1 | Page : OC05 - OC10 Full Version

Systemic Immune-inflammation Index in Acute Coronary Syndrome and its Role in Predicting Disease Severity: A Cohort Study


Published: January 1, 2022 | DOI: https://doi.org/10.7860/JCDR/2022/51979.15888
Anvith Sherwin Pinto, Akshatha Rao Aroor, Pradeep Pereira

1. Resident, Department of General Medicine, Father Muller Medical College, Mangaluru, Karnataka, India. 2. Associate Professor, Department of General Medicine, Father Muller Medical College, Mangaluru, Karnataka, India. 3. Assistant Professor, Department of Cardiology, Father Muller Medical College, Mangaluru, Karnataka, India.

Correspondence Address :
Dr. Akshatha Rao Aroor,
Associate Professor, Department of General Medicine, Father Muller Medical
College, Father Muller Road, Mangaluru, Karnataka, India.
E-mail: akshatharao0502@gmail.com

Abstract

Introduction: Systemic Immune-inflammation Index (SII) is a novel marker of inflammation, used extensively in prognosticating various cancers. Recent studies have shown SII to be a predictor of adverse events and death in Acute Coronary Syndrome (ACS) patients who undergo intervention. The role of SII in medically managed SII patients has not been studied. There are no Indian studies available which study the prognosticative role of SII in ACS.

Aim: To study systemic immune-inflammation index in acute coronary syndrome and its role in predicting disease severity and mortality.

Materials and Methods: This prospective cohort study was conducted in Department of General Medicine at Father Muller Medical College Hospital, Mangaluru, India between February 2021 and July 2021. The study included 45 ST Elevation Myocardial Infarction (STEMI) and 45 Non ST Elevation Myocardial Infarction (NSTEMI)/Unstable Angina (UA) patients, aged 30 years or more. The SII, Neutrophil-to-Lymphocyte Ratio (NLR) and Total Leucocyte Count (TLC) were compared using independent sample t-test. Killip class, Thrombolysis In Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) 2.0 scores were used to determine disease severity. Pearson’s and Spearman’s correlation coefficient were used to determine correlation between parametric and non parametric parameters, respectively. Receiver Operator Curve (ROC) was used to see for predictability of outcomes. The role of SII to predict Major Adverse Cardiac Events (MACE) and death at one month follow-up period was assessed by Kaplan-Meier analysis and Cox regression analysis.

Results: The mean SII was significantly higher in the STEMI group (20.9 vs 9.79; t-value= 3.65, p-value <0.001). SII correlated significantly with Killip class (r=0.502), TIMI (r=0.417) and GRACE 2.0 scores (r=0.529), better than NLR or TLC. High SII were associated with a higher risk of MACE (Odds ratio=13.82, p-value <0.001) and death (OR=4.413, p-value=0.015). The SII had an Area Under the Curve of 0.67 for predicting MACE and had a negative predictive value of 96%. Kaplan-Meier analysis showed that patients with higher SII had a lower survival at one month (median: 24.5 days vs 29.32 days, Log-rank=6.44, p-value=0.011). The SII predicted MACE and death better than left ventricular Ejection Fraction (EF) and troponin I.

Conclusion: The SII is a cost-effective, novel marker of inflammation that can predict short term outcomes in ACS. This was the first cohort study which studied the role of SII in ACS in patients undergoing any type of intervention.

Keywords

Global registry of acute coronary events, Killip class, Neutrophil-to-lymphocyte ratio, Thrombolysis in myocardial infarction

Cardiovascular diseases are the leading cause of mortality in India, accounting for nearly one-fourth of the total deaths(1). Ischaemic heart disease-related events lead to around 3000 disability adjusted life years lost per 1,00,000 population every year (2). The spectrum of Acute Coronary Syndrome (ACS) includes Unstable Angina (UA), Non ST Elevation Myocardial Infarction (NSTEMI) and ST Elevation Myocardial Infarction (STEMI). In the setting of an ACS, time is muscle. Early reperfusion by active intervention reduces myocardial damage, averting fatal complications and preventing mortality.

Acute coronary syndrome is a proinflammatory state leading to acute remodelling of the cardiac muscle. The inflammatory process is thought to have a favourable long-term effect, due to its angiogenesis and cellular healing abilities. However, in an acute setting, it can lead to dilation and rupture of the myocardium, further worsening the cardiac functionality. The ongoing ischaemia warrants an earlier reperfusion strategy.

In India, the problem with cardiovascular disease is two-fold. There has been a rapid epidemiological transition from infectious to non communicable diseases over the past few decades (3). Due to the adaptation of sedentary lifestyle and insalubrious practices the incidence of diabetes, hypertension and dyslipidaemia, which are also risk factors for cardiovascular disease, has risen. Adding to this is the lacunae in the country’s health infrastructure. An estimated 64.5% of the population reside in rural India where the resources are scarce. Even in urban areas, there is delay in referral of patients due to a heavy burden on the limited resources. The doctor-population ratio in India stands at just below 1 per 1000 population (4). Out of this, the number of specialist doctors is fewer. Diagnosing a patient of ACS with the help of diagnostic criteria, assessing the severity of the disease and deciding on prioritising patients for intervention can hence be challenging. Since majority of the first medical contacts in India happen in the primary care setting, simple and reliable blood tests to assess the severity of the disease are essential.

The Neutrophil-to-Lymphocyte Ratio (NLR) has been used as a novel predictor of inflammation in various conditions. Systemic Immune-inflammation Index (SII), the product of NLR and platelet count, has been proposed as a new biomarker of mortality in various cancers (5),(6),(7). The SII takes into account the proinflammatory and the prothrombotic changes in the vasculature. Lately, SII has been studied in stable coronary artery disease (8),(9), chronic heart failure (10) and ACS. It has been shown that SII predicts mortality and morbidity in ACS patients receiving coronary intervention (11),(12),(13). It has also been shown to predict the development of atrial fibrillation post STEMI (14). The SII is also studied in STEMI patients who develop no-reflow post primary Percutaneous Coronary Intervention (PCI) (15). However, there are no Indian studies done which assess the role of SII in predicting outcomes in ACS. Also, a large number of patients in developing nations do not undergo any primary intervention and are only treated medically. There are no studies that include patients who receive medical line of management alone. The present study compared SII between the two types of ACS, correlated SII and NLR with ACS severity scores and determined the role of SII in predicting major cardiac events and mortality irrespective of the type of intervention.

Material and Methods

This prospective cohort study was conducted in the Department of General Medicine, Father Muller Medical College Hospital, Mangaluru, Karnataka, India from February 2021 to July 2021. The study included 90 patients (45 STEMI and 45 NSTEMI/UA) aged above 30 years with ACS. The study was approved by the Institutional Ethics Committee (IEC No:FMIEC/CCM/78/2021). The diagnosis of ACS was according to the criteria by the ESC/ACCF/AHA/WHF task force (16).

Inclusion criteria: The STEMI was diagnosed in patients with ST-segment elevation in the Electrocardiogram (ECG) meeting the criteria, (new ST-segment elevation at the J point in two contiguous leads with the cut-off point as greater than 0.1 mV in all leads other than V2 or V3 , in leads V2-V3 the cut-off point is greater than 0.2 mV in males older than 40-year-old and greater than 0.25 in males younger than 40-year-old, or greater than 0.15 mV in females) with symptoms of ischaemia or troponin elevated above the 99th percentile of the upper reference limit.

Exclusion criteria: Patients with evidence of infection (fever with localising symptoms), low platelet count (less than 150,000 cells/mm3), haematological malignancies, and who underwent thrombolysis were excluded from the study.

Patients with a new onset Left Bundle Branch Block (LBBB) were considered to be in the STEMI group. Sgarbossa’s criteria were used in patients with a known LBBB to be considered as STEMI (17). The NSTEMI was diagnosed in patients with symptoms of ischaemia, with troponin elevated above the 99th percentile of the upper reference limit, but without ST-segment elevation. The UA was diagnosed in patients with symptoms of ischaemia without elevation in biomarkers or ST-elevation meeting the above criteria.

Patients who met the inclusion criteria were consecutively enrolled in the study. Detailed history, clinical examination was performed for all patients. All patients received the standard care of treatment with anticoagulants and antiplatelets (aspirin with clopidogrel or ticagrelor). Beta-blockers, angiotensin receptor blockers, diuretics and other medications were added when indicated. Patients subsequently underwent a PCI or received medical treatment.

Data Collection

The baseline demographic data like age, gender, history of substance abuse and co-morbidities (diabetes mellitus, hypertension, ischaemic heart disease, cerebrovascular disease) were collected. A thorough clinical examination was conducted and vitals (heart rate, blood pressure) were recorded. To assess the severity of the disease, Killip class (18), Thrombolysis In Myocardial Infarction (TIMI) score (19),(20) and Global Registry of Acute Coronary Events (GRACE) 2.0 scores (21) were used at admission. Laboratory tests included estimation of total leucocyte counts, differential leucocyte counts, platelets, creatinine, troponin and erythrocyte sedimentation rate. The NLR was calculated as the ratio of neutrophil count to lymphocyte count. SII was calculated as the product of NLR and platelet count (6).

The ECG was taken at admission. A 2-dimensional echocardiography was done within six hours of admission by a cardiologist. Coronary angiogram was performed and the lesion was graded as single, double or triple vessel disease. Since the hospital was a referral centre, with patient population referred from distant areas, many patients were not eligible for primary PCI. All patients were followed up for one month. Outcomes were defined based on the occurrence of Major Adverse Cardiac Events (MACE) or death. The MACE was defined as worsening cardiac function, either as pulmonary oedema, cardiogenic shock, arrhythmias causing haemodynamic instability, recurrent myocardial infarction or death. Follow-up was done as an outpatient or via telephone.
Statistical Analysis

Statistical analysis was conducted using Statistical Package for the Social Sciences (SPSS) statistics, version 22.0 (Armonk, NY: IBM Corp). Kolmogorov-Smirnov test used to assess normality of distribution and parameters were expressed as mean and standard deviation. Independent sample t-test was used to compare parametric variables and Mann-Whitney U was used to compare non parametric variables among the two groups. Chi-square test was used for dichotomous data, and Odds Ratio (OR) and Relative Risk (RR) were calculated. Pearson’s correlation coefficient and Spearman’s rank correlation were used to correlate parametric and non parametric variables respectively. Receiver Operator Curve (ROC) was used to predict outcomes and the area under the curve was calculated. Survival analysis was conducted by Kaplan-Meier analysis and the log-rank test was used to determine significant difference in survival between the two groups. Cox regression analysis was used to determine predictors of survival. Tests were considered to be statistically significant if the p-value was <0.05.

Results

The baseline characteristics of the population in both groups are given in (Table/Fig 1). Both the groups were comparable in terms of age, gender and co-morbidities. History of ischaemic heart disease was significantly higher in the NSTEMI/UA group. The STEMI group had a lower mean arterial pressure and EF. The NLR and SII were higher in the STEMI group. In the overall study group, history of substance abuse was present in 40 (44.4%). The most common ECG abnormality was inferior STEMI 24 (26.7%) in the STEMI group and precordial t-wave inversions in the NSTEMI/UA group. About 10 (11.1%) had an apparently normal ECG (Table/Fig 2). Echocardiographic findings commonly seen were in the anterolateral and inferior wall (Table/Fig 2). Eight (8.9%) had a normal echocardiogram. A total of 81 patients underwent coronary angiogram, out of which triple vessel occlusion was the commonest finding. The death rate in the STEMI group [n=8 (17.8%)] was higher than in the NSTEMI/UA group [n=5 (11.1%)] (p-value=0.36).

Based on the cut-off values of 13.9 for SII and 4.62 for NLR, patients were divided into two groups. A high SII was associated with a higher risk of MACE {OR=13.82 (95% Confidence Interval-CI of 2.8-66.7), p-value=0.000} and with death {OR=4.413 (1.24-15.66), p-value=0.015}. High NLR was also associated with a higher risk of MACE {OR=5.94 (1.52-23.1), p-value=0.005}. However, high NLR was not associated with a risk of death (p-value=0.18).

To determine the predictive value of SII an NLR, ROC was used and the area under the curve was calculated. For MACE, SII had a better predictability when compared to NLR or TLC (Table/Fig 3).

An SII of 13.9 had a sensitivity of 75%, specificity of 69%, negative predictive value of 96%, and a positive predictive value of 34% for predicting MACE. The NLR had a lower sensitivity (68.7%), specificity (60.8%) and negative predictive value (90%) to predict MACE. The SII was better at predicting death when compared to NLR or TLC, but it was not statistically significant (Table/Fig 4).

There was a significant correlation between SII and left ventricular EF (r=-0.28), Killip class (0.5), GRACE 2.0 score (0.529) and TIMI score (0.417). SII showed the strongest and most significant correlation with severity scores in comparison to other inflammatory markers. The TLC correlated better with troponin I and left ventricular EF.

All patients were followed-up for a duration of 30 days. Overall incidence in the time period was 17.7% for MACE, and 14.4% for death. Survival analysis showed that MACE and death were considerably higher in the high SII group than the low SII group. There were 52% MACE events in the high SII group compared to 8% in the low SII group, and 34% deaths in the high SII group compared to 8% in the low SII group (Table/Fig 5),(Table/Fig 6).

The mean duration for MACE was 21.8 days (95% CI of 17.55-26.04 days) in the high SII group compared to 28.34 days (95% CI of 26.73-29.95) in the low SII group which was significant (Log-rank=11.228, p-value=0.001). The survival curve for NLR was less significant in comparison to SII (Log-rank=4.65, p-value=0.031). However, there was no significance between the TLC groups (Log-rank=3.34, p-value=0.067). The mean survival duration was 24.5 (95% CI of 20.9-28.11) days in the high SII group compared to 29.32 (95% CI 28.23-30.41) days in the low SII group which was significant (Log-rank=6.441, p-value=0.011). There were no differences in the survival duration between the NLR (Log-rank=1.95, p-value=0.16) or the TLC groups (Log-rank=2.02, p-value=0.155).

Cox regression analysis showed that high SII was a predictor for MACE {Hazards Ratio (HR)=5.48; 95% CI of 1.76-17.04, p-value=0.001} and death (HR=4.05; 95% CI of 1.2-13.1, p-value=0.012). Univariate analysis showed that EF, TIMI score, Killip class, GRACE 2.0 score, NLR, SII, hypertension and the type of intervention were predictors of MACE. For predicting death TIMI, Killip class, GRACE 2.0 score, SII and the type of intervention had statistical significance but not NLR or EF. The SII was better than EF, TIMI score, Killip class, GRACE 2.0 score and NLR as a predictor of MACE. Only the type of intervention (medical or PCI) had a higher hazards ratio than SII. In multivariate analysis, after adjusting for haemoglobin, total counts and NLR, SII remained a predictor for MACE. SII predicted MACE, even after adjusting for the type of intervention. The association between SII and death did not remain after adjusting for the type of intervention. There was however a trend towards significance (HR=2.97, 95% CI 0.9-9.7, p-value=0.07) (Table/Fig 7),(Table/Fig 8),(Table/Fig 9).

Discussion

The study was done to determine the usefulness of SII as a marker of inflammation in patients with ACS, and its role in prognosticating patients. SII was significantly higher in patients with STEMI than with NSTEMI or UA. SII correlated with Killip, TIMI and GRACE 2.0 scores better than other inflammatory markers. The SII had a better predictive value than NLR or total counts for MACE and death. Univariate analysis showed that SII was an independent and strong predictor of MACE and death. The SII was the only laboratory parameter that could predict survival at the one-month interval. SII can hence be considered as an independent and strong predictor of cardiovascular mortality and disease severity in ACS. Furthermore, SII in the present study was better at predicting MACE or death when compared to cardiac troponin or left ventricular ejection fraction.

The SII has been used as a marker of inflammation in various malignancies, as a predictor of mortality. The SII has been also studied lately in patients with cardiovascular disease. Higher SII has been shown to increase the risk of progression to complications in patients with stable coronary artery disease (8),(9). It has also shown to be a predictor of cardiac events and mortality in elderly patients post PCI in ACS (3). The present study is the first study which analysed the role of SII in predicting outcomes in ACS patient irrespective of age and the type of intervention, and correlated it with various severity scores.

The findings of the present study are consistent with the study done by Huang J et al., (11). Similar to the present study, they showed that subjects with higher SII had a lower survival rate. However, they only included elderly patients above the age of 65 years who underwent PCI in contrast to the present study, which included patients above 30 years irrespective of the intervention. Ocal L et al., showed that SII predicted in-hospital and long term events in STEMI patients (12). A recent large retrospective study also showed SII to predict 30-day mortality in ACS, but the type of intervention received was not specified (13). In patients with STEMI, SII has a similar predictive power as C-reactive protein, and better than NLR in predicting atrial fibrillation (14). Esenbog?????a K et al. demonstrated that SII independently predicted no-reflow phenomenon post PCI in STEMI (15). SII has also been used to study the effect of antiplatelets (ticagrelor and clopidogrel), as a marker of inflammation post ACS (22).

Several studies have shown that NLR is an independent predictor of all-cause mortality in ACS (23),(24). The present study showed that NLR was a predictor of outcomes in ACS, but when SII was added to the model, the predictability of NLR became insignificant. The SII also correlated better with severity scores in the present study.

The study has many advantages. It was a prospective cohort study with defined outcomes. The SII was compared with other haematological parameters and correlated with risk scores. An SII of 13.9 had a negative predictive value of 96% for major adverse cardiac events (Table/Fig 3). This can have important practical implications in resource-scarce settings especially in rural India where the availability of treatment options is limited. The SII is a cost-effective laboratory parameter, calculated from the routine blood haemogram, which is a widely available test even in remote settings. The interpretation of SII does not require a specialist as there is no interobserver variability in interpreting the test. The high negative predictive value makes it a useful decision-making tool. Alongside clinical symptoms, it can be used as a parameter by which critical patients can be referred early especially in case of NSTEMI/UA where the ECG changes are not apparent, and when there is non availability of cardiac enzymes.

The study also validated the severity scores used in ACS, like the TIMI and the GRACE 2.0 scores. Both TIMI score and GRACE 2.0 scores have been validated to be prognosticators of ACS in various studies (19),(25). The GRACE 2.0 score and the Killip class were better predictors of mortality and adverse cardiac events than the TIMI score in our study.

Limitation(s)

It was a study done in a single centre, with a small sample size. The SII is a dynamic index, and its value can change depending on the presence of co-existing infections which can occur in patients admitted in critical care settings. Hence, the findings may not be generalisable in patients with co-existing sepsis. Also, this was a short-term follow-up study and the long-term outcomes were not established. The SII was measured at admission and was not serially monitored through the course of hospital stay. Despite all these limitations, this study shows a promising role of SII as a tool for decision making in patients with ACS. The role of inflammation as a driver of the disease process in ACS is also supported by the present study. Further multicentric studies, with a larger study population and a longer follow-up period are needed for a better understanding of the role of SII in ACS.

Conclusion

The SII is an independent prognostic marker for MACE and short-term mortality ACS. The SII also correlates strongly with Killip class, TIMI and GRACE 2.0 scores. The SII was higher in the STEMI group compared to the NSTEMI/UA group. The SII is an inexpensive, readily available parameter which has a good predictive value in categorising high-risk patients, especially in resource-scarce settings. The SII is better than TLC and NLR in predicting short term outcomes.

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DOI and Others

DOI: 10.7860/JCDR/2022/51979.15888

Date of Submission: Aug 22, 2021
Date of Peer Review: Nov 25, 2021
Date of Acceptance: Dec 03, 2021
Date of Publishing: Jan 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

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