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

Users Online : 16186

AbstractMaterial and MethodsResultsDiscussionConclusionReferencesDOI and Others
Article in PDF How to Cite Citation Manager Readers' Comments (0) Audio Visual Article Statistics Link to PUBMED Print this Article Send to a Friend
Advertisers Access Statistics Resources

Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



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 : 2023 | Month : January | Volume : 17 | Issue : 1 | Page : OC26 - OC31 Full Version

Carotid Intima Media Thickness as a Marker of Atherosclerotic Burden in Patients with Systemic Lupus Erythematosus: A Cross-sectional Study from a Tertiary Care Centre of Eastern India


Published: January 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/59731.17395
Rishav Mukherjee, Soumya Sarathi Mondal, Rishav Sanghai, Subhendu Bikash Naiya, Lamsaka Lyngdoh, Raja Bhattacharya

1. Senior Resident, Department of Internal Medicine, Medical College Kolkata, Kolkata, West Bengal, India. ORCID ID (https://orcid.org/0000-0001-5883-2908). 2. Professor, Department of Internal Medicine, Medical College Kolkata, Kolkata, West Bengal, India. ORCID ID (https://orcid.org/0000-0002-4838-7780). 3. Junior Resident, Department of Internal Medicine, Medical College Kolkata, Kolkata, West Bengal, India. ORCID ID (https://orcid.org/0000-0001-6592-8158). 4. Senior Resident, Department of Internal Medicine, Medical College Kolkata, Kolkata, West Bengal, India. 5. Senior Resident, Department of Internal Medicine, Medical College Kolkata, Kolkata, West Bengal, India. 6. Associate Professor, Department of Internal Medicine, Medical College Kolkata, Kolkata, West Bengal, India.

Correspondence Address :
Dr. Raja Bhattacharya,
Associate Professor, Department of Internal Medicine, Medical College Kolkata. Kolkata, India.
E-mail: mukherjeerishav@gmail.com; drrajabhattacharyamck@gmail.com

Abstract

Introduction: Systemic Lupus Erythematosus (SLE) patients have an increased burden of atherosclerosis leading to adverse Cardiovascular (CV) events. Alterations in endothelial function, dysregulated immune system and increased oxidative stress are implicated in their development and progression. Carotid artery ultrasound is recommended to assess and follow progression of subclinical atherosclerosis and correlate with traditional/non traditional CV risk factors in SLE.

Aim: To study the correlation between Carotid Intima Media Thickness (CIMT), traditional/non traditional CV risk factors in SLE.

Materials and Methods: The hospital-based, descriptive, cross-sectional study was conducted in the Department of Internal Medicine, Medical College Kolkata, Kolkata, West Bengal, India, from April 2019 to August 2020. Patients with SLE, diagnosed by Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria, aged >12 years, irrespective of therapy status, were recruited by consecutive sampling. Subjects were classified as Lupus Nephritis (LN) and Lupus without Nephritis (LWN). Demographic data, parameters to define SLE (SLICC 2012 criteria), blood parameters like lipid profile, fasting plasma glucose, anti-Double stranded Deoxyribose Nucleic Acid antibody (anti-dsDNA Ab), C3/C4 levels, 24 hour urine protein values, haemoglobin, C-reactive Protein (CRP), serum homocysteine and Carotid Intima Media thickness as measured by Ultrasonography (USG) doppler study, duration of disease and medication history were considered as study variables. Statistical analysis was done by using Z-test, t-test, Analysis of variance (ANOVA), Chi-square test (for categorical data) and other non parametric statistical tests and correlation tests wherever applicable. A p-value <0.05 was considered to be statistically significant.

Results: Fifty five SLE patients were studied. Subgroup analysis was performed between LN (n=36) and LWN (n=19). The mean age of the study subjects was 33 years with mean disease duration of 4.6 years. LN patients had longer disease duration, younger age of disease onset and longer duration of steroid usage. The mean systolic Blood Pressure (BP) was significantly higher in LN subgroup. Framingham Risk Scores (FRS) was positively correlated with duration of SLE disease and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) scores and duration of steroid therapy. The mean CIMT of the study population is 0.91 mm with 10.9% plaque prevalence whereas, mean CIMT of the LN subgroup and LWN subgroup was 1.02±0.27 mm and 0.86±0.3 mm, respectively; however no statistically significant difference in CIMT was observed between two subgroups. CIMT positively correlated with anti-dsDNA Ab levels, FRSs, anaemia, SLE Disease activity scores, 24 hour urine protein, duration of steroid usage, serum creatinine and CRP. No correlation between CIMT and age of subjects, Fasting Plasma Glucose (FPG), Triglycerides (TG) serum homocysteine was observed.

Conclusion: Systemic lupus erythematous patients have a high atherosclerosis burden and are at increased risk of adverse CV events. LN patients, early age of lupus onset, longer disease duration with prolonged steroid therapy, significant proteinuria, higher anti-dsDNA Ab levels and hypocomplementemia were observed to have higher mean CIMT and plaque formation.

Keywords

Cardiovascular risk, Carotid doppler ultrasonography, Endothelial dysfunction, Lupus nephritis, Prolonged steroid therapy

Systemic Lupus Erythematosus (SLE), more commonly known as lupus is an autoimmune disorder that involves multiple organ systems with a wide variety of presentations. Symptoms can range from low-grade fever, joint pains, oral ulcers, photo sensitivity, blood dyscrasias, rash and chest pain. SLE patients are at high-risk for the development of premature atherosclerosis with a long period of subclinical evolution. With the rapid development of molecular biochemistry, pathophysiological mechanisms behind atherosclerosis in SLE are better understood. It includes endothelial cell dysfunction, vasculopathy and inflammation, along with traditional cardiovascular risk factors (1).

Cardiovascular diseases and infections are the main cause of death in SLE patients. In the Framingham Offspring study, it was found that the risk of a myocardial infarction is about 5-10 times higher in SLE patients even after traditional atherosclerotic risk factors were accounted for (2). This risk was found to be even more pronounced in women with SLE aged 35-44 years, who were over 50 times more likely to have Acute Myocardial Infarction (AMI) than age/sex matched controls (2). Dyslipidemia is the best studied complication of SLE leading to atherosclerosis in both young adults and paediatric population (3).

Insulin resistance has been shown to be present in adults with SLE and is a known independent risk factor for the development of coronary artery disease (4). Accelerated atherosclerosis, which leads to CV diseases, remains one of the most common causes of death in longstanding SLE patients. The Global Burden of Disease 2015 estimated a 12.5% rise in the number of deaths due to CV diseases, increasing from 15.9 million deaths in 2005 to 17.9 million deaths in 2015 even though the age standardised mortality rate (per 100,000) fell by 15.6% (5). Hence, early detection of atherosclerosis changes is a key to achieve better long outcomes to decrease the CV morbidity and mortality from the ailment (6).

Subclinical atherosclerosis can be detected by using several modalities like measurement of Carotid Intima Media Thickness (CIMT) using carotid ultrasound, measuring the degree of coronary artery calcification by Computed Tomography (CT) scan and estimation of myocardial perfusion using Single Photon Emission Computed Tomography (SPECT). As recommended by the American Heart Association (7), measurement of CIMT, assessed by B mode ultrasound at the carotid artery level is a widely accepted, inexpensive, easily accessible, non invasive measures to assess and follow subclinical atherosclerosis.

Pivotal studies have been conducted in this field. In the Rotterdam study and CV Health Study, higher CIMT and plaque was associated with 1.5 times and 1.8 times, (respectively) incidence of stroke over a follow-up period of five years (8),(9). Presence of plaque was associated with a 2.8-fold (Hazard ratio: 2.76, 95% Confidence interval: 2.1-3.63) increased risk of stroke, MI and CV death during a mean follow-up of 6.9 years in the Northern Manhattan Study (NOMAS) study (10). When this was coupled with the Framingham Risk Scores (FRS) it had a better predictability in identifying high-risk populations. Hence, combination of traditional biomarkers along with vascular imaging improves the risk stratification in patients.

In a single-centre case study, conducted in PGIMER, India across 100 SLE patients it was observed that LN patients tend to have more severe disease and greater vascular stiffness. CIMT was influenced by age, disease activity status and low High Density Lipid-Cholesterol (HDL-C) levels (11). Bhatt SP et al., highlighted the younger age of incidence of SLE and in this study, CIMT was influenced by age, disease activity, menopause, systolic blood pressure and total cholesterol, whereas the Systemic Lupus International Collaborating Clinics (SLICC) Albumin Creatinine Ratio (ACR) damage index was the sole factor affecting the plaque incidence (12).

There is a dearth of data, in Indian population, who are genetically and ethnically predisposed to premature atherosclerosis (13). This study aimed to establish a correlation between surrogate biomarkers of subclinical atherosclerosis in SLE, as assessed by CIMT and their complex interplay with traditional and non traditional CV risk factors, which might help in risk stratification and timely initiation of specific therapy to reduce the morbidity and mortality in SLE patients.

Material and Methods

A hospital-based, descriptive, cross-sectional study was conducted in the Department of Internal Medicine, Medical College Kolkata, Kolkata, West Bengal, India, from April 2019 to August 2020. The ethical clearance was obtained from the Institutional Ethics Committee (approval no. MC/KOL/IEC/NONSPON/309/02-2019.) and a written informed consent was obtained from all the study subjects regarding their participation in the study.

Sample size: On an average, it was observed from the hospital records that around 50 to 60 SLE patients (new and follow-up cases) attend the Internal Medicine/Rheumatology Outpatient Department (OPD)/Inpatient wards of the Institute, annually hence the technique of consecutive sampling was employed in this study.

Inclusion criteria: Patients who were >12 years and diagnosed with SLE as per the SLICC 2012 criteria (14), irrespective of the therapy status were included in the study.

Exclusion criteria: Individuals with history of diabetes, hypertension, dyslipidemia, Ischemic Heart Disease (IHD), stroke or Transient Ischemic Attack (TIA), lymphoproliferative disorder, carotid dissection surgery prior to the diagnosis of SLE, smokers or those infected with Human Immunodeficiency Virus (HIV) and who underwent head and neck radiation therapy were excluded from the study.

Study Procedure

Parameters to define SLE (SLICC 2012 criteria), lipid profile, fasting plasma glucose, anti-dsDNA, C3/C4 levels, 24 hour urine protein values, haemoglobin, Erythrocyte Sedimentation Rate (ESR), serum homocysteine, carotid intimal media thickness as measured by Ultrasonography (USG) doppler study, duration of disease and medication history were considered as study variables.

A complete questionnaire with information on the patient’s demographic profile, past medical history, drug history and psychosocial history were obtained from 69 individuals. Fourteen of them were excluded from the study as per the preset criteria and further laboratory and radiological evaluation was finally done among 55 study subjects. No patient was lost to follow-up. Laboratory parameters included evaluation of complete haemogram, fasting blood glucose, lipid profile, glycosylated haemoglobin (HbA1c), inflammatory markers like Erythrocyte Sedimentation Rate (ESR), C-reactive Protein (CRP), Liver Function Test (LFT), serum electrolytes, urea and creatinine. Autoimmune antibodies like Antinuclear Antibody (ANA), anti-dsDNA, complement levels were done to assess the disease severity. A 24 hour urine Albumin Creatinine Ratio (ACR) and routine urinalysis were also performed.

Radiological analysis was performed to measure the bilateral carotid artery intimal thickness using the B-mode ultrasound scan at the Department of Radiology, Medical College and Hospital, Kolkata. The CIMT measurements were done at three levels on both sides- at the Common Carotid Artery (CCA) i.e., 10 mm caudal to the bulb of CCA; at the bulb of CCA and at the internal carotid artery (10mm cranial to the flow divider). The mean and the maximum CIMT was calculated. The mean CIMT was defined as the average of all the three readings of CIMT on each side and “maximum CIMT” was defined as the maximum of all the six readings of CIMT assessed on a single subject. The following criteria were set for the further analysis of CIMT measurement and its correlation with existing biomarkers of subclinical atherosclerosis (Table/Fig 1) (15).

The results of the study were further categorised to assess the difference in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) score and the CV risk factor using Modified Framingham Risk Score (mFRS) (16),(17).

Statistical Analysis

The data was appropriately segregated, categorised and were entered into IBM Statistical Package for the Social Sciences (SPSS) software version 16.0. They were double checked for any error while data entry. Comparisons were analysed using Z-test, t-test, Analysis of Variance (ANOVA), Chi-square test (for categorical data) and other non parametric statistical tests, correlation tests wherever applicable. An alpha level was set at 5% and a p-value <0.05 was considered statistically significant. The power of the study was 80%.

Results

Out of the 55 study subjects, 53 were females (96.36%) and two were males (3.64%). The mean age and Body Mass Index (BMI) of the study population was 33±5 years and 22.6±1.98 kg/m2, respectively. It was found that 19 (34.54%) patients had Lupus with Nephritis (LN) whereas, 36 (63.46%) patients with Lupus without Nephritis (63.46%) (LWN) as their presenting features. The demographic profile of the study subjects are described as shown in (Table/Fig 2).

Further parameters of the study were analysed by comparing them in patients with nephritis and without nephritis. The laboratory and clinical parameters of the study subjects with LN and LWN are shown in (Table/Fig 3) as follows. The results of the study were further categorised to assess the difference in the SLEDAI-2k score and the CV risk factor using mFRS. Although no significant difference was observed in the latter, SLEDAI-2k score was significantly higher (26.79±4.59, p-value=0.001) in subjects with LN as shown in (Table/Fig 4). Parametric analysis between the SLEDAI-2k and mFRS revealed a significant level of association.

The radiological parameters that were assessed using carotid doppler were analysed and it revealed notable results. The mean CIMT of the study population (N=55) was detected to be 0.91±0.3 mm. Twenty three (41.81%) patients had non thickened carotid intima media (≤0.9 mm) whereas, 32 (51.19%) patients had thickened carotid intima (>0.9 mm). Out of the 32 patients, 6 (18.75%) of them had atherosclerotic plaque. Plaques were observed among three LN, two neuropsychiatric SLE and one SLE with APS patients. The CIMT levels were subgrouped on the basis of age, as shown in (Table/Fig 5). CIMT levels were not influenced by the age of the patients and it was observed that the six patients who had atherosclerotic plaque were >30 years of age. The CIMT was influenced by the duration of the disease and it was seen that 45% of the patients who had the disease for less than five years and 77% patients with disease duration ≥5 years had thickened CIMT (>0.9 mm). The results were statistically significant with a p-value of 0.048 as shown in (Table/Fig 6). No correlation was observed between mean CIMT and serum homocysteine levels and fasting plasma glucose in this study.

A statistically significant association was seen between LDL-C and mean CIMT. Interestingly, it was noted that 70% of the individuals with a low HDL-C had thickened CIMT or plaque formation. The distribution of serum LDL-C, HDL-C, CRP and serum C3/C4 levels among study subjects with variable levels of CIMT are shown in (Table/Fig 7). The evidence of severity of the disease was reflected by hypocomplementemia, anti-dsDNA Ab levels and SLEDAI-2K scores, and it was compared with the mean CIMT levels to establish association. It was observed that 76% study subjects with hypocomplementemia had thickened CIMT or plaque formation (Table/Fig 7). Similarly statistically significant difference between Anti-dsDNA Ab levels with mean CIMT (p-value= 0.001) was observed. When analysing the SLEDAI-2K score for SLE, it was found that 27 patients had a score >20. Among them, 21 (77.78%) had either thickened intima or plaque formation as shown in (Table/Fig 8). Statistical testing showed a positive correlation and significant association of SLEDAI-2K score and CIMT (r-value=039, p-value=0.01) as shown in (Table/Fig 9). The positive correlation can be explained by the fact that patients with longer duration of disease tend to accrue disease damage and therapy related complications over time.

Also, while analysing the treatment history of the patients and the duration of steroid therapy, it was found that 29 (52.72%) participants had been receiving the treatment for one to five years and 5 (9.1%) subjects for more than five years. Twenty one of the 29 subjects (72.41%) and 4 (80%) out of 5 subjects had thickened intima or plaque formation in the respective subgroups. A statistically significant relation between duration of steroid therapy (years) with the mean CIMT exists as p-value was 0.013 as shown in (Table/Fig 5). Individuals with higher FRSs were observed to have plaques and thickened carotid intima media (as shown in (Table/Fig 10)) as shown by Pearson Correlation curve.

In this study, CIMT was positively influenced by higher disease activity scores, longer duration of steroid usage, younger age of disease onset, presence of dyslipidemia and hypertension and LN. This outlines the fact that CIMT in conjunction with other biomarkers can estimate CV risk in SLE patients.

Discussion

There is a complex interplay of diverse factors like genetics, immunogenicity, endothelial dysfunction and immune complex formation that lead to subsequent tissue damage in SLE. The natural course of the disease is characterised by phases of remission and exacerbation with intervals between flares varying considerably (18). Nevertheless, cumulative damage worsens with time and impacts patient prognosis. Mortality is bimodal with an early peak in the first years after diagnosis due to disease activity and/or infections and a later peak due to premature atherosclerotic CV events and organ failure (19). The events of atherosclerosis remain undetected due to asymptomatic nature of presentation in the early days. The subclinical events can be ascertained with the help of certain non invasive modalities like CIMT, FMD using B-mode ultrasonography at the level of the carotid artery.

Carotid intima media thickness value in this study did not significantly vary among the subgroups of LN and LWN which is similar to an Indian study (11). However, the SLEDAI-2K was significantly higher in LN when compared to LWN in the present analysis. The SLEDAI-2K is a widely used scoring scale for the disease activity in SLE that points out the disease burden. It is ingrained in clinical practice nowadays due to its simplicity to score and predict future outcomes (20). It was observed that the plaque formation in SLE is significantly associated with serum inflammatory markers like CRP, C3 complement levels, duration of disease and steroid therapy. In a prospective study conducted by Belibou C et al., on 35 female subjects, concluded that significant association exists between CIMT and duration of SLE (r-value=0.460), High-sensitivity C-reactive Protein (hsCRP) (r-value=0.436) as well as SLEDAI-2k score (r-value=0.466) and a positive correlation with FRSs. The modified CIMT (mCIMT) observed (0.89 mm) is similar to the present study (21).

In a study conducted at the University of Pittsburgh among 214 female patients with SLE, there was a focal plaque prevalence of 32% with CIMT (mean±SD) being 0.71±0.1 mm. They concluded that the risk factors associated with CV disease in SLE is primarily due to vascular stiffening and is positively correlated with high SBP, old age and higher C3 levels (22). A similar finding in the present study was seen in which the plaque prevalence is 51.19% with mean IMT as 0.91±0.3 mm. Logistic regression in a study conducted by Manzi S et al., on 175 Caucasian patients concluded that the presence of plaque is independently associated with older age, longer duration of disease and prolonged duration of steroid therapy (2). Similarly, the study by Colombo BM et al., shows that age plays a significant factor in cases of LN: however in our study no correlation was observed between age of subjects and mean CIMT (23). This is similar to the findings of a prospective cohort study conducted by Doria A et al., among 78 subjects (24). The latter study also made another interesting observation, that cumulative prednisone dose is an important non traditional risk factor for accelerated atherosclerosis. Cumulative prednisone dosage is known to be a double edged sword with proinflammatory and anti-inflammatory properties being displayed at varying dosages. Roman MJ et al., observed that the average dose of prednisone was significantly less in patients with carotid plaque in current/past users, concluding that there may be a threshold dose where the anti-inflammatory effects of glucocorticoids may be athero-protective, beyond which doses may be atherogenic (25). Studies by Manzi S et al., Kalim H et al., have shown a positive correlation between duration of steroid usage and higher CIMT values, similar to ours (2),(26).

In a case-control study among 197 patients with lupus the plaque prevalence was higher than the 197 matched controls (37.1% vs 15.2%, p-value <0.001) (25). The multivariate analysis concluded that the duration of disease, damage index score and absence of anti-smith antibodies are independent predictors of the disease, whereas no positive correlation was found between mCIMT and serum homocysteine levels. Dyslipidemia is observed in a high frequency in patients with LN. Most patients have high total Cholesterol and one in every third patient have high LDL levels along with low HDL levels as was concluded by Sajjad S et al., (27). It is in congruence with the findings of thickened intima media in patients with deranged lipid profile in this study.

Among the South Asian population, Sharma SK et al., observed a mCIMT of 0.54 mm and an inverse relationship between severity of anaemia and CIMT (11). LN patients tend to have lower mean haemoglobin values (9.96 mg/dL) compared to non LN patients. This can be attributed to the higher disease activity in LN patients, formation of anti-erythrocyte antibodies, anaemia of chronic disease due to circulating TNF-alpha and cytokines, nutritional deficiency, iron deficiency anaemia, autoimmune haemolytic anaemia and GI blood loss due to prolonged steroid usage in LN patients, although no significant difference was obtained between CIMT of LN patients and those without nephritis (11). Bhatt SP et al., made an observation in their study regarding the younger age of onset of SLE in Indians, who exhibited features of atherosclerosis even with low disease activity (12). Median age of patients was 30 years, CIMT in patients was 0.417±0.07mm as compared to 0.362±0.07mm in controls, whereas, plaques were noted in 14% patients. CIMT was influenced primarily by age, disease activity, systolic blood pressure and total cholesterol whereas the SLICC ACR damage index was the sole factor affecting the plaque incidence.

In a study conducted by Ghosh P et al., a case control study with 60 SLE patients and 38 controls were taken (28). Mean age of the patients was 31 years, the CIMT was higher in patients (mean 0.49±0.08mm) compared to controls (0.39±0.05mm). SLE damage indices were independent predictors of CIMT. The difference with the above studies in observed mean CIMT values could be due to difference in sample size, SLE type subsets, cut-off values for defining thickened CIMT and observer variations. The higher mean carotid intima values in this study can be due to average duration of disease being higher, presence of hypertension and individuals with impaired fasting glucose as comorbidity, more number of LN patients, high fraction of patients with higher SLE disease activity scores, longer duration of steroid usage. Individuals with higher FRSs were observed to have plaques and thickened carotid intima media, higher disease activity scores, longer duration of steroid usage, younger age of disease onset, presence of dyslipidemia and hypertension and LN, findings echoed by studies conducted by Zhang M et al., and Kalim H et al., (26),(29).

In view of this, laboratory markers like homocysteine, CRP, lipid profile and SLE disease specific factors and carotid intima media assessment by USG doppler study may be used to design a model to predict CV risk in SLE patients, and it may gain more acceptability, reproducibility across various age groups, population, racial subtypes and spectrum of comorbidity, which can then be utilised for risk stratification of SLE patients, to guide the initiation of disease modifying drugs, assessing therapy response and help in amelioration of disease related damage and risk factors.

Limitation(s)

Firstly, it was a cross-sectional, single-centre study with a small target population. The CIMT, which was the secondary point of the present study, was measured using doppler imaging. It is observer dependent and results can be subjective. The drug effects and role of genetics that might influence the results are not considered in detail. These are the elements that challenge the external validation of the study.

Conclusion

The SLE patients have a high atherosclerosis burden and are at increased risk of adverse CV events. This study demonstrated the increased disease severity in patients with LN, which may help to fill the gaps in the existing literature on the association of CIMT with hypocomplementemia, degree of dyslipidemia and prolonged steroid use. However, more evidence-based researches are required on this field to establish a causal relationship in understanding the implication of the disease and its effects.

References

1.
Petri MA, Kiani AN, Post W, Christopher-Stine L, Magder LS. Lupus Atherosclerosis Prevention Study (LAPS). Ann Rheum Dis. 2011;70(5):760-65. [crossref] [PubMed]
2.
Manzi S, Meilahn EN, Rairie JE, Conte CG, Medsger TA Jr, Jansen-McWilliams L, et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol. 1997;145(5):408-15. [crossref] [PubMed]
3.
Milojevic D, Ilowite NT. Dyslipoproteinemia and premature atherosclerosis in the pediatric rheumatic disease. In Atherosclerosis and Autoimmunity. 2001 Jan 1 (pp. 329-333). Elsevier. [crossref]
4.
El Magadmi M, Ahmad Y, Turkie W, Yates AP, Sheikh N, Bernstein RM, et al. Hyperinsulinemia, insulin resistance, and circulating oxidized low density lipoprotein in women with systemic lupus erythematosus. J Rheumatol. 2006;33(1):50-56.
5.
Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Brenner H, Dicker DJ, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A systematic analysis for the global burden of disease study. JAMA Oncol. 2017;3(4):524-48. Erratum in: JAMA Oncol. 2017;3(3):418.
6.
Leonard D, Akhter T, Nordmark G, Rönnblom L, Naessen T. Increased carotid intima thickness and decreased media thickness in premenopausal women with systemic lupus erythematosus: an investigation by non invasive high-frequency ultrasound. Scand J Rheumatol. 2011;40(4):279-82. [crossref] [PubMed]
7.
Urbina EM, Williams RV, Alpert BS, Collins RT, Daniels SR, Hayman L, et al. American Heart Association Atherosclerosis, hypertension, and obesity in youth committee of the council on cardiovascular disease in the young. Noninvasive assessment of subclinical atherosclerosis in children and adolescents: recommendations for standard assessment for clinical research: a scientific statement from the American Heart Association. Hypertension. 2009;54(5):919-50. Erratum in: Hypertension. 2010;56(3):e36. [crossref] [PubMed]
8.
van der Meer IM, Bots ML, Hofman A, del Sol AI, van der Kuip DA, Witteman JC. Predictive value of noninvasive measures of atherosclerosis for incident myocardial infarction: the Rotterdam Study. Circulation. 2004;109(9):1089-94. [crossref] [PubMed]
9.
Krause KJ. Screening potential elderly preferred markers: exploratory analysis of Cardiovascular Health Study (CHS) data. J Insur Med. 2004;36(3):194-99.
10.
Rundek T, Arif H, Boden-Albala B, Elkind MS, Paik MC, Sacco RL, et al. Carotid plaque, a subclinical precursor of vascular events: the Northern Manhattan Study Neurology. 2008;70(14):1200-07. [crossref] [PubMed]
11.
Sharma SK, Rathi M, Sahoo S, Prakash M, Dhir V, Singh S. Assessment of premature atherosclerosis in systemic lupus erythematosus patients with and without nephritis. Lupus. 2016;25(5):525-31. [crossref] [PubMed]
12.
Bhatt SP, Handa R, Gulati GS, Sharma S, Pandey RM, Aggarwal P, et al. Atherosclerosis in Asian Indians with systemic lupus erythematosus. Scand J Rheumatol. 2006;35:128-32. [crossref] [PubMed]
13.
Isharwal S, Arya S, Misra A, Wasir JS, Pandey RM, Rastogi K, et al. Dietary nutrients and insulin resistance in urban Asian Indian adolescents and young adults. Ann Nutr Metab. 2008;52(2):145-51. [crossref] [PubMed]
14.
Adamichou C, Nikolopoulos D, Genitsaridi I, Bortoluzzi A, Fanouriakis A, Papastefanakis E, et al In an early SLE cohort the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria classify non overlapping groups of patients: use of all three criteria ensures optimal capture for clinical studies while their modification earlier classification and treatment. Ann Rheum Dis. 2020;79(2):232-41. [crossref] [PubMed]
15.
Dalla Pozza R, Ehringer-Schetitska D, Fritsch P, Jokinen E, Petropoulos A, Oberhoffer R; Association for European Paediatric Cardiology Working Group Cardiovascular Prevention. Intima media thickness measurement in children: A statement from the Association for European Paediatric Cardiology (AEPC) Working Group on Cardiovascular Prevention endorsed by the Association for European Paediatric Cardiology. Atherosclerosis. 2015;238(2):380-87. [crossref] [PubMed]
16.
Gladman DD, Ibañez D, Urowitz MB. Systemic Lupus Erythematosus Disease Activity Index 2000. J Rheumatol. 2002;29(2):288-91.
17.
Urowitz MB, Ibañez D, Su J, Gladman DD. Modified Framingham Risk Factor Score For Systemic Lupus Erythematosus. J Rheumatol. 2016;43(5):875-879. Doi:10.3899/Jrheum.150983. [crossref] [PubMed]
18.
Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Desvarieux M, et al. Advisory Board of the 3rd Watching the Risk Symposium 2004, 13th European Stroke Conference. Mannheim intima-media thickness consensus. Cerebrovasc Dis. 2004;18(4):346-49. [crossref] [PubMed]
19.
Ajeganova S, Hafström I, Frostegård J. Patients with SLE have higher risk of cardiovascular events and mortality in comparison with controls with the same levels of traditional risk factors and intima-media measures, which is related to accumulated disease damage and antiphospholipid syndrome: a case-control study over 10 years. Lupus Sci Med. 2021;8(1):e000454. [crossref] [PubMed]
20.
Ohmura K. Which is the best SLE activity index for clinical trials? Mod Rheumatol. 2021;31(1):20-28. [crossref] [PubMed]
21.
Belibou C, Ancuta C, Ancuta E, FiloşC, Chirieac R. Carotid intima-media thickness and plaque as surrogate biomarkers of atherosclerosis among consecutive women with systemic lupus erythematosus. Rom J Morphol Embryol. 2012;53(1):29-34.
22.
Selzer F, Sutton-Tyrrell K, Fitzgerald SG, Pratt JE, Tracy RP, Kuller LH, et al. Comparison of risk factors for vascular disease in the carotid artery and aorta in women with systemic lupus erythematosus. Arthritis Rheum. 2004;50(1):151-59. [crossref] [PubMed]
23.
Colombo BM, Murdaca G, Caiti M, Rodriguez G, Grassia L, Rossi E, et al. Intima-media thickness: a marker of accelerated atherosclerosis in women with systemic lupus erythematosus. Ann NY Acad Sci. 2007;1108:121-26. [crossref] [PubMed]
24.
Doria A, Shoenfeld Y, Wu R, Gambari PF, Puato M, Ghirardello A, et al. Risk factors for subclinical atherosclerosis in a prospective cohort of patients with systemic lupus erythematosus. Ann Rheum Dis. 2003;62(11):1071-77. [crossref] [PubMed]
25.
Roman MJ, Shanker BA, Davis A, Lockshin MD, Sammaritano L, Simantov R, et al. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med. 2003;349(25):2399-406. Erratum in: N Engl J Med. 2006 Oct 19;355(16):1746. [crossref] [PubMed]
26.
Kalim H, et al. Correlation between inflammation, disease activity, corticosteroid therapy with atherosclerosis in systemic lupus erythematosus patients. Int J Rheum Dis. 2013;16:81.
27.
Sajjad S, Farman S, Saeed MA, Ahmad NM, Butt BA. Frequency of dyslipidemia in patients with lupus nephritis. Pak J Med Sci. 2017;33(2):358-62. [crossref] [PubMed]
28.
Ghosh P, Kumar A, Kumar S, Aggarwal A, Sinha N, Misra R. Subclinical atherosclerosis and endothelial dysfunction in young South-Asian patients with systemic lupus erythematosus. Clin Rheumatol. 2009;28(11):1259-65. [crossref] [PubMed]
29.
Zhang M, Qi C, Cao L, Qian J, Ni Z. Metabolic syndrome is correlated with carotid atherosclerosis in patients with lupus nephritis. Am J Med Sci. 2014;348(6):486-91. [crossref] [PubMed]

DOI and Others

DOI: 10.7860/JCDR/2023/59731.17395

Date of Submission: Aug 19, 2022
Date of Peer Review: Nov 01, 2022
Date of Acceptance: Nov 24, 2022
Date of Publishing: Jan 01, 2023

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
• The abstract of the paper has been presented at the 77th Annual Conference of The Associations of Physicians of India (APICON), 2022.

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Aug 30, 2022
• Manual Googling: Nov 08, 2022
• iThenticate Software: Nov 17, 2022 (16%)

ETYMOLOGY: Author Origin

JCDR is now Monthly and more widely Indexed .
  • Emerging Sources Citation Index (Web of Science, thomsonreuters)
  • Index Copernicus ICV 2017: 134.54
  • Academic Search Complete Database
  • Directory of Open Access Journals (DOAJ)
  • Embase
  • EBSCOhost
  • Google Scholar
  • HINARI Access to Research in Health Programme
  • Indian Science Abstracts (ISA)
  • Journal seek Database
  • Google
  • Popline (reproductive health literature)
  • www.omnimedicalsearch.com