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

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Dr Mohan Z Mani

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




Prof. Somashekhar Nimbalkar

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



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




Dr. Kalyani R

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



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




Dr. Saumya Navit

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



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




Dr. Arunava Biswas

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



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




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




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



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




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



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




Dr. Rajendra Kumar Ghritlaharey

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


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



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




Dr. Shankar P.R.

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



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

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


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

Important Notice

Original article / research
Year : 2023 | Month : June | Volume : 17 | Issue : 6 | Page : FC01 - FC04 Full Version

Impact of Atorvastatin on C-reactive Protein, Glycaemic Status and Liver Enzymes among Non Diabetic Patients: A Prospective Study


Published: June 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/62331.18036
Ramnarayan Maiti, Umakanta Mahapatra, Subhayan Das, Nabarun Mandal

1. Professor and Head, Department of Pharmacology, Midnapore Medical College, Midnapore, West Bengal, India. 2. Assistant Professor, Department of General Medicine, Midnapore Medical College, Midnapore, West Bengal, India. 3. Senior Resident, Department of Pharmacology, Midnapore Medical College, Midnapore, West Bengal, India. 4. Associate Professor, Department of Biochemistry, Raiganj Government Medical College, Raiganj, West Bengal, India.

Correspondence Address :
Subhayan Das,
Vidyasagar Road, Midnapore, Paschim Mednipur-721101, West Bengal, India.
E-mail: drsubhayandas@gmail.com

Abstract

Introduction: Atorvastatin is one of the common drugs used for primary and secondary prevention of atherosclerotic cardiovascular diseases. Various studies have suggested variation in C-Reactive Protein (CRP) value, glycaemic status and liver enzymes of patients following statin therapy. However, the adequate and exact data regarding the impact of atorvastatin on the above parameters in the population of Eastern India is still limited.

Aim: To estimate the effect of atorvastatin on CRP, glycaemic status and haepatic enzymes of non diabetic patients.

Materials and Methods: A prospective observational study was conducted in the Outpatient Department (OPD) of Internal Medicine at Midnapore Medical College and Hospital, Paschim Medinipur, West Bengal, India. The duration of the study was one year six months, from June 2020 to December 2021. A total of 150 non diabetic patients aged between 30-75 years receiving atorvastatin were enrolled in the present study. CRP, Fasting Blood Sugar (FBS), Postprandial Blood Sugar (PPBS), haepatic enzymes and lipid profile of participants were monitored at baseline, at the end of one month, six months and 12 months. The data was analysed using Statistical Package for Social Sciences (SPSS) version 22.0, Microsoft Excel and GraphPad Prism.

Results: The study population was predominantly males (69.6%), with mean age of 54±8.88 years and mean weight of 60±5.86 kg. Majority of the patients were on atorvastatin 40 mg (60.86%) followed by atorvastatin 20 mg (26.8%) and atorvastatin 10 mg (12.3%). There were statistical significant changes of mean CRP (1.502 mg/L), mean FBS (86.52 mg/dL), mean PPBS (113.57 mg/dL), mean Serum Glutamic-Oxaloacetic Transaminase (SGOT) (22.84 IU/L), mean Serum Glutamic Pyruvic Transaminase (SGPT) (25.24 IU/L) and lipid profile levels at the end of one year. None of the patients developed new onset DM at the end of one year. A 5% of patients developed prediabetes at the end of 3rd follow-up.

Conclusion: Atorvastatin usage showed that, there was a significant increase in blood glucose and haepatic enzymes level in non diabetic population. Hence, strict monitoring of blood glucose levels along with periodic monitoring of haepatic enzyme levels should be done in regular intervals.

Keywords

Cardiovascular disease, Diabetes mellitus, Statin

The Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are one of the most commonly used drugs now-a-days, for their major role in prevention of atherosclerotic cardiovascular diseases. Acute coronary syndromes typically arise from disruption of atherosclerotic plaques that leads to local thrombus formation, which contain numerous inflammatory cells. Inflammation plays a major role in plaque destabilisation. Inflammatory markers like CRP, reduces the production of nitric oxide by endothelial cells, causing increasing susceptibility of endothelial cells to destruction by cell lysis, thereby, participating in vascular inflammation and plaque destabilisation (1),(2).

CRP is an independent predictor and the most stable and reliable laboratory measure of systemic inflammation and adverse cardiovascular outcome in healthy population (3). Studies differ regarding the extent of CRP lowered by atorvastatin, its relation with standard and intensive statin therapy and its association with several other risk factors specifically like blood glucose levels, Low-density Lipoprotein (LDL), triglyceride and blood cholesterol levels (4),(5). A lower CRP level is associated with a lower risk of recurrent events in patients with acute coronary syndrome. But, as atherosclerosis is a disease of high complexity, involving multifactorial relationship, it is therefore, difficult to elucidate the mechanisms by which statin reduces CRP concentrations and exert their anti-inflammatory effect.

Though, statins (atorvastatin) causes significant reduction of cardiovascular disease mortality, various meta-analysis showed an association of statin with adverse glycaemic control (6). A safety label has been added by Food and Drug Administration (FDA) to statins, because of its propensity to increase FBS levels. A study done by Koh KK et al., showed incidence of new onset DM among patients taking atorvastatin (7). Dose dependent diabetogenic potential of statins was shown in various studies. Another study by Preiss D et al., shows 12% increased risk of New-Onset Diabetes Mellitus (NODM) with higher potency statins compared to lower potency statins (8). Use of atorvastatin has been seen to affect liver enzymes of patients particularly, when patients are taking some other medications, which may affect its metabolism. According to Motola D et al., statin associated elevated liver enzymes hold 10.9% in a total of 1245 adverse drug reaction reports from January 1950 to May 2005 (9).

Statins are among those with the highest rate of causing elevation of liver enzymes, higher than antiplatelet and non steroidal anti-inflammatory drugs, raising a potential concern to monitor atorvastatin associated effects on liver enzymes on its long-term use. Though, asymptomatic haepatic enzyme elevations are the most common forms of haepatic side effects following atorvastatin use, several forms of severe side effects such as hepatocellular injury, cholestatic injury, autoimmune type reaction and fulmitant liver failure also do occur (10). Consequently, haepatic dysfunction is a major concern for statin induced side-effects, which thereby, necessitates for strict monitoring of liver enzymes following statin use, besides its effects on glycaemic status.

Lack of adequate clinical data regarding the effect of atorvastatin on the following biochemical paremeters such as FBS, PPBS, CRP and haepatic enzymes on non diabetic Indian population. Hence, an observational longitudinal study was conducted on euglycaemic patients of Eastern India receiving statins to see its effect on CRP glycaemic status and haepatic enzymes of individuals receiving it. The hypothesis for the study was atorvastatin does not cause significant changes in FBS, PPBS, CRP and haepatic enzymes levels of non diabetic Indian population.

Material and Methods

A prospective observational study was conducted in the OPD of Internal Medicine at Midnapore Medical College and Hospital, Paschim Medinipur, West Bengal, India. The duration of the study was one year six months, from June 2020 to December 2021. The study was initiated after approval of the Instituitional Ethics Committee ((MMC/IEC-2020/309). Informed consent was taken from each of the study participants.

Inclusion criteria: Patients aged between 30-75 years, who are drug naive, and to be receiving oral atorvastatin for dyslipidemia or for secondary prevention of cardiovascular or cerebrovascular diseases were enrolled as study subjects.

Exclusion criteria: Patients with pre-existing DM, impaired fasting glucose, impaired glucose tolerance or those receiving drugs like corticosteroids, thiazide diuretics, antipsychotics which have an effect on glycaemic status, patients with known renal, haepatic disease, infective diseases like tuberculosis etc., terminally ill patients (e.g., cancer) were excluded from the study. Pregnant and lactating mothers were also excluded.

Sample size calculation: The sample size for the present study was 150. The sample size was calculated based on the equation n=4pq/L2, where p=Prevalance of prediabetes in normal Indian population (p=10.3%), q=100-p, L=absolute allowable error. Here, L is considered to be 5% (11). Simple random sampling technique was used for recruitment of study population.

Study Procedure

At the OPD, all the subjects were screened for conditions mentioned above. Assessment of plasma glucose levels- FBS (normal range: 70-110 mg/dL) and PPBS (normal range: 80-140 mg/dL), serum triglyceride level (normal range:44-165 mg/dL), blood cholesterol level (normal range: desirable <200 mg/dL), LDL (normal range:<100 mg/dL), Very Low-density Lipoprotein (VLDL) (normal range12-34 mg/dL), High-density Lipoprotein (HDL) (normal range 40-59 mg/dL), CRP (normal range: <5 mg/L), Alanine Transaminase (ALT) (normal range: <45 U/L) and Aspartate Aminotransferase (AST) (normal range: <35 U/L), Alkaline Phosphatise (ASP) levels (normal range:35-104 U/L) as baseline parameters were done (12).

Anthropometric measurements such as height, weight and Body Mass Index (BMI) of all the patients were measured at the baseline. BMI was categorised according to World Health Organisation (WHO) Asia pacific BMI (13). All the subjects were on atorvastatin therapy and were followed-up for 12 months with reassessment of the above parameters at the end of 1st, 6th and 12th month intervals. Study ended after three follow-up visits. Progression of normoglycaemic to prediabetes or diabetes, significant changes in CRP and haepatic enzymes levels were considered as primary end point.

Statistical Analysis

The data were analysed using SPSS version 22.0, Microsoft Excel and GraphPad Prism software. Analysis was done by paired Student’s t-test. Results were expressed in terms of mean, frequencies and percentages.

Results

The study was conducted to find out the impact of atorvastatin on the CRP, glycaemic status and haepatic enzymes of the individuals receiving it. Among the patients, aged between 30-75 years, attending general medicine OPD of Midnapore Medical College, 150 patients met the inclusion criteria and got enrolled in the study. A total of 12 patients were loss to follow-up. So, a total of 138 patients completed the study and were analysed accordingly. Most of the study subjects were males (69.6%) with mean age of 54±8.88 years and mean weight of 60±5.86 kg. Majority of the participants (55.1%) were from the overweight category according to their BMI, followed by normal weight (23.9%), and obese category (21%)(Table/Fig 1). Total 60.86% of their patients were on atorvastatin 40 mg, followed by atorvastatin 20 mg (26.8%) and atorvastatin 10 mg (12.3%) (Table/Fig 2). A 50-59 years age group population had highest usage of tab. atorvastatin. Atorvastatin tablets of 40 mg strength were the most commonly used dosage formulation in this group of population (50-59 years). (Table/Fig 2) shows atorvastatin dosage usage pattern in different age groups of study population.

The mean CRP, FBS level and the mean PPBS level at the beginning of the study were 1.58 mg/dL, 84.60 mg/dL and 110.43 mg/dL respectively. When they measured the serum lipid parameters, it was found that, the mean total blood cholesterol was 191.25 mg/dL and LDL was 114 mg/dL, whereas, the mean serum triglyceride was 207.63 mg/dL at the baseline. The mean ALT/SGPT, AST/SGOT and ALP values were 21.54 IU/L, 21.101 IU/L and 92.13 IU/L, respectively after initiation of atorvastatin therapy, patient’s biochemical parameters were obtained after four weeks (Ist follow-up). On comparing the baseline mean FBS, PPBS and CRP with the Ist follow-up visit values, the changes were found to be statistically non significant. On comparing the baseline mean haepatic enzymes values with that obtained after four weeks, the differences in the ALT, AST and ALP values were found to be statistically non significant. There were statistically significant differences (p-value=0.029) between baseline serum triglyceride, blood cholesterol, LDL, and VLDL values with that obtained after four weeks, whereas, mean HDL value was found to be statistically non significant (Table/Fig 3).

The mean PPBS value at baseline and at 2nd follow-up visit was 110.43 mg/dL and 112.51 mg/dL respectively. The change in PPBS value was statistically significant (p<0.05). Whereas, there were statistically non significant changes in the mean FBS and CRP value at the end of six months, when compared with the baseline. The changes in mean ALT, AST and ALP values were statistically non significant at the end of 2nd follow-up when compared with baseline. The lipid profile values: serum triglyceride, blood cholesterol, LDL, HDL and VLDL obtained at the end of 24 weeks were compared with the baseline. There was a decrease in serum triglyceride, blood cholesterol, LDL, and VLDL value and slight increase in HDL value, which were all found to be statistically significant (p<0.05) (Table/Fig 4).

The FBS, PPBS and CRP value were obtained at the end of 3rd follow-up. On comparing with the baseline values, the changes were found to be statistically significant (p<0.05). A total of seven out of 138 patients were found to be prediabetic at the end of one year (3rd follow-up). The ALT, AST and ALP values were also obtained at the end of one year (3rd follow-up). They are then compared with their respective mean baseline values. There was slight increase in mean ALT and AST values which was found to be statistically significant (p<0.05), whereas, the differences in ALP was found to be non significant at the end of the study. Finally, the lipid profile values were obtained at the end of one year and were compared with the baseline values. There were decrease in mean serum triglyceride, blood cholesterol, LDL, VLDL levels and slight increase in mean HDL level. However, all the changes were found to be statistically significant (p<0.05) (Table/Fig 5).

Discussion

Statins are the most common drugs used for primary and secondary prevention of cardiovascular diseases (14). The study subjects had a mean age of 54±8 years which collaborates with studies conducted by Sattar N et al., which also showed patients on age group between 55-76 years were at more risk of development of diabetes. They also showed a 9% increased risk of diabetes among non diabetic statin users of the above age group (15). Male predominance among statin users were seen in this study group where 69.6% are males. Similar male predominance were seen for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial (16) and Long-term Intervention with Pravastatin in Ischaemic Diseases trial (LIPID trial) where, 61.8% and 80% of study population were males (17) Collaborative Atorvastatin Diabetes study (CARDS) trial shows 84% patients were hypertensive among statin users (18).

The present study shows 65.9% incidence of hypertension among statin users. Therapy with atorvastatin has been shown not only to affect lipid and lipoprotein levels but also, haemostatic and inflammatory molecules. The study showed significant lowering of all lipid parameters except HDL with usage of atorvastatin over 12 months, which can be attributed to HMG-CoA inhibitory activity of atorvastatin molecule. The present study showed that, atorvastatin induces a transient decrease in CRP levels within few months of therapy with further decrease upto one year (p<0.05). The observation that, CRP levels are extensively reduced through treatment with atorvastatin for one year (p<0.05) may be of particular interest in view of new data on early intervention with statins in acute coronary syndrome (19).

Drug induced liver injury includes hepatocellular injury, cholestatic liver injury and mixed liver injury which are defined on the basis of serum levels of ALT and AST and the ratio of ALT/ALP (20). In the present study, authors found the statistical significant differences in mean ALT and AST values at the end of 3rd follow-up. But, as the values were within the respective normal range, they bring about limited clinical significance. However, though being one of the most commonly prescribed statin, atorvastatin induced liver injury is not common based on the postmarketing experience. Hence, frequent liver function evaluation may be beneficial for the patients on long-term statin therapy. The present study emphasised the importance of periodical careful monitoring of Liver Function Test (LFT) to avoid severe atorvastatin-associated hepatotoxicity which may be beneficial for the patients on multiple co-morbidities and on long-term statin therapy. Moreover, there are only a few studies from India, which evaluated the impact of statin on glycaemic status of patients. Though, the present study from Eastern part of India did not show any incidence of NODM among statin users, but the 5% incidence of prediabetic state among statin users definitely enlightens the suspicious impact of HMG-CoA reductase inhibitors on the glycaemic status of patients.

The study also enlightened the importance of periodical monitoring of haepatic enzymes to avoid severe atorvastatin-associated hepatotoxicity which may be beneficial for the patients on multiple co-morbidities and on long-term statin therapy. It is also suggested to use statin therapy cautiously on the patients, who already had pre-existing diabetes or on the prediabetic population.

Limitation(s)

Theoretically, it cannot be completely ruled out that the findings in the study represent a regression to the mean since, it lacked a placebo control group, which is due to ethical considerations. Genetic predisposition, dietary factors, sedentary lifestyle, metabolic syndrome are the other factors which might also have an impact on metabolic status of the patients. Further studies with control groups needs to be done to further establish the relationship.

Conclusion

The Hydroxymethylglutaryl-Coenzyme A (HMG-CoA) reductase inhibitors are one of the most common drugs used in today’s world for their potential benefit to prevent adverse cardiovascular events. But, these cholesterol lowering agents also, have showed to cause impaired glycaemic control in patients, who were euglycaemic at the beginning of therapy. So, strict monitoring of blood glucose levels of patients on atorvastatin therapy for longer periods will be beneficial for preventing development of overt diabetes in near future.

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DOI and Others

DOI: 10.7860/JCDR/2023/62331.18036

Date of Submission: Dec 23, 2022
Date of Peer Review: Feb 09, 2023
Date of Acceptance: Apr 21, 2023
Date of Publishing: Jun 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

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Dec 24, 2023
• Manual Googling: Mar 30, 2023
• iThenticate Software: Apr 19, 2023 (6%)

ETYMOLOGY: Author Origin

EMENDATIONS: 6

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