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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
Original article / research
Full Version
Assessment of Reliability of Advanced Lipid Parameters for Premature Coronary Artery Disease in Young Indians: A Case-control Study
Correspondence Address :
Dr. Rahul Patil,
Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, Karnataka, India.
E-mail: dr.rahulspatil85@gmail.com
Introduction: Coronary Artery Disease (CAD) appears even in patients with normal level of conventional lipid parameters. But due to lack of specific guidelines on Indian population, involving detection of advanced lipid indices, has resulted in inadequate finding, management, and control of cardiovascular disease risks. This emphasises the need of advanced lipid indices for prediction of CAD at younger age.
Aim: To evaluate the reliability of advanced lipid indices compared to conventional lipid parameters for diagnosis of CAD. Also, to determine the effectiveness of advanced lipid indices in screening young Indian for the risk of Premature CAD (PCAD).
Materials and Methods: A case-control study was conducted at a tertiary care centre in Bengaluru, Karnataka, India, between January 2020 to January 2022. The study enrolled total 983 subjects which were divided into cases and controls. The estimation of usual lipid profile (Triglycerides (TG), High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), and Total Cholesterol (TC)) and advanced lipid parameters, oxidized LDL, Apolipoprotein A1 (Apo A1), lipoprotein (a), small density LDL (Sd-LDL), and Apolipoprotein B-100 (Apo B) was studied for each enrolled individual. These lipid parameters were used to calculate various lipid indices like Lipid Pentad Index (LPI), Lipid Tetrad Index (LTI), Atherosclerotic Index (AI), and Advanced Atherosclerotic Index (AAI); and TC/HDL ratio. Statistical analysis was performed using Chi-square test, Fisher’s exact test, multivariate logistic regression, and Student’s t-test/Analysis of Variance (ANOVA) test.
Results: Mean age of patient in case group was 32.31±5.42 years and individuals in control group was 32.13±5.21 years. Among case group, 427 (88.04%) enrolled males had PCAD. In case group, total 45 (9.28%) had diabetes, 51 (10.51%) had family history of PCAD and 230 (47.42%) patients were smokers. The values of TC (p=0.009), LDL (p<0.001), Apo A1 (p<0.001), HDL (p<0.001) were significantly lower among cases compared to controls, lipoprotein (a) (p=0.04), Sd-LDL (p<0.001), TG (p<0.001) were significantly higher among cases compared to controls. Among the calculated lipid indices, the values of AI (p<0.001), LTI (p<0.001), LPI (p=0.001) and AAI (p=0.01) were significantly higher among cases as compared to controls.
Conclusion: Advanced lipid indices are statistically more reliable than conventional lipid parameters. Newer advanced lipid indices are effective in screening young Indian individuals for the risk of PCAD.
Atherosclerosis, Cardiovascular disease, Indian population, Lipid indices, Young patients
CAD has become a leading cause of morbidity and mortality all over the world and in developing countries like India. At present, India has become cardiovascular disease capital of the world. Indians are 3-4 times at higher risk of CAD than Americans, six times higher than Chinese, and 20 times higher than Japanese population. Even young Indians (≤45 years) are prone as a community for CAD (1),(2). PCAD is defined as cardiac events occurring before the age of 55 years in men and 65 years in women, but severe PCAD is considered as the occurrence of Ischaemic Heart Disease (IHD) at much younger age that is 40 years (3). Studies reported that CAD is affecting Indians 5-10 years earlier than western population where the incidence of PCAD is upto 5% as compared to 12-16% in Indians. In Indian, the average age of first heart attack is 10 years earlier compared to western population, and of that 25% are occurring before the age of 40 years (4),(5).
As previous landmark studies on prevention and treatment of CAD have mostly engaged Caucasian population. Therefore, western guidelines derived from these studies have failed in both primary and secondary prevention of cardiovascular disease in Indian population (1),(6). The reason for this failure might be the clear and fundamental differences in the pathophysiology and clinical features of the cardiovascular disease in Asian Indian (7). Hence, there is a need to consider cardiovascular disease among Asian Indians as distinct entity in comparison to Caucasians. On 1st April 2017, a first-of-its-kind registry was started at our centre, exclusively for PCAD patients (males <40 years, females <45 years), under the title of project PCAD to study the incidence, prevalence, clinical profile, and uniqueness of PCAD among Indians. During the enrolment for that registry, a significant observation was made that CAD occurs even in patients with normal level of conventional lipid parameters such as LDL and HDL, and the same has been reported in many previous studies (6). Similarly, a study by Bansal SK et al., suggested advanced lipid parameters (i.e. oxidized low density lipoprotein (Ox-LDL), lipoprotein (a), Apoprotein -A1 (Apo-A1), small dense LDL (Sd-LDL), Apoprotein-B (Apo-B)) as better predictors and markers for amplifying high degree of prematurity, morbidity and mortality of CAD in Indian population, as compared to conventional lipid parameters (8).
Furthermore, the manifestation of CAD in normolipidaemic individuals provide the insight to the researchers to look beyond the conventional lipid parameters. Therefore, several lipid indices such as AI, LTI, LPI, and AAI, which are derived from the conventional/advanced lipid parameters, are developed to determine the association of lipid risk factor and CAD (9),(10). Moreover, due to non availability of Indian population specific guidelines, including detection of advanced lipid parameters, has resulted in incomplete detection, treatment, and control of cardiovascular disease risks. Therefore, the present study was designed to prove the reliability of advanced lipid parameters compared to conventional lipid parameters for atherosclerosis and CAD. This study was also aimed to determine the effectiveness of advanced lipid indices in screening young Indian for the risk of PCAD.
This case-control study was conducted at a tertiary care cardiac centre in Bengaluru, Karnataka, India, between January 2020 to January 2022. The study was approved by the Medical Ethics Committee of the Institute (MEC11B-Thesis/P24,2020) and the written informed consent was obtained from all subjects before enrolment.
Inclusion criteria: Male and females, aged ≤40 years and who were diagnosed with IHD, with documented indication of acute coronary syndrome (unstable angina, ST elevation/non ST elevation myocardial infarction) or chronic stable angina with clinical evidence of CAD were included as cases. Age matched individuals from the general population who were defined as CAD free, based on clinical history or detailed examination were included as controls in the present study.
Exclusion criteria: Patients with a history of chronic alcoholism, concomitant liver, or kidney disease and acute or chronic infection; patients taking hypolipidaemic drugs, oral contraceptives, or hormone replacement therapy and patients unwilling to give informed consent were excluded from the study.
Sample size: Sample size of 1000 (500 in each group) was estimated in the present study, based on the results of a previous study which showed a difference of 7 mg/dL on Apo A1, with 90% statistical power and 5% level of significance (11).The study included a total of 983 subjects, which were divided into two groups:
1. Case group (n=485) – Patients who were diagnosed with PCAD (acute coronary syndrome and/or chronic stable angina) were included as cases.
2. Control group (n=498) – Age matched individuals from the general population who were defined as CAD free based on clinical history or detailed examination.
All enrolled patients were asked to complete a proforma covering demographic data such as age, gender, medical history, smoking habits, and medical treatment. A standardised diagnostic protocol was followed consisting of physical examination and laboratory testing in a fasting state for all the study subjects.
The fasting blood sample (5 mL) was taken from antecubital vein for the estimation of conventional lipid profile (TG, HDL, LDL, TC) and advanced lipid profile (Ox-LDL, Apo A1, lipoprotein (a), Sd-LDL, and Apo B-100). Normal range for all the parameters in given in (Table/Fig 1).
Sd- LDL was indirectly calculated using the following formula (12):
Sd-LDL = 0.94Chol – 0.94HDL – 0.19TG / Apo B – 0.09Chol + 0.09HDL – 0.08TG
These lipid parameters were used to calculate various lipid indices like LPI, LTI, AI, AAI; and total cholesterol/HDL ratio.
Formulas for calculation of various lipid indices are as follow: (12).
1. AI = (Log [TG/HDL])
2. LTI = TC × TG × lipoprotein (a) ÷ HDL
3. LPI = TC × TG × lipoprotein (a) × Apo B ÷ Apo A1
4. AAI = {Ox LDL× lipoprotein (a) × Apo B} ÷ (Apo A1 × Sd LDL)
Statistical Analysis
Statistical software R- version 4.1.3 (R Core Team, 2022, Vienna, Austria) was used for statistical analysis. All categorical data were compared between case and control by frequency and percentage with Chi-square test of independence. The continuous parameters such as age, lipid profile, and advanced lipid indices were compared by mean±SD with Student’s t-test. The predictability of advanced lipid indices was compared by Receiver Operating Characteristic (ROC) curve analysis. Sensitivity, specificity, and area under the curve (AUC) were reported with 95% confidence interval. Univariate odd ratio of PCAD for 10 unit increase of AAI, sex, age and diabetes were estimated by contingency table analysis. Further an adjusted logic regression was performed to assess the confounding effects of age, sex, diabetes on the association of PCAD and AAI. p-value <0.05 was considered as statistical significance.
A total of 983 subjects were enrolled for the study and were divided into case group (comprised of 485 patients) and control group (comprised of 498 individuals).
Mean age of the study population was 32.22±5.31 years (32.31±5.42 years for case group and 32.13±5.21 years for control group). Among case group, 427 (88.04%) enrolled males had PCAD and only 58 (11.96%) females reported PCAD. In case group, total 45 (9.28%) had diabetes, 51 (10.51%) had family history of PCAD and 230 (47.42%) patients were smokers. However, in control group, only 4 (0.8%) individuals had diabetes, 64 (12.85%) were smokers and none reported family history of PCAD (Table/Fig 2).
Mean TC level of cases was 141.07±45.11 mg/dL, whereas that of control was 145.72±36.78 mg/dL (p=0.009). Mean LDL cholesterol of cases was 84.66±39.25 mg/dL while that of control was 93.04±31.57 mg/dL (p<0.001). Though statistically significant but the values of TC (p=0.009) and LDL (p<0.001) were significantly lower among cases compared to controls. However, HDL (p<0.001) were significantly lower among cases compared to control and triglycerides (p<0.001) were significantly higher among cases compared to controls. The ratio of total cholesterol/HDL was significantly higher among cases compared to controls (p<0.001) (Table/Fig 3).
Among the lipid indices, the values of AI (p<0.001) higher in control, LTI (p<0.001), LPI (p value=0.001) and AAI (p=0.01) were significantly higher among cases compared to controls. Lipoprotein (a) (p=0.04) was significantly higher among cases compared to controls (Table/Fig 4).
Indices like AI, AAI, LTI, LPI were compared as diagnostic marker for PCAD. AI was found to be most powerful diagnostic marker among all above, exhibited 70% sensitivity but only 54% specificity (Table/Fig 5).
Estimated odds ratio (OR) by univariate logistic regression of AAI for gender (OR:1.04, CI:0.66 -1.63), diabetes (OR:7.16, CI:2.51-20.4), and smoking (OR:6.98, CI:4.52-10.79) showed higher risk for PCAD. For every 10 units increase in AAI, there was 2% increase in probability of acquiring PCAD. However, when these three factors were adjusted, the adjusted impact of AAI on PCAD was not changed. Hence, these three factors are not confounding between AAI and PCAD.
Despite conventional lipid profile (TC, LDL, HDL, and TG) being an established tool for early prediction and management of cardiovascular disease. A significant number of cardiovascular events remain unaddressed in Indian populations (13). Lipids are carried within lipoprotein which carry lipid particles that vary in size, density, charge, core lipid composition, specific apolipoproteins, and function (10). Despite availability of the large pool of information on lipids and its estimation, it is still unclear that how to utilise advanced lipid analysis for primary and secondary prevention of cardiovascular disease. Moreover, new biomarkers require standardisation and comparability, accessibility, clear indications, and lastly demonstrating cost-effectiveness (14),(15).
Literature state that advanced lipids have the potential to improve risk prediction and management of cardiovascular disease (6),(16). However, current prevention guidelines are not supporting these, owing to lack of grade-A level of evidence. The American College of Cardiology/American Heart Association (ACC/AHA) guidelines published in 2013 did not issue any recommendation for Apo B, LDL, or lipoprotein (a) due to lack of randomised trials evidence for these measures as well as non HDL as goals of therapy (3). Therefore, advanced lipids are promising biomarkers, but they are not currently recommended as routine tools for CVD risk assessment and management.
In present study, the patient population was predominantly male, while there was higher proportion of female population in controls compared to cases (88% vs 74%) (p<0.001). Similarly, there was disproportionate number of smokers and diabetic patient population. However, statistical analysis proved that these three factors are not confounding between AAI and PCAD. They are risk factors but not confounders. In a pilot study by Bansal SK et al., they studied a small sample of 120 patients among whom maximum patients were in the age of 36–45 years (80 out of 120, 66.67%), whereas the age cut-off (40 year) and average age was much lower in present study (31.22 years) hence present study population was more representative of younger population. In the study by Bansal SK et al., the values of TC (p<0.001), TG (p=0.032), LDL (p<0.001), OX LDL (p<0.001), Lipoprotein (a) (p<0.0001), and Apo B (p<0.001) were significantly higher while HDL (p<0.01), SD LDL (p<0.001), and Apo A1 (p<0.001) were significantly lower in the cases as compared to the controls (12).
However, contrary to the traditional belief of high TC and LDL cholesterol being most important lipid markers both for primary and secondary prevention of CAD, present study showed that values of TC (p=0.009) and LDL cholesterol were significantly lower among cases compared to controls (p<0.001). The Lipid ratios of TC/HDL was significantly higher among cases compared to controls (p<0.001). Among the lipid indices the values of AI (p<0.001), LTI (p<0.001), LPI (p<0.001) and AAI (p = 0.006) were significantly higher among cases compared to controls.
In the study by Bansal SK et al., the values of AI, LTI, LPI, and AAI were significantly high in cases as compared to controls. Out of all the indices newly defined AAI showed maximum correlation (p<0.001, r=0.737) with the disease as compared to AI (p<0.001, r=0.520), LTI (p<0.001, r=0.677) and LPI (p<0.001, r=0.622) (12).
In present study, advanced lipid parameters such as Sd-LDL (<0.001), lipoprotein (a) (0.04), were significantly higher among cases compared to control. However, no statistically significant difference was noted for Ox-LDL (p=0.052) and Apo-B (p=0.148) among cases and controls. In contrast to present study findings, Bansal SK et al., reported statistically significant difference (p<0.0001 for all) among cases and controls for all advanced lipid parameters suggesting more predictability of these parameters for PCAD (8).
Furthermore, the values of lipid indices such as AI, LPI, LTI and AAI which were calculated from various lipid parameters were significantly higher in PCAD patients in Indian population as compared to the controls (p<0.001). From the results of the present study, it emerges that advanced lipid parameters such as AI, LPI, LTI, and AAI has better discriminating value in CAD patients as compared to conventional indices.
In addition, as parameters involved in calculation of these indices are genetically determined, it may more precisely illuminate higher incidence, severity, and prematurity of CAD. They may be proved as an important screening test for early detection and intervention in CAD patients in the Indian population. However, their importance as markers of dyslipidaemia in premature CAD patients have to be further explored in larger and heterogenous patients and should be validated before clinical implementation.
Limitation(s)
Sample size in present study was less than the calculated sample size. Also, there was significant difference in sex ratio among cases and controls. However, statistical analysis proved that gender was not confounding between AAI and PCAD i.e. they are predictors but not confounders.
Advanced lipid parameters like Apo A1, Apo B, lipoprotein (a), Sd-LDL, and Ox-LDL were statistically more reliable of than conventional lipid parameters such as HDL, LDL, TC, and TG. Newer lipid incorporating advanced lipid indices such AI, LPI, LTI, and AAI are effective in screening young Indian individuals for risk of PCAD. Present study was single centre study predominantly involving urban and semiurban population. Hence, a multicentric study across different parts of the country would help to generalise these findings specifically for Indian population. Therefore, future studies should assess and validate the potential of advanced lipids in assessment and prevention of cardiovascular disease and its management.
DOI: 10.7860/JCDR/2022/57814.16818
Date of Submission: May 17, 2022
Date of Peer Review: Jun 02, 2022
Date of Acceptance: Aug 07, 2022
Date of Publishing: Sep 01, 2022
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA
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