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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
Plasminogen Activator Inhibitor-1 as a Marker of Thrombosis among Prehypertensive Patients: A Cross-sectional Study
Correspondence Address :
Dr. B Umadevi,
No. 167, Sapthagiri, ISEC Main Road, Nagarabhavi Village, Bangalore-560072, Karnataka, India.
E-mail: Umagresh15@gmail.com
Introduction: Impaired endogenous fibrinolysis has been shown to play a role in the pathogenesis and complications of hypertension. Plasminogen Activator Inhibitor-1 (PAI-1) is said to be a predictor of impaired fibrinolysis and thrombosis. Prehypertension is a common worldwide condition and is known to be an independent risk factor for Cardiovascular Disease (CVD).
Aim: Present study aimed to measure plasma PAI-1 levels in prehypertensive patients and normal subjects and to find the correlation between elevated PAI-1 levels with Blood Pressure (BP), triglycerides, total cholesterol, Low-Density Lipoproteins (LDL) cholesterol, High-Density Lipoproteins (HDL) cholesterol, and urine albumin.
Materials and Methods: This cross-sectional analytical study included 100 patients, comprising 50 prehypertensive individuals and 50 controls, aged between 35 and 50 years. The study was conducted at Sapthagiri Institute of Medical Sciences and Research Centre in Bangalore, India. Anthropometric measurements, PAI-1 levels, total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and urine albumin were measured using standard procedures. The data were statistically analysed using the Statistical Package for Social Sciences (SPSS) version 10.0, applying Student t-test and Chi-square test. Correlation analysis was performed to assess the relationship between PAI-1 and various parameters.
Results: A total of 100 patients were included in the study which had 64 men and 36 women with a mean age of 46±7 years. PAI-1 levels were significantly higher in the prehypertensive group compared to the control group (p-value=0.013). Participants with higher plasma PAI-1 levels had significantly elevated BP (p-value=0.001) compared to those with lower PAI-1 levels. Total cholesterol, triglycerides, and LDL cholesterol were significantly increased in prehypertensive individuals (p-value=0.001), whereas HDL cholesterol was significantly lower (p-value=0.001). The study also observed a significant increase in urine albumin in the prehypertensive group with elevated PAI-1 levels compared to the controls (p-value=0.001).
The study revealed that elevated plasma PAI-1 levels did not show a significant positive correlation with SBP and DBP (r=0.138 and 0.660, p-value of 0.338 and 0.648, respectively). Plasma PAI-1 levels were weakly correlated with total cholesterol (r=0.145, p-value 0.315), LDL cholesterol (r=-0.068, p-value 0.640), HDL cholesterol (r=0.21, p-value 0.882), and triglycerides (r=0.207, p-value 0.150). There was no significant correlation between increased PAI-1 levels and urine albumin (r=-0.225, p-value of 0.117).
Conclusion: Present study demonstrated that plasma PAI-1, total cholesterol, triglycerides, LDL cholesterol, and urine albumin were significantly elevated in prehypertensive individuals, suggesting vascular damage and inflammation. As prehypertension is often asymptomatic, patients with prehypertension should be considered to have an increased risk for CVD.
Cardiovascular disease, Fibrinolysis, Inflammation
Hypertension is an important worldwide public health problem. It is a known predictor of CVD, cerebrovascular accidents, chronic renal failure, and end-stage kidney disease. Globally, more than 17 million premature deaths are attributed directly or indirectly to hypertension and its complications (1). Hypertension is the fourth highest risk factor responsible for the greatest number of deaths and disabilities, with nearly 11% of all deaths attributable to hypertension in India (2),(3). Prehypertension is also associated with an increased risk of cardiovascular complications. The Joint National Committee (JNC7) on prevention, detection, evaluation, and treatment of high blood pressure defined prehypertension as SBP of 120 to 139 mmHg or DBP of 80 to 89 mmHg, based on two or more properly measured seated blood pressure readings on each of two or more office visits (4). Previous studies conducted on the Indian urban population have reported a prevalence of prehypertension close to 32%, which was closely associated with age groups, gender, occupation, and high Body Mass Index (BMI) (5),(6),(7).
Epidemiological studies have shown that the risk of prehypertension progressing to hypertension and developing CVD is higher in individuals with blood pressure of 130 to 139/85 to 89 mmHg than in those with blood pressure of 120 to 129/80 to 84 mmHg (8),(9),(10),(11).
The pathophysiology of hypertension is associated with impaired endogenous fibrinolytic activity, accelerated atherosclerosis, and clot formation, which play a major role in the complications of hypertension. Recent studies have demonstrated great concern about prehypertension, as it is an independent risk factor for CVD, increasing the risk of thrombosis and altered hemostasis (12),(13),(14).
Plasminogen Activator Inhibitor-1 (PAI-1), a member of the serine protease inhibitor family, is the major regulator of the endogenous fibrinolytic system. PAI-1 is the primary physiological inhibitor of plasminogen activation in the blood. It acts by inhibiting tissue-type (tPA) and urokinase-type plasminogen (uPA) activators (15). PAI-1 is largely secreted by vascular endothelial cells, platelet alpha granules, hepatocytes, adipocytes, and cardiomyocytes. In pathological conditions, PAI-1 secretion is increased by proinflammatory factors such as TNFα, TGFβ, IL6, lipoproteins, growth factors, and insulin in response to inflammation (16). Juhan-Vague et al., reported in their study on PAI-1 in cardiovascular pathology that increased plasma PAI-1 is predictive of myocardial infarction. It creates a prothrombotic state that contributes to the development of CVD. Studies also suggest that inflammation has a role in inducing the secretion of plasma fibrinolytic markers in hypertension (15),(16),(17),(18),(19). PAI-1 secretion is closely associated with the Renin-Angiotensin System (RAS), an important contributor to vascular disease initiation and progression. Treatments that inhibit the Renin Angiotensin-Aldosterone System (RAAS) also decrease PAI-1 (20).
Abnormal levels of serum lipids constitute one of the important independent risk factors for CVD and studies estimate that they account for 56% of Coronary Heart Disease (CHD). Studies have shown PAI-1 overexpression in glomerulosclerosis through interstitial macrophage recruitment and activation (1),(21). Prehypertension, most often asymptomatic and goes unrecognised, has not been widely studied regarding impaired fibrinolysis, especially in the Indian population (22).
The present study aims to measure plasma PAI-1 in prehypertensive patients and normal subjects, and to find the correlation between elevated PAI-1 levels with blood pressure, triglycerides, total cholesterol, LDL, HDL cholesterol, and urine albumin in prehypertensives.
The present study is a cross-sectional analytical study conducted on patients attending the Outpatient Department (OPD) of General Medicine at Sapthagiri Institute of Medical Sciences and Research Centre in Bangalore, India, over a period of one year from October 2020 to September 2021. The study protocol was approved by the ethical committee of the institute, ensuring the confidentiality of the data (SIMS and RC/IECC/05/2018). A total of 100 participants, including 50 prehypertensive patients and 50 controls, were included in the study in the age group of 35 to 50 years. Prehypertension was defined according to the JNC-7 classification (4). The sample size was calculated based on a prevalence of prehypertension of 32%, as determined by a previous study conducted in South India (5),(6).
n=4pq/d2 (p=prevalence (32%), q=100-p=68, d=20%)
Inclusion criteria: A total of 50 prehypertensive individuals in the age group of 35-50 years and 50 controls between 35-50 years, including both male and female patients, were included.
Exclusion criteria: Patients with the following comorbidities, such as Type 2 diabetes mellitus, individuals taking antihypertensive medication, sepsis, obesity, history of thrombosis, cardiovascular diseases, and renal diseases, were excluded from the study.
Blood Pressure (BP) was measured three times by trained staff using a standard mercury sphygmomanometer (Diamond) following a standardised protocol, after the participants had rested for at least five minutes, during two separate visits. The mean of the last two measurements was used for statistical analysis.
Body Mass Index (BMI) was calculated by dividing the weight in kilograms by the square of the height in meters (kg/m2). Waist and hip circumference were measured using a flexible plastic tape at the level of the abdomen (midway between the lower rib margin and the iliac crest) and the hip (over the greater trochanters).
Plasma PAI-1 was analysed using an Enzyme-Linked Immunosorbent Assay (ELISA) with a commercially available kit (KINESISDx Catalogue No K12-1160) from Skanda Life sciences, Bangalore. The kit is DSIR recognised and CPCSEA approved, and the Human PAI-1 ELISA Report No is: SLSPL/2021/AN/11/023/01. Venous blood samples were collected with minimal venous occlusion to prevent activation of haemostatic factors. The samples were collected between 8 am to 10 am to minimise the effects of diurnal variations on PAI-1. Blood samples were centrifuged gently for 10 minutes, and platelet-poor plasma was collected and stored at -70ºC.
Total cholesterol, triglycerides, HDL, and LDL cholesterol measurements were performed using the enzymatic method (Vitros 5600 catalogue J56001504) (23),(24). Plasma glucose was measured using the glucose 2oxidase peroxidase method (Vitros 5600 catalogue J56001504) (25), to rule out diabetes mellitus. Urine albumin was measured using the standard laboratory turbidimetry method (Vitros chemistry Products mALB Reagent) [26,27].
Statistical Analysis
The data were analysed using SPSS version 10.0. A Student’s t-test and Chi-square test were used to assess the association between different categorical variables, while Analysis of Variance (ANOVA) was applied to observe the significance of differences in normally distributed data. A probability value of less than 0.05 was considered significant.
The study included 100 participants, consisting of 50 prehypertensive patients and 50 controls, including 64 men and 36 women, with a mean age of 46±7 years. The baseline characteristics of the study participants in the two groups are shown in (Table/Fig 1).
PAI-1 levels were significantly higher in the prehypertensive group compared to the control group (p-value=0.013), although the marker was within the normal range. Participants with higher plasma PAI-1 had significantly higher blood pressure (p-value=0.001) at baseline than those with lower PAI-1. The mean age of prehypertensives with higher plasma PAI-1 was 46.78 years (p-value=0.62), BMI was 25.46 kg/m2 (p-value=0.555), waist circumference was 89.96 cm (p-value=0.014), and hip circumference was 98.46 cm (p-value=0.048). Total cholesterol, triglycerides, and LDL cholesterol were significantly higher in prehypertensives (p-value=0.001), while HDL cholesterol was significantly lower (p-value=0.001). The study also observed that urine albumin was significantly elevated in the prehypertensive group with increased PAI-1 compared to controls (p-value=0.001).
The present study revealed that elevated plasma PAI-1 did not show a significant and positive correlation with Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) (r=0.138 and 0.66, p-value of 0.338 and 0.648) in the prehypertensive group, as shown in (Table/Fig 2).
Plasma PAI-1 was weakly correlated with total cholesterol (r=0.145, p-value 0.315), LDL cholesterol (r=-0.068, p-value 0.640), HDL cholesterol (r=0.21, p-value 0.882), and triglycerides (r=0.207, p-value 0.150) in prehypertensives. Increased PAI-1 did not show any significant correlation with urine albumin (r=-0.225, p-value of 0.117) in the prehypertensive group. Such correlations were not observed in the control groups.
PAI-1 levels were used to evaluate the fibrinolytic activity in prehypertensives. An important finding in the current study is the elevated PAI-1 in prehypertensives, which can significantly contribute to the development of future hypertension and its complications. This finding is consistent with the study conducted by Wang TJ et al., which examined the association of plasma PAI-1 with incident hypertension among 1456 European whites in the Framingham offspring study and found that high PAI-1 levels contribute to the development of hypertension and its complications (28).
Ferguson TS et al., explained in their study that prehypertension is associated with a three-fold increase in the incidence of hypertension. Plasma PAI-1 may contribute to the development of hypertension by affecting vascular remodeling, reducing vessel wall elasticity, and increasing peripheral resistance (29).
Studies have shown impaired fibrinolytic activity in hypertensives, along with defects in coagulation, platelet function, and endothelial dysfunction. All of these factors may predispose individuals to a hypercoagulable state in hypertension, which can play a role in the pathogenesis and complications of hypertension (29),(30),(31).
The significantly higher waist circumference in the prehypertension group, which is a known risk factor, is consistent with the studies conducted by Rao KVM and Reddy GPK and Nkeh-Chungag BN et al., who also reported an association between waist and hip circumferences and the presence of hypertension and prehypertension in young South African adults (32),(33). This suggests that waist circumference is a better measure of cardiovascular disease risk compared to BMI, as waist circumference can be influenced by subcutaneous or visceral fat (32),(33). The study did not observe a significant difference in BMI between the two groups, whereas Ferguson TS et al., in their work on the progression from prehypertension to hypertension in a Jamaican cohort, reported that higher BMI can independently predict the development of hypertension (34).
In the present study, total cholesterol, triglycerides, and LDL cholesterol were significantly increased, while HDL cholesterol was low in the prehypertensive group. This finding is consistent with the study conducted by Mishra S et al., which showed a total prevalence of dyslipidemia of 17.4% and higher prevalence of hypercholesterolemia in prehypertensives. Karasek D et al., also explained that the prevalence of prehypertension was higher in patients with dyslipidemia [35,36]. A population study in China involving 1154 subjects found that total cholesterol and triglycerides were significantly higher in prehypertensives compared to normotensives. Studies have reported that increased cholesterol levels can upregulate the expression of PAI-1 due to vascular injury, which could potentially explain the findings in the present study as well (37),(38).
It was also observed in the current study that urine albumin was significantly elevated in the prehypertensive group compared to controls (p-value=0.001). Previous studies have also shown a close relationship between PAI-1 levels and the degree of albuminuria (39).
Regarding the correlation between variables, the present study showed no significant correlation between elevated PAI-1 levels and SBP and DBP in prehypertensives, which could potentially be attributed to prehypertension being an incidental finding during the participants’ hospital visits.
The study showed that elevated plasma PAI-1 demonstrated a weak correlation with total cholesterol, LDL cholesterol, triglycerides, HDL cholesterol, and urine albumin in prehypertensives. This weak correlation could possibly be due to the small study population. Larger populations and patient follow-ups are required to yield significant results, as explained by Peng H et al., (30). Sahay S et al., showed in their study that PAI-1 significantly correlated with triglyceride (r=0.492, p-value=0.001), LDL (r=0.604, p-value <0.001), and inversely correlated with HDL (r=-0.392, p-value=0.005) (38). Additionally, the influence of PAI-1 on the pathophysiology of prehypertension and dyslipidemia is complex and not clearly established. It may depend on genetic, environmental, and vascular interactions. Some prospective studies have also shown that dyslipidemia can strongly predict the occurrence of hypertension over the years (39),(40),(41).
This study could assist clinicians in early intervention, and prehypertensive individuals should be targeted for lifestyle modifications or other interventions to reduce the risk of cardiovascular disease. The study may contribute as a potentially valuable tool for a prospective pathophysiological diagnostic panel.
Limitation(s)
A major limitation of the study is the small sample size. The research needs to be extended to a larger population, and prehypertension being an incidental finding during the participants’ hospital visit should be taken into consideration. Although blood pressure was significantly elevated, a follow-up of these participants for at least four to five years is required to obtain significant results. Additionally, other potential predictors of blood pressure, such as gender differences, socio-economic status, physical activity, and dietary factors, could be included in future studies.
PAI-1 is a potential biomarker of impaired fibrinolysis. The main finding of the present study is that plasma PAI-1, total cholesterol, triglycerides, LDL cholesterol, and urine albumin were significantly increased in prehypertensives, suggesting vascular damage and inflammation. Waist circumference and hip circumference were also significant predictors for the development of hypertension and its complications. As prehypertension is usually asymptomatic, lack of awareness and delays in seeking healthcare facilities may increase the risk of developing hypertension and its complications. This study may help primary care physicians identify the risk and prevent further cardiovascular complications.
This research has been funded and supported by Rajiv Gandhi University of Health Sciences (RGUHS), Bangalore, Karnataka. Order No: RGU:RGU/ADV.RES/BR/018/20 18-19.
DOI: 10.7860/JCDR/2023/63325.18321
Date of Submission: Feb 06, 2023
Date of Peer Review: Mar 03, 2023
Date of Acceptance: Jul 06, 2023
Date of Publishing: Aug 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. Yes
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