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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
Comparison of Uric Acid Levels in Hypertensive Patients with and without Heart Disease: A Case-control Study
Correspondence Address :
A Pullaiah,
Associate Professor, Department of Biochemistry,
Government Medical College, Nalgonda, Telangana, India.
E-mail: a.pullaiah22@gmail.com
Introduction: Hypertensive heart disease is the 13th leading cause of death worldwide. Uric Acid (UA) is an end product of purine metabolism in humans and higher serum UA is a potential independent risk factor for Cardiovascular Disease.
Aim: To compare the levels of serum UA in hypertensive individuals with and without cardiovascular disease.
Materials and Methods: This case-control study was done at RIMS, Telangana, India from October to December 2021 including 50 individuals with hypertension and without cardiovascular disease enrolled as controls and 100 individuals with Hypertensive Heart Disease (HHD) as cases. The HHD cases were subdivided into group 2A (age <=55 years) and 2B (age >55 years). Samples were collected and analysed for UA, lipid profile, serum creatinine, fasting blood sugar, etc. Independent samples T-test was used for statistical analysis using Statistical Package for Social Sciences (SPSS) software version 28.0.1.1 (15).
Results: Males and females were taken in a ratio of 1:1. Mean age for control group was 54.6±9.6 years, for HHD ≤55 years was 50±3.232 and for HHD >55 years was 63.26±6.137 years. In males, mean values of serum UA was 5.1±0.5 mg/dL in controls, 9.2±1.0 mg/dL in HHD ≤55 years (p-value=0.03), 6.4±0.8 mg/dL in HHD >55 years (p-value=0.1). In females, mean values of serum UA was 4.8±0.4 mg/dL in controls, 10.5±0.4 mg/dL in HHD ≤55 years (p-value=0.009), 6.9±0.5 mg/dL in HHD >55 years (p-value=0.09) Standard Deviation (SD). Serum UA levels were significantly higher in patients of HHD less than 55 years of age than that of controls.
Conclusion: Based upon the findings of the study, it was concluded that hypertensive individuals with cardiac disease had higher levels of serum UA than controls, especially in females.
Blood pressure, Cardiovascular disease, Lipid profile, Purine metabolism
Hypertension (HTN) is a well-known and strong risk factor for Cardiovascular Diseases (CVD) (1). Experimental and clinical evidences support the possibility that an elevated serum UA level may independently lead to or worsen hypertension (2).
Hypertensive Heart Disease (HHD) refers to a constellation of changes in the left ventricle, left atrium, and coronary arteries as a result of chronic blood pressure elevation, which increases the workload on the heart inducing structural and functional changes (3). International Classification of Diseases (ICD)-10 definition for HHD includes heart failure and other cardiac complications of hypertension when a causal relationship between the heart disease and hypertension is stated or implied (4). Hypertension precedes heart failure in 90% of cases (5). Hypertensive heart disease was estimated to be responsible for 1.0 million deaths worldwide in 2004 (or approximately 1.7% of all deaths globally), and was ranked 13th in the leading global causes of death for all ages (6).
Uric Acid (UA) is an end product of purine metabolism in humans (7). Increased serum UA levels are independently and significantly associated with risk of cardiovascular morbidity and mortality (8). The relationship of UA with cardiovascular events is particularly strong, especially in patients at high-risk for heart disease (9). Several studies suggested a U-shaped relationship between serum UA and risks of total and cardiovascular mortality, with lower UA levels mainly increasing stroke-related mortality, and higher UA levels mainly increase heart-related mortality (1),(10),(11).
The three main factors that affect the mechanism of angiopathy due to hyperuricaemia include the effects of oxidative stress during UA production, the urate transporter disorders and hyperuricaemia induced vascular disorders (facilitation of arteriosclerosis by deposition of monosodium urate crystals) (12). In ischaemic state, hypoxanthine is converted to xanthine by Xanthine Oxidase (XO) which is further converted to UA. During this conversion, reactive oxygen is produced. Reactive Oxygen Species (ROS) stimulate proliferative effect on vascular wall and is involved in arteriosclerosis as ROS binds to Nitric Oxide (NO) and supresses its function (12).
Dyslipidaemia (Dyslipidaemia is characterised by the elevation of total cholesterol, Triglycerides (TGs), or both, or a low High-Density Lipoprotein (HDL) cholesterol level that contributes to the development of atherosclerosis), smoking, obesity and lack of physical activity were recognised as prominent risk factors for cardiovascular disease in a study by Ciumornian L et al., (13). Infectious diseases are one of the precipitating factors for cardiovascular disease in addition to lack of compliance to proper diet (14). Hyperuricaemia is associated with gout, chronic kidney disease and diabetes mellitus (15). Age also is a major risk factor for CVD as in India, approx 40% of Myocardial infarction occur in people aged <45 years and approx 33% occurs in people aged ≤55 years (16).
Serum UA assessment is less expensive when compared to assessment of other cardiac biomarkers (Troponins, CK-MB, NT-proBNP). The evidence regarding the link between serum UA levels and cardiovascular mortality in hypertensive individuals is unclear. Identifying this association may provide new insights into the management of UA levels in hypertension and in reducing mortality from HHD.
Studies were done previously to know the relationship between cardiovascular disease and serum UA levels in hypertension (1),(2),(17),(18) but no similar study was done previously in Adilabad, Telangana. Hence, present study was conducted to compare the levels of serum UA in hypertensive individuals with and without cardiovascular disease coming to this institution.
This case-control study was done at RIMS, Adilabad, Telangana, India for a duration of three months, from October to December 2021. The protocol and procedure for this study was approved by the Institutional Ethical Committee (IEC/RIMS/21/2021). Oral and written consent was taken from all participants before participating in the study.
Inclusion criteria: Individuals above 30 years of age, with both hypertension and cardiovascular disease were taken as cases. Hypertension was defined by present history of intake of blood-pressure lowering drugs (Telmisartan in our institution) and/or baseline systolic/diastolic blood pressure >140/90 mmHg (5). Age matched individuals with hypertension alone were taken as controls.
Exclusion criteria: Individuals below 30 years of age and with diabetes mellitus, gout, chronic kidney disease, infective diseases and on hyperuricaemia treatment were excluded.
Sample size: A total of 150 hypertensive individuals with and without heart disease, coming to the Department of General Medicine, RIMS, Adilabad during the three months of study period and meeting the above criteria were enrolled in the study by purposive sampling.
• Group 1: 50 individuals with hypertension alone were taken as controls and
• Group 2: 100 individuals with HHD were taken as cases
Group 2 was further subdivided into two groups with 50 individuals each:
Group 2A: Age 30-55 (<=55 years)
Group 2B: Age >55 years.
Study Procedure
History was taken from all the participants regarding age, smoking, physical activity and use of lipid lowering medications. Physical activity was assessed based on World Health Organisation (WHO) guidelines (19) and those not meeting the criteria were considered as inactive. Participants were examined for waist circumference and blood pressure. Waist circumference was measured according to CDC NHANES guidelines (20). Normal reference range for waist circumference was taken as less than 90 cm in males and less than 80 cm in females. Central obesity was defined as waist circumference more than 102 cm in males and more than 88 cm in females (21),(22).
Blood samples (5 mL) were collected in Ethylenediaminetetraacetic Acid (EDTA) vacutainers, in the morning, after participants had been fasting for atleast eight hours and sitting for 15 minutes. Aliquots of serum were immediately obtained by centrifugation (3000 RPM for 10 minutes) and stored at 2-8°C. Samples were analysed within 12 hours of collection to avoid deterioration in UA levels. The collected samples were analysed for total cholesterol, triglyceride, HDL cholesterol, fasting blood glucose, creatinine, White Blood Cell (WBC) count and UA. The test methods used and normal reference ranges for the analysed parameters are given in (Table/Fig 1) (23),(24),(25),(26),(27),(28).
Serum UA estimation: Serum UA analysis was done using Beckmann Coulter AU480 analyser by Uricase based method (Modified Fossati Method). In women, the values between 2.6-6.0 mg/dL were taken as biological reference interval and values >6.0 mg/dL were taken as hyperuricaemia. In men, the value between 3.5-7.2 mg/dL were taken as biological reference interval and values >7.2 mg/dL were taken as hyperuricaemia (29).
Statistical Analysis
Continuous data were expressed as mean±SD. Categorical data were expressed as percentage. Independent samples T-test was used for statistical analysis using SPSS software version 28.0.1.1 (15). A p-value <0.05 was considered significant.
Overall, 150 participants (75 males and 75 females) with hypertension were identified. The mean age was 54.6±9.6 years in group 1 (controls), 56.63±8.259 years in group 2 (cases total). Triglycerides were 114.16±26.234 mg/dL in group 1, 116.29± 32.781 mg/dL in group 2, 114.66± 36.212 mg/dL in group 2A and 117.92 ±29.231 mg/dL in group 2B. HDL Cholesterol were 44.29±0.662 mg/dL in group 1, 44.25±0.675 mg/dL in group 2, 44.39±0.666 mg/dL in group 2A and 44.11±0.661 mg/dL in group 2B. No significant difference was observed in smoking history, physical activity levels, waist circumference, obesity, total cholesterol, triglyceride, HDL cholesterol, fasting blood glucose, creatinine or WBC count between the case and control groups (Table/Fig 2).
General characteristics (age, number of males and females, smoking, physical activity, waist circumference, central obesity, total cholesterol, triglycerides, HDL cholesterol, fasting blood glucose, creatinine, WBC count) of total case and control groups and that of males and females of each group is shown in (Table/Fig 3). The mean values for total cholesterol were higher among males 151.72±29.811 in group 2A. The mean values of WBC count, triglycerides, and FBS were highest among females (Table/Fig 3).
Serum UA levels were significantly more in group 2A p<0.00001 in comparison to controls than those in group 2B (p=0.003). It was also seen that, females in group 2A had significantly elevated serum UA levels (p<0.00001) than males (p=0.00062). A comparison of serum UA levels among the case and control groups is shown in (Table/Fig 4).
In this study, significant elevation in blood pressure levels was seen in all patients with HHD (group 2A and 2B) as compared to individuals with hypertension alone (group 1) (p<0.05). Both males and females showed significant elevations (p<0.00001). A comparison of blood pressure levels among the case and control groups is shown in (Table/Fig 4).
In this study, hypertensive individuals had cardiovascular disease at an early age when serum UA levels were elevated. Even though significant association for serum UA was seen in both males and females, but females had greater significance, implying that females are at higher risk of cardiovascular disease than males. Total cholesterol, HDL cholesterol, triglyceride, glucose, creatinine levels and WBC count were similar between the case and control groups. These findings were consistent with other similar studies such as that done by You H et al., (1). However, they found that the mortality rates were similar in both sexes. In another study done by Turak O et al., the findings were consistent with the present study but, in contrast their study showed higher levels of HDL cholesterol, triglycerides, glucose, creatinine levels and WBC count in those with elevated UA levels (30). Similar to the present study, An Li-Na et al., study had shown no significant rise in HDL cholesterol in hyperuricaemic individuals but, in contrast creatinine and glucose levels were raised (31).
Hyperuricaemia is known as an independent risk factor for hypertension but, whether it is an independent risk factor for cardiovascular disease or not is under debate. The association of serum UA levels with cardiovascular risk in general population has been reported but most of them observed that elevated UA levels increased the risk of cardiovascular disease (8),(32),(33),(34),(35),(36). A few of them reported that serum UA elevations was not an independent risk factor for cardiovascular disease but only a marker of the pathological condition (1),(37). The heterogeneous conclusions may be partly due to the discrepancy in subjects, clinical characteristics, sample size, grouping strategy, and adjustment for confounders (1).
Recently, a few cohort studies have noted an association between serum UA levels and cardiovascular disease in hypertensive individuals (8),(10). A nationwide study conducted in China by You H et al., suggested a U-shaped relationship between serum UA and risk of mortality in hypertensive individuals, concluding that cardiovascular risk increases with elevated UA levels (1). Other studies have demonstrated that both high and low serum UA levels were related to CVD risk in hypertensives (11),(38),(39). Consistent with the above studies, the present study also showed a similar association between elevated serum UA levels and cardiovascular risk in hypertensive individuals.
A cross-sectional study conducted on 207 hypertensive women in Brazil, have demonstrated that elevated serum UA was associated with internal carotid resistive index only in women, suggesting a gender-related difference in the relationship between serum UA and vascular damage in subjects with systemic hypertension (36). Female hormones lower the serum UA levels. Hence, in postmenopausal women there is an increase in serum UA levels. So, the diagnostic evaluation of UA levels is more difficult in these women (40),(41).
The mechanism by which UA leads to cardiovascular risk remains unclear. Several studies have shown the beneficial role of antioxidant property of UA (42),(43),(44). But, under pathological conditions like atherosclerosis, UA acts as a pro-oxidant and produce reactive oxygen species, instead of acting as an antioxidant. This pro-oxidant effect of UA encourages the development and progression of cardiovascular disease (1),(7).
Monosodium urate crystals activate polymorphonuclear leucocytes, which engulf monosodium urate crystals resulting in super oxides, LDL oxidation. Disorders of endothelial cells and blood platelets facilitate arteriosclerosis (12).
Experimental data also showed that UA stimulates proliferation, inflammation and oxidative stress in vascular smooth muscle cells, induces endothelial dysfunction and activates the renin-angiotensin system (36),(45). The hypothesis of causal link between hyperuricaemia and endothelial dysfunction might be a possible mechanism for the development of cardiovascular disease in hypertensive individuals (31).
Various factors are involved in the process of UA production and secretion. For example, aggravated anaerobic metabolism in tissues due to reduced oxygen leads to increased lactic acid levels, which increases reabsorption of UA by kidneys, thus increasing serum UA levels. These factors complicate the process of identification of the reasons for the fluctuation of serum UA levels. Medications are also one of such factors which has an impact on serum UA levels. Angiotensin receptor blockers (losartan), antidyslipidemic drugs (fenofibrate) inhibit URAT1 and facilitate UA excretion. Diuretics (thiazide, furosemide) also increases serum UA (46),(47).
Treatment of hyperuricaemia with allopurinol for three months have shown results in a significant decrease in inflammation biomarkers (48). Antihyperuricemic medications showed improved angina symptoms and prevented vascular disease. Few studies have proposed that the incidence of cardiovascular event was lower in hyperuricaemic individuals on urate-lowering treatment. Hence, it can be taken as a new approach for cardiovascular risk reduction (49),(50). Large controlled trials are ongoing to assess the effect of serum UA-lowering drugs on cardiovascular events (51).
This study also showed significant rise in blood pressure levels in cases when compared with the control group. This raise could be linked to elevated serum UA levels as hyperuricaemia is an independent risk factor for hypertension. Many studies have proved that elevated serum UA levels can lead to hypertension (52),(53),(54).
Limitation(s)
First, the effects of unmeasured confounders may not be completely ruled out. Second, the causality of the link between serum UA and cardiovascular disease in hypertensive individuals could not be determined. Third, limited sample size and sampling from single institution, so further studies need to be done to generalise the findings of this study.
In present study, serum UA level was significantly higher in hypertensive individuals with cardiac disease than hypertensive controls without cardiac disease. No significant difference was observed in smoking history, physical activity levels, waist circumference, obesity, total cholesterol, triglyceride, HDL cholesterol, fasting blood glucose, creatinine or WBC count between the case and control groups. Hence, routine screening of UA levels in hypertensive individuals and taking necessary corrective steps would help prevent early progression to hypertensive heart disease, especially in females. Further follow-up studies on larger sample size are needed to establish the causality of link between elevated UA levels and cardiovascular disease in hypertensive individuals.
DOI: 10.7860/JCDR/2022/56736.16905
Date of Submission: Apr 20, 2022
Date of Peer Review: May 18, 2022
Date of Acceptance: Aug 27, 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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