Prediction of the Population at Risk of Atherothrombotic Disease: A Three Step Approach

Research Article

Prediction of the Population at Risk of Atherothrombotic Disease: A Three Step Approach

  • William E. Feeman, 1*

*Corresponding Author: William E. Feeman , Bowling Green Study, Bowling Green, Ohio, USA.

Citation: William E. Feeman, (2022) Prediction of the Population at Risk of Atherothrombotic Disease: A Three Step Approach. J. Cardiology Research and Reports 4(1); DOI: 10.31579/2692-9759/036

Copyright: © 2022, William E. Feeman, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 11 December 2021 | Accepted: 25 December 2021 | Published: 04 January 2022

Keywords: atherothrombotic disease; acute myocardial infarction; acute cerebral infarction; aortic aneurysm

Abstract

The mainstay of the prevention of atherothrombotic disease (ATD, which is atherosclerotic disease, with emphasis on the thrombosis that so often precipitates the acute ATD event, such as acute myocardial infarction, acute cerebral infarction, aortic aneurysm, etc) is the prediction of the population at risk of ATD.  There are many predictive tools, all of which use the same general risk factors, but the one favored by the author is the Bowling Green Study (BGS) graph.. This graph is based on the ATD risk factor constellations of 870 people in Bowling Green, Ohio, the county seat of Wood County, in northwest Ohio. (There is one other patient who has full lipid data and blood pressure data, but whose cigarette smoking status is not known.)  The ordinate of the graph is the lipid arm and consists of the Cholesterol Retention Fraction (CRF, defined as [LDL-HDL]/LDL).  HDL refers to high-density lipoprotein cholesterol and LDL refers to low-density lipoprotein cholesterol.  The abscissa of the graph is the blood pressure arm, represented by the systolic blood pressure (SBP).  This graph was initially developed in 1981 (using the LDL:HDL ratio) then modified in 1983 (using the CRF), and, by 1988, the author was able to generate a threshold line, which separated the main stream of ATD patients’ CRF-SBP plots from those of a few outliers. (The threshold line is not a regression line, but rather a divider, based on the principle of the fewest false negatives.)  The 1988 threshold line was modified in 2000 to its present location at CRF-SBP loci (0.74, 100) and (0.49, 140). Many of the various ATD risk predictors are complex and difficult to use, whereas the graph is simple to use and based on the risk factor constellations of actual ATD patients, wherein lies its value.

Introduction

The mainstay of the prevention of atherothrombotic disease (ATD, which is atherosclerotic disease, with emphasis on the thrombosis that so often precipitates the acute ATD event, such as acute myocardial infarction, acute cerebral infarction, aortic aneurysm, etc) is the prediction of the population at risk of ATD.  There are many predictive tools, all of which use the same general risk factors, but the one favored by the author is the Bowling Green Study (BGS) graph. [1-11]. This graph is based on the ATD risk factor constellations of 870 people in Bowling Green, Ohio, the county seat of Wood County, in northwest Ohio. (There is one other patient who has full lipid data and blood pressure data, but whose cigarette smoking status is not known.)  The ordinate of the graph is the lipid arm and consists of the Cholesterol Retention Fraction (CRF, defined as [LDL-HDL]/LDL).  HDL refers to high-density lipoprotein cholesterol and LDL refers to low-density lipoprotein cholesterol.  The abscissa of the graph is the blood pressure arm, represented by the systolic blood pressure (SBP).  This graph was initially developed in 1981 (using the LDL:HDL ratio) then modified in 1983 (using the CRF), and, by 1988, the author was able to generate a threshold line, which separated the main stream of ATD patients’ CRF-SBP plots from those of a few outliers. (The threshold line is not a regression line, but rather a divider, based on the principle of the fewest false negatives.)  The 1988 threshold line was modified in 2000 to its present location at CRF-SBP loci (0.74, 100) and (0.49, 140). [12]  Many of the various ATD risk predictors are complex and difficult to use, whereas the graph is simple to use and based on the risk factor constellations of actual ATD patients, wherein lies its value.

The Bowling Green Study (BGS) graph has been presented on numerous occasions [11-15], most recently in 2020, where the original graph was presented and then a version of the graph in which the graph was divided into 48 CRF-SBP cohorts in order to more closely determine the average ages of ATD onset in those patients in each of the CRF-SBP cohorts.  While such an approach allows more precise determination of ATD risk for a given patient with a given CRF and a given SBP, when the CRF-SBP plots of the 870 patients (or 871 patients if cigarette smoking status is not considered), the numbers of patients within any CRF-SBP cohort may vary widely.  To compensate for this disadvantage, the author, using the same graph and patients, in this manuscript, presents a three-step method of analyzing ATD risk.

Materials and Methods

 The background of the BGS is been presented on numerous occasion [13-15]. In brief, bowling green is a small college town, home of Bowling Green State University. Located in northwest Ohio, bowling green is the county seat of Wood County. The chief employer in bowling green is the University and the city of Bowling Green consists of approximately 28,000 people, about half of whom are college students.  The populace is mostly Americans of European descent, with the biggest minority being Americans of Latin American descent.  While Americans of African, Asian, and Middle Eastern descent are increasing in numbers, they make up only a small fraction of the population which forms the basis of this publication.  The main employer in the area is Bowling Green State University and the hinterland is mainly rural with farming as the chief employment.  Many small businesses exist, albeit mainly within the city.

When the author began his practice of family medicine in bowling green in late 1974, He determined to find a way to predict the population at risk of ATD and to do this, he knew that he would need an ATD risk factor database. To this end, he measured blood pressures and heights/weights (converted into body mass index) on each any every patient who presented to his office, each and every time they presented. When the author appreciated the paramount importance of cigarette smoking in ATD, after 1983, he also determined tobacco use status on each patient aged 15 years and older—and after 1993, in all patients aged 10 years or older.  The author measured lipid profiles and two hour postprandial blood sugar levels whenever indicated—and any reason to measure such ATD risk factors was considered an adequate reason.  Lipid profiles were limited to total cholesterol (CT) and triglycerides (TG) until 1 January 1978, when HDL became available and hence LDL could be calculated by the Friedewald equation [16].  These measurements were collected into a General Population database.

By 1981, the author has accumulated enough ATD patients to begin to separate an ATD database from the General Population database.  This happened because, in the 1970’s, ATD risk estimates were not very good and in any event were few in number. Additionally, medications used to treat dyslipidemia were not very good and medications to treat hypertension were limited.  Finally, in the 1970’s and afterwards, patients were not very receptive to the concept of preventive cardiology --and for that matter neither were most of the Wood County physicians. 

Inspection of the ATD database revealed that rarely did ATD patients have only one ATD risk factor—usually they were multiple.  Hence the author sought to determine which risk factor combinations best predicted ATD risk best.  The risk factor combination that was found to be the best predictor was the combination of dyslipidemia and hypertension, and this predictor was only obvious when stratified by cigarette smoking status. Risk factor analysis was straight-forward for SBP and cigarette smoking—but the lipid portion was more complex. Patients with high LDL had ATD events, as expected, but then so did patients with lower LDL levels.  People with low levels of HDL had ATD events, but then so did patients with high HDL levels.  In 1981 the author saw an article entitled “Is the LDL:HDL Ratio the Best Lipid Predictor?”  (The author regrets that the article is now lost to him, so that he cannot give appropriate credit.)  With this in mind, the author reexamined his ATD database and discovered that ATD patients with lower LDL levels usually had very low HDL levels and that ATD patients with high HDL levels usually had very high LDL levels.  (When this was not the case, the younger patients were cigarette smokers, current of past, while the older patients had hypertension, with or without diabetes.)  This finding supported and validated the article’s question, and the author began to use the LDL:HDL ratio.

In 1983, it occurred to the author that what he really wanted to know was how much cholesterol was accumulating within the artery walls. This, he reasoned, was best estimated by the difference between the cholesterol entering the artery wall (LDL) and that being removed from the artery wall by reverse cholesterol transport (HDL), expressed as a percentage of the cholesterol entering the artery wall. Thus was born the concept of the CRF. However, it also became obvious to the author that if LDL levels were exceedingly high, then HDL could no longer compensate for LDL.  The LDL level at which this occurred was 170 mg/dl (4.4 mmoles/L).  Thus was born the concept of the cholesterol threshold (C Thr), signifying that dyslipidemia worth treating was present at CRF values of 0.70 or higher or at LDL levels of 170 mg/dl (4.4 mmoles/L) or higher.  In the BGS, C Thr now forms the basis for defining dyslipidemia.

In the BGS, LDL is not measured, but rather calculated by the Friedewald equation as already noted.  The Friedewald equation was developed to estimate LDL levels based of CT, HDL, and TG/5, and HDL is this equation was measured by the precipitation method.  (CT means total cholesterol and TG means triglycerides.)  In 1999, and without notifying the medical profession, the manufacturers of the auto-analyzers changed from the precipitation method of HDL measurement to the enzymatic method.  The two different methodologies give two different values for HDL levels, the enzymatic method giving a value on the order of 10 mg/dl (0.25 mmoles/L) higher than the precipitation method.  Hence the calculated LDL value using the enzymatic method will be on the order of 10 mg/dl (0.25 mmoles/L) lower than that obtained had the precipitation method been used.  While such discrepancies are not highly significant for LDL or HDL, they have a major impact on the CRF.  This was reported in 2008. [17]  All HDL and OLDL values presented in this paper are based on the precipitation method of HDL-cholesterol  measurement. HDL-cholesterol  measurements (and hence LDL-cholesterol calculations) obtained after the methodology change (in May, 1999) are converted from the enzymatic values to the equivalent precipitation values by the formula given by the Wood County Hospital and is as follows: HDL (precipitation method)= [HDL (enzymatic method)-12]/0.93.  Formulas from other laboratories may differ.

Results

The BGS graph is shown in Figure I.  (If the enzymatic method of HDL measurement is used, the threshold line coordinates are [0.62, 100] and [0.40, 140]). If one then divides the graph into quadrants, using the SBP=140 as the site of the vertical line and CRF=0.70 as the site of the horizontal line, one can then also divide the BGS graph into four quadrants: the left upper quadrant is pure dyslipidemia;, the right upper quadrant is dyslipidemic hypertension; the right lower quadrant is pure hypertension; and the left lower quadrant is neither.  (See Figure II.) Treated hypertensives have their plots shifted to the adjacent zone on the right, whereas patients with C Thr are shifted to the adjacent zone superiorly. Dyslipidemic patients treated pharmacologically are not included, but are few in number.   Table I shows the ATD outcomes of  the patients until the end of 2003 because at the end of 2003, there was a major shift in insurance coverage when a new start-up insurance company entered the Wood County area and the author lost a sizeable portion of his practice, including many ATD patients, to the new insurance plan. Prior to this event, the author had basically full knowledge of his ATD patients’ outcomes, but not thereafter.

Figure I

CRF means Cholesterol Retention Fraction

SBP Means Systolic Blood Pressure

HDL means High Density Lipoprotei

Table I: ATD w/r to ASR Line 1974-2003

ATD means Atherothrombotic Disease

“+” means Current Cigarette Smoker

“Past” means Former Cigarette Smoker

“-“ means Never Cigarette Smoker

MSD means Multiple System Disorder

ASR Line means Angiographic Stabilization/Regression Line

Figure :2

Once the quadrant divisions are in place, the various subdivisions can be named.  The left upper quadrant is termed Zone I, with patients above the threshold line receiving the designation “A” and patients below the threshold line receiving the designation “B.”  The right upper quadrant is termed Zone II, and all plots are above the threshold line. The right lower quadrant is termed Zone III, with the subdivisions of “A” being above the threshold line and “B” being below the threshold line.  The left lower quadrant is termed Zone IV, with subdivisions of “A” being above the threshold line and “B” being below the threshold line.  (See Figure III.)Each of these subdivisions can be stratified by cigarette smoking status.  (See See Figure IV-A for males and IV-B for females, and Tables II-A for males and II-B for females.  Each subdivision demonstrates the average age of the patients in that subdivision.) 

Figure III: BGS Graph Angles and Triangles

BGS Means Bowling Green Study

ATD Means Atherothrombotic Disease

CRF Means Cholesterol Retention Fraction

SBP Means Systolic Blood Pressure

Table IIA: Zonal Incidence in Male ATD Population Vs Male General population % of Whole Cigarettes

ATD Means Atherothrombotic Disease

+ Means Current Cigarette Smoker

Past Means Past Cigarette Smoker

- Means No History of Smoking Cigarettes

? Means Unknown Smoking History

Table 2
Table IIB: Zonal Incidence in Female ATD Population Vs Female General population % of Whole Cigarettes

ATD Means Atherothrombotic Disease

+ Means Current Cigarette Smoker

Past Means Past Cigarette Smoker

- Means No History of Smoking Cigarettes

? Means Unknown Smoking History

Figure IVA: Average age of ATD Onset Male ATD Population

BGS Means Bowling Green Study

ATD Means Atherothrombotic Disease

CRF Means Cholesterol Retention Fraction

SBP Means Systolic Blood Pressure

** 4/256/64

Figure IVB: Average Age of ATD Onset Female ATD Population

BGS Means bowling green Study

ATD Means Atherothrombotic Disease

CRF Means Cholesterol Retention Fraction

SBP Means Systolic Blood Pressure

** 3/174/58

In the BGS ATD database, the quadrant with the most patients in both men and women is Zone II; however, the Zone with the youngest such patients is Zone I.  The subdivision with the youngest patients is Zone IA, Zone IB being excluded due to very small numbers.  The youngest patients in Zone IA are the cigarette smokers, followed by ex-smokers, and then by never-smokers, and this is true for all Zones.  Interestingly, the patients in Zone I tend to be younger than those in Zone II, who in turn tend to younger than those in Zone III. This demonstrates the greater importance of dyslipidemia and the lesser importance of hypertension in clinical ATD. On the other hand the incidence of cigarette smoking is greatest in Zone I patients and falls off progressively in Zones II and III. 

The patients in Zone IV have neither dyslipidemia (as the author has defined it) nor hypertension.  In men, the highest incidence of cigarette smoking is seen in Zone IV, whereas in women, the Zone IV incidence in cigarette smoking is second only to that in Zone I.  Some of the women in Zone IV had had central chest radiation for lymphomas and others were taking cyclic-sequential hormone replacement therapy (HRT), which may favorably influence lipid levels or continuous-combined HRT, which is known to promote thrombosis in susceptible women.  Other women had hypercoagulable states.  And finally, many never-smoking women suffered from passive cigarette smoking courtesy of their husbands.  All of these conditions adversely affect the age on ATD onset.  While any of these conditions may affect the age of ATD onset, the overwhelming risk factor is cigarette smoking since only 38% (15/40) of males were never cigarette smokers and only 49% (42/85) of females were never cigarette smokers.

The BGS graph can also be divided into 48 CRF-SBP cohorts, as shown in Figures V A-D.  This permits a more precise determination in average age of ATD onset, though at the expense of fewer patients per cohort.

Figure V A- means no history of cigarette smoking

CRF vs SBP: Original Logs

ΣMale & Female: Σ Cigarettes 

BGS ATD pop : Σ

CRF means Cholesterol Retention Fraction

SBP means Systolic Blood Pressure

BGS means Bowling Green Study

ATD means Atherothrombotic Disease

Figure V B- means no history of cigarette smoking

CRF means Cholesterol Retention Fraction

SBP means Systolic Blood Pressure

BGS means Bowling Green Study

ATD means Atherothrombotic Disease

Figure V C- means no history of cigarette smoking

CRF means Cholesterol Retention Fraction

SBP means Systolic Blood Pressure

BGS means Bowling Green Study

ATD means Atherothrombotic Disease

Figure V D- means no history of cigarette smoking

CRF means Cholesterol Retention Fraction

SBP means Systolic Blood Pressure

BGS means Bowling Green Study

ATD means Atherothrombotic Disease

The same graphic technique can be applied to the BGS general population base.  The data comparing the BGS ATD population and the BGS general population base is displayed in Tables II-A for males and II-B for females.  It will be noted that a CRF-SBP plot in Zones II and III favors the ATD population whereas a CRF-SBP plot in Zone IV favors the general population.

Discussion

The prediction of the population at risk of ATD requires knowledge of those persons’ ATD risk factors.  The better that a physician can predict the population at risk of ATD, the better, at least in theory, he/she can prevent clinical ATD events.  Since ATD risk factors rarely act in isolation, it is essential that the risk predictor tool utilize an integration of the individual ATD risk factors, rather than treating them as independent factors.  Moreover, as William E. Connor, MD, noted in the mid 1970’s, physicians should not treat various risk factors to an arbitrary goal, but rather to levels that prevent disease. (Medical World News, mid 1970’s, exact source lost to the author) This graph fulfills all of these criteria.

The chief ATD risk factors are cigarette smoking, dyslipidemia, and hypertension, with some contribution by the very high blood sugar levels of uncontrolled diabetes.  (18) However, the author has shown that the various ATD risk factors rarely operate independently and therefore any predictive tool must treat the various risk factors as dependent variables.  To this end, the author has presented a unique method of estimating that risk—i.e., the BGS graph.  This graph has been presented as a graph with no subdivisions—simply a determination as to whether the CRF-SBP plot is below or above the threshold line.  This graph can in turn be divided into quadrants, defining dyslipidemia and hypertension or lack thereof.  This approach has the advantage of being more specific as to degree of risk, but the numbers in each cohort will be somewhat smaller.   The graph can then be divided into 48 CRF-SBP cohorts, but while this permits more precise definition of ATD risk, the numbers in each CRF-SBP cohort will of necessity be much fewer.

 The author suggests a three-step approach.  First, obtain the patient’s CRF (or C Thr as applicable), SBP, and cigarette smoking status.  Then plot the data on the simple BGS graph.  If the patient’s plot position is below the threshold line and he/she does not have C Thr and if the patient has never smoked cigarettes, then nothing need be done since the patient is of little risk of ATD; however, periodic follow up must be done to assure that the patient remains at very low risk.  If the patient is an ex-smoker, again nothing need be done, though periodic follow-up is needed to assure that the patient remains within the low risk zone.  If the patient is a cigarette smoker, he/she must give up the smoking habit, and of course be followed periodically.

 If, on the other hand, the CRF-SBP plot lies above the threshold line (first order approximation of ATD risk), then the next step is the determination of which quadrant the CRF-SBP plot lies within and where the CRF-SBP plot lies with respect to the threshold line.  Figures III-A (males) and III-B (females) give a second order approximation of ATD risk. As noted previously, subdividing the BGS graph into its 48 CRF-SBP cohorts, will then give highest (third order) approximation of ATD risk, though the numbers of patients per cohort will be fewer.  The third order approximation of ATD risk should be definitive; however, if one lives long enough and does not die of something else, an ATD event is likely to occur sometime due to the ravages of time upon the human body.  There is no zone of “zero” ATD risk, only areas of low ATD risk.  While low risk zones imply a lack of ATD onset at early or middle ages, it does not imply a lack of ATD events in very old age.

The figures for the third order approximation are shown in Figures V A-D.  Since there are 48 possible CRF-SBP combinations and there are only 871 ATD patients, males and females are grouped together.  Figure V-A gives the averages of ATD onset per CRF-SBP cohort without regard for cigarette smoking status and thus includes the 75 year old man whose cigarette smoking status is not known.  Figure V-B gives the same data for patients currently smoking cigarettes at time of ATD onset; Figure V-C, for ex-smokers; and Figure V-D, for never smokers, though other forms of tobacco use were allowed, such as pipe or cigar smoking or tobacco chewing, provided that the patient never smoked cigarettes. Cohorts in which the average age of ATD onset is 64 years or younger are color-coded red; cohorts with an average age of ATD onset of 65-74 years, color-coded yellow; and cohorts with an average age of ATD onset of 75 years or older, color-coded green.  The patient need only go to the appropriate CRF-SBP cohort to see his/her  risk and then determine the need of urgency of treatment.   It will be noted that clear-cut zones of risk can be seen in Figures V C-D, but not for Figure V-B.  This is discussed more fully in reference 11.

The success of the above regimen depends upon the early detection of the ATD risk factors.  If the risk factors are undetected or untreated long enough, then even if the risk factors are eventually corrected, even optimally, an early ATD event may occur. The reason for this is that the plaque has a central lipid core, covered over by a fibrous cap.  It is possible to shrink the cholesterol core, but it is not possible, with today’s medications, to shrink the fibrous plaque.  The fibrous cap creates a disturbance in the laminar flow of blood, which signals the body’s homeostatic mechanism to lay down more fibrous tissue, which eventually compromises blood flow and may precipitate a thrombus, giving rise to an acute ATD event.

The success of this regimen is also dependent upon achieving risk factor control that minimizes plaque progression and maximizes plaque stabilization/regression.  This requires achieving an LDL goal of 80 mg/dl (2.0 mmoles/L) if the precipitation method of measuring HDL is used or 70 mg/dl (1.75 mmoles/L) if the enzymatic method is utilized [19-20]. Cigarette smoking must be given up.  SBP must be controlled to a minimum of 140 mm Hg.  Of course the blood sugar levels of diabetes must be controlled as well.

Conclusions

The BGS graph for the prediction of the population at risk of ATD can be presented in the three steps as noted above.  The first approach utilizes the graph with respect to the threshold line.  The second divides the graph into zones, which gives increasing accuracy of prediction per cohort but which sacrifices strength of numbers.  What the third step loses in numbers of patients per subdivision, it makes up for by increased accuracy of prediction.  The ease of this approach makes it valuable for general physicians and patients alike to understand and to use it.

References

Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

img

Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

img

Delcio G Silva Junior

Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

img

Ziemlé Clément Méda

Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

img

Mina Sherif Soliman Georgy

We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

img

Layla Shojaie

The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

img

Sing-yung Wu

Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

img

Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

img

Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

img

Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

img

Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

img

Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

img

Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

img

Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

img

Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

img

Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

img

Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

img

Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

img

Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

img

Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

img

Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

img

Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

img

Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

img

Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

img

Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

img

S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

img

Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

img

George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

img

Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

img

Khurram Arshad

Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.

img

Gomez Barriga Maria Dolores

The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

img

Lin Shaw Chin

Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

img

Maria Dolores Gomez Barriga

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.

img

Dr Maria Dolores Gomez Barriga

Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.

img

Dr Maria Regina Penchyna Nieto

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.

img

Dr Marcelo Flavio Gomes Jardim Filho

Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”

img

Zsuzsanna Bene

Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner

img

Dr Susan Weiner

My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.

img

Lin-Show Chin

My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.

img

Sonila Qirko

My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.

img

Luiz Sellmann