AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2640-1053/025
*Corresponding Author: Danielle Gal, Department of Surgical Oncology , Israel
Citation: Danielle Gal, Cardiovascular comorbidities Common in patients with metastatic colorectal cancer, J Cancer Research and Cellular Therapeutics, Doi:10.31579/2640-1053/025
Copyright: © 2018 Danielle Gal. This is an open-access article distributed under the terms of The Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 30 January 2018 | Accepted: 20 February 2018 | Published: 25 March 2018
Keywords: comorbidities; metastatic colorectal cancer
Aim: As comorbidities may impact treatment decisions, prognoses and quality of care, this study determined the rate of comorbid cardiovascular diseases in patients with metastatic colorectal cancer (mCRC).
Methods: From the PHARMO Record Linkage System in The Netherlands, all patients with a hospital discharge code for CRC and distant metastasis from 2000–2008 were selected. Prevalent cardiovascular comorbidities were assessed during the 12 months prior to the index date (the first discharge diagnosis defining metastases). Cardiovascular comorbidities were captured using cardiovascular drug use and hospital admission data. 2964 patients with mCRC were included in the analysis. Mean (± standard deviation) age at diagnosis was 68 (± 12) years and 53% were male.
Results: Cardiovascular comorbidities were observed in 52% of patients. Of patients identified by drug use, the most commonly used agents were antithrombotic agents (54%), beta-blocking agents (46%), and agents acting on the renin-angiotensin system (45%). Of patients hospitalised for cardiovascular comorbidities, about one-third were hospitalised for cardiac dysrhythmia (39%), followed by congestive heart failure (19%) and hypertension (18%).
Conclusions: Cardiovascular comorbidities are common in patients with mCRC, which is likely to be explained by the high mean age at diagnosis. Consideration of these conditions should be integral to the treatment strategy in individual patients with mCRC.
Colorectal cancer (CRC) is one of the most common malignancies, third after lung and prostate cancer in men and second only to breast cancer in women [1]. In a significant proportion of patients with CRC, metastases are already present at diagnosis and many patients diagnosed at earlier stages will also eventually develop metastatic disease [2].
Current pharmacological treatment options for patients with metastatic CRC (mCRC) include the use of chemotherapy in combination with monoclonal antibodies targeting vascular endothelial growth factor (VEGF) or the epidermal growth factor receptor (EGFR) (in patients with wild-type KRAS tumours). These treatments have led to significant improvements in the treatment outcomes of mCRC patients in recent years [3]. With the incidence rates of mCRC increasing and the treatment outcomes improving, the number of prevalent mCRC cases keeps increasing [4]. Therefore, many more patients with mCRC will be undergoing treatment, and cope with this progressive disease for a longer period of time. Many of these patients will have concomitant conditions which have various clinical implications. Comorbidities, defined as medical conditions exist simultaneously but independently with the primary medical condition in a patient, often necessitate modifications of and/or adversely influence the chosen therapy; concomitant diseases are independent determinants of prognosis (regardless of the chosen therapy) and their presence is also an indicator of the complexity of the clinical needs of each patient [5]. Evaluation of the presence of cardiovascular comorbidities is particularly important in the mCRC population as some of the newer treatments are associated with adverse events related to the cardiovascular system [6,7]. These adverse events include, among others, thromboembolism, hypertension, haemorrhage and cardiotoxicity, and may be even more dramatic when concomitant cardiovascular disease is present.
Data regarding the prevalence of cardiovascular comorbidities in patients with mCRC are, however, limited. This study, therefore, assessed the prevalence of pre-existing cardiovascular comorbidities (existence of cardiovascular diseases with mCRC at the same time) among a population-based cohort of patients with mCRC in The Netherlands.
Data source
Data were obtained from the PHARMO medical record linkage system (PHARMO RLS), which consists of multiple observational databases linked on a patient level, covering 3.2 million inhabitants of geographic defined areas in The Netherlands. Databases relevant for this study include the Dutch National Medical Register (LMR) and the community pharmacy database (outpatient). The hospital records contain detailed information concerning admissions for more than 24 hours and admissions for less than 24 hours for which a bed is required, including primary and secondary diagnoses, procedures and dates of hospital admission and discharge [8]. All diagnoses are coded according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). The drug dispensing histories from outpatient pharmacies contain data on the dispensed drug, prescriber, dispensing date, amount dispensed, prescribed dose regimens and thus the duration of use. All drugs are coded according to the Anatomical Therapeutic Chemical (ATC) Classification.
Patients aged ≥18 years diagnosed with mCRC were identified by hospitalisation codes between 1 January 2000 and 31 December 2008. All patients with a primary or secondary hospital discharge diagnosis for CRC (ICD-9-CM code 153.x (excluding 153.5), 154.0, 154.1, and 154.8) and metastasis (ICD-9-CM code 196.0, 196.1, 196.3, 196.5, 197.x (excluding 197.5), 198.x, and 199.0) were selected [9,10].
To be included in the study, the hospital admission date for distant metastasis needed to occur no more than 30 days before the hospital admission date for CRC or anywhere after the hospital admission date for CRC, on condition that the patient was not hospitalised for cancer other than CRC. The first metastasis discharge diagnosis date served as the index date. Patients with metastasis diagnosis within 10 years before the index date were excluded as these metastases might be related to a primary tumour other than CRC. To be able to define comorbidities in recent history based on drug use as well as hospitalisations, patients needed to have at least 12 months of history in the PHARMO RLS.
For all study patients the following characteristics were determined at index date: gender, age, site of primary tumour (colon or rectal), site of metastasis and available history in PHARMO RLS. Prevalent comorbidities were assessed during the first year prior to the index date. Cardiovascular comorbidities were identified using drug dispense information in the outpatient setting and discharge diagnoses in the hospital admission database. Information on drugs dispensed in the outpatient setting included: antihypertensives (ATC code C02), diuretics (ATC code C03 (excluding C03C), beta-blocking agents (ATC code C07), calcium-channel blockers (ATC code C08), agents acting on the renin-angiotensin system (ATC code C09 (excluding C09X), antithrombotic agents (ATC code B01), and cardiac therapy (ATC code C01). In the hospital admission database, cardiovascular comorbidities were determined based on primary and secondary hospital discharge diagnoses, including: hypertension (ICD-9-CM code 401-405), coronary artery disease (ICD-9-CM code 414.0), cardiac dysrhythmia (ICD-9-CM code 427), congestive heart failure (ICD-9-CM code 402.01, 402.11, 402.91 and 428), acute myocardial infarction (ICD-9-CM code 410), other ischaemic heart disease (ICD-9-CM code 411, 413 and 414 (excluding 414.0), venous thromboembolism (ICD-9-CM code 451.1, 451.2, 451.81, 451.9, 453.2, 453.8 and 453.9), arterial thromboembolism (ICD-9-CM code 444), and stroke (ICD-9-CM code 362.3, 433.1, 434.1, 435 and 436).
Patient characteristics and cardiovascular comorbidities prior to mCRC diagnosis were presented descriptively by the number and proportion of patients receiving these agents or being hospitalised for these diagnoses, with 95% confidence intervals. All data were analysed using SAS programs organised within SAS® Enterprise Guide version 4.0 (SAS Institute Inc, Cary, NC, USA) and conducted under UNIX using SAS version 9.2.
Overall, 2964 patients with mCRC were included in the analyses. The study population included similar numbers of males and females (Table 1) and patients aged 70–79 represented the largest group by age (32%); mean (± SD) age was 68 (± 12) years. Colon cancer was more common than rectal cancer as primary tumour (69% and 31%, respectively). The most common location of metastases was the liver (43% in patients with colon cancer and 42% in patients with rectal cancer as primary tumour).
The prevalence of cardiovascular comorbidities, as identified by drug use and/or hospitalisations, in the year prior to index date is shown in( Table 2) Overall, cardiovascular comorbidities were observed in 52% of patients. The majority of these patients were identified by drug use (96%) and only a small proportion (19%) was identified by hospitalisations. Of all patients identified by drug use, the most commonly used agents were antithrombotic agents (54%), followed by beta-blocking agents (46%), and agents acting on the renin-angiotensin system (45%). Of the patients hospitalised for cardiovascular comorbidities in the year prior to index date, about one-third was hospitalised for cardiac dysrhythmia (39%), followed by congestive heart failure (19%) and hypertension (18%).
To our knowledge, there are limited data on the prevalence of cardiovascular comorbidities in patients with mCRC. In this retrospective cohort study the prevalence of cardiovascular comorbidities among patients with mCRC was determined using both cardiovascular drug use and hospital admission data. Our analyses illustrate that cardiovascular comorbid conditions were observed in more than half of patients in the year prior to the first mCRC hospitalisation. Most patients used antithrombotic agents, followed by beta-blocking agents and agents acting on the renin-angiotensin system. This high prevalence might be anticipated given that the majority of patients were >65 of age.
The rates of cardiovascular comorbidities that were observed in this study can be compared with another study evaluating the extent of cardiovascular comorbidities identified on the basis of ICD-9 diagnosis codes in patients with mCRC [11]. Using this approach, pre-existing cardiovascular diseases were observed in 62% of 12,648 newly diagnosed patients with mCRC in the USA. Our results using pharmacy and hospitalisation data are therefore broadly similar to those from the US study using diagnostic criteria. It should be noted, however, that our results reflect the population in The Netherlands and might not be applicable to mCRC populations in other countries. A previous Dutch study on newly diagnosed patients with CRC in the period 1995–1999 showed that about 32% of the patients suffered from cardiovascular disease and 26% suffered from hypertension [12]. This would result in a prevalence of 58% maximally, as more than one condition per patient was possible, which is comparable to our prevalence estimate.
Our results were generated using outpatient drug dispensing data and hospitalisation discharge diagnoses that are related to cardiovascular diseases as a proxy for the presence of cardiovascular comorbid conditions. Hospital admission data were used to select the cardiovascular morbidities that led to hospitalisation. Pharmacy data were used to select the cardiovascular conditions that were treated in outpatient setting and to provide a more complete list of actively treated conditions [13]. However, algorithms for identifying comorbidities based on pharmacy drug use have been reported to be more specific but less sensitive than algorithms based on diagnosis criteria [14]. This may reflect the fact that this approach will only identify patients who receive pharmacological treatment for their disease. It is also worth to note that some patients might have received adjuvant therapies before metastasis diagnosis and some of adjuvant therapies, such as 5-fluorouracil therapy, could cause cardiotoxicity [15]. However, use of adjuvant therapy was not included in the current analysis.
In conclusion, cardiovascular comorbidities are common in patients with mCRC, which is likely to be explained by the high mean age at diagnosis. Consideration of these comorbid conditions should be an integral part of the treatment strategy in individual patients with mCRC.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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!
"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".
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.
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.
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.
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.
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.
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.
“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”.
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.
