Prevalence and associated factors of dyslipidemia among adults with coexisting chronic disease in Ethiopia: A systematic review and meta-analysis

Tadesse Mekonen Zeleke; Fitsum Endale Liben; Tinsae Shemelise Tesfaye; Abiyu Legesse Munea; Fekede Asefa Kumsa

doi:10.1371/journal.pone.0320119

Peer Review History

Original SubmissionJanuary 13, 2024
13 Jan 2024 Author Response https://doi.org/10.1371/journal.pone.0320119.r001
7 Nov 2024 Decision Letter - Paolo Magni, Editor PONE-D-24-01697Dyslipidemia and associated factors among adults with coexisting chronic disease in Ethiopia: a systematic review and meta-analysisPLOS ONE Dear Dr. Zeleke, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please carefully address all the issues raised by reviewer 2. Please submit your revised manuscript by Dec 22 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: This metanalysis studies already known risk factors. Nothing new is added to the already existing knowledge. Most of the studies included are in specific populations. Hence the results are not generalizable . Reviewer #2: General: This research is highly relevant and timely, given the rising burden of dyslipidemia as a modifiable risk factor for cardiovascular diseases, particularly in low-resource settings like Ethiopia. Understanding the prevalence and associated risk factors is crucial for developing targeted public health interventions. Your study contributes valuable insights into this pressing health issue. Title: The title effectively conveys the study's focus on dyslipidemia among adults with chronic diseases in Ethiopia. However, consider specifying "prevalence" or "risk factors" to enhance clarity. Abstract: The abstract is well-structured and provides a clear overview of the study’s objectives, methods, results, and conclusions. However, breaking up some of the longer sentences could improve readability. Introduction: The introduction offers a comprehensive overview of dyslipidemia and its implications. Streamlining certain sentences could enhance clarity and flow. For example, transitioning between the global context and the specific situation in Ethiopia could be smoother. The statistics on dyslipidemia prevalence in Africa and Ethiopia are compelling. It would be beneficial to briefly mention healthcare challenges in Ethiopia—such as access to care and lifestyle changes—that contribute to the rising prevalence. Linking the statistics on cardiovascular disease (CVD) more directly to the Ethiopian context would strengthen the urgency of your argument. Citing local data on CVD mortality could be particularly impactful. While the references are relevant, ensure that they are current and accessible. Additionally, highlighting the significance of your findings for public health policy or clinical practice at the end of the introduction would provide a stronger rationale for the study. Recommendations: - Streamline sentences for clarity and flow. - Provide context regarding healthcare challenges in Ethiopia. - Directly link global statistics to the Ethiopian situation. - Ensure references are up to date. - Highlight the significance of your findings for public health or clinical practice more explicitly. Methods The methods section is well-organized and adheres to PRISMA guidelines, which is commendable. However, simplifying some lengthy sentences could improve clarity. The inclusion and exclusion criteria are well-defined, but it would be helpful to briefly justify why certain populations (e.g., children and adolescents) are excluded, especially regarding dyslipidemia prevalence. While the definition of dyslipidemia is clear, it would be useful to highlight the varying cut-off values across studies as a potential source of variability in prevalence estimates. Discussing how this variability might impact the results could add depth. The study selection and data extraction processes are well-articulated. Mentioning specific software used for data extraction, in addition to Excel, would enhance the methodological rigor. Results and Discussion: The prevalence rates are striking and provide a solid overview. To enhance clarity, consider stating, "Our prevalence rates are significantly higher than those reported in China and Sub-Saharan Africa." The discussion on lifestyle factors contributing to low HDL-c is insightful. Expanding on how these choices are influenced by socio-economic and cultural factors in Ethiopia could strengthen your argument. The comparisons with other meta-analyses and studies are valuable. Highlighting potential reasons for discrepancies in prevalence findings—such as differences in study populations or methodologies—would provide important context. While the identification of significant risk factors is well-articulated, mentioning the public health implications of these modifiable risk factors—such as potential interventions—earlier in the discussion could enhance the practical relevance of your findings. Limitations: Acknowledging the considerable heterogeneity among studies is essential for transparency. Briefly discussing potential sources of this heterogeneity—such as differences in study design or diagnostic criteria—could give readers a clearer understanding of the limitations. While it's good to note that subgroup and sensitivity analyses were performed, elaborating on what aspects of heterogeneity remain unexplained could provide more context for those interested in the methodological rigor of your analysis. Overall, this research holds significant potential to inform public health strategies and interventions in Ethiopia. Thank you for your important work in this area! ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy . Reviewer #1: Yes: Dr. Archith Boloor Reviewer #2: Yes: Natan Mulubrhan Alemseged ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0320119.r002
Revision 1
13 Jan 2025 Author Response Feedback of reviewers Reviewer #1 (Comments to the Author): Thank you for your comments and suggestions. We truly appreciate your time in reviewing our paper. Reviewer #1: This metanalysis studies already known risk factors. Nothing new is added to the already existing knowledge. Most of the studies included are in specific populations. Hence the results are not generalizable. Response: this review is the first of its kind to provide a comprehensive analysis of dyslipidemia prevalence and its components (elevated TC, TG, LDL-c, and low HDL-c) among adults with coexisting chronic diseases in Ethiopia. Notably, we present pooled prevalence estimates across various chronic diseases and geographic regions, offering new insights into the distribution and burden of dyslipidemia. However, the generalizability of the study findings may be limited because the regional representation was uneven, with the majority of the studies (43 out of 62) originating from Addis Ababa city (the capital city) and two regional states (Amhara and Oromia). Also, there was lack of studies in certain regions of the country. This limitation may affect the generalizability of our findings, as addressed in our manuscript in lines 339 - 341 “Another potential limitation is the generalizability of the study findings, as the included participants were not representative of the national population.” Despite the limitations, we strongly believe that the findings make a valuable contribution to the existing body of literature. Reviewer #2: General: This research is highly relevant and timely, given the rising burden of dyslipidemia as a modifiable risk factor for cardiovascular diseases, particularly in low-resource settings like Ethiopia. Understanding the prevalence and associated risk factors is crucial for developing targeted public health interventions. Your study contributes valuable insights into this pressing health issue. Thank you for your thoughtful comments and suggestions. We sincerely appreciate the time and effort you dedicated to review our paper. Title: The title effectively conveys the study's focus on dyslipidemia among adults with chronic diseases in Ethiopia. However, consider specifying "prevalence" or "risk factors" to enhance clarity. Response: we have revised the title in lines 1-2, which now read “Prevalence and associated factors of dyslipidemia among adults with coexisting chronic disease in Ethiopia: a systematic review and meta-analysis” Abstract: The abstract is well-structured and provides a clear overview of the study’s objectives, methods, results, and conclusions. However, breaking up some of the longer sentences could improve readability. Response: we agree with the reviewer’s point on the importance of breaking up of some of the longer sentences. We have revised the whole abstract accordingly, and for instance lines 33 - 34, now read “Out of 640 initially identified articles, 104 underwent full-text review, and 62 met the inclusion criteria for the final analysis.” Introduction: The introduction offers a comprehensive overview of dyslipidemia and its implications. Streamlining certain sentences could enhance clarity and flow. For example, transitioning between the global context and the specific situation in Ethiopia could be smoother. Response: effort has been made to streamline sentences in the introduction part to enhance flow and clarity, line 62-69 now read “CVD is a chronic non-communicable disease (NCD) and one of the leading causes of global mortality. According to the American Heart Association, the annual number of CVD-related deaths was 19 million in 2020 and is estimated to reach 22.2 million in 2030 (12, 13). Over the past four decades, there has been a significant surge in the prevalence of cardiovascular diseases (CVD) in Africa. And it is anticipated to overtake infectious diseases as the leading cause of death by 2030 (14). Ethiopia has made inadequate progress in reducing cardiovascular and other non-communicable diseases, with CVDs are one of the leading causes of premature mortality and death (15, 16).” The statistics on dyslipidemia prevalence in Africa and Ethiopia are compelling. It would be beneficial to briefly mention healthcare challenges in Ethiopia—such as access to care and lifestyle changes—that contribute to the rising prevalence. Response: healthcare challenges were considered as one of contributing factors for increased prevalence of dyslipidemia in Ethiopia. Please see lines 69 - 73: “Access to public healthcare facilities and availability of health services in Ethiopia are generally limited. Furthermore, there are substantial disparities in accessibility and inequalities in the distribution of healthcare resources (17-19). These healthcare challenges might also contribute to the rising prevalence of dyslipidemia and present significant barriers to its prevention and management.” Linking the statistics on cardiovascular disease (CVD) more directly to the Ethiopian context would strengthen the urgency of your argument. Citing local data on CVD mortality could be particularly impactful. Response: a sentence reflecting CVDs mortality in Ethiopia is added and line 67 - 69 read: “Ethiopia has made inadequate progress in reducing cardiovascular and other non-communicable diseases, with CVDs are one of the leading causes of premature mortality and death (15, 16).” While the references are relevant, ensure that they are current and accessible. Response: we have reviewed all the references and ensure they are up-to-date and accessible. Additionally, highlighting the significance of your findings for public health policy or clinical practice at the end of the introduction would provide a stronger rationale for the study. Response: we have added the significance of the study to the last paragraph of the introduction (line 74 - 80) which now reads “This review will enable researchers to evaluate the burden of dyslipidemia, where existing evidence is often hospital-based, fragmented and inconsistent. Understanding the prevalence and factors associated with dyslipidemia can also provide valuable insights for researchers and policymakers, in designing targeted interventions and strategies for effective disease management and the prevention of further complications. Therefore, this study aimed to systematically review and pool the prevalence of dyslipidemia, its components, and associated factors among adults with coexisting chronic disease in Ethiopia.” Recommendations: - Streamline sentences for clarity and flow. - Provide context regarding healthcare challenges in Ethiopia. - Directly link global statistics to the Ethiopian situation. - Ensure references are up to date. - Highlight the significance of your findings for public health or clinical practice more explicitly. Response: we have already addressed the points raised in the recommendation in the responses above. Methods The methods section is well-organized and adheres to PRISMA guidelines, which is commendable. However, simplifying some lengthy sentences could improve clarity. Response: we appreciate the reviewer’s point on the importance of simplifying lengthy sentences. The whole method section have been edited accordingly: For instance line 124 - 125 read “To ensure data quality and reliability, two independent reviewers (TMZ and FEL) conducted the extraction process.” The inclusion and exclusion criteria are well-defined, but it would be helpful to briefly justify why certain populations (e.g., children and adolescents) are excluded, especially regarding dyslipidemia prevalence. Response: exclusion based on age was performed because of not having eligible studies on dyslipidemia in children and adolescents with coexisting chronic disease in Ethiopia. Now, we have tried to include justification and line 98 - 101 reads “We included original studies reporting the prevalence and factors associated with overall dyslipidemia, elevated TC, LDL-c, TG, or low HDL-c among adult patients (aged ≥ 18 years) in Ethiopia, as no eligible studies on dyslipidemia in children and adolescents with coexisting chronic illnesses were identified.” While the definition of dyslipidemia is clear, it would be useful to highlight the varying cut-off values across studies as a potential source of variability in prevalence estimates. Discussing how this variability might impact the results could add depth. Response: we agree that various studies used various diagnostic cutoff values to define dyslipidemia. However, this study considered those articles which define dyslipidemia based on the National Cholesterol Education Program Adult Treatment Panel III cut-off points. Besides, we further considered the two most frequently used HDL cut-off values (HDL < 40 mg/dl, and HDL < 40 mg/dl for males and < 50 mg/dl for female). Hence, based on our sub group analyses by HDL cut-off values, the pooled prevalence of overall dyslipidemia was high, regardless of the HDL-c cut-off used. The prevalence was 68% (0.56 – 0.81, I2 = 98.39) and 60% (0.45 – 0.75, I2 = 98.80) for studies used HDL < 40 mg/dl, and HDL < 40 mg/dl for males and < 50 mg/dl for female, respectively (S4 Appendix (A)). Based on this finding, it is difficult to consider dyslipidemia cut-off values as potential source of heterogeneity (I2 = 98.39 for HDL < 40 mg/dl and I2 = 98.80 for HDL < 40 mg/dl for males and < 50 mg/dl for female). Furthermore, the confidence interval for the two prevalence estimate overlaps and we assume that the pooled prevalence of overall dyslipidemia isn’t varied significantly by utilizing the two HDL cut-off values. The study selection and data extraction processes are well-articulated. Mentioning specific software used for data extraction, in addition to Excel, would enhance the methodological rigor. Response: we utilized covidence, a web-based software, for study selection and duplicate removal. This has already been detailed in the Methods section, as indicated in the corresponding line 113 - 115 “Studies were identified using search terms and database filters, then imported them into covidence, a systematic review software (Melbourne, Australia, Veritas Health Innovation) to remove duplicates and conduct screening. Results and Discussion: The prevalence rates are striking and provide a solid overview. To enhance clarity, consider stating, "Our prevalence rates are significantly higher than those reported in China and Sub-Saharan Africa." Response: we have revised part of the discussion accordingly and for instance, sentence in lines 382 - 284, which now read “In the present review, the prevalence of overall dyslipidemia (64%) is significantly higher than those reported in china (42.1%) (87), Sub-Saharan Africa (38.38%) (88), Italy (17.5%) (89) and Africa (16.5%) (90).” The discussion on lifestyle factors contributing to low HDL-c is insightful. Expanding on how these choices are influenced by socio-economic and cultural factors in Ethiopia could strengthen your argument. Response: we totally agree with the comment, yet we have tried to discuss about socio-economic and cultural factors in the final paragraph of discussion section (Line 316 - 321) “In this meta-analysis, the finding of high overall dyslipidemia and its components in adults with coexisting chronic disease is hardly wondering given the rapid urbanization, dietary and behavioral changes, and widespread adoption of unhealthy lifestyles occurring across Ethiopia (93, 94). Literacy status and lack of awareness of common cardiovascular risk factors may also play an important roles and should be considered in prevention and treatment approaches of dyslipidemia (95).” The comparisons with other meta-analyses and studies are valuable. Highlighting potential reasons for discrepancies in prevalence findings—such as differences in study populations or methodologies—would provide important context. Response: we have included the potential reasons for discrepancy in line 299 – 301, now read “Discrepancy in prevalence estimates across studies can be attributed to the differences in diagnostic cut-offs, dyslipidemia components assessed, study settings, populations, period, and differences in lifestyle.” While the identification of significant risk factors is well-articulated, mentioning the public health implications of these modifiable risk factors—such as potential interventions—earlier in the discussion could enhance the practical relevance of your findings. Response: we accept the feedback and revised line 312 - 315: “As most of risk factors are modifiable, excluding age, it is crucial to deliver behavioral interventions targeting the identified risk factors. It is highly recommended that performing physical activity, reducing alcohol consumption, and quitting smoking will help to prevent and control dyslipidemia (21).” Limitations: Acknowledging the considerable heterogeneity among studies is essential for transparency. Briefly discussing potential sources of this heterogeneity—such as differences in study design or diagnostic criteria—could give readers a clearer understanding of the limitations. While it's good to note that subgroup and sensitivity analyses were performed, elaborating on what aspects of heterogeneity remain unexplained could provide more context for those interested in the methodological rigor of your analysis. Overall, this research holds significant potential to inform public health strategies and interventions in Ethiopia. Thank you for your important work in this area! Response: we have acknowledged heterogeneity among studies in lines 336 - 340: “The considerable heterogeneity observed among the included studies was not fully explained through sensitivity or subgroup analyses based on the cut-off used to define dyslipidemia, region and types of coexisted chronic diseases. The heterogeneity between studies is inevitable (97) and could arise from difference in study settings, sample sizes, and the method used to measure dyslipidemia.” Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0320119.r003
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Formally Accepted
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