Assessment of Pharmacotherapy and Clinical Outcomes of Treatment for the Development of Cardiovascular Disease among Tuberculosis Patients

Assessment of Pharmacotherapy and Clinical Outcomes of Treatment for the Development of Cardiovascular Disease among Tuberculosis Patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Assessment of Pharmacotherapy and Clinical Outcomes of Treatment for the Development of Cardiovascular Disease among Tuberculosis Patients Bheesham Kingrani, Amer Hayat Khan, Sabariah Noor Harun, irfhan Ali Hyder Ali, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8338608/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 13 You are reading this latest preprint version Abstract Background: Tuberculosis (TB) continues to impose a substantial morbidity and mortality burden globally, particularly in developing countries. Growing evidence suggests an epidemiological and pathological interplay between TB and cardiovascular disease (CVD). Beyond conventional cardiovascular risk factors such as diabetes mellitus, hypertension, and dyslipidemia, there are other factors, including chronic inflammation, immune activation, and metabolic disruption, that are caused by Mycobacterium tuberculosis and may also contribute to cardiovascular complications. Chronic immune activation involving monocytes, macrophages, lymphocytes, and cytokines, which are crucial for TB defense, may also contribute to atherogenesis and cardiovascular dysfunction. Objective: The main objective of this study was to evaluate anti-tuberculosis pharmacotherapy patterns and clinical outcomes among patients without cardiovascular disease (CVD). Methodology: This retrospective cohort study with an observational analytic design, was conducted at Penang General Hospital, Malaysia, from January 2023 to August 2023 using medical records from January 2015 to December 2022, evaluated 402 TB patients without pre-existing CVD. The study assessed the association between anti-tuberculosis pharmacotherapy patterns, adverse drug reactions, drug-resistant TB, clinical treatment outcomes, and the development of CVD during TB therapy using chi-square tests. Results: The predominant anti-tuberculosis regimen was 2HRZE/4HR, commonly administered as fixed-dose combinations. Adverse drug reactions were observed, including transaminitis (8.3%), skin rashes (6.3%), nausea/vomiting (4.7%), hyperbilirubinemia (4.2%), blurred vision (2.3%), thrombocytopenia (2.1%), and drug-induced hepatitis (2.6%). Drug-resistant TB constituted 6.5% of cases, comprising mono-drug resistance (3.4%), MDR-TB (1.4%), and poly-drug resistance (0.9%). Regarding clinical outcomes, 41.5% of patients were cured, 21.9% completed treatment, 15.2% died, and 5.5% were lost to follow-up, with a treatment failure rate of 0.7%. A significant association was found between the type of TB case and clinical outcomes (χ² = 15.826, p < 0.05). New TB cases showed higher cure and completion rates. Cardiovascular disease developed in 41 patients and was associated with markedly increased mortality (28/41) and significantly poorer treatment outcomes (p < 0.001). Comorbidities, including diabetes mellitus (χ² = 14.720, p = 0.012), HIV infection (χ² = 28.727, p = 0.001), acute kidney injury (χ² = 22.156, p < 0.001), and anaemia (χ² = 16.872, p = 0.005), were significantly linked to adverse clinical outcomes. Conclusions: TB patients who developed cardiovascular disease exhibited significantly higher mortality and reduced treatment success. Comorbidities such as diabetes, HIV, acute kidney injury, and anaemia further compromised clinical outcomes. These findings highlight the need for routine cardiovascular risk assessment during TB therapy. Early identification of high-risk patients and integrated, multidisciplinary management approaches are essential. Strengthening combined care for infectious and non-communicable diseases may improve survival in resource-limited settings. tuberculosis cardiovascular disease anti-tubercular pharmacotherapy drug-resistant tuberculosis treatment outcomes Full Text Additional Declarations No competing interests reported. Supplementary Files Supplimentaryfiles4thArticle.pdf Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 27 Jan, 2026 Reviews received at journal 25 Jan, 2026 Reviews received at journal 25 Jan, 2026 Reviewers agreed at journal 23 Jan, 2026 Reviewers agreed at journal 21 Jan, 2026 Reviews received at journal 21 Jan, 2026 Reviewers agreed at journal 20 Jan, 2026 Reviewers agreed at journal 19 Jan, 2026 Reviewers invited by journal 19 Jan, 2026 Editor invited by journal 16 Jan, 2026 Editor assigned by journal 16 Dec, 2025 Submission checks completed at journal 16 Dec, 2025 First submitted to journal 11 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8338608","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":560442741,"identity":"f5dd9c76-9dc7-4a6f-a546-efba2640854e","order_by":0,"name":"Bheesham Kingrani","email":"data:image/png;base64,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","orcid":"","institution":"Universiti Sains Malaysia","correspondingAuthor":true,"prefix":"","firstName":"Bheesham","middleName":"","lastName":"Kingrani","suffix":""},{"id":560442742,"identity":"f3cf8fe9-c3c9-4c70-a634-9a04d982edfc","order_by":1,"name":"Amer Hayat Khan","email":"","orcid":"","institution":"Universiti Sains Malaysia","correspondingAuthor":false,"prefix":"","firstName":"Amer","middleName":"Hayat","lastName":"Khan","suffix":""},{"id":560442749,"identity":"e37ad5f4-ef93-4e43-962e-a1c6949e6851","order_by":2,"name":"Sabariah Noor Harun","email":"","orcid":"","institution":"Universiti Sains Malaysia","correspondingAuthor":false,"prefix":"","firstName":"Sabariah","middleName":"Noor","lastName":"Harun","suffix":""},{"id":560442750,"identity":"853ae2e0-16c7-4c86-ade7-6ab5f607507c","order_by":3,"name":"irfhan Ali Hyder Ali","email":"","orcid":"","institution":"Hospital Pulau Pinang","correspondingAuthor":false,"prefix":"","firstName":"irfhan","middleName":"Ali Hyder","lastName":"Ali","suffix":""},{"id":560442751,"identity":"204ed6f4-6e81-41ea-b637-11499fa15f0d","order_by":4,"name":"Azfar Athar Ishaqi","email":"","orcid":"","institution":"King Khalid University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Azfar","middleName":"Athar","lastName":"Ishaqi","suffix":""}],"badges":[],"createdAt":"2025-12-11 16:09:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8338608/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8338608/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":98436354,"identity":"2be056ef-3eec-40ca-ad53-937546de5b66","added_by":"auto","created_at":"2025-12-17 16:55:29","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1053024,"visible":true,"origin":"","legend":"","description":"","filename":"FinalVersionofArticleAssessmentofPharmacotherapy.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8338608/v1_covered_67c4a848-4e0b-414a-90cd-3045988c650e.pdf"},{"id":98290971,"identity":"358863e3-e3c1-4b59-9711-fbe5e4152917","added_by":"auto","created_at":"2025-12-16 08:15:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":833445,"visible":true,"origin":"","legend":"","description":"","filename":"Supplimentaryfiles4thArticle.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8338608/v1/0de02a58d7e000bafed435a1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eAssessment of Pharmacotherapy and Clinical Outcomes of Treatment for the Development of Cardiovascular Disease among Tuberculosis Patients\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"tuberculosis, cardiovascular disease, anti-tubercular pharmacotherapy, drug-resistant tuberculosis, treatment outcomes","lastPublishedDoi":"10.21203/rs.3.rs-8338608/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8338608/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Tuberculosis (TB) continues to impose a substantial morbidity and mortality burden globally, particularly in developing countries. Growing evidence suggests an epidemiological and pathological interplay between TB and cardiovascular disease (CVD). Beyond conventional cardiovascular risk factors such as diabetes mellitus, hypertension, and dyslipidemia, there are other factors, including chronic inflammation, immune activation, and metabolic disruption, that are caused by \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e and may also contribute to cardiovascular complications. Chronic immune activation involving monocytes, macrophages, lymphocytes, and cytokines, which are crucial for TB defense, may also contribute to atherogenesis and cardiovascular dysfunction.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eThe main objective of this study was to evaluate anti-tuberculosis pharmacotherapy patterns and clinical outcomes among patients without cardiovascular disease (CVD). \u003cstrong\u003eMethodology:\u003c/strong\u003e This retrospective cohort study with an observational analytic design, was conducted at Penang General Hospital, Malaysia, from January 2023 to August 2023 using medical records from January 2015 to December 2022, evaluated 402 TB patients without pre-existing CVD. The study assessed the association between anti-tuberculosis pharmacotherapy patterns, adverse drug reactions, drug-resistant TB, clinical treatment outcomes, and the development of CVD during TB therapy using chi-square tests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The predominant anti-tuberculosis regimen was 2HRZE/4HR, commonly administered as fixed-dose combinations. Adverse drug reactions were observed, including transaminitis (8.3%), skin rashes (6.3%), nausea/vomiting (4.7%), hyperbilirubinemia (4.2%), blurred vision (2.3%), thrombocytopenia (2.1%), and drug-induced hepatitis (2.6%). Drug-resistant TB constituted 6.5% of cases, comprising mono-drug resistance (3.4%), MDR-TB (1.4%), and poly-drug resistance (0.9%). Regarding clinical outcomes, 41.5% of patients were cured, 21.9% completed treatment, 15.2% died, and 5.5% were lost to follow-up, with a treatment failure rate of 0.7%. A significant association was found between the type of TB case and clinical outcomes (χ² = 15.826, p \u0026lt; 0.05). New TB cases showed higher cure and completion rates. Cardiovascular disease developed in 41 patients and was associated with markedly increased mortality (28/41) and significantly poorer treatment outcomes (p \u0026lt; 0.001). Comorbidities, including diabetes mellitus (χ² = 14.720, p = 0.012), HIV infection (χ² = 28.727, p = 0.001), acute kidney injury (χ² = 22.156, p \u0026lt; 0.001), and anaemia (χ² = 16.872, p = 0.005), were significantly linked to adverse clinical outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e TB patients who developed cardiovascular disease exhibited significantly higher mortality and reduced treatment success. Comorbidities such as diabetes, HIV, acute kidney injury, and anaemia further compromised clinical outcomes. These findings highlight the need for routine cardiovascular risk assessment during TB therapy. Early identification of high-risk patients and integrated, multidisciplinary management approaches are essential. Strengthening combined care for infectious and non-communicable diseases may improve survival in resource-limited settings.\u003c/p\u003e","manuscriptTitle":"Assessment of Pharmacotherapy and Clinical Outcomes of Treatment for the Development of Cardiovascular Disease among Tuberculosis Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-16 08:15:26","doi":"10.21203/rs.3.rs-8338608/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-27T13:48:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-25T16:50:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-25T16:33:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"133885481459209131916145180053748224373","date":"2026-01-23T12:11:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"160400078602436154317354032870361319661","date":"2026-01-21T13:35:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-21T05:11:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"158815721895201780655222173320300794098","date":"2026-01-20T17:13:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"217366605346771227476767300936401583572","date":"2026-01-19T13:37:59+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-19T12:36:24+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-16T12:14:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-16T23:09:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-16T23:08:19+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2025-12-11T15:44:43+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"464c6762-2c8e-4d33-a18d-036f2e435eae","owner":[],"postedDate":"December 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-01-27T13:55:26+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-16 08:15:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8338608","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8338608","identity":"rs-8338608","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}