{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T17:55:29Z","timestamp":1782496529914,"version":"3.54.5"},"reference-count":34,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"unspecified","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Health Commission of Jilin Province","award":["2025WS-ZA004"],"award-info":[{"award-number":["2025WS-ZA004"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,1,13]]},"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality. Arterial stiffness, an independent predictor of cardiovascular risk, enables detection of early vascular alterations preceding major clinical outcomes, making it critical for COPD management. Pharmacotherapy currently represents a major focus of therapeutic research for arterial stiffness modulation in this population. However, while current evidence supports specific pharmacological approaches, such as statins\u2019 vascular modulation in certain subgroups, their clinical efficacy remains inconclusively demonstrated across trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>To address this critical knowledge gap, we propose a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review and meta-analysis focusing specifically on COPD patients with concomitant arterial stiffness, aiming to evaluate the efficacy of vascular-targeted pharmacotherapies (statins, phosphodiesterase-4 inhibitors, long-acting bronchodilators). We conduct an extensive search across various databases (including MEDLINE and Embase, the Cochrane Central Register of Controlled Trials, Epistemonikos, Scopus, Web of Science Core Collection and China National Knowledge Infrastructure). The search will focus on randomised controlled trials (RCTs) of pharmacotherapy interventions associated with concurrent arteriosclerosis in COPD patients published from the date of creation of these databases to 1 May 2025. The primary outcome will be arterial pulse wave velocity, with secondary outcomes encompassing vascular function biomarkers, COPD clinical characteristics, systemic inflammatory markers (including tumour necrosis factor-alpha), clinical remission rate and adverse events. Two independent reviewers will systematically search seven biomedical databases using validated strategies, followed by risk-of-bias assessment (Cochrane RoB 2.0) and evidence quality grading (Grading of Recommendations Assessment, Development and Evaluation). Subgroup analyses will be initiated contingent on identification of significant statistical heterogeneity. Stratification variables may include, but are not limited to, disease severity (Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), cumulative smoking exposure (quantified in pack-years) and comorbidity burden (eg, cardiovascular\/metabolic disorders). Both conventional pairwise and network meta-analyses will be implemented to hierarchically rank therapeutic interventions and identify the optimal regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This systematic review protocol is based on published RCTs and does not contain private information about the patient; therefore, ethical approval is not required.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD42024628739.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-104689","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T15:41:20Z","timestamp":1770219680000},"page":"e104689","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of pharmacotherapy in COPD with arteriosclerosis: protocol for a systematic review and network meta-analysis"],"prefix":"10.1136","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7734-4299","authenticated-orcid":false,"given":"Xiaotong","family":"Wei","sequence":"first","affiliation":[{"name":"Changchun University of Chinese Medicine, Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siping","family":"Wang","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine, Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongpeng","family":"Yu","sequence":"additional","affiliation":[{"name":"Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shi","sequence":"additional","affiliation":[{"name":"Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"2026062610403768000_16.2.e104689.1","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1093\/eurjpc\/zwaf119","article-title":"Identification and management of cardiopulmonary risk in patients with chronic obstructive pulmonary disease: a multidisciplinary consensus and modified Delphi study","volume":"32","author":"Gale","year":"2025","journal-title":"Eur J Prev Cardiol"},{"key":"2026062610403768000_16.2.e104689.2","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1042\/CS20210835","article-title":"Chronic obstructive pulmonary disease and atherosclerosis: common mechanisms and novel therapeutics","volume":"136","author":"Brassington","year":"2022","journal-title":"Clin Sci (Lond)"},{"key":"2026062610403768000_16.2.e104689.3","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1152\/japplphysiol.00580.2018","article-title":"CT-measured lung air-trapping is associated with higher carotid artery stiffness in individuals with chronic obstructive pulmonary disease","volume":"125","author":"Luehrs","year":"2018","journal-title":"J Appl Physiol"},{"key":"2026062610403768000_16.2.e104689.4","doi-asserted-by":"crossref","unstructured":"Ragnoli B , Chiazza F , Tarsi G , et al . Biological pathways and mechanisms linking COPD and cardiovascular disease. Ther Adv Chronic Dis 2025;16. doi:10.1177\/20406223251314286","DOI":"10.1177\/20406223251314286"},{"key":"2026062610403768000_16.2.e104689.5","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1042\/CS20180316","article-title":"New frontiers in the treatment of comorbid cardiovascular disease in chronic obstructive pulmonary disease","volume":"133","author":"Brassington","year":"2019","journal-title":"Clin Sci (Lond)"},{"key":"2026062610403768000_16.2.e104689.6","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.314599"},{"key":"2026062610403768000_16.2.e104689.7","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1161\/HYPERTENSIONAHA.121.18075","article-title":"Arteriosclerosis, Atherosclerosis, and Cardiovascular Health: Joint Relations to the Incidence of Cardiovascular Disease","volume":"78","author":"Vasan","year":"2021","journal-title":"Hypertension"},{"key":"2026062610403768000_16.2.e104689.8","doi-asserted-by":"crossref","unstructured":"Balbirsingh V , Mohammed AS , Turner AM , et al . 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