{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:59:29Z","timestamp":1753891169862,"version":"3.41.2"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The leading cause of death in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) is cardiovascular disease. The objective of this study was to determine whether the use of selective serotonin reuptake inhibitors (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRI) in veterans with GCA and PMR could have a cardio-modulatory effect as compared to nonuse. Patients with GCA and PMR were identified through the Veterans Affairs Informatics and Computing Infrastructure. After a 2:1 propensity score matching for SSRI or SNRI users, we identified nonusers with similar covariates. We then applied a multivariate logistic regression (MLR), to calculate the odds ratio (OR) for cardiovascular event (CVE) outcomes within 5 years after the index date. Related hazard ratios (HR) were also calculated to validate the discovery of our findings. We identified 2249 patients with GCA and 3906 patients with PMR. Among patients with GCA, 174 (27%) SSRI users had incident cardiovascular disease as compared to 47 (28%) SNRI users and 277 (19%) nonusers; in the PMR cohort, 108 (13%) were SSRI users compared to 71 (15%) SNRI users and 255 (11%) nonusers. The adjusted ORs of the CVE outcome associated with venlafaxine (2.44, p=0.01) and sertraline (1.45, p=0.04) were significantly greater than 1 in GCA, with similar results observed in the PMR cohort (2.01, p=0.02, and 1.45, p=0.04, respectively). Cox-regression analysis was also conducted, and the hazard ratios were qualitatively consistent with the MLR analysis. In conclusion, the adjusted risk of CVE in patients with GCA or PMR using either venlafaxine or sertraline was higher than that in the non-exposed groups.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1509941","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T05:25:22Z","timestamp":1745472322000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of SSRI and SNRI use with incidence of cardiovascular events in veterans with giant cell arteritis and polymyalgia rheumatica"],"prefix":"10.3389","volume":"16","author":[{"given":"Tianyu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris A.","family":"Gentry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole M.","family":"Kuderer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary H.","family":"Lyman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Despina","family":"Michailidou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kew273","article-title":"The spectrum of giant cell arteritis and polymyalgia rheumatic: revisiting the concept of the disease","volume":"56","author":"Dejaco","year":"2017","journal-title":"Rheumatol (Oxford)."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1080\/08916930902832629","article-title":"Leukocyte and platelet activation in patients with giant cell arteritis and polymyalgia rheumatica: a clue to thromboembolic risks","volume":"42","author":"Maugeri","year":"2009","journal-title":"Autoimmunity"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2023.109274","article-title":"Neutrophil extracellular trap formation in anti-neutrophil cytoplasmic autoantibody-associated vasculitis and large-vessel vasculitis","volume":"249","author":"Michailidou","year":"2023","journal-title":"Clin Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/acr2.70021","article-title":"Mitochondrial-mediated platelet activation in patients with polymyalgia rheumatica","volume":"7","author":"Michailidou","year":"2025","journal-title":"ACR Open Rheumatol"},{"key":"B5","article-title":"Mechanism action of platelets and crucial blood coagulation pathways in hemostasis","volume":"11","author":"Periayah","year":"2017","journal-title":"Int J Hematol Oncol Stem Cell Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1080\/00015385.2017.1281560","article-title":"Platelets and cardiovascular risk","volume":"72","author":"Renga","year":"2018","journal-title":"Acta Cardiol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1093\/rheumatology\/kev262","article-title":"Increased risk of cardiovascular disease in giant cell arteritis: a general population-based study","volume":"55","author":"Amiri","year":"2016","journal-title":"Rheumatol (Oxford)."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2021.02.001","article-title":"Myocardial infarction during giant cell arteritis: A cohort study","volume":"89","author":"Greigert","year":"2021","journal-title":"Eur J Intern Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1002\/acr.22416","article-title":"Cardiovascular risk and acute coronary syndrome in giant cell arteritis: a population-based retrospective cohort study","volume":"67","author":"Udayakumar","year":"2015","journal-title":"Arthriits Care Res (Hoboken)."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.140266","article-title":"Risk of vascular events in patients with polymyalgia rheumatica","volume":"186","author":"Hancock","year":"2014","journal-title":"CMAJ."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.881924","article-title":"Serotonin reuptake inhibitor antidepressants (SSRIs) against atherosclerosis","volume":"17","author":"Wozniak","year":"2011","journal-title":"Med Sci Monit"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.121","article-title":"Effects of selective serotonin reuptake inhibitor therapy on endothelial function and inflammatory markers in patients with coronary heart disease","volume":"86","author":"Pizzi","year":"2009","journal-title":"Clin Pharmacol Ther"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2587","DOI":"10.3390\/ijms23052587","article-title":"The antidepressant duloxetine inhibits platelet function and protects against thrombosis","volume":"23","author":"Lozano","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.annepidem.2007.11.004","article-title":"A secondary analysis of a duration response association between selective serotonin reuptake inhibitor use and the risk of acute myocardial infarction in the aging population","volume":"18","author":"Blanchette","year":"2008","journal-title":"Ann Epidemiol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.2165\/11589340-000000000-00000","article-title":"Effects of selective serotonin reuptake inhibitors on platelet function: mechanisms, clinical outcomes, and implications for use in elderly patients","volume":"28","author":"de Abajo","year":"2011","journal-title":"Drugs Aging"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1161\/hc4101.097519","article-title":"Selective serotonin reuptake inhibitors and myocardial infarction","volume":"104","author":"Sauer","year":"2001","journal-title":"Circulation"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.6.701","article-title":"Sertraline treatment of major depression in patients with acute MI or unstab le angina","volume":"288","author":"Glassman","year":"2002","journal-title":"JAMA."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1046\/j.0306-5251.2001.01426.x","article-title":"Use of selective serotonin reuptake inhibitors and risk of developing first time acute myocardial infarction","volume":"52","author":"Meier","year":"2001","journal-title":"Br J Clin Pharmacol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13446","article-title":"Risk of venous and arterial thromboembolism in patients with giant cell arteritis and\/or polymyalgia rheumatica: A Veterans Health Administration population-based study in the United States","volume":"291","author":"Michailidou","year":"2022","journal-title":"J Intern Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.997347","article-title":"Predictive models for thromboembolic events in giant cell arteritis: A US veterans health administration population-based study","volume":"13","author":"Michailidou","year":"2022","journal-title":"Front Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/acr2.11218","article-title":"Identification of acute giant cell arteritis in real-world data using administrative claims-based algorithms","volume":"3","author":"Lee","year":"2021","journal-title":"ACR Open Rheumatol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-019-04387-5","article-title":"Prevalence of polymyalgia rheumatica in Colombia: data from the national health registry 2012\u2013 2016","volume":"39","author":"Fernandez-Avila","year":"2019","journal-title":"Rheumatol Int"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3399\/bjgp10X515089","article-title":"Cardiovascular events in patients with obesity: an observational study","volume":"60","author":"Buitrago","year":"2010","journal-title":"Br J Gen Pract"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.96.9.3243","article-title":"Cigarette smoking, cardiovascular disease, and stroke: a\u00a0statement for healthcare professionals from the American Heart Association","volume":"96","author":"Ockene","year":"1997","journal-title":"Am\u00a0Heart Assoc Task Force Risk Reduction. Circulation."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1539","article-title":"Cancer and heart disease: associations and relations","volume":"21","author":"de Boer","year":"2019","journal-title":"Eur J Heart Fail"},{"key":"B26","article-title":"Charlson comorbidity index: ICD-9 update and ICD-10 translation","volume":"12","author":"Glasheen","year":"2019","journal-title":"Am Health Drug Benefits."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.14240","article-title":"High blood pressure and cardiovascular disease","volume":"75","author":"Fuchs","year":"2020","journal-title":"Hypertension."},{"key":"B28","doi-asserted-by":"publisher","first-page":"rkae013","DOI":"10.1093\/rap\/rkae013","article-title":"Anxiety and depression in patients with giant cell arteritis","volume":"8","author":"Martins-Martinho","year":"2024","journal-title":"Rheumatol Adv Pract"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-017-3691-9","article-title":"How common is depression in patients with polymyalgia rheumatica","volume":"37","author":"Vivekanantham","year":"2018","journal-title":"Clin\u00a0Rheumatol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2016.181","article-title":"Depression and coronary heart disease","volume":"14","author":"Carney","year":"2017","journal-title":"Nat Rev Cardiol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2147\/NDT.S63904","article-title":"Exploring the risk-factor association between depression and incident stroke: a\u00a0systematic review and meta-analysis","volume":"11","author":"Barlinn","year":"2015","journal-title":"Neuropsychiatr Dis Treat"},{"key":"B32","article-title":"Increased mortality due to cardiovascular disease in patients with giant cell arteritis in northern Sweden","volume":"29","author":"Uddhammar","year":"2002","journal-title":"J Rheumatol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2023-003960","article-title":"Myocardial infarction in a population-based cohort of patients with biopsy-confirmed giant cell arteritis in southern Sweden","volume":"10","author":"Stamatis","year":"2024","journal-title":"RMD Open"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.299.6698.549","article-title":"Death rates and causes of death in 284 consecutive patients with giant cell arteritis confirmed by biopsy","volume":"299","author":"Nordborg","year":"1989","journal-title":"BMJ"},{"key":"B35","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1080\/03009740310000382","article-title":"Causes of death in polymyalgia rheumatica. A prospective longitudinal study of 315 cases and matched population controls","volume":"32","author":"Mykelbust","year":"2003","journal-title":"Scand J Rheumatol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1136\/ard.55.12.927","article-title":"Von\u00a0Willebrand factor in the outcome of temporal arteritis","volume":"55","author":"Cid","year":"1996","journal-title":"Ann Rheum Dis"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1136\/ard.56.11.698","article-title":"Long-term follow up of von Willebrand factor and plasminogen activator inhibitor-1 in patients with polymyalgia rheumatica","volume":"56","author":"Uddhammar","year":"1997","journal-title":"Ann Rheum Dis"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000085163.21752.0A","article-title":"Platelet\/endothelial biomarkers in depressed patients treated with the selective serotonin reuptake inhibitor sertraline after acute coronary events: the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART) Platelet Substudy","volume":"108","author":"Serebruany","year":"2003","journal-title":"Circulation"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1097\/PSY.0000000000000163","article-title":"Effects of long-term sertraline treatment and depression on coronary artery atherosclerosis in premenopausal female primates","volume":"77","author":"Shively","year":"2015","journal-title":"Psychosom Med"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2016.08.037","article-title":"The impact of treatment with treatment with selective serotonin reuptake inhibitors on primate cardiovascular disease, behavior, and neuroanatomy","volume":"74","author":"Shively","year":"2017","journal-title":"Neurosci Biobehav Rev"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.310536","article-title":"Chronic intake of the selective serotonin reuptake inhibitor fluoxetine enhances atherosclerosis","volume":"38","author":"Rami","year":"2018","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.3310\/hta15280","article-title":"A study of the safety and harms of antidepressant drugs for older people: a cohort study using a large primary care database","volume":"15","author":"Coupland","year":"2011","journal-title":"Health Technol Assessment."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3109\/15622970802573246","article-title":"Pro-inflammatory biomakers in depression: treatment with venlafaxine","volume":"10","author":"Piletz","year":"2009","journal-title":"World J Biol Psychiatry"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2003.11.006","article-title":"Stimulatory effect of antidepressants on the production of IL-6","volume":"4","author":"Kubera","year":"2004","journal-title":"Int Immunopharmacol."},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.319077","article-title":"Interleukin-6 Signaling and anti-interleukin-6 therapeutics\u00a0in cardiovascular disease","volume":"128","author":"Ridker","year":"2021","journal-title":"Circ Res"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200005)43:5<1041:AID-ANR12>3.0.CO;2-7","article-title":"Treatment of giant cell arteritis: interleukin-6 as a biologic marker of disease activity","volume":"43","author":"Weyand","year":"2000","journal-title":"Arthritis Rheumatol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.159.6.577","article-title":"Corticosteroid requirements in polymyalgia rheumatica","volume":"159","author":"Weyand","year":"1999","journal-title":"Arch Intern Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11041005","article-title":"An updated review of cardiovascular events in giant cell arteritis","volume":"11","author":"de Boysson","year":"2022","journal-title":"J Clin Med"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1002\/acr.25354","article-title":"Altered plasma levels and tissue expression of fibroblast activation protein alpha in giant cell arteritis","author":"Xu","year":"2024","journal-title":"Arthritis Care Res (Hoboken)."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-014-7251-9","article-title":"Use of selective serotonin reuptake inhibitors and risk of stroke: a systematic review and meta-analysis","volume":"261","author":"Shin","year":"2014","journal-title":"J Neurol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(11)61588-X","article-title":"Association of antidepressant medications with carotid intima media thickness in middle aged veteran twins","volume":"57","author":"Shah","year":"2011","journal-title":"JACC."},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000000701","article-title":"Cerebrovascular, cardiovascular, and mortality events in new users of selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors","volume":"37","author":"Leong","year":"2017","journal-title":"J Clin Psychopharmacol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1509941\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T05:25:23Z","timestamp":1745472323000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1509941\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,24]]},"references-count":52,"alternative-id":["10.3389\/fimmu.2025.1509941"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1509941","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2025,4,24]]},"article-number":"1509941"}}