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Pepper Older Americans Independence Center"},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL 147862"],"award-info":[{"award-number":["R01 HL 147862"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL 151431"],"award-info":[{"award-number":["R01 HL 151431"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Randomized clinical trials of hypertension treatment intensity evaluate the effects on incident major adverse cardiovascular events (MACEs) and serious adverse events (SAEs). Occurrences after a non-fatal index event have not been rigorously evaluated. The aim of this study was to evaluate the association of intensive (&amp;lt;120 mmHg) to standard (&amp;lt;140 mmHg) blood pressure (BP) treatment with mortality mediated through a non-fatal MACE or non-fatal SAE in 9361 participants in the Systolic Blood Pressure Intervention Trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Logistic regression and causal mediation modelling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cardiovascular (CVM) and non-CV mortality (non-CVM). The direct effect of intensive treatment was a lowering of ACM [odds ratio (OR) 0.75, 95% confidence interval (CI): 0.60\u20130.94]. The MACE-mediated effect substantially attenuated (OR 0.96, 95% CI: 0.92\u20130.99) ACM, while the SAE-mediated effect was associated with increased (OR 1.03, 95% CI: 1.01\u20131.05) ACM. Similar patterns were noted for intensive BP treatment on CVM and non-CVM. We also noted that SAE incidence was 3.9-fold higher than MACE incidence (13.7 vs. 3.5%), and there were a total of 365 (3.9%) ACM cases, with non-CVM being 2.6-fold higher than CVM [2.81% (263\/9361) vs. 1.09% (102\/9361)]. The SAE to MACE and non-CVM to CVM preponderance was found across all age groups, with the \u226580-year age group having the highest differences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The current analytic techniques demonstrated that intensive BP treatment was associated with an attenuated mortality benefit when it was MACE-mediated and possibly harmful when it was SAE-mediated. Current cardiovascular trial reporting of treatment effects does not allow expansion of the lens to focus on important occurrences after the index event.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwad132","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T20:21:23Z","timestamp":1682454083000},"page":"996-1004","source":"Crossref","is-referenced-by-count":10,"title":["The association of intensive blood pressure treatment and non-fatal cardiovascular or serious adverse events in older adults with mortality: mediation analysis in SPRINT"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7892-0726","authenticated-orcid":false,"given":"Ashok","family":"Krishnaswami","sequence":"first","affiliation":[{"name":"Section of Geriatric Medicine, Division of Primary Care and Population Health, Stanford University ,","place":["USA"]},{"name":"Geriatric Research Education and Clinical Center, US Department of Veterans Affairs, VA Palo Alto Health Care System ,","place":["USA"]},{"name":"Division of Cardiology , 270 International Circle, Building 3, 2nd Floor ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W","family":"Rich","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Washington University ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Ji","family":"Kwak","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at Houston , Houston, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7474-3737","authenticated-orcid":false,"given":"Parag","family":"Goyal","sequence":"additional","affiliation":[{"name":"Program for The Care and Study of the Aging Heart, Department of Medicine, Weill Cornell Medicine , New York, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E","family":"Forman","sequence":"additional","affiliation":[{"name":"Department of Medicine (Geriatrics and Cardiology), University of Pittsburgh , Pittsburgh, PA ,","place":["USA"]},{"name":"Pittsburgh GRECC, VA Pittsburgh Healthcare System , Pittsburgh, PA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulla A","family":"Damluji","sequence":"additional","affiliation":[{"name":"The Inova Center of Outcomes Research, Inova Heart and Vascular Institute ,","place":["USA"]},{"name":"Division of Cardiology, The Johns Hopkins University School of Medicine ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Solomon","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Kaiser Permanente Oakland Medical Center ,","place":["USA"]},{"name":"Division of Research, Kaiser Permanente Northern California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamal S","family":"Rana","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Kaiser Permanente Oakland Medical Center ,","place":["USA"]},{"name":"Division of Research, Kaiser Permanente Northern California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah M","family":"Kado","sequence":"additional","affiliation":[{"name":"Section of Geriatric Medicine, Division of Primary Care and Population Health, Stanford University ,","place":["USA"]},{"name":"Geriatric Research Education and Clinical Center, US Department of Veterans Affairs, VA Palo Alto Health Care System ,","place":["USA"]},{"name":"Department of Medicine\/Primary Care and Population Health, Stanford University ,","place":["USA"]},{"name":"Department of Epidemiology and Population Health, Stanford University ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle C","family":"Odden","sequence":"additional","affiliation":[{"name":"Geriatric Research Education and Clinical Center, US Department of Veterans Affairs, VA Palo Alto Health Care System ,","place":["USA"]},{"name":"Department of Epidemiology and Population Health, Stanford University ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"2026041420224609000_zwad132-B1","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1161\/CIRCULATIONAHA.117.033065","article-title":"Comparison of time-to-first event and recurrent-event methods in randomized clinical trials","volume":"138","author":"Claggett","year":"2018","journal-title":"Circulation"},{"key":"2026041420224609000_zwad132-B2","volume-title":"Explanation in Causal Inference. 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