{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:46:15Z","timestamp":1794008775288,"version":"4.8.0"},"reference-count":61,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:sec id=\"ab-hoi240028-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Blood pressure response during acute exercise (exercise blood pressure [EBP]) is associated with the future risk of hypertension and cardiovascular disease (CVD). Biochemical characterization of EBP could inform disease biology and identify novel biomarkers of future hypertension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi240028-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To identify protein markers associated with EBP and test their association with incident hypertension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi240028-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This study assayed 4977 plasma proteins in 681 healthy participants (from 763 assessed) of the Health, Risk Factors, Exercise Training and Genetics (HERITAGE; data collection from January 1993 to December 1997 and plasma proteomics from January 2019 to January 2020) Family Study at rest who underwent 2 cardiopulmonary exercise tests. Individuals were free of CVD at the time of recruitment. Individuals with resting SBP \u2265160 mm Hg or DBP \u2265100 mm Hg or taking antihypertensive drug therapy were excluded from the study. The association between resting plasma protein levels to both resting BP and EBP was evaluated. Proteins associated with EBP were analyzed for their association with incident hypertension in the Framingham Heart Study (FHS; n\u2009=\u20091177) and validated in the Jackson Heart Study (JHS; n\u2009=\u2009772) and Multi-Ethnic Study of Atherosclerosis (MESA; n\u2009=\u20091367). Proteins associated with incident hypertension were tested for putative causal links in approximately 700\u202f000 individuals using cis-protein quantitative loci mendelian randomization (cis-MR). Data were analyzed from January 2023 to January 2024.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi240028-7\">\n                    <jats:title>Exposures<\/jats:title>\n                    <jats:p>Plasma proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi240028-8\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>EBP was defined as the BP response during a fixed workload (50 W) on a cycle ergometer. Hypertension was defined as BP \u2265140\/90 mm Hg or taking antihypertensive medication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi240028-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the 681 participants in the HERITAGE Family Study, the mean (SD) age was 34 (13) years; 366 participants (54%) were female; 238 (35%) were self-reported Black and 443 (65%) were self-reported White. Proteomic profiling of EBP revealed 34 proteins that would not have otherwise been identified through profiling of resting BP alone. Transforming growth factor \u03b2 receptor 3 (TGFBR3) and prostaglandin D2 synthase (PTGDS) had the strongest association with exercise systolic BP (SBP) and diastolic BP (DBP), respectively (TGFBR3: exercise SBP, \u03b2 estimate, \u22123.39; 95% CI, \u22124.79 to \u22122.00;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20092.33\u2009\u00d7\u200910\n                      <jats:sup>\u22126<\/jats:sup>\n                      ; PTGDS: exercise DBP \u03b2 estimate, \u22122.50; 95% CI, \u22123.29 to \u22121.70;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20091.18\u2009\u00d7\u200910\n                      <jats:sup>\u22129<\/jats:sup>\n                      ). In fully adjusted models, TGFBR3 was inversely associated with incident hypertension in FHS, JHS, and MESA (hazard ratio [HR]: FHS, 0.86; 95% CI, 0.75-0.97;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.01; JHS, 0.87; 95% CI, 0.77-0.97;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.02; MESA, 0.84; 95% CI, 0.71-0.98;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.03; pooled cohort, 0.86; 95% CI, 0.79-0.92;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20096\u2009\u00d7\u200910\n                      <jats:sup>\u22125<\/jats:sup>\n                      ). Using cis-MR, genetically predicted levels of TGFBR3 were associated with SBP, hypertension, and CVD events (SBP: \u03b2, \u22120.38; 95% CI, \u22120.64 to \u22120.11;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.006; hypertension: odds ratio [OR], 0.99; 95% CI, 0.98-0.99;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001; heart failure with hypertension: OR, 0.86; 95% CI, 0.77-0.97;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.01; CVD: OR, 0.84; 95% CI, 0.77-0.92;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20098\u2009\u00d7\u200910\n                      <jats:sup>\u22125<\/jats:sup>\n                      ; cerebrovascular events: OR, 0.77; 95% CI, 0.70-0.85;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20095\u2009\u00d7\u200910\n                      <jats:sup>\u22127<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-hoi240028-10\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>Plasma proteomic profiling of EBP identified a novel protein, TGFBR3, which may protect against elevated BP and long-term CVD outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamacardio.2024.1397","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T11:00:51Z","timestamp":1718190051000},"page":"713","source":"Crossref","is-referenced-by-count":18,"title":["Plasma Proteomics of Exercise Blood Pressure and Incident Hypertension"],"prefix":"10.1001","volume":"9","author":[{"given":"Prashant","family":"Rao","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts"},{"name":"CardioVascular Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle. 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