{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:08:37Z","timestamp":1789013317734,"version":"build-2803163510"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Childhood adversity (CA) is associated with cardiovascular disease (CVD). Proteomic profiling may help elucidate underlying mechanisms. This study aimed to explore how CA and genetic risk jointly impact CVD and the potential role of proteomic biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">A total of 14\u2009508 participants without baseline CVD and with available proteomics data from the UK Biobank were included. CA was assessed using the Childhood Trauma Screener questionnaire. Proteomic signatures were derived using least absolute shrinkage and selection operator regression. Cox proportional hazard models were used to examine the associations of CA with CVD, and mediation analyses were conducted to assess the extent to which proteomic biomarkers explained these associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Over a median follow\u2010up of 13.5\u2009years, 2286 incident CVD events were identified. The per\u2010score increase in CA score was associated with all\u2010cause and cause\u2010specific CVD, with hazard ratios (HRs) for all\u2010cause CVD, coronary heart disease, arrhythmia\/conduction disorder, and heart failure being 1.049 (95% CI, 1.031\u20131.068), 1.039 (95% CI, 1.009\u20131.070), 1.041 (95% CI, 1.015\u20131.067), and 1.066 (95% CI, 1.012\u20131.122), respectively. No significant interaction between CA and genetic risk was observed. Participants with both high CA and high genetic risk had the highest all\u2010cause CVD risk (HR, 1.847 [95% CI, 1.380\u20132.472]). Several proteins (pro\u2010adrenomedullin, agrin, AHNAK, CD302, CD83, and yes\u2010associated protein 1) explained 1.58% to 9.98% of the associations between CA and all\u2010cause and cause\u2010specific CVD. Proteomic signatures statistically mediated 3.68% to 10.80% of these associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">CA and genetic susceptibility jointly contributed to increased CVD risk. Proteomic biomarkers partially mediate the CA\u2013CVD associations, providing insight into biological pathways linking early\u2010life adversity and CVD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.048564","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T10:27:13Z","timestamp":1784975233000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Childhood Adversity and Cardiovascular Disease Risk: Unraveling Plasma Proteomic Pathways and Moderating Role of Genetic Predisposition"],"prefix":"10.1161","volume":"15","author":[{"given":"Jiang\u2010Yan","family":"Wang","sequence":"first","affiliation":[{"name":"Cheeloo College of Medicine, Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Cheeloo College of Medicine, Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Yu","family":"Jia","sequence":"additional","affiliation":[{"name":"Cheeloo College of Medicine, Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0115-491X","authenticated-orcid":false,"given":"Jia\u2010Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"Cheeloo College of Medicine, Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2651-147X","authenticated-orcid":false,"given":"Cun\u2010Xian","family":"Jia","sequence":"additional","affiliation":[{"name":"Cheeloo College of Medicine, Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1277-7397","authenticated-orcid":false,"given":"Bao\u2010Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Cheeloo College of Medicine, Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","unstructured":"World Health Organization . 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