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This study examined the association between adulthood SLEs and incident CVD and evaluated mediation by depression, physical inactivity, and smoking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed harmonized data from two nationally representative aging cohorts: the US Health and Retirement Study and the English Longitudinal Study of Ageing. SLEs were assessed at baseline, and incident CVD was physician-diagnosed. We used Cox and restricted mean survival time (RMST) regression to estimate hazard ratios (HRs) and RMST differences, set at the time point when 90% of incident CVD events had accrued (7.8 years). Population attributable fractions (PAFs) based on RMST and mediation analyses via RMST pseudo-value regression quantified contributions of SLEs and behavioral pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 18,898 participants without baseline cardiovascular disease (mean age 64.5 years; 39.8% male), 2,782 incident CVD cases were documented (incidence rate: 2.51 per 100 person-years). RMST analysis showed that any SLE exposure was related to significant reductions in event-free survival, including a 2.22-month decrease for CVD (95% CI: -2.90 to -1.53), a 1.57-month decrease for heart disease (95% CI: -2.16 to -0.99), and a 0.79-month decrease for stroke (95% CI: -1.16 to -0.41), with a clear dose-response relationship. Corresponding Cox proportional hazards models showed adjusted HRs of 1.20 (95% CI: 1.11\u20131.30) for CVD, 1.16 (95% CI: 1.07\u20131.27) for heart disease, and 1.26 (95% CI: 1.09\u20131.46) for stroke. Each additional SLE increased CVD, heart disease, and stroke risks by 11%, 10%, and 11%. PAFs attributable to SLEs exposure were 2.6% for CVD, 1.7% for heart disease, and 0.8% for stroke. Mediation analyses revealed that depression, physical inactivity, and current smoking accounted for 7.2%, 4.5%, and 4.5% of the total effect of SLEs on CVD, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Adulthood SLEs are independently associated with increased CVD risk, with depression, physical inactivity, and smoking explaining a modest proportion of this association.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12916-026-04890-0","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T02:45:38Z","timestamp":1776998738000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adulthood stressful life events as predictors of incident cardiovascular disease: insights from two prospective cohorts"],"prefix":"10.1186","volume":"24","author":[{"given":"Shuang","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyang","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghui","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory Y. 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The English Longitudinal Study of Ageing was approved by the London Multi-Centre Research Ethics Committee (MREC\/01\/2\/91), and all participants provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not available.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Clinical Trial"}},{"value":"Gregory Y. H. Lip \u2013 X: @LiverpoolCCS.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 social media handles"}},{"value":"The authors declare no competing interests.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"349"}}