{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:59:34Z","timestamp":1790189974041,"version":"4.1.0"},"reference-count":78,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"37","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,9,12]]},"abstract":"<jats:p>\n                    Observational evidence suggests that subjective well-being (SWB) is inversely associated with cardiovascular (CV) events, yet whether this link is causal and through which pathways remains unclear. To test this, we performed a two-sample bidirectional Mendelian randomization (MR) analysis using genetic instruments for SWB (N\u2005=\u20052370,390) and major adverse cardiovascular events (MACE; N\u2005=\u2005500,348). All the data were from the largest available genome-wide association studies in populations of European descent. In univariable MR, each 1-standard-deviation increase in genetically predicted SWB reduced the odds of MACE by 39% (odds ratio\u2005=\u20050.61; 95% confidence interval, 0.50\u20130.74;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2005=\u20055.82\u2005\u00d7\u200510\u207b\u2077). This association remained after multivariable MR adjustment for general medical conditions \u2013 Alzheimer disease, hypothyroidism, hyperthyroidism, multiple sclerosis, Addison disease, Cushing syndrome, Parkinson disease, systemic lupus erythematosus, and epilepsy \u2013 which often co-occur with mood symptoms and may also influence CV risk. Two-step MR analysis identified 3 out of 46 candidates as mediators between SWB and MACE: body mass index, diastolic blood pressure and triglycerides, accounting for 13.97% (95% confidence interval, 6.34%\u201321.60%), 6.05% (95% confidence interval, 0.00%\u201312.10%) and 10.53% (95% confidence interval, 4.45%\u201316.60%) of the total effect of SWB on MACE, respectively. Sensitivity analyses were directionally consistent, whereas MR-Egger did not reach statistical significance. Taken together, these results suggest that higher SWB may be associated with a lower risk of CV events, partly through metabolic and hemodynamic pathways. Targeting SWB may therefore complement conventional risk-factor management in CV prevention.\n                  <\/jats:p>","DOI":"10.1097\/md.0000000000044482","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T21:02:53Z","timestamp":1757970173000},"page":"e44482","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Genetic association and potential mediators between subjective well-being and cardiovascular events: A bidirectional two-sample, two-step Mendelian randomization study"],"prefix":"10.1097","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8807-9523","authenticated-orcid":false,"given":"Rui","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Cardiology, German Heart Center, TUM University Hospital, TUM School of Medicine and Health, Technical University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Lyu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Fifth People\u2032s Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Fifth People\u2032s Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Fifth People\u2032s Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6538-1113","authenticated-orcid":false,"given":"Yingjia","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, National Clinical Research Center for Aging and 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