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Study of Adult Men, leisure time physical activity was self-reported at Ages 50, 60, and 70. At Age 70, 720 plasma proteins were analysed in 782 participants with up to 19.3 years of follow-up for MI and 26.3 years follow-up for mortality. In the nested case-cohort study Markers of Imminent Myocardial Infarction, plasma proteins were measured in disease-free individuals from six European cohorts. Cases (n = 420) were those with acute MI within 6 months of a blood draw, with up to four cohort representatives per case (n = 1598). A higher level of leisure time physical activity level was inversely associated with 12 plasma proteins after adjusting for age, education, smoking, and established cardiovascular risk factors (Bonferroni-corrected P &amp;lt; 0.000069). Of these 12 proteins, interleukin-6 was associated with increased incidence of imminent MI [hazard ratio, HR 1.22; 95% confidence interval, CI (1.09\u20131.37)], tumour necrosis factor receptor superfamily member 11A was associated with increased long-term MI incidence [HR 1.22 (1.01\u20131.48)] and 11 proteins were associated with increased mortality [HR 1.14\u20131.30 (1.01\u20131.42)].<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings confirm and extend our understanding of how physical activity could assert its beneficial effect on cardiovascular health through proteins involved with modulating inflammatory, immune, and metabolic pathways. Further research is needed to explore the causal mechanisms behind these associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Lay summary<\/jats:title>\n                    <jats:p>In this study, we aimed to investigate (i) whether leisure time physical activity level cumulated over 20 years is associated with 720 plasma proteins and (ii) if proteins that are significantly associated with leisure time physical activity level across 20 years in Part 1 are also associated with imminent and long-term risk of myocardial infarction (MI) and mortality.Higher physical activity level over 20 years was inversely associated with 12 plasma proteins involved in inflammatory, immune, and metabolic processes. Several plasma proteins were in turn associated with MI and mortality.Findings confirm and extend our understanding how physical activity could assert its beneficial effect on cardiovascular health via the circulating plasma proteins.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwag016","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T12:28:31Z","timestamp":1767702511000},"page":"2286-2297","source":"Crossref","is-referenced-by-count":1,"title":["The proteomic profile of leisure time physical activity across two decades: implications for future cardiovascular risk and mortality"],"prefix":"10.1093","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8416-703X","authenticated-orcid":false,"given":"Malin","family":"Enarsson","sequence":"first","affiliation":[{"name":"Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institute , Alfred Nobels All\u00e9 23, Stockholm SE 14183 ,","place":["Sweden"]},{"name":"Center for Clinical Research Dalarna , Nissers vag 3, Falun 79182 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5894-0351","authenticated-orcid":false,"given":"Stefan","family":"Gustafsson","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Clinical Epidemiology, Uppsala University , Uppsala ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3268-8810","authenticated-orcid":false,"given":"Erik","family":"Lampa","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Clinical Epidemiology, Uppsala University , Uppsala ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Rudholm Feldreich","sequence":"additional","affiliation":[{"name":"School of Health and Social Studies, Dalarna University , Falun ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3903-9941","authenticated-orcid":false,"given":"Sara","family":"Beigrezaei","sequence":"additional","affiliation":[{"name":"Department of Global Public Health and Bioethics, Julius Centre for Health Sciences and Primary Care, University Medical Centre (UMC) Utrecht , Utrecht ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6915-9015","authenticated-orcid":false,"given":"Adam S","family":"Butterworth","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, British Heart Foundation Cardiovascular Epidemiology Unit, University of Cambridge , Cambridge ,","place":["UK"]},{"name":"Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge , Cambridge ,","place":["UK"]},{"name":"British Heart Foundation Centre of Research Excellence, University of Cambridge , Cambridge ,","place":["UK"]},{"name":"National Institute for Health and Care Research Blood and Transplant Research Unit in Donor Health and Behaviour, University of Cambridge , Cambridge ,","place":["UK"]},{"name":"Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge , Cambridge ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7153-5414","authenticated-orcid":false,"given":"S\u00f6lve","family":"Elmst\u00e5hl","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Lund University , Malm\u00f6 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8618-9152","authenticated-orcid":false,"given":"Gunnar","family":"Engstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Lund University , Malm\u00f6 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8157-9744","authenticated-orcid":false,"given":"Kristian","family":"Hveem","sequence":"additional","affiliation":[{"name":"K.G. 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