{"doi":"10.1371/journal.pmed.1004561","title":"Association between cigarette smoking status, intensity, and cessation duration with long-term incidence of nine cardiovascular and mortality outcomes: The Cross-Cohort Collaboration (CCC)","abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background</jats:title>\n                    <jats:p>Uncertainties persist regarding the precise shape of the smoking-outcome curves across various cardiovascular and mortality endpoints. This study aims to elucidate the relationships among smoking burden, intensity, and cessation duration across multiple cardiovascular outcomes.</jats:p>\n                  </jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings</jats:title>\n                    <jats:p>\n                      Cox proportional hazard models were constructed to evaluate the association between pack-years, cigarettes per day (CPD), and years since cessation with cardiovascular outcomes in participants from 22 prospective cohort studies within the Cross-Cohort Collaboration Tobacco Working Group. We evaluated myocardial infarction (MI), stroke, coronary heart disease (CHD; MI, coronary revascularization, or coronary death), cardiovascular disease (CVD; stroke or cardiovascular death), heart failure (HF), atrial fibrillation (AFib), CHD mortality, CVD mortality, and all-cause mortality. Median follow-up varied across outcomes, with 14.4 years for MI (17,570 events), 19.3 years for CHD (30,625 events), 18.6 years for CVD (54,078 events), and approximately 19.4–19.9 years for mortality outcomes (CHD mortality: 17,429 events; CVD mortality: 33,120 events; all-cause mortality: 125,044 events). Spline terms were used to investigate the nonlinear association of continuous smoking/cessation measures with the examined outcomes. Models were adjusted for demographic, socioeconomic, and other cardiovascular risk factors. The study included 323,826 adults (148,635 non-mortality and 176,396 mortality outcomes with 25 and 16 million person-years at risk, respectively). Compared to never-smokers, current smokers had significantly increased risks for CVD (hazard ratio (HR) 1.74, 95% confidence intervals (CIs) [1.66,1.83] in men; HR 2.07, 95% CI [2.00,2.14] in women) and all-cause mortality (HR 2.17, 95% CI [2.09,2.25] in men; HR 2.43, 95% CI [2.38,2.48] in women; all\n                      <jats:italic>p</jats:italic>\n                       &lt; 0.001). Compared with never-smokers, participants with 2–5 CPD demonstrated substantially elevated cardiovascular risks, with HR ranging from 1.26 (95% CI [1.09,1.45],\n                      <jats:italic>p</jats:italic>\n                       = 0.002) for AFib to 1.57 (95% CI [1.39,1.78],\n                      <jats:italic>p</jats:italic>\n                       &lt; 0.001) for HF. Smoking 2–5 CPD was associated with increased CVD mortality (HR 1.57, 95% CI [1.41,1.75]), and all-cause mortality (HR 1.60, 95% CI [1.52,1.69]; both\n                      <jats:italic>p</jats:italic>\n                       &lt; 0.001). Smoking 11–15 CPD conferred a higher risk of CVD (HR 1.87, 95% CI [1.69,2.06]) and all-cause mortality (HR 2.30, 95% CI [2.14,2.47]; both\n                      <jats:italic>p</jats:italic>\n                       &lt; 0.001). The increased risk associated with the evaluated outcomes was steeper for the initial 20 pack-years and 20 CPD, respectively, compared to further smoking exposure. The most substantial reduction in risk across all outcomes was observed within the first 10 years after smoking cessation. However, the progressive risk reduction continues over extended time periods, with former smokers demonstrating over 80% lower relative risk than those of current smokers within 20 years of cessation. Limitations include potential exposure misclassification due to reliance on single baseline self-reported smoking measurements with extended follow-up periods, which may underestimate true risk associations, and lack of data on other tobacco products and electronic nicotine delivery systems, preventing analysis of dual- and poly-use patterns.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusion</jats:title>\n                    <jats:p>Lower-intensity smoking is associated with cardiovascular risk and the primary public health message for current smokers should be early cessation, rather than reducing the amount of smoking. Cessation provides substantial immediate risk reduction, although risk continues to decrease significantly for the following two decades.</jats:p>\n                  </jats:sec>","journal":"PLOS Medicine","year":2025,"id":628593,"datarank":0.40620753016533157,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.0,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":71972,"name":"Zhiqi Yao","orcid":"0009-0007-7803-4357","position":1,"is_corresponding":false},{"id":284561,"name":"Zeina Dardari","orcid":"0000-0001-6026-3329","position":2,"is_corresponding":false},{"id":892879,"name":"Kunal Jha","orcid":"0000-0002-3166-9335","position":3,"is_corresponding":false},{"id":667959,"name":"Ngozi Osuji","orcid":"0000-0002-4772-8213","position":4,"is_corresponding":false},{"id":1322285,"name":"Tanuja Rajan","orcid":"0000-0003-3419-3560","position":5,"is_corresponding":false},{"id":653012,"name":"Ellen Boakye","orcid":"0000-0002-7625-9487","position":6,"is_corresponding":false},{"id":22652,"name":"Kunihiro Matsushita","orcid":"0000-0002-7179-718X","position":7,"is_corresponding":false},{"id":264194,"name":"Eleanor M. Simonsick","orcid":"0000-0002-5460-3494","position":8,"is_corresponding":false},{"id":1627533,"name":"Joao A. C. Lima","orcid":null,"position":9,"is_corresponding":false},{"id":73086,"name":"Donald M. Lloyd-Jones","orcid":null,"position":10,"is_corresponding":false},{"id":283063,"name":"Debbie L. Cohen","orcid":"0000-0002-1325-315X","position":11,"is_corresponding":false},{"id":277163,"name":"Lawrence J. Appel","orcid":"0000-0002-0673-6823","position":12,"is_corresponding":false},{"id":30754,"name":"Amit Khera","orcid":null,"position":13,"is_corresponding":false},{"id":24967,"name":"Michael E. Hall","orcid":"0000-0002-5733-1025","position":14,"is_corresponding":false},{"id":74988,"name":"Carlos J. Rodriguez","orcid":null,"position":15,"is_corresponding":false},{"id":74972,"name":"Suzanne E. Judd","orcid":"0000-0001-7594-6587","position":16,"is_corresponding":false},{"id":246476,"name":"Shelley A. Cole","orcid":"0000-0002-2651-0127","position":17,"is_corresponding":false},{"id":24661,"name":"Ramachandran S. Vasan","orcid":"0000-0001-7357-5970","position":18,"is_corresponding":false},{"id":1034,"name":"Emelia J. Benjamin","orcid":"0000-0003-4076-2336","position":19,"is_corresponding":false},{"id":22638,"name":"Paulo A. Lotufo","orcid":"0000-0002-4856-8450","position":20,"is_corresponding":false},{"id":98936,"name":"Márcio Sommer Bittencourt","orcid":"0000-0002-3711-1754","position":21,"is_corresponding":false},{"id":309258,"name":"Samar R. El Khoudary","orcid":"0000-0003-2913-0821","position":22,"is_corresponding":false},{"id":341542,"name":"Rebecca C. Thurston","orcid":"0000-0001-6580-1202","position":23,"is_corresponding":false},{"id":388827,"name":"Carol A. Derby","orcid":"0000-0002-5657-4519","position":24,"is_corresponding":false},{"id":17625,"name":"Bruce M. Psaty","orcid":"0000-0002-7278-2190","position":25,"is_corresponding":false},{"id":133659,"name":"Charles B. Eaton","orcid":null,"position":26,"is_corresponding":false},{"id":61604,"name":"Michael J. Lamonte","orcid":"0000-0002-6669-5242","position":27,"is_corresponding":false},{"id":109435,"name":"Peggy M. Cawthon","orcid":"0000-0003-4938-9478","position":28,"is_corresponding":false},{"id":1627535,"name":"Eric S. Orwoll","orcid":null,"position":29,"is_corresponding":false},{"id":355675,"name":"Aruni Bhatnagar","orcid":"0000-0001-6818-0384","position":30,"is_corresponding":false},{"id":456720,"name":"Andrew P. DeFilippis","orcid":"0000-0002-5135-9748","position":31,"is_corresponding":false},{"id":71977,"name":"Michael J. Blaha","orcid":"0000-0001-5138-9683","position":32,"is_corresponding":false},{"id":1020091,"name":"Erfan Tasdighi","orcid":"0000-0003-2146-7083","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Association between cigarette smoking status, intensity, and cessation duration with long-term incidence of nine cardiovascular and mortality outcomes: The Cross-Cohort Collaboration (CCC)","abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background</jats:title>\n                    <jats:p>Uncertainties persist regarding the precise shape of the smoking-outcome curves across various cardiovascular and mortality endpoints. This study aims to elucidate the relationships among smoking burden, intensity, and cessation duration across multiple cardiovascular outcomes.</jats:p>\n                  </jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings</jats:title>\n                    <jats:p>\n                      Cox proportional hazard models were constructed to evaluate the association between pack-years, cigarettes per day (CPD), and years since cessation with cardiovascular outcomes in participants from 22 prospective cohort studies within the Cross-Cohort Collaboration Tobacco Working Group. We evaluated myocardial infarction (MI), stroke, coronary heart disease (CHD; MI, coronary revascularization, or coronary death), cardiovascular disease (CVD; stroke or cardiovascular death), heart failure (HF), atrial fibrillation (AFib), CHD mortality, CVD mortality, and all-cause mortality. Median follow-up varied across outcomes, with 14.4 years for MI (17,570 events), 19.3 years for CHD (30,625 events), 18.6 years for CVD (54,078 events), and approximately 19.4–19.9 years for mortality outcomes (CHD mortality: 17,429 events; CVD mortality: 33,120 events; all-cause mortality: 125,044 events). Spline terms were used to investigate the nonlinear association of continuous smoking/cessation measures with the examined outcomes. Models were adjusted for demographic, socioeconomic, and other cardiovascular risk factors. The study included 323,826 adults (148,635 non-mortality and 176,396 mortality outcomes with 25 and 16 million person-years at risk, respectively). Compared to never-smokers, current smokers had significantly increased risks for CVD (hazard ratio (HR) 1.74, 95% confidence intervals (CIs) [1.66,1.83] in men; HR 2.07, 95% CI [2.00,2.14] in women) and all-cause mortality (HR 2.17, 95% CI [2.09,2.25] in men; HR 2.43, 95% CI [2.38,2.48] in women; all\n                      <jats:italic>p</jats:italic>\n                       &lt; 0.001). Compared with never-smokers, participants with 2–5 CPD demonstrated substantially elevated cardiovascular risks, with HR ranging from 1.26 (95% CI [1.09,1.45],\n                      <jats:italic>p</jats:italic>\n                       = 0.002) for AFib to 1.57 (95% CI [1.39,1.78],\n                      <jats:italic>p</jats:italic>\n                       &lt; 0.001) for HF. Smoking 2–5 CPD was associated with increased CVD mortality (HR 1.57, 95% CI [1.41,1.75]), and all-cause mortality (HR 1.60, 95% CI [1.52,1.69]; both\n                      <jats:italic>p</jats:italic>\n                       &lt; 0.001). Smoking 11–15 CPD conferred a higher risk of CVD (HR 1.87, 95% CI [1.69,2.06]) and all-cause mortality (HR 2.30, 95% CI [2.14,2.47]; both\n                      <jats:italic>p</jats:italic>\n                       &lt; 0.001). The increased risk associated with the evaluated outcomes was steeper for the initial 20 pack-years and 20 CPD, respectively, compared to further smoking exposure. The most substantial reduction in risk across all outcomes was observed within the first 10 years after smoking cessation. However, the progressive risk reduction continues over extended time periods, with former smokers demonstrating over 80% lower relative risk than those of current smokers within 20 years of cessation. Limitations include potential exposure misclassification due to reliance on single baseline self-reported smoking measurements with extended follow-up periods, which may underestimate true risk associations, and lack of data on other tobacco products and electronic nicotine delivery systems, preventing analysis of dual- and poly-use patterns.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusion</jats:title>\n                    <jats:p>Lower-intensity smoking is associated with cardiovascular risk and the primary public health message for current smokers should be early cessation, rather than reducing the amount of smoking. Cessation provides substantial immediate risk reduction, although risk continues to decrease significantly for the following two decades.</jats:p>\n                  </jats:sec>","is_dataset_classified":null,"base_score":2.639057329615259,"endowment":2.639057329615259,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41252354","pmcid":"PMC12626310","openalex_id":"https://openalex.org/W4416323391","authors":[],"funders":[{"funder_name":"National Heart, Lung, and Blood Institute","grant_id":"U54HL120163","title":null},{"funder_name":"NIH","grant_id":"T32 HL007227","title":null},{"funder_name":"NIH","grant_id":"1K01HL154130","title":null},{"funder_name":"American Heart Association","grant_id":"AF AHA_18SFRN34110082 and 2U54HL120163","title":null},{"funder_name":"Framingham Heart Study","grant_id":"NIH 75N92019D00031","title":null},{"funder_name":"NIH","grant_id":"2U54HL120163","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92019D00027","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92020D00007","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201500003C","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201700004C","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201700005C","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"N01 HC095160","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"N01 HC095162","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"N01 HC095165","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"N01 HC095167","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"P20 GM109036","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG027576","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL109301","title":null},{"funder_name":"NIA NIH HHS","grant_id":"U01 AG017719","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL041642","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"UL1 RR024131","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92020D00004","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92023D00004","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201200036C","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201700001C","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201800012I","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"N01 HC095163","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG005394","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"R01 AR035582","title":null},{"funder_name":"NIA NIH HHS","grant_id":"U01 AG012495","title":null},{"funder_name":"NIA NIH HHS","grant_id":"U01 AG012539","title":null},{"funder_name":"NIA NIH HHS","grant_id":"U01 AG012554","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"U01 DK060984","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"U01 DK061022","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"U01 DK061028","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL065521","title":null},{"funder_name":"NINR NIH HHS","grant_id":"U01 NR004061","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"U01 NS041588","title":null},{"funder_name":"NCATS NIH HHS","grant_id":"UL1 TR001105","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92020D00006","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92021D00006","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201700002I","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201700004I","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201800011I","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"N01 HC025195","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"N01 HC095169","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG007181","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK119199","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL091357","title":null},{"funder_name":"NICHD NIH HHS","grant_id":"R03 HD102403","title":null},{"funder_name":"NIA NIH HHS","grant_id":"U01 AG012546","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"U01 DK061021","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL041652","title":null},{"funder_name":"NIA NIH HHS","grant_id":"U19 AG063720","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92020D00003","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201500001C","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201500003I","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201600003C","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201600004C","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"K01 HL154130","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"N01 HC085081","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK031801","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL109315","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"U01 DK060963","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL041654","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92019D00029","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92019D00030","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92020D00002","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92020D00005","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201600001C","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201700002C","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201800001C","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201800010I","title":null},{"funder_name":"NIMHD NIH HHS","grant_id":"HHSN268201800013I","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"N01 HC055222","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"N01 HC085079","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"N01 HC085080","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"N01 HC095159","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"N01 HC095166","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"N01 HC095168","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG005407","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG023629","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG027574","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL109284","title":null},{"funder_name":"NIA NIH HHS","grant_id":"U01 AG012531","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL084756","title":null},{"funder_name":"NCATS NIH HHS","grant_id":"UL1 TR000003","title":null},{"funder_name":"NCATS NIH HHS","grant_id":"UL1 TR000040","title":null},{"funder_name":"NCATS NIH HHS","grant_id":"UL1 TR000433","title":null},{"funder_name":"NCATS NIH HHS","grant_id":"UL1 TR001420","title":null},{"funder_name":"NCATS NIH HHS","grant_id":"UL1 TR002369","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92020D00001","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92023D00003","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92023D00005","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92023D00006","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201800014I","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"M01 RR016500","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"N01 HC085083","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"N01 HC095161","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK072488","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG028507","title":null},{"funder_name":"NIA NIH HHS","grant_id":"U01 AG012505","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"U01 DK060990","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL065520","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"U01 HL130114","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"UL1 RR029879","title":null},{"funder_name":"NCATS NIH HHS","grant_id":"UL1 TR001079","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92019D00028","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92019D00031","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"75N92023D00002","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268200800007C","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201600002C","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HHSN268201600018C","title":null},{"funder_name":"NHLBI NIH 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