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Relative risks (RRs) for cardiovascular disease (CVD) by smoking rate exhibit a concave pattern, with RRs in low rate smokers exceeding a linear extrapolation from higher rate smokers. However, cigarettes/day does not by itself fully characterize smoking-related risks. A reexamination of the concave pattern using a comprehensive representation of smoking may enhance insights.Data were from the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort enrolled in four areas of the US in 1987-1989. Follow-up was through 2008. Analyses included 14,233 participants, 245,915 person-years, and 3,411 CVD events.The concave RRs with cigarettes/day were consistent with cigarettes/day modifying a linear RR association of pack-years with CVD (i.e., strength of the pack-years association depended on cigarettes/day, indicating that the manner of pack-years accrual impacted risk). Smoking fewer cigarettes/day for longer duration was more deleterious than smoking more cigarettes/day for shorter duration (P < 0.01). For 50 pack-years (365,000 cigarettes), estimated RRs of CVD were 2.1 for accrual at 20 cigarettes/day and 1.6 for accrual at 50 cigarettes/day. Years since smoking cessation did not alter the diminishing strength of association with increasing cigarettes/day. Analyses that accounted for competing risks did not affect findings.Pack-years remained the primary determinant of smoking-related CVD risk; however, accrual influenced RRs. For equal pack-years, smoking fewer cigarettes/day for longer duration was more deleterious than smoking more cigarettes/day for shorter duration. This observation provides clues to better understanding the biological mechanisms, and reinforces the importance of cessation rather than smoking less to reduce CVD risk.


Journal article


Epidemiology (Cambridge, Mass.)

Publication Date





395 - 404


From the aScientist Emeritus, Biostatistics Branch, Division of Cancer Epidemiology and Genetics, US National Cancer Institute, National Institutes of Health, Bethesda, MD; bClinical Professor and Deputy Director, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC; cAssistant Professor, Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN; dProfessor of Biostatistics, The George Institute for Global Health, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; eThe George Institute for Global Health, University of Sydney, Sydney, NSW, Australia; fDepartment of Epidemiology, Johns Hopkins University, Baltimore, MD; gProfessor, Department of Public Health, Fujita Health University School of Medicine Toyoake Aichi, Japan; and hProfessor, School of Public Health, Curtin University, Perth, Australia.