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Association of Smoking Cessation With Subsequent Risk of Cardiovascular Disease

Educational Objective
To understand that the excess risk of cardiovascular disease attributable to smoking can persist for many years after smoking cessation.
1 Credit CME
Key Points

Question  Among heavy smokers (ie, ≥20 pack-years), what is the association between time since smoking cessation and subsequent risk of cardiovascular disease?

Findings  In this observational cohort study of 8770 participants, former heavy smokers’ risk of cardiovascular disease was significantly lower within 5 years of smoking cessation relative to current smokers (hazard ratio, 0.61) but remained significantly elevated for at least 5 to 10 years and possibly for 25 years after cessation relative to never smokers.

Meaning  Compared with never smokers, former heavy smokers may have significantly elevated cardiovascular disease risk beyond 5 years after cessation.


Importance  The time course of cardiovascular disease (CVD) risk after smoking cessation is unclear. Risk calculators consider former smokers to be at risk for only 5 years.

Objective  To evaluate the association between years since quitting smoking and incident CVD.

Design, Setting, and Participants  Retrospective analysis of prospectively collected data from Framingham Heart Study participants without baseline CVD (original cohort: attending their fourth examination in 1954-1958; offspring cohort: attending their first examination in 1971-1975) who were followed up through December 2015.

Exposures  Time-updated self-reported smoking status, years since quitting, and cumulative pack-years.

Main Outcomes and Measures  Incident CVD (myocardial infarction, stroke, heart failure, or cardiovascular death). Primary analyses included both cohorts (pooled) and were restricted to heavy ever smokers (≥20 pack-years).

Results  The study population included 8770 individuals (original cohort: n = 3805; offspring cohort: n = 4965) with a mean age of 42.2 (SD, 11.8) years and 45% male. There were 5308 ever smokers with a median 17.2 (interquartile range, 7-30) baseline pack-years, including 2371 heavy ever smokers (406 [17%] former and 1965 [83%] current). Over 26.4 median follow-up years, 2435 first CVD events occurred (original cohort: n = 1612 [n = 665 among heavy smokers]; offspring cohort: n = 823 [n = 430 among heavy smokers]). In the pooled cohort, compared with current smoking, quitting within 5 years was associated with significantly lower rates of incident CVD (incidence rates per 1000 person-years: current smoking, 11.56 [95% CI, 10.30-12.98]; quitting within 5 years, 6.94 [95% CI, 5.61-8.59]; difference, −4.51 [95% CI, −5.90 to −2.77]) and lower risk of incident CVD (hazard ratio, 0.61; 95% CI, 0.49-0.76). Compared with never smoking, quitting smoking ceased to be significantly associated with greater CVD risk between 10 and 15 years after cessation in the pooled cohort (incidence rates per 1000 person-years: never smoking, 5.09 [95% CI, 4.52-5.74]; quitting within 10 to <15 years, 6.31 [95% CI, 4.93-8.09]; difference, 1.27 [95% CI, −0.10 to 3.05]; hazard ratio, 1.25 [95% CI, 0.98-1.60]).

Conclusions and Relevance  Among heavy smokers, smoking cessation was associated with significantly lower risk of CVD within 5 years relative to current smokers. However, relative to never smokers, former smokers’ CVD risk remained significantly elevated beyond 5 years after smoking cessation.

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Article Information

Corresponding Author: Meredith S. Duncan, MA, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, 2525 West End Ave, Ste 300-A, Nashville, TN 37203 (meredith.s.duncan@vumc.org).

Author Contributions: Ms Duncan and Dr Tindle had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Duncan, Freiberg, Greevy, Vasan, Tindle.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Duncan, Freiberg, Vasan, Tindle.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Duncan, Freiberg, Greevy, Kundu.

Obtained funding: Vasan, Tindle.

Administrative, technical, or material support: Vasan, Tindle.

Supervision: Freiberg, Greevy, Vasan, Tindle.

Conflict of Interest Disclosures: Dr Tindle reported providing input on design for a phase 3 trial of cytisine proposed by Achieve Life Sciences and being a principal investigator of National Institutes of Health–sponsored studies for smoking cessation that include medications donated by the manufacturers. No other disclosures were reported.

Funding/Support: Dr Freiberg is supported by the Dorothy and Laurence Grossman Chair in Cardiology. Dr Vasan is supported in part by the Evans Medical Foundation and the Jay and Louis Coffman Endowment from the Department of Medicine, Boston University School of Medicine. Dr Tindle is supported by the William Anderson Spickard Jr Chair in Medicine and the National Cancer Institute Moonshot Initiative (grant 3P30CA068485-22S3). The FHS received the support of contracts NO1-HC-25195, HHSN268201500001I, and 75N92019D00031 from the National Heart, Lung, and Blood Institute for this research.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Additional Contributions: We acknowledge the dedication of the FHS study participants and staff, without whom this research would not be possible.

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