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Comparative Study
. 2019 Aug 20;322(7):642-650.
doi: 10.1001/jama.2019.10298.

Association of Smoking Cessation With Subsequent Risk of Cardiovascular Disease

Free PMC article
Comparative Study

Association of Smoking Cessation With Subsequent Risk of Cardiovascular Disease

Meredith S Duncan et al. JAMA. .
Free PMC article


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.

Conflict of interest statement

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.


Figure 1.
Figure 1.. Sample Derivation
CVD indicates cardiovascular disease; FHS, Framingham Heart Study. aTwo participants in the FHS offspring cohort were ineligible for sample inclusion because their last follow-up date was equal to their examination 1 date. bPrevalent CVD defined as definite myocardial infarction, stroke (excluding transient ischemic attack), and heart failure. cIncludes individuals who at baseline reported being a never smoker but with a greater than 0 pack-year history, had an age at quitting smoking that was older than their baseline age, or were completely missing smoking data. dTo accurately calculate cumulative pack-years of smoking during the follow-up period, a reliable measure of smoking history at baseline was essential. Individuals excluded were missing pack-years of smoking at baseline because of inability to report age at starting/stopping smoking and/or intensity of smoking (cigarettes per day) prior to baseline. eOriginal cohort participants were seen approximately every 2 years. After 5 years without an update (effectively 1 missed examination plus an additional year), individuals were censored to avoid carrying values forward for an extended period without reassessment. Similarly, offspring participants were seen approximately every 4 years and were thus censored after 9 years without an update (also corresponding to a single missed examination plus an additional year).
Figure 2.
Figure 2.. Risk of Incident CVD in Heavy Ever and Never Smokers
Plotted data are limited to never smokers and heavy ever smokers with at least 20 cumulative pack-years and are adjusted for age, sex, education, examination decade, systolic blood pressure, antihypertensive medication use, diabetes mellitus, body mass index, total cholesterol, and alcohol consumption. Dynamic variables are updated. Splines have 5 knots at 1, 4, 9, 15, and 22 years since quitting. Data from 3274 participants over 23 437 person-examinations contributed to the comparison of former vs current smokers in both panels. Shaded areas indicate 95% CIs. Panel A includes current smokers at years since quitting = 0 in the comparison of cardiovascular disease (CVD) risk among former smokers vs never smokers and contains data from 6720 individuals over 52 526 person-examinations. This anchors the hazard ratio at years since quitting = 0 to capture the steep decline in the first 4 years since quitting but creates some instability in the hazard ratio estimate around 4 years since quitting. Panel B excludes current smokers at years since quitting = 0 from the comparison of CVD risk among former smokers vs never smokers and contains data from 5190 individuals over 38 641 person-examinations. This plot cannot reflect the steep decline in the hazard ratio over the first 4 years but provides a more stable estimate of years since quitting.

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