smoking cessation and persistent cardiovasc risk

smoking cessation and persistent cardiovasc risk

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You forwarded this message on Fri 9/13/2019 6:36 AM

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Geoff A. Modest, M.D.

Thu 9/12/2019 8:08 AM

• Geoff A. Modest, M.D.

A retrospective analysis of prospectively collected data from the Framingham Heart Study and the Offspring Cohort found that the risk for cardiovascular events continued for 10-15 years after smoking cessation (see cad smoking cessation framstudy jama2019 in dropbox or doi:10.1001/jama.2019.10298)

Details:

-- Framingham Heart Study participants: no baseline CVD, attending the 4th examination in 1954-58, n= 3805

-- Framingham Offspring Cohort: attending their 1st examination in 1971-75, followed until 2016, n= 4965

-- pooled cohort population was 8770 individuals, mean age 42, 45% male, 25% less than high school graduates/32% high school graduates/43% more, blood pressure 127/81 mmHg, hypertension 27%, diabetes 2%, BMI 25, current drinker 78%, current smoker 47%/former 14%/never 40%, median 20 cigarettes per day in current smokers, median years since quitting smoking 6

    -- 5308 ever-smokers with a median of 17 baseline pack years of cigarettes, including 2371 heavy smokers (17% were former smokers and 83% current smokers)

-- smoking assessments were done at baseline and at subsequent cycles every 2 to 4 years

-- of the 4115 current smokers in the combined cohort at baseline, 1589 (39%) quit and never relapsed, while 2117 (51%) continue to smoke; 85% of baseline former smokers remained abstinent during follow-up

-- main outcome: incident CVD (MI, stroke, heart failure, and cardiovascular death). Primary analysis pooled both cohorts, restricted to heavy ever-smokers (> 20 pack-years)

Results:

-- 1st CVD events among heavy smokers: 2435, over 26.4 median follow-up years, 1612 in the original cohort (665 among heavy smokers), 823 in the offspring cohort (430 in heavy smokers)

-- compared with current smokers, by multivariable adjusted risk:

    -- quitting within 5 years was associated with significantly lower rates of incident CVD (incidence rates per 1000 person-years): current smokers: 11.56 (10.30-12.98); quitting within 5 years: 6.94 (5.61-8.59), and essentially the same at 5-10 years

        -- difference of -4.51 (-5.90  to -2.77), 39% lower incident CVD events, HR 0.61 (0.49-0.76)

        -- the graph of the risk of CVD comparing former smokers (but excluding current smokers) vs never-smokers showed a very steep decline starting almost immediately until 5 years, a slight increase over the next  5 years, then a more gradual decrease until the 25 year mark, though this risk was only statistically significant until 10-15 years after secession

    -- compared with never smoking, quitting smoking was not significantly associated with greater CVD risk between 10 and 15 years after cessation, incidence rates per 1000 person-years never smoking 5.09 (4.52-5.74); quitting within 10 to 15 years 6.31 (4.93-8.09), and no statistically significant difference at the 15-25 year mark

        -- difference of 1.27 (-0.10 to 3.05), HR 1.25 (0.98-1.60), not statistically significant

        -- the graph of the risk of former heavy smokers (but excluding current smokers) vs never smokers showed a very gradual decline over the 25 years

--in looking at the 2 cohorts individually: the more recent Offspring Cohort had a persistent increased CVD risk extending to the 15-25 year post-cessation time period

Commentary:

-- cigarette smoking is responsible for 20% of CVD deaths in the United States

-- though smoking cessation decreases CVD risk, there’s wide variability in the estimates of that time-course. And, some clinical CVD risk calculators do not differentiate between former and never smokers. The new  ASCVD Risk Estimator Plus considers the risk of smoking cessation after 5 years to be equivalent to that of never-smokers

-- the Framingham data above revealed a quite dramatic 45% decrease in CVD risk in the 1st 5 years, with about a 30% decrease in the 1st 2 years.

--several older studies have suggested that the effects of cigarette smoking on cardiovascular disease is somewhat complex, with a major decrease within the 1st 1-2 years: part of the issue may be related to the effects of cigarettes on prothrombotic/ inflammatory markers, including fibrinogen levels; part perhaps related to a potentially direct atherosclerotic effect.

    -- Fibrinogen:

        --fibrinogen levels increase dramatically with cigarette smoking and slowly returned to normal levels within 2-5 years. A report from the Framingham study in 1987 noted an increase in cardiovascular disease correlating with progressively increased fibrinogen values (see Kannel WB. Am Heart J 1987; 113(4): 1006)

        --other inflammatory markers are also increased, including tissue plasminogen activator, increased platelet aggregation, increased expression of tissue factor, CRP levels, WBC counts. Also there are associated changes in other cardiovascular risk factors, including increases in  blood pressure and lipids as well as increases in vascular resistance (some of these are related to increases in sympathetic activity)

        --one finding consistent with a role of these thrombotic factors is that there is a larger thrombus component in those with acute coronary syndromes that are more susceptible to fibrinolytic therapy, so that smokers develop higher patency rates

    --atherosclerosis:

        --there are several potentially direct effects between smoking and developing atherosclerosis itself, including as mediated by changes in lipids and blood pressure noted above, also by oxidative stress, platelet-derived growth factors, vascular smooth muscle cell proliferation, and other direct effects on cells involved in plaque formation (see cad smoking pathogenesis athero2011 in dropbox, or or doi:10.1016/j.atherosclerosis.2011.01.003 )

    --the point here is that the effect of smoking cessation, even from 30 year old studies, is that there seems to be a rapid decrease in CVD events associated with smoking cessation (perhaps attributed to the more rapid changes in prothrombotic factors associated with smoking), and then a more gradual decrease over longer time (perhaps associated with stabilization/improvement in atherosclerosis itself).  One added factor in the past few decades is the role of inflammation and oxidative stress, also increased in smoking

--the differences found between the original Framingham Study and the Offspring Study may well be attributed to some secular changes in overall risk factors over the time period (people ate differently in the 2 time periods, likely exercised differently, and likely other differences not accounted for in their modeling

--the increase in CVD events in those stopping smoking after 10 years may be artefactual: it still was within the 95% confidence intervals. But were there other changes which might have played a part?  Did people gain weight or eat/exercise differently many years after stopping smoking?

--limitations of study: self-reported smoking and numbers of cigarettes (though at least they asked the same questions and had in-person reporting on a regular basis); were there unaccounted for other differences over time (this did have data over more than ¼ of a century. And lots change in that time period); this was not an RCT intervention study, so there may have been unaccounted for confounders/differences in those who smoked and didn’t; and the population was from a mostly white and somewhat insular community (so are the results generalizable?)

So, the importance of this study:

--there clearly are lingering increased risks of CVD events in those who quit smoking, and it may be as long as 25 years later (per the Offspring Cohort)

--more and more people are quitting smoking, meaning that the current cohort of quitters is growing relative to current smokers

--and, our risk calculators do not include any assessment of this continued increased risk: ie, they are underestimating the actual persistent CVD risk

--so, we clinicians and patients should understand that for those quitting smoking, there may well be a higher risk than we had considered, and that we should perhaps be more aggressive in encouraging healthy lifestyle changes and in resorting to more aggressive lipid med treatment.  that being said, patients should also realize that there are really huge cardioprotective effects of smoking cessation that occur quite rapidly after quitting

geoff​

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