CVD Risk for Ex-Smokers May Linger a Decade or More

Pauline Anderson

August 20, 2019

The risk of cardiovascular disease (CVD) for former smokers doesn't reach that of people who have never smoked until up to 15 years after quitting, new research has demonstrated.

"The conventional wisdom is that the risk goes away within 5 years," lead author Meredith S. Duncan, MA, database administrator, division of cardiovascular medicine, and a PhD candidate, department of epidemiology, Vanderbilt University, Nashville, Tennessee, told | Medscape Cardiology.

Meredith Duncan

"It's really important to keep in mind that patients who are former heavy smokers may still be at increased risk for CVD based on these new findings, so physicians may want to help guide these patients on other lifestyle modifications," Duncan said.

The study was published online today in the Journal of the American Medical Association (JAMA).

Studies have shown widely varying times for CVD risks in former smokers to match the level of people who have never smoked. Estimates vary from as little as 2 years to as many as 20 years.

Duncan noted that some CVD risk calculators don't distinguish between 'never smokers' and former smokers. And although the Atherosclerotic CVD (ASCVD) Risk Estimator Plus does allow clinicians to identify former smokers, it considers their CVD risk to be identical to never smokers after five years. This risk estimator was developed by the American College of Cardiology (ACC) and was based on the American Heart Association (AHA) 2013 risk guideline.

It's important to determine the time course of CVD risk reduction following smoking cessation, as quitters represent a growing group in the US, the researchers note.

Framingham Data

The new study used data from two cohorts from the Framingham Heart Study (FHS): the original cohort and the offspring cohort.

The total study population included 8770 participants (mean age 42 years, 56% female).

Researchers had data on smoking from repeated assessments over time. At the baseline examination — which was 1954–1958 for the original cohort and 1971–1975 for the offspring cohort — 46.9% of the total cohort were smokers, 13.6% were former smokers, and 39.5% had never smoked. Among smokers, the median number of cigarettes per day was 20. In quitters, the median number of years since cessation was 5.9.

The median pack years in the pooled analysis was 18.8 for current smokers and 12.0 for former smokers. Pack years refers to the number of packs of cigarettes smoked per day multiplied by the years smoked.

Investigators had information on other risk factors and CVD outcomes, including myocardial infarction, stroke, heart failure, and CVD deaths.

They looked at the association between years since smoking cessation and subsequent CVD risk among former smokers compared with persistent smokers and never smokers.

"The strength of our investigation is that we used more than 50 years' worth of data, so our capture of smoking history and intensity was perhaps more accurate than what's been studied in other examinations," said Duncan.

Researchers accounted for a number of variables, including established Framingham CVD risk factors (age, sex, systolic blood pressure, antihypertensive medication use, diabetes mellitus, and total cholesterol), body mass index (BMI), alcohol consumption, and educational attainment.

They did not include diet or exercise as potential confounders because these were infrequently captured in the original cohort.

During a median follow-up of over 26 years, there were 2435 first CVD events. Current smoking was associated with significantly higher CVD incidence rates per 1000 person-years vs never smoking in both the pooled cohort and in each cohort separately.

In adjusted models, smoking cessation was associated with an almost immediate and rapid decline in CVD risk vs continued smoking. The risk was significantly lower within 5 years of cessation in the pooled cohort (hazard ratio [HR] 0.61; 95% confidence interval [CI], 0.49 - 0.76; difference in incidence rate per 1000 person-years between current smoking and quitting within 5 years, −4.51; 95% CI, −5.90 to −2.77).

"Immense Benefit"

"This finding reinforces the immense benefit of quitting smoking," said Duncan. "Even among heavy smokers, once they had quit for 5 years, their CVD risk declined by 39% relative to people who continued to smoke at high levels, which is huge."

All ex-smokers seemed to reap the benefit from quitting, said Duncan. "Our models included people who were young, who were old, and who had a variety of other risk factors."

However, it took 10 to 15 years for former heavy smokers in the pooled cohort to reach the same CVD risk as never smoking (HR, 1.25; 95% CI, 0.98 - 1.60; incidence rate difference between never smoking and quitting within 10-15 years, 1.27; 95% CI, −0.10 to 3.05).

The time course of CVD risk differed by cohort. In the original cohort, former heavy smoking was no longer significantly associated with increased CVD risk compared with never smoking within 5 to 10 years of cessation. But it took even longer — at least 25 years — for the offspring cohort to reach that risk level.

Clinicians may want to "err on the side of caution" and consider their former heavy smoker patients to be at risk for CVD for up to a decade after they quit, said Duncan.

"That was kind of the lower end of that 10- to 15-year range that we found in our study. This is one study; we don't want to overhype our results." 

It's not clear why it took longer for CVD risk in the offspring cohort to reach never smoking levels, but age might explain the difference. Duncan pointed out that the mean baseline age was 50 years in the original cohort but 36 years in the offspring cohort, a difference of 14 years, which is significant in terms of cardiovascular risk.

As people get older, things like smoking and blood pressure are still important risks for CVD, but "age becomes the overwhelming factor," said Duncan.

The difference could also be due to "different temporal trends" in smoking patterns over time, said Duncan. The composition of cigarettes has changed, and they have become more harmful and more addictive.

Controlling for diet and exercise might have affected the results, said Duncan. A healthy diet and physical activity are among the lifestyle habits the AHA recommends for heart health, and people who quit smoking tend to have increased lung capacity — and thus may be able to exercise more.

To date, none of the CVD risk calculators incorporates either diet or exercise, said Duncan.

The study didn't address light smokers. "It's important to minimize the number of analyses you do to maintain statistical power, so we decided ahead of time that we were going to focus on heavier smokers," explained Duncan. "Based on our prior work in lung cancer, we knew the risk would be much higher in heavy smokers."

However, based on results of this one study, which included mostly white subjects of European ancestry, "it's a little premature" to suggest changing risk calculators, said Duncan.

The next step for her research group is to take the data from the Framingham Heart Study and try to replicate the methods used for the ASCVD risk calculator, but adding in the additional information on smoking.

"Sobering" Implications

In an accompanying Editor's Note, Thomas Cole, MD, associate editor for JAMA, said the estimates of cardiovascular risk among former smokers in the study "are likely to be more precise and accurate than those of previous studies."

This new information is important for clinicians and patients, he said.

On a population level, the implications of the study are "sobering" said Cole. Reductions in CVD associated with declining smoking rates in countries such as the US and Japan can be expected to lag quit rates by 10 to 15 years; in countries where smoking rates appear to be increasing, such as China and Indonesia, rates of CVD are likely to increase for decades into the future.

All countries, particularly those most vulnerable to tobacco marketing, should implement tobacco control strategies to prevent smoking initiation and motivate current smokers to quit, said Cole.

These new findings are consistent with those of another study published last month in the Journal of the American College of Cardiology. However, in this current study, the contribution of smoking lasted up to 25 years after cessation; in the earlier JACC study, it was 20 years after cessation.

An author of that earlier study, Kunihiro Matsushita, MD, PhD, Johns Hopkins School of Medicine, Baltimore, Maryland, told | Medscape Cardiology that the two studies had some different elements.

"For example, this study explored a composite CVD including coronary disease, stroke, and heart failure, whereas our study contrasted peripheral artery disease, coronary disease, and stroke," he said.

Having results for the original and offspring Framingham Heart Study cohorts for this new study may have enhanced the findings, said Matsushita.

"This approach increases statistical power and allows the authors to explore whether the impact of smoking may differ between two cohorts with different birth years and different age ranges."

This new study "is well-designed and well-analyzed," said Matsushita, adding that he didn't see any major limitations, "although lack of racial diversity is a well-known limitation of the Framingham Heart Study."

Matsushita noted that both the AHA/ACC and European Society of Cardiology (ESC) risk calculators include smoking as a dichotomous predictor (current vs non-current).

"In this context, this study — and ours — shows that more granular information on smoking, for example pack-years and duration after smoking cessation, can refine risk classification."

Cole is the associate editor of the Journal of the American Medical Association. The study authors and Matsushita have disclosed no relevant financial relationships.

JAMA. Published online August 20, 2019. Abstract, Editor's Note

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