Subclinical cardiac damage evident among cigarette smokers, even quitters
Key takeaways:
- Smoking was link to elevated markers of heart damage, including inflammation, thrombosis and atherosclerosis.
- Coronary calcium remained elevated, even 30 years after smoking cessation.
Markers of subclinical heart damage were observed among individuals who smoke cigarettes, even decades after quitting, according to a study published in the Journal of the American College of Cardiology.
New data from the Cross-Cohort Collaboration-Tobacco Work Group showed that cigarette smoking was associated with elevated markers of inflammation, thrombosis and atherosclerosis, all of which decreased after cessation, except for coronary calcium, which remained elevated 30 years later.
“Understanding the mechanisms of smoking-related injury and the most sensitive biomarkers of subclinical harm is critical to clinical trial planning and tobacco regulatory policy, and might be important for planning studies and informing regulatory of new and emerging tobacco products as well,” Michael J. Blaha, MD, MPH, professor of medicine and director of clinical research at the Ciccarone Center for the Prevention of Cardiovascular Disease at Johns Hopkins Medicine, told Healio. “The degree to which new and emerging tobacco products affect these same biomarkers will need to be explored.”
The data included 22 studies with 182,364 participants with at least one of nine markers of subclinical CVD measured at baseline: high-sensitivity C-reactive protein, interleukin-6, glycoprotein acetylation, fibrinogen, D-dimer, coronary artery calcium, carotid intima-media thickness, carotid plaque and ankle-brachial index.
All patients (mean age, 58 years; 69% women) self-reported smoking status, intensity and/or pack-years.
Overall, 15.3% of participants reported currently smoking, with an average of 16.7 cigarettes per day and a mean of 30 pack-years.
More than one-third (34.6%) of participants reported formerly smoking, with a median of 19 years since quitting and mean of 22.4 pack-years.
Cigarettes and markers of CV damage
The researchers reported that, compared with never smokers, all former and current smokers had higher levels of all imaging and physiological markers for subclinical atherosclerosis (P for all < .05) and all blood markers of inflammation and thrombosis (P for all < .05), except for D-dimer among former smokers (OR = 1; 95% CI, 0.96-1.04).
Among participants who reported currently smoking, Blaha and colleagues observed a 1% to 9% increase in all imaging, physiological and blood markers, except for D-dimer, per 10 cigarettes smoked.
Beyond the smoking intensity of 20 cigarettes per day, levels of blood markers of subclinical CV damage plateaued while markers of atherosclerosis continued to rise, according to the study.
“Smoking affects a diverse array of biomarkers of subclinical CV injury across multiple domains — inflammation, thrombosis and atherosclerosis — which is quite alarming,” Blaha told Healio. “Even low levels of smoking cause cardiovascular injury that can persistent long after dose reduction — less cigarettes per day — or cessation.”
Reduction of most markers after cessation
Among participants who reported they quit smoking, the researchers observed lower levels of markers of subclinical CV harm as time since quitting increased, with most markers no different compared with never smokers by 30 years after cessation; however, CAC score remained approximately 19% higher, even beyond 30 years, among former smokers compared with never smokers.
“Unlike measures of inflammation, coronary calcium levels do not go down,” Blaha said. “They reflect a history of CV injury in the years leading up to the coronary calcium measurement. As such, coronary calcium values remain much higher than in nonsmokers for many years to decades after smoking cessation, as vascular injury has already built up over time.”
Changes in cigarette composition a limitation
The researchers noted that a limitation of the study is the differing time periods in which participant data were collected across the 22 studies from the Cross-Cohort Collaboration-Tobacco Work Group. Specifically, the changes in cigarette composition and ingredients from one time point to the next.
“We had a focus on regulatory science with this research,” Blaha told Healio. “We hope to inform the regulation of cigarettes and other tobacco products via a comprehensive understanding of the mechanisms and biomarkers of subclinical CV injury that might precede CV events by years to decades. This is important for planning studies of smoking cessation — for example, by using alternative tobacco products — and measuring the anticipated impact of such use patterns on future CVD.”
Blaha also highlighted prior work by the Cross-Cohort Collaboration-Tobacco Work Group evaluating the impact of cigar, pipe, smokeless tobacco and e-cigarette use on subclinical CV damage and adverse outcomes. Those data were previously published in Circulation, JAMA Network Open and American Heart Journal.
“As for clinical practice, these data can be used to inform discussions with patients,” Blaha said. “Even low levels of smoking exposure affect multiple domains of subclinical CV injury. So even if patients have not had an event yet, they can perhaps better understand the ongoing remarkably unfavorable effects on CV function.”
For more information:
Michael J. Blaha, MD, MPH, can be reached at @MichaelJBlaha on X (Twitter).
References:
- Tasdighi E, et al. JAMA Netw Open. 2025;doi:10.1001/jamanetworkopen.2024.53987.
- Yao Z, et al. Am Heart J. 2025;doi:10.1016/j.ahj.2024.10.012.
- Yao Z, et al. Circulation. 2025;doi:10.1161/CIRCULATIONAHA.124.070852.
Collapse