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The following is a summary of “Association Between Cigarette Smoking and Subclinical Markers of Cardiovascular Harm,” published in the March 2025 issue of the Journal of the American College of Cardiology by Yao et al.

Cigarette smoking remains a significant risk factor for cardiovascular disease, yet the precise relationships between smoking intensity, cumulative exposure, and cessation duration with subclinical markers of cardiovascular harm remain inadequately defined. This study aimed to comprehensively investigate these associations across three key domains: inflammation, thrombosis, and subclinical atherosclerosis. Researchers analyzed data from 182,364 participants (mean age 58.2 years, 69.0% female) across 22 cohorts from the Cross Cohort Collaboration, incorporating self-reported smoking status, smoking intensity, and cumulative pack-years alongside concurrent measurements of cardiovascular biomarkers. The assessed markers included inflammatory indicators—high-sensitivity C-reactive protein, interleukin-6, and glycoprotein acetylation; thrombosis-related markers—fibrinogen and D-dimer; and atherosclerotic indicators—coronary artery calcium, carotid intima-media thickness, carotid plaque, and ankle-brachial index. 

Using multivariate regression models and restricted cubic splines, the study group evaluated associations between smoking-related parameters and these subclinical markers. Of the study population, 15.3% were current smokers (mean 16.7 cigarettes/day, mean 30.0 pack-years), and 34.6% were former smokers (median 19.0 years since cessation, mean 22.4 pack-years). Both current and former smokers exhibited elevated levels across all subclinical markers compared to never-smokers, with stronger associations observed in active smokers. Among current smokers, smoking intensity demonstrated a clear dose-response relationship with all markers except D-dimer, with each additional 10 cigarettes per day correlating with a 1% to 9% increase in subclinical marker levels. This trend plateaued for inflammatory and thrombosis-related biomarkers beyond 20 cigarettes per day but continued to rise for atherosclerosis markers. 

Similarly, among ever-smokers, pack-years showed robust dose-dependent associations with all markers, with a sustained albeit attenuated effect beyond 20 pack-years. Among former smokers, biomarker levels declined progressively with longer cessation durations, approximating levels seen in never-smokers after 30 years, except for coronary artery calcium, which remained 19% higher even after three decades of cessation. These findings underscore the strong and quantifiable dose-response relationships between smoking parameters and subclinical cardiovascular markers, emphasizing the persistent long-term effects of smoking on atherosclerosis. The sensitivity of these biomarkers to even small increments in cigarette exposure highlights their potential role in shaping regulatory policies for new and existing tobacco products.

Source: sciencedirect.com/science/article/abs/pii/S0735109725002013