Cumulative smoking exposure and prevalence of silent atherosclerosis in the REACT study

Background

Smoking is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD), yet the dose–response relationship between cumulative smoking exposure and silent atherosclerosis remains poorly characterised.

Purpose

We aimed to assess the association between lifetime smoking exposure and imaging-defined silent atherosclerosis.

Methods

We included asymptomatic participants aged 18-70 years at baseline in the cross-sectional multicentre prospective REACT cohort study in Spain and Denmark. Smoking status was obtained via a self-administered questionnaire. Cumulative smoking exposure was assessed as pack-years (continuous variable) and categorically using smoking status; never, former or current smoker, and among ever-smokers, tertiles of pack-years. The presence of atherosclerotic plaque was assessed bilaterally in the carotid and femoral arteries using 3D vascular ultrasound (3DVUS) and in the coronary arteries using CT angiography. Odds ratios (ORs) for silent atherosclerosis were estimated using multivariable logistic regression, adjusting for age, sex, physical activity, LDL-cholesterol and HbA1c.

Results (preliminary)

Information on smoking was available in 4,449 participants (mean age 47, SD = 13; 51 % men). Among these, 2,143 (48%) reported a history of smoking with a mean of 12 pack-years (SD = 12), and 550 (12 %) were current smokers. Ever-smoking was significantly associated with plaque presence compared to never-smokers (OR 1.24; 95% CI 1.0 - 1.4, p = 0.02). A dose-response relationship was observed for smoking burden expressed as tertiles of pack-years in adjusted analyses (Figure 1). Compared with never smokers (reference, n = 2,306), individuals in the highest tertile (T3, n = 672; range 14.0 - 133.0) had a significantly increased odds of plaque presence (OR 1.9; 95% CI 1.5 – 2.4, p < 0.001).

Conclusion

Cumulative smoking exposure was significantly associated with the presence of silent atherosclerosis after adjusting for conventional risk factors. These findings highlight the importance of cumulative smoking exposure being a driver of subclinical atherosclerosis, reinforcing smoking cessation as a key preventive target against developing atherosclerosis.

Figure 1. Forest plot; Adjusted odds ratios (95% CI) for the presence of subclinical atherosclerosis by smoking burden (pack-year tertiles; T1-T3) versus never-smokers (reference group, OR = 1.0), adjusted for age, sex, physical activity, LDL cholesterol, and HbA1c.Figur 1.Forest plot