Cigarette Smoking, Coronary Plaque Burden and Phenotype: A Multimodality Meta-Analysis and Implications for Coronary Artery Calcium Scoring in Prevention

BACKGROUND: Cigarette smoking is a major modifiable risk factor for cardiovascular disease. Despite the widespread use of coronary artery calcium (CAC) scoring as a risk stratifier for preventive therapy, smokers frequently present with acute coronary syndromes despite minimal coronary calcification. We performed a multimodality meta-analysis to quantify the association between smoking and coronary plaque burden and phenotype using CCTA, IVUS, and OCT. METHODS AND RESULTS: We systematically searched multiple databases through June 2026 for imaging studies comparing smokers with never-smokers. Random-effects meta-analyses using inverse-variance weighting were performed to pool odds ratios (ORs) for plaque presence and specific phenotypes; heterogeneity was assessed using the I2 statistic. Sixteen studies (n = 251,839; mean age 58 years; 65% male) met the inclusion criteria. In pooled analyses, smokers had higher odds of any detectable coronary plaque (OR 1.42; 95% CI 1.32-1.53). Smoking was associated with increased odds of both calcified plaque (OR 1.33; 95% CI 1.11-1.58) and non-calcified plaque (OR 1.59; 95% CI 1.47-1.73), with a more consistent and homogeneous association observed for non-calcified plaque. Mixed plaque was also more frequent in smokers (OR 1.52; 95% CI 1.31-1.78). CONCLUSIONS: Cigarette smoking is associated with greater coronary plaque burden and a relative excess of non-calcified plaque compared with never-smoking. These findings suggest that plaque phenotypes in smokers may not be fully reflected by CAC scoring alone. Prospective multimodality cohorts with individual-level CAC and plaque characterization are needed to further refine risk stratification in this population.