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.