Coronary Artery Calcification Burden in Cancer vs Non-Cancer Populations: A Systematic Review and Meta-Analysis

Project Description: Title: Coronary Artery Calcification Burden in Cancer vs Non-Cancer Populations: A Systematic Review and Meta-Analysis Purpose and Rationale: Cardiovascular disease has emerged as a major cause of long-term morbidity and mortality in cancer survivors, increasingly rivalling recurrence as a determinant of outcomes. Coronary artery disease (CAD), in particular, appears more prevalent in cancer patients, but the underlying mechanisms remain poorly understood. Traditional cardiovascular risk models often fail to account for the unique pathophysiological stressors associated with cancer and its treatment, including systemic inflammation, endothelial injury, and metabolic disturbances. Coronary artery calcium (CAC) scoring, assessed through CT imaging, is a validated surrogate marker of subclinical atherosclerosis and an independent predictor of cardiovascular events. However, whether cancer patients demonstrate increased CAC burden compared to non-cancer populations has not been systematically quantified. Project Aims: This project aimed to evaluate and compare the prevalence and severity of CAC in adult cancer patients and matched non-cancer controls using data from observational studies. Our goal was to determine whether cancer survivors exhibit greater subclinical atherosclerosis and to explore factors that might moderate this relationship. Methods: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines. MEDLINE, EMBASE, and Cochrane databases were searched up to 21 January 2025. Eligible studies included adult cancer patients with a documented history of malignancy and matched non-cancer control groups, with CAC measured by CT-based imaging. The primary outcomes were: CAC prevalence (defined as CAC score > 0) CAC severity (quantified by continuous Agatston scores) Pooled effect estimates were calculated using a random-effects model. Risk differences were used for CAC prevalence and Cohen’s d for CAC severity. Meta-regression analyses were performed to identify moderators of effect size. Key Findings and Expected Outcomes: Twelve studies met inclusion criteria (n = 18,706 participants; 2,182 cancer patients and 16,524 controls). Cancer patients were generally older and more often male, with a different cardiovascular risk profile: hypertension and diabetes were less common, but dyslipidaemia was more prevalent. CAC prevalence did not significantly differ between cancer and non-cancer groups (risk difference 0.05; 95% CI: –0.03 to 0.12). CAC severity was significantly higher in cancer patients (Cohen’s d = 0.29; 95% CI: 0.01 to 0.57), indicating a modest but meaningful increase in atherosclerotic burden. Meta-regression identified female sex as a significant moderator, accounting for over 50% of between-study heterogeneity. Conclusion and Implications: Despite similar CAC prevalence, cancer survivors exhibit significantly greater CAC severity than non-cancer controls, pointing toward a more advanced subclinical atherosclerotic burden. This finding supports the hypothesis that cancer and its treatments may contribute to accelerated vascular ageing or injury not captured by traditional risk models. These results lay the foundation for future research into cancer-specific cardiovascular screening strategies and may inform the development of tailored risk assessment tools that incorporate oncological exposures. Expected Impact: This work addresses a critical knowledge gap at the intersection of oncology and cardiology. By highlighting the need for more nuanced cardiovascular surveillance in cancer populations, it contributes to ongoing efforts in preventive cardio-oncology. Ultimately, the findings may inform the design of future prospective studies and guideline updates that enable earlier CAD detection, risk stratification, and personalised intervention for cancer survivors.