Abstract Background Advances in congenital heart disease management have significantly increased the life expectancy of affected individuals, leading to a growing population of adults with congenital heart disease (ACHD). This shift has brought a new challenge: the increased prevalence of acquired atherosclerotic cardiovascular disease, including coronary artery disease (CAD), in ACHD patients. The extent of this association and the interplay between traditional cardiovascular risk factors and congenital heart defects remain unclear. Purpose To assess CAD prevalence in ACHD patients compared to the general population, with stratification by defect severity, and to evaluate the impact of traditional risk factors on this association. Methods We conducted a systematic review and meta-analysis following PRISMA guidelines, including all relevant observational studies indexed in PubMed, Embase, and Web of Science, up to January 2025. Primary analysis estimated the pooled odds ratio (OR) of CAD in ACHD versus non-ACHD individuals using a random-effects model. Subgroup analyses assessed CAD risk in moderate-or-severe (mod/sev) and mild ACHD patients versus non-ACHD. Meta-regression was conducted to examine the influence of traditional cardiovascular risk factors on CAD prevalence, and determine the independent effect of ACHD on CAD. Additional analyses included meta-proportions for CAD prevalence in specific moderate or severe congenital defects. Results Across included studies, comprising 357,700 individuals after outlier exclusion, ACHD patients had a significantly elevated risk of CAD compared to non-ACHD individuals (OR: 1.49, 95% CI: 1.10–2.01, p=0.0097). The risk was primarily driven by mod/sev ACHD (OR: 1.87, 95% CI: 1.66–2.10, p0.0001) compared to mild ACHD (OR: 1.33, 95% CI: 0.74–2.39, p=0.34). Meta-regression revealed a significant impact of diabetes mellitus (DM, OR: 1.79 per unit increase in log prevalence ratio, p0.0001), dyslipidemia (DLD, OR: 1.72 per log unit increase, p=0.0007), and hypertension (HTN, OR: 5.08 per log unit increase, p0.0001) on CAD prevalence, while ACHD remained an independent predictor of CAD when adjusted for risk factors. Finally, individuals with Tetralogy of Fallot, Coarctation of Aorta and Transposition of the Great Arteries, were found with pooled CAD prevalences as high as 5.6% (95% CI: 1.9–15.0), 5.1% (95% CI: 3.2–7.9) and 9.4% (95% CI: 0.9–54.6), respectively. Conclusions Adults with ACHD, particularly those with at least moderate defects, have an increased burden of CAD, which persists even after adjustment for traditional risk factors. Given the significant contribution of diabetes mellitus, dyslipidemia, and hypertension, personalised management strategies are essential. These findings underscore the need for ACHD-specific cardiovascular screening and prevention guidelines to mitigate long-term atherosclerotic risk in this population.Forest plots of CAD prevalence in ACHD Meta-regression of risk factors
Goliopoulou et al. (2025) studied this question.