Atherosclerotic disease in adults with congenital heart disease (ACHD): High adverse event and comorbidity rates despite a favorable conventional risk factor profile

Background Survival prospects for adults with congenital heart defects (ACHD) have improved significantly over the last decades. As ACHD reach a higher age, acquired heart disease and atherosclerosis become a growing concern besides heart defect related morbidity and mortality. Purpose This study aims to characterize differences in cardiovascular risk profile, major adverse clinical events (MACE), and comorbidities between ACHD and matched controls with diagnosed atherosclerotic disease. Methods Using a German health claims database (AOK Bayern, 2012–2021), adults with both an ICD-10 coded atherosclerotic disease and a concomitant congenital heart defect diagnosis were identified. The ACHD patients were compared to an age-, gender-, and ambulatory healthcare utilization-matched control group with atherosclerotic disease. Results Real-world data from 35,064 ACHD patients (91% mild, 7% moderate, 2% severe heart defect complexity) revealed a striking ‘risk paradox’. The ACHD cohort exhibited a remarkably lower prevalence of conventional risk factors - including obesity, hyperlipidemia, smoking, and diabetes - across nearly all age deciles compared to matched controls. Despite this favorable risk profile, especially ACHD with more complex defects suffered a disproportionately higher burden of MACE, especially stroke, and comorbidities, such as infective endocarditis and cardiac arrhythmias, at younger ages. To account for an unavoidable ascertainment bias in this dataset (the ICD-10 code for Atrial Septal Defect (ASD) includes Patent Foramen Ovale, which is only diagnosed in cases of stroke due to paradoxical shunting), the data is presented stratified accordingly in Figure 1 with details on prevalence by age. Conclusion This large-scale study provides insights into differences in atherosclerotic disease between ACHD and matched controls. Our findings suggest a risk paradox in ACHD where we found a disproportionately higher adverse event and comorbidity burden at younger ages despite a favorable conventional risk factor profile. Whether event thresholds in ACHD with atherosclerosis are reached prematurely needs further investigation in prospective studies. Clinical management must shift toward early and rigorous risk factor management to reduce the potential risk of exceedingly poor outcomes when ACHD and atherosclerosis co-occur.