Life-Course Noncardiac Comorbidity Burden and Mortality in Lower-Complexity Congenital Heart Disease

Lower-complexity congenital heart disease (CHD) is generally perceived as a low-risk condition. However, its long-term systemic comorbidity burden and impact on survival remain poorly defined, despite increasing recognition of lifelong care needs.

The authors aimed to determine whether lower-complexity CHD is a life-course condition characterized by high noncardiac comorbidity burden and mortality among adults.

This population-based prospective cohort study identified 3,316 adults with lower-complexity CHD and 492,232 individuals without CHD from the UK Biobank. The primary outcome was the first occurrence of 9 system-specific noncardiac comorbidities, with relative rates estimated by multivariable Cox regression models and lifetime risk from age 40 to 90 assessed using life-table methods. The secondary outcome was all-cause mortality among individuals with lower-complexity CHD, assessed according to baseline and incident comorbidity status using time-varying Cox regression models. The median follow-up was approximately 13 years.

Compared to individuals without CHD, adults with lower-complexity CHD had significantly elevated relative rates of noncardiac comorbidities across 9 organ systems, particularly for blood, endocrine, and pulmonary diseases. Comorbidity incidence diverged from midlife and accelerated with age. Absolute lifetime risks ranged from 17.1% (skin disease) to 45.8% (digestive disease), with the largest excess risks observed in endocrine (18.6%), digestive (15.7%), and pulmonary (12.5%) systems. Among individuals with CHD, incident noncardiac comorbidities were independently associated with increased subsequent all-cause mortality, with pulmonary disease conferring the strongest relative rate.

Lower-complexity CHD is associated with higher lifetime noncardiac comorbidity burden and increased subsequent mortality. These findings support a shift toward integrated, life-course clinical management.