Comorbidity Clusters in Congenital Heart Disease Patients - Accelerated Disease Trajectories Across the Lifespan

BackgroundResearch has shown that patients with congenital heart disease (CHD) are at risk for the development of cardiac and other systemic complications. No methods have been identified to measure the disease trajectories for cardiovascular and systemic complications across the lifespan. In this study, we tackle the temporal sequence and interrelationships among clusters of comorbidities to explore the trajectories of developing comorbidities in CHD patients across the lifespan. The findings will provide potentially useful information for predicting long-term health outcomes in this patient population.MethodsThis longitudinal cohort study utilized the Quebec CHD database, encompassing 35 years (1983-2017) of follow-up with data in demographics, inpatient visits, hospitalization records, and death registry. Comorbidities were coded according to ICD-9 and ICD-10 codes. A total of 39 comorbidities were included comprising clusters of cardiovascular, respiratory, renal, digestive, endocrine/metabolic, infectious and neurological diseases, as well as cancer and mental disorders. We mapped the temporal sequences of comorbidities by aligning them along age axis using the median age of disease onset. The associations between disease pairs were estimated by Cox proportional hazard model adjusting for competing risk of death and taking into account the time-varying nature of the predictor disease. They were quantified using hazard ratios (HRs). To ensure robustness, a conservative approach was adopted by taking the lower limit of 95% confidence interval rather than the point estimate of HRs and a threshold of 2.0 to indicate the connectedness between disease pairs. Also, only disease pairs with >= 5 years gap in age of onset were considered in association analyses to take into account the variation in disease presentation and diagnoses. Patients with severe and non-severe CHD lesions were studied separately.ResultsThe study cohort comprised 9,764 individuals diagnosed with severe CHD lesion and 127,729 with non-severe CHD lesion. The median follow-up duration was 25.3 years for severe CHD and 21.7 years for non-severe CHD. The cumulative probability of developing at least one vascular disease by early adulthood (age=40 years) were around 70% and 25% in severe and non-severe patients respectively. Analysis of disease onset revealed that severe CHD patients predominantly developed morbid diseases between the ages of 25 and 40 years, whereas non-severe CHD patients exhibited a peak in comorbidity onsets between their 50s and 70s. In severe CHD, the trajectory of sequalae commenced with childhood cardiovascular diseases such as childhood heart failure, progressing to systemic diseases in early childhood such as diabetes, hypertension, chronic liver disease, acute/chronic kidney diseases, and followed by adulthood heart failure and dementia. It is worth to note that mental disorders, such as psychoses, anxiety, depression, manifested during the third to fourth decade of life, showing association with acute/chronic kidney diseases. We also observed an association between obesity and systemic and cardiac diseases for severe CHD patients. For non-severe CHD group, we observed additional connections between diseases, such as mental illnesses exhibiting an elevated association with dementia. ConclusionsOur study revealed measurable trajectories of clusters of multimorbidities among CHD patients demonstrating distinct patterns of disease onset between severe and non-severe CHD patients. Early child and adulthood systemic diseases were found to be pivotal in determining the trajectory of subsequent complications underscoring the importance of timely interventions for comorbidity prevention. The study shed light on understanding comorbidities trajectories across the lifespan in complex cardiovascular disease

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