Lifetime risk of comorbidity in patients with simple congenital heart disease: a Danish nationwide study

Abstract

Aims: In a continuously ageing population of patients with congenital heart disease (CHD), understanding the long-term risk of morbidity is crucial. The aim of this study was to compare the lifetime risks of developing comorbidities in patients with simple CHD and matched controls.

Methods and results: Using the Danish nationwide registers spanning from 1977 to 2018, simple CHD cases were defined as isolated atrial septal defect (ASD), ventricular septal defect (VSD), pulmonary stenosis, or patent ductus arteriosus in patients surviving until at least 5 years of age. There were 10 controls identified per case. Reported were absolute lifetime risks and lifetime risk differences (between patients with simple CHD and controls) of incident comorbidities stratified by groups and specific cardiovascular comorbidities. Of the included 17 157 individuals with simple CHD, the largest subgroups were ASD (37.7%) and VSD (33.9%), and 52% were females. The median follow-up time for patients with CHD was 21.2 years (interquartile range: 9.4-39.0) and for controls, 19.8 years (9.0-37.0). The lifetime risks for the investigated comorbidities were higher and appeared overall at younger ages for simple CHD compared with controls, except for neoplasms and chronic kidney disease. The lifetime risk difference among the comorbidity groups was highest for neurological disease (male: 15.2%, female: 11.3%), pulmonary disease (male: 9.1%, female: 11.7%), and among the specific comorbidities for stroke (male: 18.9%, female: 11.4%). The overall risk of stroke in patients with simple CHD was mainly driven by ASD (male: 28.9%, female: 17.5%), while the risks of myocardial infarction and heart failure were driven by VSD. The associated lifetime risks of stroke, myocardial infarction, and heart failure in both sexes were smaller in invasively treated patients compared with untreated patients with simple CHD.

Conclusion: Patients with simple CHD had increased lifetime risks of all comorbidities compared with matched controls, except for neoplasms and chronic kidney disease. These findings highlight the need for increased attention towards early management of comorbidity risk factors.

Keywords: Adult congenital heart disease; Comorbidity burden; Epidemiology; Lifetime risks; Mortality; Procedures; Register studies; Surgery.

Structured Graphical Abstract

Background, methods, and highlighted results of the current study investigating the lifetime risks of comorbidities and mortality in patients with simple congenital heart disease compared with sex- and birth-year-matched controls. ‘Excess risk’ means the excess risk among simple congenital heart disease patients compared with sex- and birth-year-matched controls. CHD, congenital heart disease.

Figure 1

Flow chart depicting study inclusion, exclusion, and sampling of cases and controls from the Danish nationwide registers. Of 34 512 patients with the relevant simple congenital heart disease diagnoses (atrial septal defect, ventricular septal defect, patent ductus arteriosus, pulmonary stenosis), 6470 (37.7%) were diagnosed with simple atrial septal defect, 5814 (33.9%) with simple ventricular septal defect, 4095 (23.9%) with simple patent ductus arteriosus, and 778 (4.5%) with simple pulmonary stenosis. The 10 controls per simple congenital heart disease (n = 171 570) case, matched on sex and birth year, were identified using the nationwide Danish registers. Non-simple congenital heart disease = any additional congenital heart disease diagnosis other than atrial septal defect, ventricular septal defect, patent ductus arteriosus, or pulmonary stenosis.

Figure 2

Forest plot showing the lifetime risk of developing first-time comorbidities for patients with simple congenital heart disease and matched controls. The x-axis depicts the lifetime risk estimates (bullet) with 95% confidence interval (parentheses) and the y-axis depicts the comorbidity groups stratified by patients with congenital heart disease and matched controls (non-congenital heart disease). Risk difference depicts excess risk among patients with congenital heart disease compared with non-congenital heart disease controls, an asterisk (*) after the 95% confidence interval signals that the risk difference is statistically significant. (A) Analyses for male patients. (B) Analyses for female patients. The specific lifetime risk estimates and the 95% confidence intervals are provided to the left of the graph, while the risk difference between simple congenital heart disease and matched controls with corresponding 95% confidence intervals is provided to the right.

Figure 3

Forest plot showing the lifetime risk of developing first-time specific comorbidities for patients with simple congenital heart disease and matched controls. The x-axis depicts the lifetime risk estimates (bullet) with 95% confidence interval (parentheses) and the y-axis depicts the specific comorbidities stratified by patients with congenital heart disease and matched controls (non-congenital heart disease). Risk difference depicts excess risk among patients with congenital heart disease compared with non-congenital heart disease controls, an asterisk (*) after the 95% confidence interval signals that the risk difference is statistically significant. (A) Analyses for male patients. (B) Analyses for female patients. The specific lifetime risk estimates and the 95% confidence intervals are provided to the left of the graph, while the risk difference between simple congenital heart disease and matched controls with corresponding 95% confidence intervals is provided to the right.