C-reactive protein in adults with pulmonary arterial hypertension associated with congenital heart disease and its prognostic value.
OBJECTIVE
To assess the relationship of C-reactive protein (CRP) to clinical outcome and mortality in adults with pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH).


BACKGROUND
Approximately 5-10% of adults with congenital heart disease (ACHD) develop PAH, which in turn is associated with substantial morbidity and mortality. Although CRP is known to predict outcome in idiopathic PAH, little is known regarding its prognostic value in CHD-PAH.


METHODS
We obtained and analysed 1936 CRP values in a total of 225 adults with CHD-PAH (median age at study entry 34.0 years (27.0-41.7); 32.9% male, 35% with Down syndrome), performed over a 12-year period. High CRP values related to infection or blood transfusions were excluded from the analysis.


RESULTS
During a median follow-up of 4.8 years (1149 patients-years), 50 patients died. The median CRP concentration on the last assessment was 5.0 mg/L (IQR 2.0-10.0), higher in deceased patients compared with survivors (11.5 mg/L (6.0-23.0) vs 4.0 mg/L (1.5-8.0), p<0.0001). Following univariate Cox regression analysis, CRP emerged as a strong predictor of mortality (HR 1.18; 95% CI 1.11 to 1.26, p<0.0001) and remained significant after adjustment for age, presence of Down syndrome and advanced PAH therapy. Survival-receiver-operator characteristic analysis identified an optimal cut-off value of 10 mg/L. Patients with CRP >10 mg/L had more than a threefold increased risk of death (HR 3.63, 95% CI 2.07 to 6.38, p<0.0001).


CONCLUSIONS
Serum CRP is a simple but powerful marker of mortality in CHD-PAH patients and should be incorporated in the risk stratification and routine assessment of these patients.
Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK Department of Cardiology, Second University of Naples, Monaldi Hospital, Naples, Italy.
Giancarlo
G
Scognamiglio
Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, UK Division of Adult Congenital and Valvular Heart Disease, Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany.
Aleksander
A
Kempny
Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
Laura C
LC
Price
Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, UK.
Rafael
R
Alonso-Gonzalez
Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, UK.
Philip
P
Marino
Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, UK.
Lorna
L
Swan
Department of Cardiology, Second University of Naples, Monaldi Hospital, Naples, Italy.
Michele
M
D' Alto
Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK.
James
J
Hooper
Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, UK.
Michael A
MA
Gatzoulis
Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, UK.
Konstantinos
K
Dimopoulos
Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension, Royal Brompton Hospital, London, UK NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, UK National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
Stephen J
SJ
Wort
D000328:Adult; D000367:Age Factors; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D016009:Chi-Square Distribution; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006330:Heart Defects, Congenital / Q000150:complications* / Q000401:mortality; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000401:mortality; D053208:Kaplan-Meier Estimate; D008131:London; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors; D017741:Survivors; D062606:Tertiary Care Centers; D013997:Time Factors
D015415:Biomarkers; D002097:C-Reactive Protein