Cardiovascular risk in pulmonary alveolar proteinosis

ABSTRACT

We hypothesized that cardiovascular events and/or indices of cardiac dysfunction may be increased in pulmonary alveolar proteinosis (PAP). Systemic and pulmonary arterial hypertension, arrhythmias, pulmonary embolism, stroke and ischemic heart attack were reported. Patients underwent serum anti-GM-CSF antibodies, disease severity score (DSS), Doppler transthoracic echocardiograph, glucose, thyroid hormones, lipids, troponin and pro-Brain natriuretic peptide (BNP) examination. Thirteen patients (8 female) were studied, median age of 47. Pro-BNP inversely related to DLCO% and TLC%; troponin directly related to DSS, age, P(A-a)O₂, left atrium-, left ventricle-end-diastole diameter and BMI. On multiple regression analysis DSS was the only parameter significantly and strongly related with troponin (R² = 0.776, p = 0.007). No cardiovascular event was reported during follow-up. In PAP cardiovascular risk indices relate to lung disease severity. Therefore, PAP patients could be at increased risk for cardiovascular events. Quantitation of its magnitude and potential links to lungs’ physiologic derangement will be addressed in future studies.

KEYWORDS:

• Pulmonary alveolar proteinosis
• autoimmune pulmonary alveolar proteinosis
• inhaled GM-CSF
• pulmonary arterial hypertension
• serum lipids
• cardiovascular events
• pro-BNP
• troponin
• disease severity

Financial & competing interests disclosure

The authors were supported in part by the German Federal Ministry of Education and Research (EuPAPNet project inside ERARE, Number 01GM1011A) and the chILD-EU project (FP7-305653). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• In patients with PAP several factors of cardiovascular risk are constantly present. Such risk factors include progressive hypoxemia, smoking history (reported in up to two-thirds of patients) and higher serum levels of triglycerides and cholesterol.

• However, there are no studies examining cardiovascular risk and events in patients with PAP. We hypothesized that cardiovascular events and indices of cardiac dysfunction may be increased in PAP patients.

• In the present study it is shown that significant associations exist between cardiovascular risk indices such as troponin and pro-BNP and disease severity indices such as DSS, TLC% and DLCO%, despite the absence of a noteworthy increase in the overt cardiovascular complications in PAP patients.

• In PAP patients indices of cardiovascular risk correlate to markers of disease severity.

• PAP patients might be at increased risk of cardiovascular events. The magnitude and the potential links with the lungs’ physiologic derangement need to be addressed in future studies.