High Creatinine, NT-proBNP Levels Found to Be Mortality Risk Factors

Elevated blood levels of the kidney disease biomarker creatinine and the heart failure biomarker NT-proBNP were found to be independent predictors of mortality for older people with pulmonary arterial hypertension (PAH) who were born with congenital heart disease (CHD).

A medical records analysis found that patients ages 40 and older with higher levels of these biomarkers face an increased risk of death.

These findings support ongoing blood analysis to identify PAH patients who are at risk, the researchers said.

Although a history of heart arrhythmia was not identified as an independent risk factor in this study, as it was in previous reports, the scientists suggested this was due to the small number of patients investigated here. Thus, further research into that potential risk factor is needed, they said. 

The study, “Pulmonary Arterial Hypertension Associated with Congenital Heart Disease in Adults over the Age of 40 Years,” was published in the Journal of Clinical Medicine. 

Over the past few decades, the life expectancy of people born with heart defects — known as congenital heart disease — has improved, with the median age of CHD adults reaching 40 years. 

However, adults with congenital heart disease who also have PAH (PAH-ACHD) live with significant disease and continue to have one of the highest mortality rates, even at a younger age. 

To address this knowledge gap, researchers based at the Technical University of Munich, in Germany, examined the medical records of 65 people with PAH-ACHD, ages 40 or older, to identify risk factors for mortality by any cause. 

The mean age of participants was 45.19 years, and 67.7% were women. Among the patients, 46 (70.8%) had an unrepaired hole (shunt lesion) between vessels or chambers of the heart, and 12 (18.5%) had more complex heart defects (complex CHD). Additionally, seven (10.8%) had segmental PAH-ACHD, characterized by lung segments affected by hypertension rather than the entire lung. Down syndrome occurred in 13 patients (20.0%).

During a median follow-up of 4.2 years, nine patients (13.8%) had blood clot-related events, while two (3.1%) had airway bleeding events, 15 (23.1%) had arrhythmia of the heart atrium, and six (9.2%) had arrhythmia in the heart ventricles. 

A study to assess arrhythmia involved four patients (6.2%), and 12 individuals (18.5%) received electric shocks or medications to restore a normal heart rhythm (cardioversion). 

Surgery to implant supportive devices was performed in 12 participants, including defibrillator implantation — to detect and restore regular heartbeats — event recorder implantation, or a change in device.

A total of 47 patients (72.3%) were hospitalized, in which 21 had unplanned or emergency admissions. Specifically, 18 had unplanned/emergency hospitalization due to cardiac issues, two as a result of infections, and one for airway bleeding. 

During follow-up, 16 patients (24.6%) died. The cause of death was cardiac problems in three patients, respiratory failure in one, cerebrovascular accident in one, and 11 deaths from an unknown cause.

Statistical analysis of individual risk factors found elevated levels of creatinine in the blood — a kidney disease biomarker — and higher levels of the heart failure biomarker NT-proBNP were predictors of all-cause mortality. A previous history of ventricular arrhythmias also was identified as a risk factor in this analysis.

When the team completed a comparison of multiple risk factors, only creatinine and NT-proBNP were independent predictors of death by any cause. The risk from elevated creatinine was found to be 16.3 times higher, while NT-proBNP was determined to carry a 4.1 times higher risk.

As arrhythmias were not identified as risk factors using multiple parameters in the analysis, the team suggested it “may be due to the small number of patients in our cohort,” considering other studies have shown “arrhythmias in PAH-ACHD were a strong predictor of mortality even when managed in a specialist center.”

“New approaches regarding their prevention and treatment seem to be necessary,” the researchers wrote. 

An additional calculation found diminished survival in patients with blood creatinine levels above 0.73 mg/deciliter (dL) and NT-proBNP above 1,250 nanograms/L. 

“In conclusion, in patients with PAH-ACHD over the age of 40 years, a substantial number of unplanned/emergency hospital admissions as well as significant mortality were observed,” the researchers wrote.

“Close surveillance, including regular blood analysis, is necessary to identify patients at risk,” they concluded.