Predictors of Elevated NT-proBNP Levels in a High-Risk Outpatient Population for Heart Failure: Determination Using...

Aim        To identify predictors of increased N-terminal pro-brain natriuretic peptide (NT-proBNP) in a population of outpatients at a high risk for chronic heart failure (CHF) using methods based on the clinical decision limit (CDL), reference intervals (RI), and age- and sex-adjusted NT-proBNP ratio.Material and methods    Timely diagnosis and initiation of treatment at the early stages of CHF improve the prognosis of patients. Accordingly, a program for supporting patients at a high-risk of CHF by measuring NT-proBNP was implemented in all federal districts (FDs) of the Russian Federation. The analysis included 11,740 patients at high risk of developing CHF, who had a single NT-proBNP measurement in an outpatient setting. The inclusion criteria were age >18 years, symptoms and signs of CHF and/or abnormalities on electrocardiogram and/or the presence of diseases (arterial hypertension and/or any form of ischemic heart disease). The analysis included determining the proportion of patients with NT-proBNP test results above the CDL (NT-proBNP ≥125 pg/ml) and above the RI (97.5th percentile). For additional assessment, the age- and gender-adjusted NT-proBNP ratio was used. The risk of elevated NT-proBNP was assessed based on CDL, RI, and the NT-proBNP ratio.Results  The median age of patients was 66 [58.0; 73.0] years, 55.8% were >65 years, and 59.3% were women. In 43.5% of patients, the NT-proBNP concentration was less than 125 pg/ml. The risk of achieving CDL was 50% higher among men, associated with the patient's age, and increased by 73% in the 45-54 age group, 2.52 times in the 55-64 age group, and 6.62 times in the >65 years age group compared to the 18-44 age group. Living in a city with a population of less than one million people increased the risk of achieving CDL by 17% compared to living in a city with a population of over a million. NT-proBNP values above the RI were achieved by 22% of patients, with the risk being 69% higher among men and 24% higher among patients living in cities with a population of less than one million. Evaluation of the NT-proBNP test results using the RI criterion showed that 44.3% of patients with normal RI values had NT-proBNP values above the CDL (≥125 pg/ml). The NT-proBNP ratio was the lowest in the Ural Federal District and the highest in the Far Eastern Federal District. The risk of an increased NT-proBNP ratio ≥1 was higher among men by 67% (p<0.001), for residents of small towns by 21% (p<0.001), and for residents of the Far Eastern Federal District compared to any other region (p<0.001).Conclusion         Independent risk factors for elevated NT-proBNP when assessed by the RI and NT-proBNP ratio included male gender, residence in cities with a population of less than one million, and residence in the Far Eastern Federal District. Assessing the NT-proBNP test solely based on the CDL, without taking into account physiological changes related to gender and age, carries a risk of overdiagnosis of CHF.