Long-term biological variability and the generation of a new reference interval for plasma N-terminal pro-B-type natriuretic peptide in Labrador retrievers

Objectives First, to investigate the biological variability of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in healthy Labrador retrievers and compare this with current laboratory recommendations for dilated cardiomyopathy screening. Second, to calculate a breed-specific reference interval and validate it in a retrospective cohort. Materials and Methods Plasma NT-proBNP was measured in 51 clinically healthy Labrador retrievers at 0, 2, 4, 6 and 8 weeks. Coefficient of variation for individual dogs over time, the coefficient of variation for the group at each time point and the index of individuality were calculated. A reference interval was derived and tested on a clinical dataset available from four UK cardiology referral centres. Results Median NT-proBNP was 865 pmol/L (315 to 2064 pmol/L). Mean individual coefficient of variation was 19% (95% CI: 16 to 21%) and group coefficient of variation was 43% (95% CI: 41 to 46%), with index of individuality at 0.44. The breed-specific reference interval was 275 to 2100 pmol/L. In the validation group, 93% of NT-proBNP measurements from healthy dogs were within the reference interval. NT-proBNP measurements exceeded the reference interval in 82% of dogs with dilated cardiomyopathy. The upper bound of the reference interval (2100 pmol/L) had a positive predictive value of 90% and a negative predictive value of 87% for identification of dilated cardiomyopathy in this population. Clinical Significance Breed-specific reference intervals might improve the diagnostic accuracy of NT-proBNP measurement. Applying the currently recommended general cut-off value to Labradors is likely to result in frequent false positives and diagnosis would be improved by application of the new breed-specific reference interval calculated here.