Liew et al. (1) are correct in their premise that their study likely represents a different population of patients than our study (2). While their study looked at a very early, asymptomatic population of diabetic subjects who were free of overt heart disease or hypertension, our patient population was a Veterans Administration population with many risk factors for heart disease; hence, they are a very high-risk population.
The positive predictive value of any test becomes much stronger as the prevalence of disease increases. The negative predictive value is strong in both studies. The two peptides B-type natriuretic peptide (BNP), and the inactive NH2-terminal pro-BNP, are cleaved from the same precursor molecule, prepro BNP. Although NH2-terminal pro-BNP has exclusive renal clearance and a longer half-life than BNP, these factors should not account for the differences. However, it is possible that the elevation of NH2-terminal pro-BNP (and not BNP) with even small amounts of renal dysfunction might obscure the ability to detect cardiac abnormalities.
Liew et al. (1) conclude that NH2-terminal pro-BNP has little utility for early screening of left ventricular dysfunction in patients with diabetes. This may be true in a relatively asymptomatic low-risk group, but is unlikely to be true in the majority of patients with type 2 diabetes, who have many other risk factors. It is likely that their patients had no cardiac dysfunction, whereas in our study, almost all of the patients with high BNP levels did have diastolic or systolic dysfunction, even when asymptomatic. We found a particularly high incidence of diastolic dysfunction in this group of patients.
We now have 3–4 years of follow-up data on this group of patients (V. Epshteyn, K. Morrison, P. Krishnaswamy, R. Kazanegra, P. Clopton, S. Mudaliar, S. Edelman, R.H., A. Maisel, unpublished data), and BNP turns out to be an extremely strong predictor of future cardiac events. We believe that if Liew et al. continue to follow peptide levels in these patients, they will begin to see increases in levels as the ventricle begins to either stiffen and/or fail. This may be the opportune time to maximize cardiac work-up and treatment in these patients.