Myeloperoxidase and C-reactive protein augment the specificity of B-type natriuretic peptide in community screening for systolic heart failure.
BACKGROUND
N-terminal pro-B-type natriuretic peptide (N-BNP) is elevated in left ventricular systolic dysfunction (LVSD) and may be cost-effective for screening in the community but is relatively nonspecific. We sought to improve specificity using inflammatory markers such as C-reactive protein (CRP) and myeloperoxidase (MPO), which have been implicated in cardiovascular disease.


METHODS
A total of 1360 subjects (45-80 years) were invited in this prospective screening study for undiagnosed LVSD (defined as wall motion score >1.8 [ejection fraction < or = 40%]), and 1331 had analyzable echocardiographic scans and plasma specimens. Peptides were measured using immunoluminometric assays.


RESULTS
Twenty-eight patients with LVSD had elevated plasma N-BNP, CRP, and MPO levels compared with healthy subjects (P < .0005). Receiver operating characteristic curve areas for N-BNP, CRP, and MPO were 0.839, 0.824, and 0.909, respectively. All tests had high negative predictive values (>99%). Specificity was maximized to 88.4% in a logistic model with all 3 markers (all independent predictors, accounting for 44.8% of the variance). This reduced the number of cases to scan to detect 1 case of LVSD from 29.7 (using N-BNP alone) to 6.6. Using plasma MPO (at 33.9 ng/mL) or urinary N-BNP (at 10.7 fmol/mL) as initial screening tests, combinations of plasma N-BNP, MPO, and CRP can achieve specificities up to a maximum of 94.3%. Costs were minimized by using urinary N-BNP as the initial screening test, followed by plasma biomarkers.


CONCLUSIONS
Plasma CRP and MPO increased the specificity of N-BNP in LVSD screening. Screening is optimized by urinary N-BNP as an initial test, followed by plasma CRP, N-BNP, and MPO.
Ng
Leong L
LL
Department of Cardiovascular Sciences, University of Leicester, UK. lln1@le.ac.uk
Pathik
Bhupesh
B
Loke
Ian W
IW
Squire
Iain B
IB
Davies
Joan E
JE
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis*; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D009195:Peroxidase / Q000097:blood*; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis* / Q000209:etiology
D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein; D009195:Peroxidase