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J Am Coll Cardiol, 2005; 45:1043-1050, doi:10.1016/j.jacc.2004.12.058
© 2005 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: HEART FAILURE

Community screening for left ventricular systolic dysfunction using plasma and urinary natriuretic peptides

Leong L. Ng, MD*,*, Ian W. Loke, MB*, Joan E. Davies, PhD*,{ddagger}, Sandeep Geeranavar, BSc*, Kamlesh Khunti, MD{dagger}, Margaret A. Stone, PhD{dagger}, Derek T. Chin, MB{ddagger} and Iain B. Squire, MD*

* Department of Cardiovascular Sciences, University of Leicester, United Kingdom
{dagger} Department of Health Sciences, University of Leicester, United Kingdom
{ddagger} Department of Cardiology, Glenfield Hospital, Leicester, United Kingdom

Manuscript received May 17, 2004; accepted December 10, 2004.

* Reprint requests and correspondence: Prof. Leong L. Ng, Department of Cardiovascular Sciences, Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, United Kingdom (Email: lln1{at}le.ac.uk).

OBJECTIVES: We sought to compare urinary and plasma N-terminal pro-brain natriuretic peptide (N-BNP) in left ventricular systolic dysfunction (LVSD) diagnosis.

BACKGROUND: Plasma N-BNP is elevated in LVSD. Renal tubule cells produce BNP. We tested the incremental value of urinary N-BNP in LVSD diagnosis.

METHODS: In this prospective, community-screening study of undiagnosed LVSD, 1,360 subjects (45 to 80 years of age) were invited, and 1,308 had analyzable echocardiographic scans and urine and plasma specimens. The criterion standard for LVSD was defined as a wall motion score over 1.8 (ejection fraction ≤40%).

RESULTS: Twenty-eight patients with LVSD had elevated urinary and plasma N-BNP levels compared with normal subjects (p < 0.0005). Receiver-operating characteristic (ROC) areas under the curve (AUCs) for urinary and plasma N-BNP were 0.831 and 0.840, respectively. Both tests had high negative predictive values (>99%) for excluding LVSD. Urinary N-BNP was more specific (67.2%) than plasma N-BNP (41%). The plasma/urinary N-BNP product yielded a higher ROC-AUC (0.923) and specificity (78%), reducing the number of cases to scan to detect one case of LVSD to 11.4 (compared with 16.6 [urinary N-BNP] and 29.0 [plasma N-BNP]). Sequential application of tests (urinary N-BNP, then plasma N-BNP in the urine-"positive" cases) achieved similar reductions in the number of cases to scan (10.8), while limiting the number of N-BNP tests to be performed. Urinary N-BNP performed poorly in detection of other cardiac abnormalities with preserved systolic function. It was less costly to test urinary N-BNP in the whole population as compared with other strategies, including scanning high-risk cases with N-BNP testing in the remainder.

CONCLUSIONS: Urinary N-BNP used together with plasma N-BNP could reduce the echocardiographic burden in screening programs.

Abbreviations and Acronyms
  AF = atrial fibrillation
  AUC = area under the curve
  IHD = ischemic heart disease
  LVSD = left ventricular systolic dysfunction
  LVWMI = left ventricular wall motion index
  N-BNP = N-terminal pro-brain natriuretic peptide
  NPV = negative predictive value
  PPV = positive predictive value
  ROC = receiver-operating characteristic




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