Published Online
on November 29, 2004

A more recent version of this article appeared on January 1, 2005

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Submitted on September 17, 2004
Revised on October 7, 2004

Prediction of Heart Failure by Amino Terminal-pro-B-Type Natriuretic Peptide and C-Reactive Protein in Subjects With Cerebrovascular Disease

Duncan J. Campbell^*; Mark Woodward; John P. Chalmers; Samuel A. Colman; Alicia J. Jenkins; Bruce E. Kemp; Bruce C. Neal; Anushka Patel; and Stephen W. MacMahon

From the St. Vincent’s Institute of Medical Research (D.J.C., B.E.K.), Fitzroy, Victoria; the Department of Medicine (D.J.C., A.J.J., B.E.K.), University of Melbourne, St. Vincent’s Hospital, Fitzroy, Victoria; Commonwealth Scientific and Industrial Research Organization Health Sciences and Nutrition (B.E.K.), Parkville, Victoria; and The George Institute for International Health (M.W., J.P.C., S.A.C., B.C.N., A.P., S.W.M.), University of Sydney, Newtown, New South Wales, Australia.

^* To whom correspondence should be addressed. E-mail: dcampbell{at}svi.edu.au.

Abstract--B-type natriuretic peptide (BNP) and C-reactive protein (CRP) are elevated in persons at risk for congestive heart failure (CHF). However, limited data are available directly comparing BNP-related peptides and CRP in persons at risk of CHF. To evaluate amino terminal-pro-BNP (NT-proBNP) and CRP, separately and together, for assessment of risk of CHF, we performed a nested case-control study of the 6105 participants of the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure-lowering regimen among individuals with previous stroke or transient ischemic attack (TIA). Each of 258 subjects who developed CHF resulting in death, hospitalization, or withdrawal of randomized therapy during a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. NT-proBNP and CRP predicted CHF; the odds ratio for subjects in the highest compared with the lowest quarter was 4.5 (95% confidence interval, 2.7 to 7.5) for NT-proBNP and 2.9 (confidence interval, 1.9 to 4.7) for CRP, and each remained a predictor of CHF after adjustment for all other predictors. Screening for both markers provided better prognostic information than screening for either alone. Elevation of NT-proBNP above 50 pmol/L and CRP above 0.84 mg/L predicted CHF with sensitivity of 64% and specificity of 66%. NT-proBNP and CRP predicted CHF in subjects receiving perindopril-based therapy. We conclude that NT-proBNP and CRP are independent predictors of CHF risk after stroke or TIA. Moreover, NT-proBNP and CRP may be markers of mechanisms of CHF pathogenesis distinct from those responsive to angiotensin-converting enzyme inhibitor-based therapy.

Key words: heart failure • natriuretic peptides • cerebrovascular disorders • stroke • renin

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