Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis
Creators: name: Ballantyne, Christie M.
name: Levy, Daniel
name: Hofman, Albert
name: Devereux, Richard B.
name: Barrett-Connor, Elizabeth
name: Gansevoort, Ron T.
name: Maisel, Alan S.
name: Nordestgaard, Børge G.
name: Cook, Nancy R.
name: Lima, João A.
name: Nambi, Vijay
name: Olsen, Michael Hecht
name: Yarnell, John W.G.
name: Whincup, Peter H.
name: Raymond, Ilan
name: Casas, Juan-Pablo
name: Manson, JoAnn E.
name: Jukema, J. Wouter
name: Ikram, M. Arfan
name: Luchner, Andreas
name: Zethelius, Björn
name: Pradhan, Aruna D.
name: Hoogeveen, Ron C.
name: Safford, Monika M.
name: Franco, Oscar H.
name: Andersson, Jonas
name: Stark, Klaus
name: Salonen, Jukka T.
name: Dehghan, Abbas
name: Kavousi, Maryam
name: Santer, Peter
name: Lindahl, Bertil
name: Rubattu, Speranza
name: Kistorp, Caroline N.
name: Jørgensen, Torben
name: Schou, Morten
name: Peters, Annette
name: van den Meiracker, Anton H.
name: Lind, Lars
name: Dieplinger, Benjamin
name: Haltmayer, Meinhard
name: Ruskoaho, Heikki
name: Kizer, Jorge R.
name: Strazzullo, Pasquale
name: Kiechl, Stefan
name: Everett, Brendan M.
name: de Craen, Anton J.M.
name: Agarwal, Sunil K.
name: Panagiotakos, Demosthenes B.
name: Ridker, Paul M.
name: Wannamethee, S. Goya
name: McGuire, Darren K.
name: Willeit, Johann
name: Kee, Frank
name: Melander, Olle
name: Das, Sandeep R.
name: Ford, Ian
name: Wennberg, Patrik
name: Zakai, Neil A.
name: Best, Lyle G.
name: Lawlor, Debbie A.
name: Zeller, Tanja
name: Rosenberg, Jens
name: Psaty, Bruce M.
name: Gudnason, Vilmundur
name: Trompet, Stella
name: Andresdottir, Margret B.
name: Stott, David J.
name: Drazner, Mark H.
name: Cushman, Mary
name: Gustafsson, Finn
name: Hildebrandt, Per R.
name: Ninomiya, Toshiharu
name: Agnarsson, Uggi
name: Hata, Jun
name: Bakker, Stephan J.L.
name: Welsh, Paul
name: de Boer, Rudolf A.
name: Mueller, Thomas
name: Giedraitis, Vilmantas
name: Howard, Virginia J.
name: Kauhanen, Jussi
name: DeFilippi, Christopher
name: Laukkanen, Jari A.
name: Willeit, Peter
name: Volpe, Massimo
name: de Lemos, James A.
name: Kiyohara, Yutaka
name: Evans, Alun
name: van Rooij, Frank J.A.
name: Venge, Per
name: Salomaa, Veikko
name: Jansson, Jan-Håkan
name: Heid, Iris M.
name: Aspelund, Thor
name: Kronmal, Richard A.
name: Eiriksdottir, Gudny
name: Lannfelt, Lars
name: Harald, Kennet
name: Schett, Georg
name: Tuomainen, Tomi-Pekka
name: Vartiainen, Erkki
name: Judd, Suzanne
name: Packard, Chris J.
name: Daniels, Lori B.
name: Ärnlöv, Johan
name: Sattar, Naveed
name: Umans, Jason G.
name: Ligthart, Symen
name: Heckbert, Susan R.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2016

description: BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment.

METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure.

FINDINGS: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure.

INTERPRETATION: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention.

FUNDING: British Heart Foundation, Austrian Science Fund, UK Medical Research Council, National Institute for Health Research, European Research Council, and European Commission Framework Programme 7.