Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis

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

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Abstract

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.

Original languageEnglish
Pages (from-to)840-849
Number of pages10
JournalThe Lancet Diabetes and Endocrinology
Volume4
Issue number10
DOIs
Publication statusPublished - Oct 1 2016

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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    Nambi, V., Ballantyne, C. M., Hoogeveen, R. C., Agarwal, S. K., Panagiotakos, D. B., Wannamethee, S. G., Whincup, P. H., Kiechl, S., Willeit, J., Schett, G., Santer, P., Willeit, P., Casas, J. P., Lawlor, D. A., DeFilippi, C., Kronmal, R. A., Psaty, B. M., Cushman, M., Nordestgaard, B. G., ... Welsh, P. (2016). Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis. The Lancet Diabetes and Endocrinology, 4(10), 840-849. https://doi.org/10.1016/S2213-8587(16)30196-6