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

Natriuretic Peptides Studies Collaboration, Peter Willeit, Stephen Kaptoge, Paul Welsh, Adam Butterworth, Rajiv Chowdhury, Sarah Spackman, Lisa Pennells, Pei Gao, Stephen Burgess, Daniel Freitag, Michael Sweeting, Angela Wood, Nancy Cook, Suzanne Judd, Stella Trompet, Vijay Nambi, Michael Olsen, Brendan Everett, Frank KeeJohan Ärnlöv, Veikko Salomaa, Daniel Levy, Jussi Kauhanen, Jari Laukkanen, Maryam Kavousi, Toshiharu Ninomiya, Juan-Pablo Casas, Lori Daniels, Lars Lind, Caroline Kistorp, Jens Rosenberg, Thomas Mueller, Speranza Rubattu, Demosthenes Panagiotakos, Oscar Franco, James de Lemos, Andreas Luchner, Jorge Kizer, Stefan Kiechl, Jukka Salonen, S Goya Wannamethee, Rudolf de Boer, Børge Nordestgaard, Jonas Andersson, Torben Jørgensen, Olle Melander, Christie Ballantyne, Christopher DeFilippi, Paul Ridker, Mary Cushman, Wayne Rosamond, Simon Thompson, Vilmundur Gudnason, Naveed Sattar, John Danesh, Emanuele Di Angelantonio

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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 & endocrinology
Volume4
Issue number10
Early online date03 Sep 2016
DOIs
Publication statusPublished - Oct 2016

Keywords

  • Journal Article

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