TY - JOUR T1 - Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis. JF - Lancet Diabetes Endocrinol Y1 - 2016 A1 - Willeit, Peter A1 - Kaptoge, Stephen A1 - Welsh, Paul A1 - Butterworth, Adam A1 - Chowdhury, Rajiv A1 - Spackman, Sarah A1 - Pennells, Lisa A1 - Gao, Pei A1 - Burgess, Stephen A1 - Freitag, Daniel A1 - Sweeting, Michael A1 - Wood, Angela A1 - Cook, Nancy A1 - Judd, Suzanne A1 - Trompet, Stella A1 - Nambi, Vijay A1 - Olsen, Michael A1 - Everett, Brendan A1 - Kee, Frank A1 - Arnlöv, Johan A1 - Salomaa, Veikko A1 - Levy, Daniel A1 - Kauhanen, Jussi A1 - Laukkanen, Jari A1 - Kavousi, Maryam A1 - Ninomiya, Toshiharu A1 - Casas, Juan-Pablo A1 - Daniels, Lori A1 - Lind, Lars A1 - Kistorp, Caroline A1 - Rosenberg, Jens A1 - Mueller, Thomas A1 - Rubattu, Speranza A1 - Panagiotakos, Demosthenes A1 - Franco, Oscar A1 - de Lemos, James A1 - Luchner, Andreas A1 - Kizer, Jorge A1 - Kiechl, Stefan A1 - Salonen, Jukka A1 - Goya Wannamethee, S A1 - de Boer, Rudolf A1 - Nordestgaard, Børge A1 - Andersson, Jonas A1 - Jørgensen, Torben A1 - Melander, Olle A1 - Ballantyne, Christie A1 - DeFilippi, Christopher A1 - Ridker, Paul A1 - Cushman, Mary A1 - Rosamond, Wayne A1 - Thompson, Simon A1 - Gudnason, Vilmundur A1 - Sattar, Naveed A1 - Danesh, John A1 - Di Angelantonio, Emanuele KW - Aged KW - Biomarkers KW - Cardiovascular Diseases KW - Female KW - Humans KW - Male KW - Middle Aged KW - Natriuretic Peptide, Brain KW - Peptide Fragments KW - Prospective Studies KW - Risk Assessment AB -

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.

VL - 4 IS - 10 ER -