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



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.



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.



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.



British Heart Foundation, Austrian Science Fund, UK Medical Research Council, National Institute for Health Research, European Research Council, and European Commission Framework Programme 7.
Natriuretic Peptides Studies Collaboration
Peter
P
Willeit
Stephen
S
Kaptoge
Paul
P
Welsh
Adam
AS
Butterworth
Rajiv
R
Chowdhury
Sarah
SA
Spackman
Lisa
L
Pennells
Pei
P
Gao
Stephen
S
Burgess
Daniel
DF
Freitag
Michael
M
Sweeting
Angela
AM
Wood
Nancy
NR
Cook
Suzanne
S
Judd
Stella
S
Trompet
Vijay
V
Nambi
Michael
MH
Olsen
Brendan
BM
Everett
Frank
F
Kee
Johan
J
Ärnlöv
Veikko
V
Salomaa
Daniel
D
Levy
Jussi
J
Kauhanen
Jari
JA
Laukkanen
Maryam
M
Kavousi
Toshiharu
T
Ninomiya
Juan-Pablo
JP
Casas
Lori
LB
Daniels
Lars
L
Lind
Caroline
CN
Kistorp
Jens
J
Rosenberg
Thomas
T
Mueller
Speranza
S
Rubattu
Demosthenes
DB
Panagiotakos
Oscar
OH
Franco
James
JA
de Lemos
Andreas
A
Luchner
Jorge
JR
Kizer
Stefan
S
Kiechl
Jukka
JT
Salonen
S
S
Goya Wannamethee
Rudolf
RA
de Boer
Børge
BG
Nordestgaard
Jonas
J
Andersson
Torben
T
Jørgensen
Olle
O
Melander
Christie
ChM
Ballantyne
Christopher
Ch
DeFilippi
Paul
PM
Ridker
Mary
M
Cushman
Wayne
WD
Rosamond
Simon
SG
Thompson
Vilmundur
V
Gudnason
Naveed
N
Sattar
John
J
Danesh
Emanuele
E
Di Angelantonio
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D018570:Risk Assessment
D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain