Relations of biomarkers of distinct pathophysiological pathways and atrial fibrillation incidence in the community.
BACKGROUND
Biomarkers of multiple pathophysiological pathways have been related to incident atrial fibrillation (AF), but their predictive ability remains controversial.


RESULTS
In 3120 Framingham cohort participants (mean age 58.4+/-9.7 years, 54% women), we related 10 biomarkers that represented inflammation (C-reactive protein and fibrinogen), neurohormonal activation (B-type natriuretic peptide [BNP] and N-terminal proatrial natriuretic peptide), oxidative stress (homocysteine), the renin-angiotensin-aldosterone system (renin and aldosterone), thrombosis and endothelial function (D-dimer and plasminogen activator inhibitor type 1), and microvascular damage (urinary albumin excretion; n=2673) to incident AF (n=209, 40% women) over a median follow-up of 9.7 years (range 0.05 to 12.8 years). In multivariable-adjusted analyses, the biomarker panel was associated with incident AF (P<0.0001). In stepwise-selection models (P<0.01 for entry and retention), log-transformed BNP (hazard ratio per SD 1.62, 95% confidence interval 1.41 to 1.85, P<0.0001) and C-reactive protein (hazard ratio 1.25, 95% confidence interval 1.07 to 1.45, P=0.004) were chosen. The addition of BNP to variables recently combined in a risk score for AF increased the C-statistic from 0.78 (95% confidence interval 0.75 to 0.81) to 0.80 (95% confidence interval 0.78 to 0.83) and showed an integrated discrimination improvement of 0.03 (95% confidence interval 0.02 to 0.04, P<0.0001), with 34.9% relative improvement in reclassification analysis. The combined analysis of BNP and C-reactive protein did not appreciably improve risk prediction over the model that incorporated BNP in addition to the risk factors.


CONCLUSIONS
BNP is a predictor of incident AF and improves risk stratification based on well-established clinical risk factors. Whether knowledge of BNP concentrations may be used to target individuals at risk of AF for more intensive monitoring or primary prevention requires further investigation.
Schnabel
Renate B
RB
National Heart, Lung, and Blood Institute's and Boston University's Framingham Study, Framingham, Mass, USA.
Larson
Martin G
MG
Yamamoto
Jennifer F
JF
Sullivan
Lisa M
LM
Pencina
Michael J
MJ
Meigs
James B
JB
Tofler
Geoffrey H
GH
Selhub
Jacob
J
Jacques
Paul F
PF
Wolf
Philip A
PA
Magnani
Jared W
JW
Ellinor
Patrick T
PT
Wang
Thomas J
TJ
Levy
Daniel
D
Vasan
Ramachandran S
RS
Benjamin
Emelia J
EJ
D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D015415:Biomarkers / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D011237:Predictive Value of Tests; D012111:Residence Characteristics; D015398:Signal Transduction
D015415:Biomarkers; D020097:Natriuretic Peptide, Brain