Assessment of conventional cardiovascular risk factors and multiple biomarkers for the prediction of incident heart failure and atrial fibrillation.
OBJECTIVE
the purpose of this study was to assess the predictive accuracy of conventional cardiovascular risk factors for incident heart failure and atrial fibrillation, and the added benefit of multiple biomarkers reflecting diverse pathophysiological pathways.


BACKGROUND
heart failure and atrial fibrillation are interrelated cardiac diseases associated with substantial morbidity and mortality and increasing incidence. Data on prediction and prevention of these diseases in healthy individuals are limited.


METHODS
in 5,187 individuals from the community-based MDCS (Malmö Diet and Cancer Study), we studied the performance of conventional risk factors and 6 biomarkers including midregional pro-atrial natriuretic peptide (MR-proANP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional pro-adrenomedullin, cystatin C, C-reactive protein (CRP), and copeptin.


RESULTS
during a mean follow-up of 14 years, 112 individuals were diagnosed with heart failure and 284 individuals with atrial fibrillation. NT-proBNP (hazard ratio [HR]: 1.63 per SD, 95% confidence interval [CI]: 1.29 to 2.06, p < 0.001), CRP (HR: 1.57 per SD, 95% CI: 1.28 to 1.94, p < 0.001), and MR-proANP (HR: 1.26 per SD, 95% CI: 1.02 to 1.56, p = 0.03) predicted incident heart failure independently of conventional risk factors and other biomarkers. MR-proANP (HR: 1.62, 95% CI: 1.42 to 1.84, p < 0.001) and CRP (HR: 1.18, 95% CI: 1.03 to 1.34, p = 0.01) independently predicted atrial fibrillation. Addition of biomarkers to conventional risk factors improved c-statistics from 0.815 to 0.842 for heart failure and from 0.732 to 0.753 for atrial fibrillation and the integrated discrimination improvement for both diseases (p < 0.001). Net reclassification improvement (NRI) with biomarkers was observed in 22% of individuals for heart failure (NRI, p < 0.001) and in 7% for atrial fibrillation (NRI, p = 0.06), mainly due to up-classification of individuals who developed disease (heart failure: 29%, atrial fibrillation: 19%). Addition of CRP to natriuretic peptides did not improve discrimination or reclassification.


CONCLUSIONS
conventional cardiovascular risk factors predict incident heart failure and atrial fibrillation with reasonable accuracy in middle-age individuals free from disease. Natriuretic peptides, but not other biomarkers, improve discrimination modestly for both diseases above and beyond conventional risk factors and substantially improve risk classification for heart failure.
Department of Clinical Sciences, Lund University, Malmö, Sweden. gustav.smith@med.lu.se
J Gustav
JG
Smith
Christopher
C
Newton-Cheh
Peter
P
Almgren
Joachim
J
Struck
Nils G
NG
Morgenthaler
Andreas
A
Bergmann
Pyotr G
PG
Platonov
Bo
B
Hedblad
Gunnar
G
Engström
Thomas J
TJ
Wang
Olle
O
Melander
D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications / Q000453:epidemiology*; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D016001:Confidence Intervals; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D016017:Odds Ratio; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors; D012372:ROC Curve; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors
D015415:Biomarkers; D010446:Peptide Fragments; D011498:Protein Precursors; C552580:midregional pro-atrial natriuretic peptide, human; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D002097:C-Reactive Protein