Contribution of 30 biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: the MONICA, risk, genetics, archiving, and monograph (MORGAM) biomarker project.
BACKGROUND
Cardiovascular risk estimation by novel biomarkers needs assessment in disease-free population cohorts, followed up for incident cardiovascular events, assaying the serum and plasma archived at baseline. We report results from 2 cohorts in such a continuing study.


RESULTS
Thirty novel biomarkers from different pathophysiological pathways were evaluated in 7915 men and women of the FINRISK97 population cohort with 538 incident cardiovascular events at 10 years (fatal or nonfatal coronary or stroke events), from which a biomarker score was developed and then validated in the 2551 men of the Belfast Prospective Epidemiological Study of Myocardial Infarction (PRIME) cohort (260 events). No single biomarker consistently improved risk estimation in FINRISK97 men and FINRISK97 women and the Belfast PRIME Men cohort after allowing for confounding factors; however, the strongest associations (with hazard ratio per SD in FINRISK97 men) were found for N-terminal pro-brain natriuretic peptide (1.23), C-reactive protein (1.23), B-type natriuretic peptide (1.19), and sensitive troponin I (1.18). A biomarker score was developed from the FINRISK97 cohort with the use of regression coefficients and lasso methods, with selection of troponin I, C-reactive protein, and N-terminal pro-brain natriuretic peptide. Adding this score to a conventional risk factor model in the Belfast PRIME Men cohort validated it by improved c-statistics (P=0.004) and integrated discrimination (P<0.0001) and led to significant reclassification of individuals into risk categories (P=0.0008).


CONCLUSIONS
The addition of a biomarker score including N-terminal pro-brain natriuretic peptide, C-reactive protein, and sensitive troponin I to a conventional risk model improved 10-year risk estimation for cardiovascular events in 2 middle-aged European populations. Further validation is needed in other populations and age groups.
Blankenberg
Stefan
S
Department of Medicine II, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany. blankenberg@2-med.klinik.uni-mainz.de
Zeller
Tanja
T
Saarela
Olli
O
Havulinna
Aki S
AS
Kee
Frank
F
Tunstall-Pedoe
Hugh
H
Kuulasmaa
Kari
K
Yarnell
John
J
Schnabel
Renate B
RB
Wild
Philipp S
PS
Münzel
Thomas F
TF
Lackner
Karl J
KJ
Tiret
Laurence
L
Evans
Alun
A
Salomaa
Veikko
V
D000328:Adult; D000368:Aged; D018070:Biological Specimen Banks / Q000592:standards; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis; D015331:Cohort Studies; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D009660:Northern Ireland; D011159:Population Surveillance / Q000379:methods*; D011446:Prospective Studies; D012307:Risk Factors; D013223:Statistics as Topic / Q000379:methods
D015415:Biomarkers