Lipid-related markers and cardiovascular disease prediction.
BACKGROUND
The value of assessing various emerging lipid-related markers for prediction of first cardiovascular events is debated.


OBJECTIVE
To determine whether adding information on apolipoprotein B and apolipoprotein A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 to total cholesterol and high-density lipoprotein cholesterol (HDL-C) improves cardiovascular disease (CVD) risk prediction.


METHODS
Individual records were available for 165,544 participants without baseline CVD in 37 prospective cohorts (calendar years of recruitment: 1968-2007) with up to 15,126 incident fatal or nonfatal CVD outcomes (10,132 CHD and 4994 stroke outcomes) during a median follow-up of 10.4 years (interquartile range, 7.6-14 years).


METHODS
Discrimination of CVD outcomes and reclassification of participants across predicted 10-year risk categories of low (<10%), intermediate (10%-<20%), and high (≥20%) risk.


RESULTS
The addition of information on various lipid-related markers to total cholesterol, HDL-C, and other conventional risk factors yielded improvement in the model's discrimination: C-index change, 0.0006 (95% CI, 0.0002-0.0009) for the combination of apolipoprotein B and A-I; 0.0016 (95% CI, 0.0009-0.0023) for lipoprotein(a); and 0.0018 (95% CI, 0.0010-0.0026) for lipoprotein-associated phospholipase A2 mass. Net reclassification improvements were less than 1% with the addition of each of these markers to risk scores containing conventional risk factors. We estimated that for 100,000 adults aged 40 years or older, 15,436 would be initially classified at intermediate risk using conventional risk factors alone. Additional testing with a combination of apolipoprotein B and A-I would reclassify 1.1%; lipoprotein(a), 4.1%; and lipoprotein-associated phospholipase A2 mass, 2.7% of people to a 20% or higher predicted CVD risk category and, therefore, in need of statin treatment under Adult Treatment Panel III guidelines.


CONCLUSIONS
In a study of individuals without known CVD, the addition of information on the combination of apolipoprotein B and A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 mass to risk scores containing total cholesterol and HDL-C led to slight improvement in CVD prediction.
Emanuele
E
Di Angelantonio
Pei
P
Gao
Lisa
L
Pennells
Stephen
S
Kaptoge
Muriel
M
Caslake
Alexander
A
Thompson
Adam S
AS
Butterworth
Nadeem
N
Sarwar
David
D
Wormser
Danish
D
Saleheen
Christie M
CM
Ballantyne
Bruce M
BM
Psaty
Johan
J
Sundström
Paul M
PM
Ridker
Dorothea
D
Nagel
Richard F
RF
Gillum
Ian
I
Ford
Pierre
P
Ducimetiere
Stefan
S
Kiechl
Wolfgang
W
Koenig
Robin P F
RP
Dullaart
Gerd
G
Assmann
Ralph B
RB
D'Agostino
Gilles R
GR
Dagenais
Jackie A
JA
Cooper
Daan
D
Kromhout
Altan
A
Onat
Robert W
RW
Tipping
Agustín
A
Gómez-de-la-Cámara
Annika
A
Rosengren
Susan E
SE
Sutherland
John
J
Gallacher
F Gerry R
FG
Fowkes
Edoardo
E
Casiglia
Albert
A
Hofman
Veikko
V
Salomaa
Elizabeth
E
Barrett-Connor
Robert
R
Clarke
Eric
E
Brunner
J Wouter
JW
Jukema
Leon A
LA
Simons
Manjinder
M
Sandhu
Nicholas J
NJ
Wareham
Kay-Tee
KT
Khaw
Jussi
J
Kauhanen
Jukka T
JT
Salonen
William J
WJ
Howard
Børge G
BG
Nordestgaard
Angela M
AM
Wood
Simon G
SG
Thompson
S Matthijs
SM
Boekholdt
Naveed
N
Sattar
Chris
C
Packard
Vilmundur
V
Gudnason
John
J
Danesh
D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology*; D008076:Cholesterol, HDL / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment
D015415:Biomarkers; D008076:Cholesterol, HDL; D008074:Lipoproteins