Lipoprotein(a) as a cardiovascular risk factor: current status.
OBJECTIVE
The aims of the study were, first, to critically evaluate lipoprotein(a) [Lp(a)] as a cardiovascular risk factor and, second, to advise on screening for elevated plasma Lp(a), on desirable levels, and on therapeutic strategies.


RESULTS
The robust and specific association between elevated Lp(a) levels and increased cardiovascular disease (CVD)/coronary heart disease (CHD) risk, together with recent genetic findings, indicates that elevated Lp(a), like elevated LDL-cholesterol, is causally related to premature CVD/CHD. The association is continuous without a threshold or dependence on LDL- or non-HDL-cholesterol levels. Mechanistically, elevated Lp(a) levels may either induce a prothrombotic/anti-fibrinolytic effect as apolipoprotein(a) resembles both plasminogen and plasmin but has no fibrinolytic activity, or may accelerate atherosclerosis because, like LDL, the Lp(a) particle is cholesterol-rich, or both. We advise that Lp(a) be measured once, using an isoform-insensitive assay, in subjects at intermediate or high CVD/CHD risk with premature CVD, familial hypercholesterolaemia, a family history of premature CVD and/or elevated Lp(a), recurrent CVD despite statin treatment, ≥3% 10-year risk of fatal CVD according to European guidelines, and/or ≥10% 10-year risk of fatal + non-fatal CHD according to US guidelines. As a secondary priority after LDL-cholesterol reduction, we recommend a desirable level for Lp(a) <80th percentile (less than ∼50 mg/dL). Treatment should primarily be niacin 1-3 g/day, as a meta-analysis of randomized, controlled intervention trials demonstrates reduced CVD by niacin treatment. In extreme cases, LDL-apheresis is efficacious in removing Lp(a).


CONCLUSIONS
We recommend screening for elevated Lp(a) in those at intermediate or high CVD/CHD risk, a desirable level <50 mg/dL as a function of global cardiovascular risk, and use of niacin for Lp(a) and CVD/CHD risk reduction.
Nordestgaard
Børge G
BG
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, DK-2730 Herlev, Denmark. brno@heh.regionh.dk
Chapman
M John
MJ
Ray
Kausik
K
Borén
Jan
J
Andreotti
Felicita
F
Watts
Gerald F
GF
Ginsberg
Henry
H
Amarenco
Pierre
P
Catapano
Alberico
A
Descamps
Olivier S
OS
Fisher
Edward
E
Kovanen
Petri T
PT
Kuivenhoven
Jan Albert
JA
Lesnik
Philippe
P
Masana
Luis
L
Reiner
Zeljko
Z
Taskinen
Marja-Riitta
MR
Tokgözoglu
Lale
L
Tybjærg-Hansen
Anne
A
D000367:Age Factors; D000818:Animals; D002318:Cardiovascular Diseases / Q000097:blood* / Q000235:genetics / Q000517:prevention & control; D003327:Coronary Disease / Q000097:blood / Q000235:genetics / Q000517:prevention & control; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D006951:Hyperlipoproteinemias / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D007118:Immunoassay / Q000379:methods; D017270:Lipoprotein(a) / Q000097:blood* / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018579:Patient Selection; D012307:Risk Factors; D012737:Sex Factors
D017270:Lipoprotein(a)