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Lipoprotein(a) as a cardiovascular risk factor: current status.

Nordestgaard BG, Chapman MJ, Ray K, Borén J, Andreotti F, Watts GF, Ginsberg H, Amarenco P, Catapano A, Descamps OS, Fisher E, Kovanen PT, Kuivenhoven JA, Lesnik P, Masana L, Reiner Z, Taskinen MR, Tokgözoglu L, Tybjærg-Hansen A, European Atherosclerosis Society Consensus Pan - Eur. Heart J. (2010)

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, DK-2730 Herlev, Denmark. brno@heh.regionh.dk

ABSTRACT

Aims: 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.

Methods and 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).

Conclusion: 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.

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Related in: MedlinePlus

Typical distributions of lipoprotein(a) levels in the general population. These graphs are based on non-fasting fresh serum samples from ∼3000 men and 3000 women from the Copenhagen General Population Study collected from 2003 through 2004.2 Green colour indicates levels below the 80th percentile, whereas red colour indicates levels above the 80th percentile.
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EHQ386F2: Typical distributions of lipoprotein(a) levels in the general population. These graphs are based on non-fasting fresh serum samples from ∼3000 men and 3000 women from the Copenhagen General Population Study collected from 2003 through 2004.2 Green colour indicates levels below the 80th percentile, whereas red colour indicates levels above the 80th percentile.

Mentions: Typical distributions of Lp(a) in Caucasians are shown in Figure 2: plasma levels of Lp(a) are similar in men and women and are skewed in the population with a tail towards the highest levels. Levels are lowest in non-Hispanic Caucasians (e.g. median: 12 mg/dL; inter-quartile range: 5–32),5 Chinese (11, 4–22), and Japanese (13, 5–26), slightly higher in Hispanics (19, 8–43), and even higher levels in Blacks (39, 19–69).1,5 It is significant that Lp(a) has been surrounded by controversy among clinicians for more than 20 years, and the various conceptions and misconceptions are summarized and explained in Supplementary material online, Table S1.Figure 2


Lipoprotein(a) as a cardiovascular risk factor: current status.

Nordestgaard BG, Chapman MJ, Ray K, Borén J, Andreotti F, Watts GF, Ginsberg H, Amarenco P, Catapano A, Descamps OS, Fisher E, Kovanen PT, Kuivenhoven JA, Lesnik P, Masana L, Reiner Z, Taskinen MR, Tokgözoglu L, Tybjærg-Hansen A, European Atherosclerosis Society Consensus Pan - Eur. Heart J. (2010)

Typical distributions of lipoprotein(a) levels in the general population. These graphs are based on non-fasting fresh serum samples from ∼3000 men and 3000 women from the Copenhagen General Population Study collected from 2003 through 2004.2 Green colour indicates levels below the 80th percentile, whereas red colour indicates levels above the 80th percentile.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3295201&req=5

EHQ386F2: Typical distributions of lipoprotein(a) levels in the general population. These graphs are based on non-fasting fresh serum samples from ∼3000 men and 3000 women from the Copenhagen General Population Study collected from 2003 through 2004.2 Green colour indicates levels below the 80th percentile, whereas red colour indicates levels above the 80th percentile.
Mentions: Typical distributions of Lp(a) in Caucasians are shown in Figure 2: plasma levels of Lp(a) are similar in men and women and are skewed in the population with a tail towards the highest levels. Levels are lowest in non-Hispanic Caucasians (e.g. median: 12 mg/dL; inter-quartile range: 5–32),5 Chinese (11, 4–22), and Japanese (13, 5–26), slightly higher in Hispanics (19, 8–43), and even higher levels in Blacks (39, 19–69).1,5 It is significant that Lp(a) has been surrounded by controversy among clinicians for more than 20 years, and the various conceptions and misconceptions are summarized and explained in Supplementary material online, Table S1.Figure 2

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, DK-2730 Herlev, Denmark. brno@heh.regionh.dk

ABSTRACT

Aims: 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.

Methods and 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).

Conclusion: 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.

Show MeSH
Related in: MedlinePlus