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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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Mean lipoprotein(a) levels in the Copenhagen City Heart Study as a function of quartiles of apolipoprotein(a) KIV-2 repeats. P-value is for the Cuzick non-parametric test for trend of mean lipoprotein(a) levels. Participants in the 1991–94 or 2001–03 examination were included (n= 9867). KIV-2, kringle IV type 2. Error bars indicate 95% confidence intervals. Modified from Kamstrup et al.2
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EHQ386F6: Mean lipoprotein(a) levels in the Copenhagen City Heart Study as a function of quartiles of apolipoprotein(a) KIV-2 repeats. P-value is for the Cuzick non-parametric test for trend of mean lipoprotein(a) levels. Participants in the 1991–94 or 2001–03 examination were included (n= 9867). KIV-2, kringle IV type 2. Error bars indicate 95% confidence intervals. Modified from Kamstrup et al.2

Mentions: The number of kringle IV type 2 repeats (sum of repeats on both alleles) ranged from 6 to 99 and explained 21 and 27% of all variation in plasma lipoprotein(a) levels in the CCHS and the CGPS, respectively.2 Mean lipoprotein(a) levels were 56, 31, 20, and 15 mg/dL for the first, second, third, and fourth quartiles of kringle IV type 2 repeats in the CCHS, respectively (trend P< 0.001; Figure 6); corresponding values in the CGPS were 60, 34, 22, and 19 mg/dL (trend P< 0.001).Figure 6


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)

Mean lipoprotein(a) levels in the Copenhagen City Heart Study as a function of quartiles of apolipoprotein(a) KIV-2 repeats. P-value is for the Cuzick non-parametric test for trend of mean lipoprotein(a) levels. Participants in the 1991–94 or 2001–03 examination were included (n= 9867). KIV-2, kringle IV type 2. Error bars indicate 95% confidence intervals. Modified from Kamstrup et al.2
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

EHQ386F6: Mean lipoprotein(a) levels in the Copenhagen City Heart Study as a function of quartiles of apolipoprotein(a) KIV-2 repeats. P-value is for the Cuzick non-parametric test for trend of mean lipoprotein(a) levels. Participants in the 1991–94 or 2001–03 examination were included (n= 9867). KIV-2, kringle IV type 2. Error bars indicate 95% confidence intervals. Modified from Kamstrup et al.2
Mentions: The number of kringle IV type 2 repeats (sum of repeats on both alleles) ranged from 6 to 99 and explained 21 and 27% of all variation in plasma lipoprotein(a) levels in the CCHS and the CGPS, respectively.2 Mean lipoprotein(a) levels were 56, 31, 20, and 15 mg/dL for the first, second, third, and fourth quartiles of kringle IV type 2 repeats in the CCHS, respectively (trend P< 0.001; Figure 6); corresponding values in the CGPS were 60, 34, 22, and 19 mg/dL (trend P< 0.001).Figure 6

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