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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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Risk of myocardial infarction by levels of lipoprotein(a) in the general population. Hazard ratios (HRs) are adjusted for cardiovascular risk factors (multivariable) or for these factors as well as kringle IV type 2 (KIV-2) genotype. P-values are test for trend of hazard ratios where lipoprotein(a) groups with increasing levels were coded 1, 2, 3, 4, and 5. Values are from the 1991–94 examination of the Copenhagen City Heart Study with up to 16 years of follow-up (n= 7524). CI, confidence interval. Modified from Kamstrup et al.2
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EHQ386F5: Risk of myocardial infarction by levels of lipoprotein(a) in the general population. Hazard ratios (HRs) are adjusted for cardiovascular risk factors (multivariable) or for these factors as well as kringle IV type 2 (KIV-2) genotype. P-values are test for trend of hazard ratios where lipoprotein(a) groups with increasing levels were coded 1, 2, 3, 4, and 5. Values are from the 1991–94 examination of the Copenhagen City Heart Study with up to 16 years of follow-up (n= 7524). CI, confidence interval. Modified from Kamstrup et al.2

Mentions: On the basis of the Copenhagen City Heart Study (CCHS), the Copenhagen General Population Study (CGPS), and the Copenhagen Ischemic Heart Disease Study (CIHDS) with 40 000 individuals genotyped for the kringle IV type 2 size polymorphism in the apolipoprotein(a) gene, a large Mendelian randomization study was published in 2009.2 In the CCHS, multifactorially adjusted hazard ratios for myocardial infarction for elevated lipoprotein(a) levels were 1.2 (95% CI: 0.9–1.6) for the 22nd–66th percentile, 1.6 (1.1–2.2) for the 67th–89th percentile, 1.9 (1.2–3.0) for the 90th–95th percentile, and 2.6 (1.6–4.1) for levels >95th percentile, respectively, vs. levels <22nd percentile (trend P< 0.001; Figure 5).2,11Figure 5


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)

Risk of myocardial infarction by levels of lipoprotein(a) in the general population. Hazard ratios (HRs) are adjusted for cardiovascular risk factors (multivariable) or for these factors as well as kringle IV type 2 (KIV-2) genotype. P-values are test for trend of hazard ratios where lipoprotein(a) groups with increasing levels were coded 1, 2, 3, 4, and 5. Values are from the 1991–94 examination of the Copenhagen City Heart Study with up to 16 years of follow-up (n= 7524). CI, confidence interval. Modified from Kamstrup et al.2
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

EHQ386F5: Risk of myocardial infarction by levels of lipoprotein(a) in the general population. Hazard ratios (HRs) are adjusted for cardiovascular risk factors (multivariable) or for these factors as well as kringle IV type 2 (KIV-2) genotype. P-values are test for trend of hazard ratios where lipoprotein(a) groups with increasing levels were coded 1, 2, 3, 4, and 5. Values are from the 1991–94 examination of the Copenhagen City Heart Study with up to 16 years of follow-up (n= 7524). CI, confidence interval. Modified from Kamstrup et al.2
Mentions: On the basis of the Copenhagen City Heart Study (CCHS), the Copenhagen General Population Study (CGPS), and the Copenhagen Ischemic Heart Disease Study (CIHDS) with 40 000 individuals genotyped for the kringle IV type 2 size polymorphism in the apolipoprotein(a) gene, a large Mendelian randomization study was published in 2009.2 In the CCHS, multifactorially adjusted hazard ratios for myocardial infarction for elevated lipoprotein(a) levels were 1.2 (95% CI: 0.9–1.6) for the 22nd–66th percentile, 1.6 (1.1–2.2) for the 67th–89th percentile, 1.9 (1.2–3.0) for the 90th–95th percentile, and 2.6 (1.6–4.1) for levels >95th percentile, respectively, vs. levels <22nd percentile (trend P< 0.001; Figure 5).2,11Figure 5

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