Lipoprotein(a) as a cardiovascular risk factor: current status
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Open Access
- 21 October 2010
- journal article
- review article
- Published by Oxford University Press (OUP) in European Heart Journal
- Vol. 31 (23) , 2844-2853
- https://doi.org/10.1093/eurheartj/ehq386
Abstract
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. 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). 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.Keywords
This publication has 52 references indexed in Scilit:
- Use of the Thyroid Hormone Analogue Eprotirome in Statin-Treated DyslipidemiaNew England Journal of Medicine, 2010
- Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosisPublished by Elsevier ,2010
- Lipoprotein(a) Concentration and the Risk of Coronary Heart Disease, Stroke, and Nonvascular MortalityJAMA, 2009
- Antisense Oligonucleotide Directed to Human Apolipoprotein B-100 Reduces Lipoprotein(a) Levels and Oxidized Phospholipids on Human Apolipoprotein B-100 Particles in Lipoprotein(a) Transgenic MiceCirculation, 2008
- Lipoprotein(a), Hormone Replacement Therapy, and Risk of Future Cardiovascular EventsJournal of the American College of Cardiology, 2008
- A Polymorphism in the Protease-Like Domain of Apolipoprotein(a) Is Associated With Severe Coronary Artery DiseaseArteriosclerosis, Thrombosis, and Vascular Biology, 2007
- Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts)European Journal of Preventive Cardiology, 2007
- Oxidized Phospholipids, Lp(a) Lipoprotein, and Coronary Artery DiseaseNew England Journal of Medicine, 2005
- Ethnic differences in cardiovascular risk factor burden among middle-aged women: Study of Women's Health Across the Nation (SWAN)American Heart Journal, 2005
- Modification of apolipoprotein(a) lysine binding site reduces atherosclerosis in transgenic mice.Journal of Clinical Investigation, 1997