Lipoprotein(a) as a cardiovascular risk factor: Current status

Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, DK-2730 Herlev, Denmark.
European Heart Journal (Impact Factor: 15.2). 10/2010; 31(23):2844-53. DOI: 10.1093/eurheartj/ehq386
Source: PubMed


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.

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    • "Lp(a) has similarities to both LDL and plasminogen and has therefore been proposed to possess proatherogenic properties, as well as prothrombotic properties16. The proposed proatherogenic mechanisms in vivo are numerous17. It has been suggested that Lp(a) or the apo(a) molecule contributes to foam cell formation, smooth muscle cell (SMC) proliferation and migration, endothelial dysfunction and vascular inflammation, all known as part of the atheroma development1819. "
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    ABSTRACT: Lipoprotein (a) [Lp(a)] is a low density lipoprotein (LDL) with one apolipoprotein (a) molecule bound to the apolipoprotein B-100 of LDL. Lp(a) is an independent risk factor for cardiovascular disease (CVD). However, the relationship of Lp(a) to diabetes and metabolic syndrome, both known for increased CVD risk, is controversial. In a population based study on type two diabetes mellitus (T2DM) development in women, Lp(a) plasma levels showed the well known skewed distribution without any relation to diabetes or impaired glucose tolerance. A modified clot lysis assay on a subset of 274 subjects showed significantly increased clot lysis times in T2DM subjects, despite inhibition of PAI-1 and TAFI. Lp(a) plasma levels significantly increased the maximal peak height of the clot lysis curve, indicating a change in clot structure. In this study Lp(a) is not related to the development of T2DM but may affect clot structure ex vivo without a prolongation of the clot lysis time.
    Scientific Reports 06/2014; 4:5318. DOI:10.1038/srep05318 · 5.58 Impact Factor
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    • "For sensitivity analysis in the KORA studies (fully adjusted models), the Lp(a) levels were dichotomized, applying a threshold value of 30 mg/dL as well as the recently suggested threshold value of 50 mg/dL.21 We observed significant associations with decreasing continuous ABI values in KORA F3 for Lp(a) >30 mg/dL (β = −0.016; "
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    ABSTRACT: The relevance of lipoprotein(a) [Lp(a)] concentrations and low molecular weight (LMW) apo(a) phenotypes in peripheral arterial disease (PAD) has only been investigated by few studies. Therefore, we analyzed this association in three independent cohorts and performed a Mendelian Randomization approach using instrumental variable regression.Methods&ResultsLp(a) concentrations, apo(a) phenotypes and one SNP in the LPA gene (rs10455872) were measured in the CAVASIC Study including 241 male patients with intermittent claudication and 246 age- and diabetes-matched controls as well as in the two population-based studies KORA F3 (n=3184) and KORA F4 (n=3080). In KORA F3/F4, 109/80 persons suffered from intermittent claudication, 200/144 from PAD and 128/103 showed an ankle-brachial index (ABI) <0.9. In CAVASIC adjusted logistic regression analyses revealed significant associations between an increase of log-Lp(a) per one standard deviation (SD) (OR=1.28, p=0.02) as well as LMW apo(a) phenotypes and symptomatic PAD (OR=1.65, p=0.03). Linear regression models with continuous ABI showed a significant association in the combined analyses of KORA F3/F4: an increase in log-Lp(a) per one SD (ß=-0.006, p=0.005) and the presence of LMW apo(a) phenotypes (ß=-0.011, p=0.02) or the minor allele of rs10455872 (ß=-0.016, p=0.03) were associated with a decrease in ABI in the fully adjusted linear and instrumental variable regression models. Analyses in three independent populations showed significant associations of Lp(a) concentrations, LMW apo(a) phenotypes and rs10455872 with PAD. This points to a causal relationship between Lp(a) and PAD since the genetically determined apo(a) phenotypes and SNP alleles are indeed associated with PAD.
    Cardiovascular Research 04/2014; 103(1). DOI:10.1093/cvr/cvu107 · 5.94 Impact Factor
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    • "Lp(a) is an LDL-like particle which has been linked to a glycoprotein which has been named as apolipoprotein(a). There is substantial evidence to suggest that elevated serum Lp(a) levels contribute significantly to the development of CHD [1] [2] [3] [4] [5]. "
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    ABSTRACT: Background and objective: Changes in plasma lipid concentrations are well known metabolic consequences of thyroid dysfunction. The alterations are most prominent in hypothyroidism which is typically associated with pronounced hypercholesterolaemia and frequently with moderate hypertriglyceridaemia. In cases of hypothyroidism, how the serum Lp(a) levels are influenced by thyroid hormone remains unknown and contradictory results on the effect of thyroid hormone on serum Lp(a) levels have been reported. There is substantial evidence to suggest that elevated serum Lp(a) levels contribute significantly to the development of CHD. The present study was designed to determine the lipoprotein(a) [Lp(a)], lipid profile and thyroid hormone levels in newly diagnosed hypothyroid patients and to find any correlation that existed between Lp(a) and other parameters. Materials and methods: Untreated hypothyroid (n=50) patients were included in the study. We also included 40 normal healthy subjects as controls. Lipid profile, Lp(a) and thyroid profile were estimated by using autoanalyzers. Results: The results of this study showed that levels of HDL-cholesterol were significantly decreased (p<0.001), whereas those of other lipid parameters and Lp(a) levels were found to be significantly increased (p<0.001) in hypothyroid patients as compared to those in controls. Correlation study revealed a significant positive correlation between Lp(a) and TSH levels in hypothyroid patients. Conclusion: Our present findings indicated that hypothyroidism could be strongly associated with lipid abnormalities that enhanced the development of cardiovascular diseases. Also, Lp(a) and non-HDL-C should be estimated with other lipid parameters as a useful index for measuring the cardiac risk in hypothyroid patients. A recommended screening should be advised for any patient with thyroid dysfunction, especially hypothyroidism, to assess lipid abnormalities by using Lp(a) and non- HDL-C and he/she should treated at the earliest.
    Journal of Clinical and Diagnostic Research 02/2014; 8(2):37-9. DOI:10.7860/JCDR/2014/7817.4001 · 0.23 Impact Factor
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