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: 14.72). 10/2010; 31(23):2844-53. DOI: 10.1093/eurheartj/ehq386
Source: PubMed

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.

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Available from: Edward Fisher, Aug 27, 2015
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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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    • "This proof of concept imaging study compared the effect of weekly specific Lp(a) apheresis with standard medical approach on coronary disease progression. As an acute effect, Lp(a) apheresis reduced Lp(a) to a mean of 30 mg/ dL which is currently considered an appropriate target level [1]. In both regimens, mean values of LDL-C reached recommended goals less than 2.6 mmol/L during the whole study period. "
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    ABSTRACT: To evaluate the effect of specific lipoprotein(a) [Lp(a)] apheresis on coronary atherosclerosis progression in coronary heart disease (CHD) patients with elevated Lp(a) levels. A total of 30 subjects (mean age 53.5 ± 8.3 years, 70% male) with CHD verified by angiography, Lp(a) > 50 mg/dL, and low density lipoprotein cholesterol (LDL-C) ≤ 2.5 mmol/L on chronic statin treatment were prospectively evaluated for 18 months. Patients were allocated to receive specific Lp(a) apheresis, which was carried out weekly with Lp(a) Lipopak(®) columns (POCARD Ltd., Russia) (n = 15), or atorvastatin only (n = 15). Blinded quantitative coronary angiography analyses of percent diameter stenosis and minimal lumen diameter (MLD) were performed at baseline and after the 18-month treatment period. By the single specific Lp(a) apheresis procedure, Lp(a) level decreased by an average of 73 ± 12% to a mean of 29 ± 16 mg/dL, and mean Lp(a)-corrected LDL-C decreased by 7% to a mean of 1.4 mmol/L. Median percent diameter stenosis was reduced by -2.0 (95% confidence interval [CI], -5.0-0.0) with apheresis (p < 0.01 in comparison with baseline), and increased by 3.5 (0.0-6.9) with atorvastatin (p < 0.001 between the groups). The effect on MLD was more favorable with apheresis than with atorvastatin: 0.20 ± 0.39 mm, as compared with 0.01 ± 0.34 mm, p = 0.04. Lp(a) apheresis had greater efficacy regarding the amount of regressed/stabilized coronary segments than atorvastatin alone in the majority of patients (chi-square test 13.61, p < 0.005). Specific Lp(a) apheresis for 18 months produced coronary atherosclerosis regression in stable CHD patients with high Lp(a) levels and reached LDL-C goals.
    Atherosclerosis. Supplements 01/2013; 14(1):93-9. DOI:10.1016/j.atherosclerosissup.2012.10.015 · 9.67 Impact Factor
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    • "Although plasma levels of Lp(a) are similar in both men and women, gender influences the cardiovascular risk. At similarly high levels of plasma Lp(a), women are more likely to experience CHD than men [2] [17]. "
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    ABSTRACT: BACKGROUND AND PURPOSE: Lipoprotein (Lp) (a) is a neglected element of the blood lipid profile. It is now recognized as a determinant of coronary heart disease progression and its role in atherosclerosis and its ability to induce thrombosis make it potentially important in the course of normal and complicated pregnancies. Pregnancy involves a major transformation of metabolism to sustain fetal growth. Multiple studies have been conducted on Lp(a) in pregnancy, and it is timely to synthesize and evaluate this evidence. METHODS AND SUBJECTS: We reviewed the MEDLINE database for all articles published concerning "lipoprotein a" and "pregnancy" from May 2003 to May 2012. A previous comprehensive review assessed the literature up to May 2003. RESULTS: We critically analyzed 14 studies detailing the effect of complications in pregnancy on Lp(a) profile, and subsequent pregnancy outcomes where available. Studies evaluating the normal metabolic response to pregnancy, pregnancies complicated by pre-eclampsia and intra-uterine growth restriction were reviewed. CONCLUSIONS: A substantial mass of data has accumulated describing Lp(a) changes in pregnancy. The diversity of study design limits the ability to draw broad-ranging conclusions, but brings into focus the important questions remaining, which we discuss.
    Journal of Cardiology 11/2012; 61(1-2). DOI:10.1016/j.jjcc.2012.09.009 · 2.57 Impact Factor
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