Emerging Pharmacotherapy to Reduce Elevated Lipoprotein(a) Plasma Levels

Eraikhuemen, Nathaniel; Lazaridis, Dovena; Dutton, Matthew

doi:10.1007/s40256-020-00437-7

Cited by 15 publications

(8 citation statements)

References 47 publications

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“…Bile acid sequestrants (colesevalem, cholestyramine, and colestipol) interrupt the enterohepatic circulation of bile acids [ 70 ]. Thus, they increase the conversion of cholesterol into bile acids and upregulate LDL receptors.…”

Section: Lp(a)-lowering Therapiesmentioning

confidence: 99%

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Effects of Lipid-Modifying and Other Drugs on Lipoprotein(a) Levels—Potent Clinical Implications

et al. 2023

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The past few years have shown an ongoing interest in lipoprotein(a) (Lp(a)), a lipid molecule that has been proven to have atherogenic, thrombogenic, and inflammatory properties. Several lines of evidence, indeed, have demonstrated an increased risk of cardiovascular disease as well as calcific aortic valve stenosis in patients with elevated Lp(a) levels. Statins, the mainstay of lipid-lowering therapy, slightly increase Lp(a) levels, while most other lipid-modifying agents do not significantly alter Lp(a) concentrations, except for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. The latter have been shown to reduce Lp(a) levels; however, the clinical significance of this effect has not been clearly elucidated. Of note, the pharmaceutical lowering of Lp(a) may be achieved with novel treatments specifically designed for this purpose (i.e., antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs)). Large clinical trials with cardiovascular outcomes with these agents are ongoing, and their results are eagerly awaited. Furthermore, several non-lipid-modifying drugs of various classes may influence Lp(a) concentrations. We have searched MEDLINE, EMBASE, and CENTRAL databases up to 28 January 2023 and summarized the effects of established and emerging lipid-modifying drugs and other medications on Lp(a) levels. We also discuss the potent clinical implications of these alterations.

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Section: Lp(a)-lowering Therapiesmentioning

confidence: 99%

“…Thus, they increase the conversion of cholesterol into bile acids and upregulate LDL receptors. These drugs have not been shown to affect Lp(a) levels [ 70 ].…”

Section: Lp(a)-lowering Therapiesmentioning

confidence: 99%

Effects of Lipid-Modifying and Other Drugs on Lipoprotein(a) Levels—Potent Clinical Implications

et al. 2023

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“…There is a consensus of the European Atherosclerosis Society that Lp(a) levels >50 mg/dL (corresponding to approximately 120 nmol/L) represent a risk factor for CHD and require treatment. In a recent review article, Eraikhuemen et al [ 34 ] comprehensively addressed this topic. For a long time, no medication was available that substantially lowered Lp(a).…”

Section: Lp(a)—one Of the Most Atherogenic Lipoproteinsmentioning

confidence: 99%

“…We can only summarize from data reported in Refs. [ 34 , 35 , 36 ] and state that: (1) There is no inherent effect on plasma Lp(a) levels caused by T1DM. (2) T1DM patients that are well-controlled have comparable Lp(a) levels to controls.…”

Section: Lp(a) and Diabetes Mellitus (Dm)mentioning

confidence: 99%

Lp(a) and the Risk for Cardiovascular Disease: Focus on the Lp(a) Paradox in Diabetes Mellitus

Kostner

2022

IJMS

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Lipoprotein(a) (Lp(a)) is one of the strongest causal risk factors of atherosclerotic disease. It is rich in cholesteryl ester and composed of apolipoprotein B and apo(a). Plasma Lp(a) levels are determined by apo(a) transcriptional activity driven by a direct repeat (DR) response element in the apo(a) promoter under the control of (HNF)4α Farnesoid-X receptor (FXR) ligands play a key role in the downregulation of APOA expression. In vitro studies on the catabolism of Lp(a) have revealed that Lp(a) binds to several specific lipoprotein receptors; however, their in vivo role remains elusive. There are more than 1000 publications on the role of diabetes mellitus (DM) in Lp(a) metabolism; however, the data is often inconsistent and confusing. In patients suffering from Type-I diabetes mellitus (T1DM), provided they are metabolically well-controlled, Lp(a) plasma concentrations are directly comparable to healthy individuals. In contrast, there exists a paradox in T2DM patients, as many of these patients have reduced Lp(a) levels; however, they are still at an increased cardiovascular risk. The Lp(a) lowering mechanism observed in T2DM patients is most probably caused by mutations in the mature-onset diabetes of the young (MODY) gene and possibly other polymorphisms in key transcription factors of the apolipoprotein (a) gene (APOA).

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“…The LPA is atherogenic lipoprotein that was synthesized by the liver and has a strong genetic regulation by a single gene, so its plasma concentration is a hereditary character [8] . Plasma LPA was not affected by statins thus its turnover was not through LDL receptors [9] , but was taken by macrophage (M) receptors to form foam cells responsible for the development and progression of atherosclerosis [10] .…”

Section: Introductionmentioning

confidence: 99%

The Relation between Deregulated Immune Milieu and Atherogenic Lipids Might Underlie the Development of Pregnancy-induced Hypertensive Disorders

Zaher

Rageh

Morsy

2023

Evidence Based Women's Health Journal

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Objectives: Evaluation of the relation between plasma lipoprotein(a) (LPA) and serum tumor necrosis factor-α (TNF-α) levels estimated in blood samples (S1 sample) obtained at the 6th gestational week (GW; T1 time) and the development of preeclampsia (PE) as judged by blood pressure measures at the time of diagnosis of PE (T2 time). Patients and Methods: 140 newly pregnant women gave S1 sample at T1 time; during pregnancy 19 women developed early-onset PE (EOPE) and 51 women developed late-onset PE (LOPE); 16 women developed severe PE (SPE) and 54 women developed mild PE (MPE), while 70 women were normotensive (NT) till the end of pregnancy. At T2 time, all patients gave S2 sample for ELISA estimation of plasma LPA and serum TNF-α level in both samples. Results: Serum TNF-α and plasma LPA levels were significantly higher in all S2 than S1 samples, in both samples of PE than NT women, and in both samples of women who developed EOPE and/or SPE than in samples of women who developed LOPE and/or MPE, respectively. Regression analysis of T1 data defined high body mass index; BMI (β=0.162, P=0.028), high S1 levels of TNF-α (β=0.424, P<0.001), and LPA (β=0.314, P<0.001) as predictors for development of PE as judged by SBP measures at T2 time. Correlation analysis showed a positive significant (P<0.001) correlation between at-T2-SBP measures with at-T1 BMI and S1 levels of TNF-α and LPA with a positive significant correlation between levels of both variables and with at-T1 BMI. Conclusion: High serum levels of TNF-α and plasma LPA levels early in pregnancy could predict the development of PE and its severity.

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Emerging Pharmacotherapy to Reduce Elevated Lipoprotein(a) Plasma Levels

Cited by 15 publications

References 47 publications

Effects of Lipid-Modifying and Other Drugs on Lipoprotein(a) Levels—Potent Clinical Implications

Effects of Lipid-Modifying and Other Drugs on Lipoprotein(a) Levels—Potent Clinical Implications

Lp(a) and the Risk for Cardiovascular Disease: Focus on the Lp(a) Paradox in Diabetes Mellitus

The Relation between Deregulated Immune Milieu and Atherogenic Lipids Might Underlie the Development of Pregnancy-induced Hypertensive Disorders

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