Lipoprotein(a): novel target and emergence of novel therapies to lower cardiovascular disease risk

Current Opinion in Endocrinology, Diabetes, and Obesity
Sotirios Tsimikas

Abstract

This article summarizes recent observations on the role of lipoprotein(a) [Lp(a)] as a risk factor mediating cardiovascular disease. Lp(a) is a highly prevalent cardiovascular risk factor, with levels above 30 mg/dl affecting 20-30% of the global population. Up until now, no specific therapies have been developed to lower Lp(a) levels. Three major levels of evidence support the notion that elevated Lp(a) levels are a causal, independent, genetic risk factor for cardiovascular disease: epidemiologic studies and meta-analyses, genome-wide association studies and Mendelian randomization studies. Recent studies also have noted that individuals with low levels of Lp(a) are associated with a higher risk of incident type 2 diabetes mellitus, and conversely individuals with high levels have a lower risk, but this association does not appear to be causal. Novel therapies to lower Lp(a) include PCSK9 inhibitors and antisense oligonucleotides directly preventing translation of apolipoprotein(a) mRNA. With this robust and expanding clinical database, a reawakening of interest in Lp(a) as clinical risk factor is taking place. Trials are underway with novel drugs that substantially lower Lp(a) and may reduce its contribution to cardiovascula...Continue Reading

References

Aug 26, 1998·Arteriosclerosis, Thrombosis, and Vascular Biology·D L Rainwater, S M Haffner
Apr 19, 2000·JAMA : the Journal of the American Medical Association·M G ShlipakS B Hulley
Feb 11, 2003·Journal of the American College of Cardiology·Sotirios TsimikasJoseph L Witztum
Mar 17, 2004·Current Opinion in Lipidology·Marlys L Koschinsky, Santica M Marcovina
Sep 9, 2004·Circulation·Sotirios TsimikasUNKNOWN Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators
Jan 27, 2006·European Journal of Clinical Investigation·C H SaelyH Drexel
Jun 16, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·May M LukeStephen G Ellis
Jun 11, 2009·JAMA : the Journal of the American Medical Association·Pia R KamstrupBørge G Nordestgaard
Jul 23, 2009·JAMA : the Journal of the American Medical Association·UNKNOWN Emerging Risk Factors CollaborationJohn Danesh
Dec 25, 2009·The New England Journal of Medicine·Robert ClarkeUNKNOWN PROCARDIS Consortium
Jun 1, 2010·Clinical Chemistry·Samia MoraPaul M Ridker
Oct 23, 2010·European Heart Journal·Børge G NordestgaardUNKNOWN European Atherosclerosis Society Consensus Panel
Apr 9, 2011·Journal of the American College of Cardiology·Esther MerkiSotirios Tsimikas
Oct 20, 2011·Circulation. Cardiovascular Genetics·Yonghong LiJames J Devlin
Aug 30, 2012·Journal of Lipid Research·Indumathi ChennamsettyGerhard M Kostner
Sep 25, 2012·Journal of Internal Medicine·F Kronenberg, G Utermann
Dec 4, 2012·Nature Genetics·Panos DeloukasNilesh J Samani
Oct 29, 2013·Journal of the American College of Cardiology·Michelle L O'DonoghueMarc S Sabatine
Mar 14, 2014·The Lancet. Diabetes & Endocrinology·Pia R Kamstrup, Børge G Nordestgaard
Sep 12, 2015·Journal of the American College of Cardiology·Romain CapouladeSotirios Tsimikas

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Citations

Apr 28, 2016·Journal of Diabetes and Its Complications·Calvin Yeang, Sotirios Tsimikas
Jun 2, 2016·Expert Opinion on Biological Therapy·Anthony S Wierzbicki, Adie Viljoen
Aug 9, 2016·Progress in Cardiovascular Diseases·Sotirios Tsimikas
Nov 3, 2016·Journal of Lipid Research·Børge G Nordestgaard, Anne Langsted
May 11, 2018·Clinical Cardiology·Jay KhambhatiLaurence S Sperling
Jun 8, 2018·Current Opinion in Lipidology·Valentina RodriguezArthur Z Schwartzbard
Jul 13, 2018·Clinical Pharmacology and Therapeutics·William Virgil Brown
Oct 28, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Steve VarvelSotirios Tsimikas
Dec 22, 2017·Critical Reviews in Clinical Laboratory Sciences·Corey A ScipioneMichael B Boffa
Jan 6, 2018·Expert Review of Clinical Pharmacology·Niki KatsikiDimitri P Mikhailidis
Apr 28, 2020·Circulation Journal : Official Journal of the Japanese Circulation Society·Albert Youngwoo JangKwang Kon Koh
Sep 25, 2019·Journal of Atherosclerosis and Thrombosis·Yuji Hirowatari, Hiroshi Yoshida
Apr 21, 2020·Vascular Health and Risk Management·I Dewa Gde Dwi SumarjayaAnak Agung Wiradewi Lestari
Mar 7, 2019·Clinical Research in Cardiology Supplements·V J J SchettlerUNKNOWN Scientific Board of GLAR for the German Apheresis Working Group
Nov 13, 2020·Circulation Journal : Official Journal of the Japanese Circulation Society·Albert Youngwoo JangKwang Kon Koh
Feb 11, 2021·British Journal of Pharmacology·Andrew P Sage, Charalambos Antoniades
Jan 21, 2021·Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·Yehuda HandelsmanKathleen L Wyne
Feb 20, 2021·Diabetes & Metabolic Syndrome·Sridevi Devaraj, Ishwarlal Jialal

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Methods Mentioned

BETA
antisense oligonucleotide
transgenic
antisense oligonucleotides

Clinical Trials Mentioned

NCT02160899
NCT02414594

Software Mentioned

JUPITER

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