Per American Heart Association (AHA), cardiovascular disease (CVD) remained number one cause of mortality in 2017 within United States with ~2.9 million deaths and ~17.8 million deaths globally [1]. Given the rising burden of CVD globally and many factors which lead to CVD, it has become crucial to explore and invest in its multi-faceted prevention. Lipoprotein (a) (Lp(a)) is an atherothrombotic molecule which may be overlooked in standard clinical practice when managing lipids and can lead to premature coronary artery disease, stroke [2,3] and aortic valve stenosis. Lp(a) is composed of apolipoprotein B-100, apolipoprotein (a) and low-density lipoprotein (LDL) like particle. Its atherogenic potential is supported by the LDL-like particle while the apo(a) brings about its thrombotic properties by meddling in plasminogen activation [4]. The Lp(a) is inherited and exists in variations > 1000 fold in-range (< 0.1 mg/dL to > 100 mg/dL) within the population with apolipoprotein (a) gene contributing to ~91% of this variation [5].

References

1. M Chang AR., et al. “Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association”. Circulation9 (2020): e139-e596.
2. Grützmacher P., et al. “Primary and secondary prevention of cardiovascular disease in patients with hyperlipoproteinemia (a)”. Clinical Research in Cardiology 12 (2017): 22-26.
3. Kostner KM., et al. “When should we measure lipoprotein (a)?” European Heart Journal 34 (2013): 3268-3276.
4. Allen S., et al. “Expression of adhesion molecules by lp(a): a potential novel mechanism for its atherogenicity”. The FASEB Journal 12 (1998): 1765-1776.
5. Boerwinkle E., et al. “Apolipoprotein (a) gene accounts for greater than 90% of the variation in plasma lipoprotein (a) concentrations”. Journal of Clinical Investigation 90 (1992): 52.
6. Sumarjaya IDGD., et al. “High Lipoprotein(a) Levels as a Predictor of Major Adverse Cardiovascular Events in Hospitalized-Acute Myocardial Infarction Patients”. Vascular Health and Risk Management 16 (2020): 125-132.
7. Schwartz GG., et al. “Peripheral Artery Disease and Venous Thromboembolic Events After Acute Coronary Syndrome”. Circulation20 (2020): 1608-1617.
8. Marston NA., et al. “The Effect of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibition on the Risk of Venous Thromboembolism”. Circulation 20 (2020): 1600-1607.
9. Shi Z., et al. “Serum Lipoprotein (a) on Postoperative Day 3: A Strong Predictor of Portal and/or Splenic Vein Thrombosis in Cirrhotic Patients With Splenectomy”. Clinical and Applied Thrombosis/Hemostasis 26 (2020): 107602962091202.
10. Ray KK., et al. “Lipoprotein(a) reductions from PCSK9 inhibition and major adverse cardiovascular events: Pooled analysis of alirocumab phase 3 trials”. Atherosclerosis 288 (2019): 194-202.
11. O’Donoghue ML., et al. “Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk”. Circulation12 (2019): 1483-1492.
12. Burgess S., et al. “Association of LPAV ariants With Risk of Coronary Disease and the Implications for Lipoprotein(a)-Lowering Therapies”. JAMA Cardiology7 (2018): 619.
13. Khan TZ., et al. “Impact of lipoprotein apheresis on thrombotic parameters in patients with refractory angina and raised lipoprotein(a): Findings from a randomized controlled cross-over trial”. Journal of Clinical Lipidology 5 (2019): 788-796.
14. Warden BA., et al. “Impact of PCSK9 inhibitors on plasma lipoprotein(a) concentrations with or without a background of niacin therapy”. Journal of Clinical Lipidology4 (2019): 580-585.
15. Greco MF., et al. “Lipoprotein(a) Lowering-From Lipoprotein Apheresis to Antisense Oligonucleotide Approach”. Journal of Clinical Medicine7 (2013): 2103.
16. Langsted A and Nordestgaard BG. “Antisense Oligonucleotides Targeting Lipoprotein(a)”. Current Atherosclerosis Reports 8 (2019): 30.
17. Stiekema LCA., et al. “Potent lipoprotein(a) lowering following apolipoprotein(a) antisense treatment reduces the pro-inflammatory activation of circulating monocytes in patients with elevated lipoprotein(a)”. European Heart Journal24 (2020): 2262-2271.
18. Moriarty PM., et al. “Lipoprotein(a) and Its Potential Association with Thrombosis and Inflammation in COVID-19: a Testable Hypothesis”. Current Atherosclerosis Reports9 (2020): 48.