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lipoprotein cholesterol in serum; Lp(a)-cholesterol in serum

Indications: - unclear* - evaluation of dyslipidemia - evaluation of refractory angina pectoris [6] * no role for routine measurement [2] Reference interval: 1) 30 mg/dL (300 mg/L) is arbitrarily set as an "upper limit of normal" 2) > 30 mg/dL in 25% of US population 3) normal serum levels difficult to determine, because levels of Lp are widely disparate & not distributed in a gaussian manner 4) blacks have levels twice whites Clinical significance: 1) conventional serum LDL cholesterolincludes cholesterol attributable to Lp(a)-cholesterol in serum due to their overlapping densities. 2) postulated independent risk factor for coronary artery disease 3) poorly cleared from plasma 4) levels > 180 mg/dL may identify persons at high cardiovascular risk [8] - levels > 44 mg/dL in women associated with increased risk of cardiovascular disease (hazzard ratio: 1.47) [4] - higher Lp(a) levels are associated with increased risk of a major lower-limb vascular events (limb amputation, peripheral revascularization) in hospitalized patients [10] 5) absolute reduction in serum Lp(a) cholesterol of 100 mg/dL needed to achieve a similar cardiovascular risk reduction as seen with 39 mg/dL reduction in serum LDL cholesterol [7] 6) elevated serum Lp(a) cholesterol associated with elevated cardiovascular risk in patients with hypertension [11] - no such association in patients without hypertension [11] 7) correction of serum LDL-cholesterol for serum Lp(a)-cholesterol content does not provide meaningful additional information on cardiovascular risk at the population level Management: 1) resistant to most lipid-lowering drugs - statins may increase Lp(a) levels [8] 2) modest reduction in Lp(a) levels by PCSK-9 inhibitors [8], estrogens & niacin 3) persons at high cardiovascular risk - address modifiable cardiovascular risk factors - high-intensity statin therapy + aspirin 81 mg QD [9] 4) antisense oligonucleotide/siRNA hepatic apoLp messenger RNA suggest that plasma Lp(a) cholesterol can be significantly & safely lowered [12] 5) lepodisiran is an investigational extended-duration siRNA targeting lipoprotein(a) [13]

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lipoprotein in serum lipoprotein ; Lp

General

special chemistry test

References

  1. Grainger et al Science 260:1655 1993
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 17. American College of Physicians, Philadelphia 1998, 2015
  3. Tietz Textbook of Clinical Chemistry, 2nd ed. Burtis CA & Ashwood ER (eds), WB Saunders Co, Philadelphia PA, 1993, pg 1023-24
  4. Suk Danik J et al, Lipoprotein(a), measured with an assay independent of apolipoprotein(a) isoform size, and risk of future cardiovascular events among initially healthy women. JAMA 2006, 296:1363 PMID: 16985228
  5. Bennet A, Di Angelantonio E, Erqou S, Eiriksdottir G, et al, Lipoprotein(a) Levels and Risk of Future Coronary Heart Disease: Large-Scale Prospective Data. Arch Intern Med. 2008 Mar 24;168(6):598-608. PMID: 18362252
  6. Larkin M Lipoprotein Apheresis May Be Useful in Refractory Angina Medscape - May 12, 2017. http://www.medscape.com/viewarticle/879959 - Khan TZ, Rhodes S, Pottle A et al High prevalence of raised lipoprotein(a) in patients with refractory angina. Glob Cardiol Sci Pract. 2015 Jul 7;2015(2):28. PMID: 26779510 Free PMC Article - Khan TZ, Hsu LY, Arai AE et al Apheresis as novel treatment for refractory angina with raised lipoprotein(a): a randomized controlled cross-over trial. Eur Heart J. 2017 Apr 26. PMID: 28453721
  7. Davenport L Large Lipoprotein(a) Reductions Needed for Clinical Benefit. Medscape - May 08, 2018. https://www.medscape.com/viewarticle/896333
  8. Miksenas H, Januzzi JL Jr, Natarajan P. Lipoprotein(a) and Cardiovascular Diseases JAMA. Published online July 8, 2021 PMID: 34236417 https://jamanetwork.com/journals/jama/fullarticle/2781946
  9. Agarwala A, Ballantyne C, Stone NJ Primary Prevention Management of Elevated Lipoprotein(a) JAMA Cardiol. 2022;7(7):760-769 PMID: 35583875 Free PMC article https://jamanetwork.com/journals/jamacardiology/article-abstract/2792280
  10. Guedon AF, De Freminville JB, Mirault T et al Association of Lipoprotein(a) Levels With Incidence of Major Adverse Limb Events. JAMA Netw Open. 2022;5(12):e2245720 PMID: 36480201 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2799310
  11. Wendling P High Lipoprotein(a) Levels Plus Hypertension Add to CVD Risk. Medscape. Dec 14, 2022 https://www.medscape.com/viewarticle/985601 - Rikhi R, Bhatia HS, Schaich CL et al Association of Lp(a) (Lipoprotein[a]) and Hypertension in Primary Prevention of Cardiovascular Disease: The MESA Hypertension. 2022. Dec 13. PMID: 36511156 https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.122.20189
  12. Leahy DR Universal Testing for Lp(a): What Are We Waiting For? Medscape. Feb 1, 2023 https://www.medscape.com/viewarticle/987221 - ClinicalTrials.gov Assessing the Impact of Lipoprotein (a) Lowering With Pelacarsen (TQJ230) on Major Cardiovascular Events in Patients With CVD (Lp(a)HORIZON). https://www.clinicaltrials.gov/ct2/show/NCT04023552 - ClinicalTrials.gov Olpasiran Trials of Cardiovascular Events and Lipoprotein(a) Reduction (OCEAN(a)) - Outcomes Trial. https://clinicaltrials.gov/ct2/show/NCT05581303
  13. Nissen SE, Linnebjerg H, Shen X et al Lepodisiran, an Extended-Duration Short Interfering RNA Targeting Lipoprotein(a). A Randomized Dose-Ascending Clinical Trial. JAMA. Published online November 12, 2023 PMID: 37952254 PMCID: PMC10641766 (available on 2024-05-12) https://jamanetwork.com/journals/jama/fullarticle/2811935
  14. Arnold A, Blaum C, GoBling et al; BiomarCaRE Investigators. Impact of Lipoprotein(a) Level on Low-Density Lipoprotein Cholesterol- or Apolipoprotein B-Related Risk of Coronary Heart Disease. J Am Coll Cardiol. 2024 Jul 9;84(2):165-177. PMID: 38960510