lipoprotein <a> cholesterol in serum; Lp(a)-cholesterol in serum
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Indications
- unclear*
- evaluation of dyslipidemia
- evaluation of refractory angina pectoris[6]
* no role for routine measurement[2]
Reference interval
- 30 mg/dL (300 mg/L) is arbitrarily set as an "upper limit of normal"
- > 30 mg/dL in 25% of US population
- normal serum levels difficult to determine, because levels of Lp<a> are widely disparate & not distributed in a gaussian manner
- blacks have levels twice whites
Clinical significance
- conventional serum LDL cholesterolincludes cholesterol attributable to Lp(a)-cholesterol in serum due to their overlapping densities.
- postulated independent risk factor for coronary artery disease
- poorly cleared from plasma
- 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]
- 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]
- elevated serum Lp(a) cholesterol associated with elevated cardiovascular risk in patients with hypertension[11]
- no such association in patients without hypertension[11]
- 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
- resistant to most lipid-lowering drugs
- modest reduction in Lp(a) levels by PCSK-9 inhibitors[8], estrogens & niacin
- persons at high cardiovascular risk
- address modifiable cardiovascular risk factors
- high-intensity statin therapy + aspirin 81 mg QD[9]
- antisense oligonucleotide/siRNA hepatic apoLp<a> messenger RNA suggest that plasma Lp(a) cholesterol can be significantly & safely lowered[12]
- lepodisiran is an investigational extended-duration siRNA targeting lipoprotein(a)[13]
More general terms
Additional terms
References
- ↑ Grainger et al Science 260:1655 1993
- ↑ 2.0 2.1 Medical Knowledge Self Assessment Program (MKSAP) 11, 17. American College of Physicians, Philadelphia 1998, 2015
- ↑ Tietz Textbook of Clinical Chemistry, 2nd ed. Burtis CA & Ashwood ER (eds), WB Saunders Co, Philadelphia PA, 1993, pg 1023-24
- ↑ 4.0 4.1 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: https://www.ncbi.nlm.nih.gov/pubmed/16985228
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/18362252
- ↑ 6.0 6.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/28453721 - ↑ 7.0 7.1 Davenport L Large Lipoprotein(a) Reductions Needed for Clinical Benefit. Medscape - May 08, 2018. https://www.medscape.com/viewarticle/896333
- ↑ 8.0 8.1 8.2 8.3 Miksenas H, Januzzi JL Jr, Natarajan P. Lipoprotein(a) and Cardiovascular Diseases JAMA. Published online July 8, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34236417 https://jamanetwork.com/journals/jama/fullarticle/2781946
- ↑ 9.0 9.1 Agarwala A, Ballantyne C, Stone NJ Primary Prevention Management of Elevated Lipoprotein(a) JAMA Cardiol. 2022;7(7):760-769 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35583875 Free PMC article https://jamanetwork.com/journals/jamacardiology/article-abstract/2792280
- ↑ 10.0 10.1 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: https://www.ncbi.nlm.nih.gov/pubmed/36480201 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2799310
- ↑ 11.0 11.1 11.2 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: https://www.ncbi.nlm.nih.gov/pubmed/36511156 https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.122.20189 - ↑ 12.0 12.1 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 - ↑ 13.0 13.1 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: https://www.ncbi.nlm.nih.gov/pubmed/37952254 PMCID: PMC10641766 (available on 2024-05-12) https://jamanetwork.com/journals/jama/fullarticle/2811935
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/38960510