cholesterol LDL in serum
Genetics
- variations in NPC1L1 that inhibit its function that lower plasma LDL cholesterol levels & a reduce the risk of coronary artery disease[12]
- gene mutations* for familial hypercholesterolemia in < 2% of patients with LDL cholesterol level > 190 mg/dL[13]
* genetic testing for familial hypercholesterolemia
Indications
- dyslipidemia
- cardiovascular disease
- cardiovascular risk factors
- general health screening (health maintenance)
- see lipid panel for screening intervals
- primary utility of serum LDL cholesterol is identifying patients who will benefit from statin therapy & to assess response to statin therapy[2]
Reference interval
mg/dL -> mmol/L, multiply by 0.0259
risk | LDL cholesterol |
---|---|
high-risk | > 160 mg/dL (< 4.14 mmol/L) |
borderline | 130 - 159 mg/dL (3.37 - 4.12 mmol/L) |
desirable | < 130 mg/dL (< 3.37 mmol/L) |
vasculopathy* | < 100 mg/dL (< 2.50 mmol/L) |
intensive control | < 70 mg/dL (< 1.8 mmol/L)[4][5][16][18] |
* vasculopathy = CAD, diabetes, ischemic stroke target LDL for high risk patients with coronary artery disease (CAD) has been lowered to 70 mg/dL[3]. (NCEP)
Clinical significance
- an LDL/HDL ratio of > 4 predicts increased risk of CAD, lowering of total cholesterol & LDL cholesterol to levels within NCEP guidelines reduces coronary artery disease related deaths in men & women
- benefits in the young & the elderly have not yet been demonstrated (20 > age > 65).
- LDL cholesterol not associated cardiovascular disease in elderly > 75 years[21]
- low cholesterol absorption efficiency in elderly predicts all-cause mortality[24]
- cholesterol synthesis diminishes in elderly, but does not predict mortality[24]
- frailty & poor health decrease LDL cholesterol
- high LDL cholesterol associated with lower mortality in most people over 60 years of age[15]
- high LDL cholesterol not associated with increased mortality in women > 68 years of age[23]
- LDL cholesterol > 160 mg/dL associated with increased mortality in low-risk patients[19]
- LDL cholesterol has a U-shaped association with all-cause mortality
- LDL-cholesterol-lowering with statins, ezetimibe, or PCSK9 inhibitors significantly lowers risk for vascular events in adults of all ages[25]
- 7% of adults have LDL cholesterol level > 190 mg/dL[13]
- patients with LDL cholesterol > 190 mg/dL should be
- treated with a high-intensity statin
- atorvastatin 40-80 mg QD, rosuvastatin 20-40 mg QD
- evaluated for familial hypercholesterolemia, & secondary causes of hyperlipidemia including glucocorticoid use, diabetes mellitus, & hypothroidism
- treated with a high-intensity statin
- higher LDL cholesterol associated with diminished risk of type 2 diabetes[14]
- for patients on a PCSK9 inhibitor, estimate LDL-cholesterol with Martin/Hopkins estimation[17]
intensive lipid-lowering therapy to very low LDL cholesterol
- intensive lipid-lowering therapy to very low LDL cholesterol levels is not associated with diminished mortality[4][5]
- intensive lipid-lowering therapy of LDL cholesterol to < 70 mg/dL slows atherosclerotic plaque progression assessed by CT angiography[16]
- adding evolocumab & ezetimibe to a statin in high-risk patients with LDL cholesterol < 70 mg/dL further decreases risk of cardiovascular event (21% for 39 mg/dL decrease in LDL cholesterol)[18]
- AHA states that intensive lipid lowering therapy does not adversely affect risk of cognitive impairment or dementia or hemorrhagic stroke, but admits there is some disagreement in the literature & stops short in its abstract of expressing this claim in terms of numbers[28]
Increases
- hypothyroidism
- poorly controlled diabetes mellitus
- nephrotic syndrome
- medications:
Decreases
- poor health
Procedure
LDL-cholesterol is generally calculated from measurements of total cholesterol, HDL-cholesterol & triglycerides obtained from a lipid panel & the assumption that the VLDL-cholesterol is equal to 1/5 of the triglyceride concentration, using the formula:
[[[A144160|LDL]]-chol] = [total chol] - [HDL-chol] - [[[A18141|triglycerides]]/5]
This equation works well for triglycerides < 400 mg/dL in the absence of dysbetalipoproteinemia.
The lipoprotein LDL may be measured directly using lipoprotein electrophoresis or determined from apolipoprotein B measurement.
Management
- high-dose statin (atorvastatin 40 mg QD) for patients with known cardiovascular disease
- dose to achieve > 50% reduction in LDL cholesterol
- add ezetimibe as needed & then a PCSK9 inhibitor for high-risk patients with LDL cholesterol > 70 mg/dL[20]
- for LDL cholesterol > 190 mg/dL, high-intensity maximally tolerated statin
- ezetimibe as needed
- moderate intensity statin for patients with diabetes mellitus without cardiovascular disease & LDL cholesterol > 70 mg/dL
- check LDL cholesterol 1-3 months after treatment change
Comparative biology
- CRISPR knock out of the PCSK9 gene in the livers of mice increases LDL receptors & reduces plasma LDL cholesterol without observable adverse effects[1]
More general terms
More specific terms
- cholesterol LDL-1 in serum
- cholesterol LDL-2 in serum
- cholesterol LDL-3 in serum
- cholesterol LDL-4 in serum
Additional terms
- cholesterol LDL in serum calculated
- LDL triglycerides in serum/plasma
- low density lipoprotein (LDL, beta-lipoprotein)
Component of
- lipid panel (fasting lipid panel, FLP)
- cholesterol LDL/apolipoprotein B in serum/plasma
- apolipoprotein B/LDL cholesterol in serum/plasma
- cholesterol LDL/cholesterol HDL in serum/plasma
- cholesterol total/cholesterol LDL in serum/plasma
- cholesterol LDL/cholesterol total in serum/plasma
References
- ↑ 1.0 1.1 Tietz Textbook of Clinical Chemistry, 2nd ed. Burtis CA & Ashwood ER (eds), WB Saunders Co, Philadelphia PA, 1993, pg 1055-56
- ↑ 2.0 2.1 2.2 2.3 Medical Knowledge Self Assessment Program (MKSAP) 11, 18, 19. American College of Physicians, Philadelphia 1998, 2018, 2021.
- ↑ 3.0 3.1 Prescriber's Letter 11(8): 2004 New National Cholesterol Education Program (NCEP) Recommendations Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200801&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 4.0 4.1 4.2 Wiviott SD, Cannon CP, Morrow DA, Ray KK, Pfeffer MA, Braunwald E; PROVE IT-TIMI 22 Investigators. Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy. J Am Coll Cardiol. 2005 Oct 18;46(8):1411-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16226163
- ↑ 5.0 5.1 5.2 Hayward RA, Hofer TP, Vijan S. Narrative review: lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem. Ann Intern Med. 2006 Oct 3;145(7):520-30. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17015870
- ↑ LDL Cholesterol, Direct Laboratory Test Directory ARUP: http://www.aruplab.com/guides/ug/tests/0020257.jsp
- ↑ Panel of 6 tests Laboratory Test Directory ARUP: http://www.aruplab.com/guides/ug/tests/0020421.jsp
- ↑ Panel of 6 tests Laboratory Test Directory ARUP: http://www.aruplab.com/guides/ug/tests/0020468.jsp
- ↑ Panel of 6 tests Laboratory Test Directory ARUP: http://www.aruplab.com/guides/ug/tests/0050021.jsp
- ↑ 10.0 10.1 Panel of 7 tests Laboratory Test Directory ARUP: http://www.aruplab.com/guides/ug/tests/0080503.jsp
- ↑ Ding Q et al Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing. Circ Res 2014 Jun 10 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24916110 <Internet> http://circres.ahajournals.org/content/early/2014/06/10/CIRCRESAHA.115.304351
- ↑ 12.0 12.1 The Myocardial Infarction Genetics Consortium Investigators Inactivating Mutations in NPC1L1 and Protection from Coronary Heart Disease. N Engl J Med. Nov 12, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25390462 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1405386
- ↑ 13.0 13.1 13.2 Watson KE How Many Patients with Severe Hypercholesterolemia Have FH? NEJM Journal Watch. April 19, 2016 Massachusetts Medical Society (subscription needed) http://www.jwatch.org
- ↑ 14.0 14.1 White J, Swerdlow DI, Preiss D et al. Association of lipid fractions with risks for coronary artery disease and diabetes. JAMA Cardiol 2016 Aug 3 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27487401
- ↑ 15.0 15.1 Ravnskov U, Diamond DM, Hama R et al Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review. BMJ Open. 2016 Jun 12;6(6):e010401. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27292972 Free PMC Article <Internet> http://bmjopen.bmj.com/content/6/6/e010401.full
- ↑ 16.0 16.1 16.2 Shin S et al. Impact of intensive LDL cholesterol lowering on coronary artery atherosclerosis progression: A serial CT angiography study. JACC Cardiovasc Imaging 2016 Oct 19; PMID: https://www.ncbi.nlm.nih.gov/pubmed/27771404
Ahmadi A, Narula J. Primary and secondary prevention, or subclinical and clinical atherosclerosis. JACC Cardiovasc Imaging 2016 Oct 19; PMID: https://www.ncbi.nlm.nih.gov/pubmed/27771400 - ↑ 17.0 17.1 Martin SS, Giugliano RP, Murphy SA et al Comparison of Low-density Lipoprotein Cholesterol Assessment by Martin/Hopkins Estimation, Friedewald Estimation, and Preparative Ultracentrifugation. Insights From the FOURIER Trial. JAMA Cardiol. Published online June 13, 2018. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29898218 https://jamanetwork.com/journals/jamacardiology/fullarticle/2684503
Stone NJ Measuring Low-Density Lipoprotein Cholesterol. When Is More Accurate Better? JAMA Cardiol. Published online June 13, 2018. https://jamanetwork.com/journals/jamacardiology/fullarticle/2684505 - ↑ 18.0 18.1 18.2 Sabatine MS, Wiviott SD, Im K et al Efficacy and Safety of Further Lowering of Low-Density Lipoprotein Cholesterol in Patients Starting With Very Low Levels. A Meta-analysis. JAMA Cardiol. Published online August 1, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30073316 https://jamanetwork.com/journals/jamacardiology/fullarticle/2695047
Gotto AM Jr Low-Density Lipoprotein Cholesterol and Cardiovascular Risk Reduction. How Low Is Low Enough Without Causing Harm? JAMA Cardiol. Published online August 1, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30073330 https://jamanetwork.com/journals/jamacardiology/article-abstract/2695045 - ↑ 19.0 19.1 Abdullah SM, Defina LF, Leonard D et al Long-Term Association of Low-Density Lipoprotein Cholesterol With Cardiovascular Mortality in Individuals at Low 10-Year Risk of Atherosclerotic Cardiovascular Disease. Results From the Cooper Center Longitudinal Study. Circulation. Aug 16, 2018 Not indexed in PubMed https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.034273
Virani SS, Ballantyne CM Low-Density Lipoprotein Cholesterol. Circulation. Aug 16, 2018 Not indexed in PubMed https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.034922 - ↑ 20.0 20.1 Grundy SM, Stone NJ, Bailey AL 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 Nov 3. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30423391
Grundy SM, Stone NJ, Bailey AL et al. AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018 Nov 8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30423393 https://www.sciencedirect.com/science/article/pii/S073510971839034X - ↑ 21.0 21.1 Nanna MG, Navar AM, Wojdyla D, Peterson ED. The association between low-density lipoprotein cholesterol and incident atherosclerotic cardiovascular disease in older adults: Results from the National Institutes of Health pooled cohorts. J Am Geriatr Soc 2019 Dec; 67:2560 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31411740 https://onlinelibrary.wiley.com/doi/abs/10.1111/jgs.16123
- ↑ Pooled Cohort Risk Assessment Equations. Predicts 10-year risk for a first atherosclerotic cardiovascular disease (ASCVD) event. ClinCalc.com http://clincalc.com/cardiology/ascvd/pooledcohort.aspx
- ↑ 23.0 23.1 Maihofer AX, Shadyab AH, Wild RA, LaCroix AZ. Associations between serum levels of cholesterol and survival to age 90 in postmenopausal women. J Am Geriatr Soc 2020 Feb; 68:288 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31930739 https://onlinelibrary.wiley.com/doi/abs/10.1111/jgs.16306
- ↑ 24.0 24.1 24.2 Sittiwet C. Simonen P. Gylling H, Strandberg TE Mortality and Cholesterol Metabolism in Subjects Aged 75 Years and Older: The Helsinki Businessmen Study. J Am Geriatr Soc. 2020 Feb;68(2):281-287. Epub 2020 Jan 13. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31930737 https://onlinelibrary.wiley.com/doi/full/10.1111/jgs.16305
- ↑ 25.0 25.1 Mortensen MB, Nordestgaard BG. Elevated LDL cholesterol and increased risk of myocardial infarction and atherosclerotic cardiovascular disease in individuals aged 70-100 years: A contemporary primary prevention cohort. Lancet 2020 Nov 21; 396:1644. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33186534 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32233-9/fulltext
Gencer B et al Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2020. Nov 10 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33186535 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32332-1/fulltext
Raal FJ, Mohamed F. Never too old to benefit from lipid-lowering treatment. Lancet 2020 Nov 21; 396:1608 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33186536 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32333-3/fulltext - ↑ 26.0 26.1 26.2 Johannesen CDL et al. Association between low density lipoprotein and all cause and cause specific mortality in Denmark: Prospective cohort study. BMJ 2020 Dec 8; 371:m4266 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33293274 PMCID: PMC7722479 Free PMC article https://www.bmj.com/content/371/bmj.m4266
- ↑ Arigi EA High LDL-C Bad for CAD but Good for CKD? Optimal Range Proposed. Medscape. 2022. March 17 https://www.medscape.com/viewarticle/970468 (Paper retracted by authors)
- ↑ 28.0 28.1 Goldstein LB, Toth PP, Dearborn-Tomazos JL et al Aggressive LDL-C Lowering and the Brain: Impact on Risk for Dementia and Hemorrhagic Stroke: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol. 2023;43. Sept 14. https://www.ahajournals.org/doi/abs/10.1161/ATV.0000000000000164