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cholesterol LDL in serum

Indications: - dyslipidemia - cardiovascular disease - coronary artery disease - cerebrovascular disease - peripheral artery disease - cardiovascular risk factors - diabetes mellitus - hypertension - chronic renal failure - 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) 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: [LDL-chol] = [total chol] - [HDL-chol] - [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. 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 - all-cause mortality was lowest at an LDL cholesterol level of 140 mg/dL [26] - U-shaped association with all-cause mortality not apparent in statin users [26] - 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 - 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] 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 - LDLR gene mutations - APOB gene+LDLR gene mutations - APOB+LDLR+PCSK9 gene mutations Increases: - hypothyroidism - poorly controlled diabetes mellitus - nephrotic syndrome - medications: - glucocorticoids - diuretics - amiodarone [2] Decreases: - poor health 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] 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] - mortality risks decrease as statin doses increase [10] - no benefit in lowering LDL cholesterol below 70 mg/dL [2] - 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

Related

cholesterol LDL in serum calculated LDL triglycerides in serum/plasma low density lipoprotein (LDL, beta-lipoprotein)

Specific

cholesterol LDL-1 in serum cholesterol LDL-2 in serum cholesterol LDL-3 in serum cholesterol LDL-4 in serum

General

cholesterol LDL in body fluid

Figures/Diagrams

Dyslipoproteinemias

References

  1. Tietz Textbook of Clinical Chemistry, 2nd ed. Burtis CA & Ashwood ER (eds), WB Saunders Co, Philadelphia PA, 1993, pg 1055-56
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 18, 19. American College of Physicians, Philadelphia 1998, 2018, 2021.
  3. Prescriber's Letter 11(8): 2004 New National Cholesterol Education Program (NCEP) Recommendations Detail-Document#: 200801 (subscription needed) http://www.prescribersletter.com
  4. 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: 16226163
  5. 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: 17015870
  6. LDL Cholesterol, Direct Laboratory Test Directory ARUP: 20257
  7. Panel of 6 tests Laboratory Test Directory ARUP: 20421
  8. Panel of 6 tests Laboratory Test Directory ARUP: 20468
  9. Panel of 6 tests Laboratory Test Directory ARUP: 50021
  10. Panel of 7 tests Laboratory Test Directory ARUP: 80503
  11. Ding Q et al Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing. Circ Res 2014 Jun 10 PMID: 24916110 http://circres.ahajournals.org/content/early/2014/06/10/CIRCRESAHA.115.304351
  12. The Myocardial Infarction Genetics Consortium Investigators Inactivating Mutations in NPC1L1 and Protection from Coronary Heart Disease. N Engl J Med. Nov 12, 2014 PMID: 25390462 http://www.nejm.org/doi/full/10.1056/NEJMoa1405386
  13. 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. 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: 27487401
  15. 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. PMID: 27292972 Free PMC Article http://bmjopen.bmj.com/content/6/6/e010401.full
  16. 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: 27771404 - Ahmadi A, Narula J. Primary and secondary prevention, or subclinical and clinical atherosclerosis. JACC Cardiovasc Imaging 2016 Oct 19; PMID: 27771400
  17. 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: 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. 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: 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: 30073330 https://jamanetwork.com/journals/jamacardiology/article-abstract/2695045
  19. 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. 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: 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: 30423393 https://www.sciencedirect.com/science/article/pii/S073510971839034X
  21. 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: 31411740 https://onlinelibrary.wiley.com/doi/abs/10.1111/jgs.16123
  22. 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. 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: 31930739 https://onlinelibrary.wiley.com/doi/abs/10.1111/jgs.16306
  24. 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: 31930737 https://onlinelibrary.wiley.com/doi/full/10.1111/jgs.16305
  25. 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: 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: 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: 33186536 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32333-3/fulltext
  26. 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: 33293274 PMCID: PMC7722479 Free PMC article https://www.bmj.com/content/371/bmj.m4266
  27. 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. 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

Component-of

apolipoprotein B/LDL cholesterol in serum/plasma cholesterol LDL/apolipoprotein B in serum/plasma cholesterol LDL/cholesterol HDL in serum/plasma cholesterol LDL/cholesterol total in serum/plasma cholesterol total/cholesterol LDL in serum/plasma lipid panel (fasting lipid panel, FLP)