Measurement of blood lipids and lipoproteins
- Robert S Rosenson, MD
Robert S Rosenson, MD
- Professor of Medicine
- Mount Sinai School of Medicine
- Director, Cardiometabolic Disorders
- Mount Sinai Heart
Lipids, such as cholesterol and triglyceride, are insoluble in plasma. They are made soluble by attachment to circulating lipoproteins that transport lipids to various tissues for energy utilization, lipid deposition, steroid hormone production, and bile acid formation. The lipoprotein consists of esterified and unesterified cholesterol, triglycerides, and phospholipids, and protein.
There are five major lipoproteins in blood: chylomicrons; very low density lipoprotein (VLDL); intermediate density lipoprotein; low density lipoprotein (LDL); and high density lipoprotein. Each of these classes of lipoproteins carries cholesterol and triglyceride to a varying degree, with LDL carrying the majority of cholesterol, and VLDL carrying the majority of triglyceride.
In general, patient care issues related to screening, diagnosis, and treatment are based on the results of the measurement of serum lipids, which is generally accomplished by obtaining a lipid profile. On occasion, measurement of serum lipoproteins is necessary for one or more of these purposes. This topic will discuss the issues relevant to the measurement of serum lipids and lipoproteins. Other issues related to lipids and lipoproteins, such as their role in atherosclerosis, are discussed separately. (See "Lipoprotein classification, metabolism, and role in atherosclerosis".)
LIPID PROFILE AND COMPONENTS
A standard serum lipid profile measures the concentration of total and HDL-cholesterol (HDL-C) as well as the triglycerides. With these values, the LDL cholesterol (LDL-C) concentration can be estimated. (See 'LDL-cholesterol' below.)
Total and HDL-C — Serum total and HDL-C are measured directly and can be obtained in fasting or nonfasting individuals; there are only small, clinically insignificant differences in these values between measurements in the fasting or non-fasting state . (See 'Fasting versus non-fasting tests' below.)
- Craig SR, Amin RV, Russell DW, Paradise NF. Blood cholesterol screening influence of fasting state on cholesterol results and management decisions. J Gen Intern Med 2000; 15:395.
- Cooper GR, Myers GL, Smith SJ, Schlant RC. Blood lipid measurements. Variations and practical utility. JAMA 1992; 267:1652.
- US Preventive Services Task Force. Guide to clinical preventive services, 2nd ed, Williams and Wilkins, Baltimore 1996. p.15.
- Belsey R, Baer DM. Cardiac risk classification based on lipid screening. JAMA 1990; 263:1250.
- Bachorik PS, Cloey TA, Finney CA, et al. Lipoprotein-cholesterol analysis during screening: accuracy and reliability. Ann Intern Med 1991; 114:741.
- Ockene IS, Chiriboga DE, Stanek EJ 3rd, et al. Seasonal variation in serum cholesterol levels: treatment implications and possible mechanisms. Arch Intern Med 2004; 164:863.
- Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18:499.
- Davidson M, Liu SX, Barter P, et al. Measurement of LDL-C after treatment with the CETP inhibitor anacetrapib. J Lipid Res 2013; 54:467.
- Stein EA, Raal FJ. Targeting LDL: is lower better and is it safe? Best Pract Res Clin Endocrinol Metab 2014; 28:309.
- Miller WG, Myers GL, Sakurabayashi I, et al. Seven direct methods for measuring HDL and LDL cholesterol compared with ultracentrifugation reference measurement procedures. Clin Chem 2010; 56:977.
- Meeusen JW, Snozek CL, Baumann NA, et al. Reliability of Calculated Low-Density Lipoprotein Cholesterol. Am J Cardiol 2015; 116:538.
- Martin SS, Blaha MJ, Elshazly MB, et al. Friedewald-estimated versus directly measured low-density lipoprotein cholesterol and treatment implications. J Am Coll Cardiol 2013; 62:732.
- Martin SS, Blaha MJ, Elshazly MB, et al. Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile. JAMA 2013; 310:2061.
- Miller M. Lipid levels in the post-acute coronary syndrome setting: destabilizing another myth? J Am Coll Cardiol 2008; 51:1446.
- Rosenson RS. Myocardial injury: the acute phase response and lipoprotein metabolism. J Am Coll Cardiol 1993; 22:933.
- Rauoof MA, Iqbal K, Mir MM, Tramboo NA. Measurement of plasma lipids in patients admitted with acute myocardial infarction or unstable angina pectoris. Am J Cardiol 2001; 88:165.
- Ettinger WH, Varma VK, Sorci-Thomas M, et al. Cytokines decrease apolipoprotein accumulation in medium from Hep G2 cells. Arterioscler Thromb 1994; 14:8.
- Genest JJ, Corbett HM, McNamara JR, et al. Effect of hospitalization on high-density lipoprotein cholesterol in patients undergoing elective coronary angiography. Am J Cardiol 1988; 61:998.
- Pitt B, Loscalzo J, Ycas J, Raichlen JS. Lipid levels after acute coronary syndromes. J Am Coll Cardiol 2008; 51:1440.
- Cromwell WC, Otvos JD. Low-density lipoprotein particle number and risk for cardiovascular disease. Curr Atheroscler Rep 2004; 6:381.
- Rosenson R, Lloyd-Jones D, Working group from the Adult Treatment Panel III of the National Cholesterol Educational Program. Critical appraisal of revised cholesterol guidelines for the very high-risk patient. Expert Rev Cardiovasc Ther 2005; 3:173.
- Rosenson RS, Davidson MH, Pourfarzib R. Underappreciated opportunities for low-density lipoprotein management in patients with cardiometabolic residual risk. Atherosclerosis 2010; 213:1.
- Ip S, Lichtenstein AH, Chung M, et al. Systematic review: association of low-density lipoprotein subfractions with cardiovascular outcomes. Ann Intern Med 2009; 150:474.
- Rosenson RS. Clinical role of LDL and HDL subclasses and apolipoprotein measurement. ACC Curr J Rev 2004; 13:33.
- Brunzell JD, Davidson M, Furberg CD, et al. Lipoprotein management in patients with cardiometabolic risk: consensus conference report from the American Diabetes Association and the American College of Cardiology Foundation. J Am Coll Cardiol 2008; 51:1512.
- Cui Y, Blumenthal RS, Flaws JA, et al. Non-high-density lipoprotein cholesterol level as a predictor of cardiovascular disease mortality. Arch Intern Med 2001; 161:1413.
- National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002; 106:3143.
- Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2010; 56:e50.
- Nordestgaard BG, Benn M. Fasting and nonfasting LDL cholesterol: to measure or calculate? Clin Chem 2009; 55:845.
- Doran B, Guo Y, Xu J, et al. Prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol levels on long-term mortality: insight from the National Health and Nutrition Examination Survey III (NHANES-III). Circulation 2014; 130:546.
- Eckel RH. LDL cholesterol as a predictor of mortality, and beyond: to fast or not to fast, that is the question? Circulation 2014; 130:528.
- Nordestgaard BG, Langsted A, Mora S, et al. Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cut-points-a joint consensus statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine. Eur Heart J 2016; 37:1944.
- Sidhu D, Naugler C. Fasting time and lipid levels in a community-based population: a cross-sectional study. Arch Intern Med 2012; 172:1707.
- Fukuyama N, Homma K, Wakana N, et al. Validation of the Friedewald Equation for Evaluation of Plasma LDL-Cholesterol. J Clin Biochem Nutr 2008; 43:1.
- Jepsen AM, Langsted A, Varbo A, et al. Increased Remnant Cholesterol Explains Part of Residual Risk of All-Cause Mortality in 5414 Patients with Ischemic Heart Disease. Clin Chem 2016; 62:593.
- Rosenson RS, Davidson MH, Hirsh BJ, et al. Genetics and causality of triglyceride-rich lipoproteins in atherosclerotic cardiovascular disease. J Am Coll Cardiol 2014; 64:2525.
- LIPID PROFILE AND COMPONENTS
- Total and HDL-C
- Total cholesterol to HDL cholesterol ratio
- - Friedewald equation
- - Direct measurement
- - Other indirect methods
- Causes of inaccurate results
- - After an ACS
- LDL PARTICLE SIZE AND NUMBER
- NON-HDL CHOLESTEROL
- INDICATIONS FOR MEASUREMENT
- Lipid profile
- Other measurements of LDL
- FASTING VERSUS NON-FASTING TESTS
- SUMMARY AND RECOMMENDATIONS