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Lipid Panel

Cholesterol and triglycerides are the major lipids that are transported in plasma by lipoproteins. The liver combines a single apolipoprotein B molecule, triglycerides and cholesterol into an apo-B lipoprotein particle (apoB). After the liver secretes apoB into plasma, it is called very low- density lipoprotein (VLDL).

Triglycerides are rapidly removed by the enzyme lipoprotein lipase and used for energy consumption and storage. As triglycerides are progressively removed, the lipoprotein is referred to as a VLDL remnant particle. After most of the triglycerides have been removed, the lipoprotein becomes denser and is referred to as low-density lipoprotein (LDL). The conversion of VLDL to LDL takes approximately 6 hours. It is important to realize that a VLDL particle, a VLDL remnant particle, and an LDL particle are really different names for the same circulating apoB lipoprotein at different stages in its lifecycle, depending on its lipid content.

LDL remains in the circulation for about 48 hours. Under normal physiological conditions, LDL is removed from the circulation by LDL receptors on hepatocytes. At any point in its lifecycle, regardless of its lipid content, an apoB lipoprotein less than 70 nm in diameter can cross the endothelium, where it may be returned to circulation via the lymphatic system or become trapped in an arterial wall. Trapping of apoB lipoprotein in the arterial wall increases endothelial permeability and causes inflammation. Endothelial cells express adhesion molecules that capture monocytes which transform to macrophages. Release of cholesterol to macrophages results in the creation of foam cells. Over time, the atherosclerotic plaque slowly enlarges as more apoB-containing VLDL, remnant, and LDL particles become trapped in the artery wall. Smooth muscle cells are transferred from the middle layer of the arterial wall into the tunica intima and begin forming a fibrous cap. In advanced lesion, smooth muscle cells and macrophages die by apoptosis and contribute extracellular lipid and necrotic debris to the core of the atheroma. If the fibrous cap of a plaque ruptures, the coagulation cascade is activated  and thrombosis occurs. Atherosclerotic cardiovascular diseases (ASCVD) include stroke, transient ischemic attack (TIA), coronary artery disease (CAD) with stable angina, acute coronary syndromes (ACS), peripheral vascular disease, and aortic aneurysm.

Lipid profiles are recommended for adults undergoing risk assessment for ASCVD and for children with obesity or family history of early ASCVD. The commonly ordered lipid panel includes total cholesterol, LDL cholesterol (LDL-C), non-HDL cholesterol, HDL cholesterol (HDL-C) and triglycerides.

Elevated LDL cholesterol is a major cause of atherosclerotic cardiovascular disease (ASCVD).  The relationship between LDL cholesterol levels and CHD risk is continuous over a broad range of LDL levels. LDL-C is the total cholesterol content carried by LDL particles. LDL-C can either be directly measured by immunoassay or estimated using the Friedewald equation.

LDLC = Total Cholesterol – HDL cholesterol − Triglycerides/5

Plasma triglyceride concentration (mg/dL) divided by 5 is an estimate of the cholesterol content carried by triglyceride-rich lipoproteins, which is an estimate of the concentration of circulating VLDL and remnant particles

The Friedewald equation increasingly underestimates the true LDL-C value as triglyceride levels increase. For this reason, most laboratories do not report LDL levels when triglycerides are above 400 mg/dL. But the calculation is affected to some extent at all triglyceride levels above 100 mg/dL. A falsely low LDL-C level may give a patient and their physician a false sense of reassurance. Patients with diabetic dyslipidemia and related conditions, such as the metabolic syndrome, often have elevated triglycerides, low HDL, and relatively normal calculated LDL values.

Sustained hypertriglyceridemia results in elevated levels of very low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and small dense atherogenic LDL particles. Calculation of non-HDL cholesterol provides a single index of all these apolipoprotein B-containing lipoproteins, essentially acting as a surrogate for direct measurement of apolipoprotein B. Non-HDL cholesterol is calculated by subtracting HDL-C from total cholesterol.

Non-HDL cholesterol is a stronger predictor of coronary risk than LDL or triglycerides in certain patient populations, since it reflects the sum of serum cholesterol carried by all of the potentially atherogenic lipoproteins including LDL, VLDL, IDL, and other remnant lipoproteins. Moreover, since it is calculated from total cholesterol and HDL cholesterol, both of which are measured directly, it is not affected by the triglyceride level and does not require a fasting specimen.

Numerous epidemiological and interventional studies have documented that HDL cholesterol (HDL-C) is a major independent risk factor for coronary heart disease (CHD). Low HDL cholesterol is a strong independent predictor of ASCVD and is considered to be a major risk factor. Low HDL cholesterol is defined as a level below 40 mg/dL in men and below 50 mg/dL in women. AHA/ACC guidelines do not specify a therapeutic goal for raising HDL; instead, the emphasis is on reducing LDL cholesterol.

Triglycerides are esters of glycerol and, usually, three different fatty acids.  They are the main form of storage lipid in man and are transported in plasma, mostly in the form of chylomicrons and very low-density lipoprotein (VLDL).  Plasma levels of triglycerides vary widely throughout the day because many grams of dietary fat are absorbed after each meal.  Multivariate analyses have demonstrated that triglycerides are an independent risk factor for CAD even after adjustment for HDL cholesterol. The American Heart Association and the American College of Cardiology have endorsed a desirable triglyceride level of 150 mg/dL or less in women and diabetic patients.

Clinical thresholds for each component in the lipid panel are listed in the following table

Lipid Low Desirable Borderline High High Very High
Non-HDL-C   <130 160-189 190-219 220 or >
LDL-C   <100 130-159 160-189 190 or >
Cholesterol   <200 200-239 240 or >  
HDL-C Men <40        
HDL-C Women <50        
Triglycerides   <150 150-199 200-499 500 or >

Emerging evidence suggests that the optimal lipid-lowering therapy for any person is the one that produces the greatest absolute reduction in apoB lipoprotein. Under most circumstances, 90% of circulating apoB lipoprotein particles are LDL particles. Therefore, it is easier and cheaper to base therapy on LDL-C levels than separately measuring apoB lipoprotein by a immunoassay.  

The American Heart Association (AHA) and the American College of Cardiology published new guidelines for management of blood cholesterol on November 10, 2018. These guidelines recommend lowering LDL-C with statins, ezetimibe, or a PCSK9 inhibitor because these therapies have been shown to reduce the risk of ASCVD events in randomized trials. Each of these therapies reduces LDL-C by reducing the number of circulating LDL particles through upregulation of the LDL receptor.

Treatment goals are are summarized in the following table.  

Clinical Status Age Range Statin Intensity LDL-C % Reduction Goal LDL-C Level Goal (mg/dL)
Primary Prevention        
LDL > 190 20-75 High 50 or > <100
Diabetes LDL>70 40-75 Moderate 30 or >  
High Risk, LDL >70 40-75 High 50 or >  
Intermed Risk,LDL >70 40-75 Moderate 30 or >  
Secondary Prevention        
Very high risk ASCVD >18 High 50 or > <70
All other ASCVD >18 High 50 or >  


For primary prevention in patients with LDL-C of 190 mg/dL or higher, high-intensity statin therapy is recommended to reduce LDL-C by more than 50% and to less than 100 mg/dL. For primary prevention in all other patients between the ages of 40 and 75 years, the decision to actively treat lipids is largely based on risk estimated from the ACC/AHA Pooled Cohort Equations CV Risk Calculator, which now labels low risk as less than 5.0% over 10years, borderline as 5.0%to 7.4%, intermediate as 7.5% to 19.9%, and high as 20%or higher.

Patients with intermediate-risk should achieve more than 30% reduction, while high-risk patients should initiate statin therapy with a goal of more than 50% LDL-C reduction. Patients aged 40 to 75 years who also have diabetes and LDL-C of 70 mg/dL or higher should receive moderate-intensity statin therapy.

For secondary prevention, the guidelines recommend initial treatment with high intensity statins to reduce LDL-C by greater than 50%. Patients with very high risk ASCVD have a second goal of reducing LDL-C to less than 70 mg/dL. If this cannot be achieved with a high intensity statin, treatment with ezetimibe or a PCSK9 inhibitor (alirocumab and evolocumab) is recommended.


1. Wilson PWF, Polonsky TS, Miedema MD, et al. Systematic review for the 2018 AHA/ACC/AACVPR/ AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol [published online November 10, 2018].J AmColl Cardiol. doi:10.1016/j.jacc.2018.11.004

2. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/ APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol [published online November 10, 2018]. J AmColl Cardiol. doi:10.1016/j.jacc.2018.11.003

3. Doran B, Guo Y, Xu J, et al. Prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol levels on long-term mortality. Circulation. 2014;130(7):546-553.

4. Alenghat FJ and Davis AM, Management of Blood Cholesterol, JAMA Clinical Guidelines Synopsis.  (published on line Feb 4, 2019) doi:10.1001/jama.2019.0015

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