_______________________________________ Hyperlipidemias and Atherosclerotic Cardiovascular Disease
PLASMA LIPOPROTEINS
Characteristic
Chylomicrons
Very-Low-Density Lipoprotein (VLDL)
Intermediate- Density Lipoprotein (IDL)
Low-Density Lipoprotein (LDL)
High-Density Lipoprotein (HDL)
Density
<0.95 g/mL 0.95–1.006 g/mL 1.006–1.019 g/mL 1.019–1.063 g/mL 1.063–1.210 g/mL
Diameter
75–1,200 nm 30–80 nm
25–35 nm
18–25 nm
5–12 nm
Protein
2%
10% 90% 50% 22% 18%
18% 82% 31% 29% 22%
25% 75% 10% 45% 20%
33% 67%
Total lipid
98% 83%
Triglycerides Cholesterol Phospholipid Major apoproteins
8%
8% 7%
30% 29%
Apo B-48 Apo C-II Apo E
Apo B-100 Apo C-II Apo E
Apo B-100 Apo C-II
Apo B-100
APO A-I APO A-II Apo C-II Apo E
Source: Compiled by Author
Table 2
CLASSES OF LIPOPROTEINS AND LIPOPROTEIN PHYSIOLOGY Lipoproteins are classified by size and density. Because proteins are denser than lipids, the greater the protein content, the greater the density of the lipoprotein. There are five types of lipoproteins: chylomicrons, VLDLs, intermediate-density lipoproteins (IDLs), LDLs, and HDLs ( Table 2 ). Plasma Lipid Profiles Prior to discussing the properties of the various lipoproteins, it is important to review the most pertinent information related to plasma lipid profiles. In fasting individuals, total cholesterol in plasma is carried primarily in VLDL, LDL, and HDL. Accordingly, total cholesterol is equal to the sum of VLDL, HDL, and LDL. Clinical laboratories measure total cholesterol, HDL, and triglycerides. Most triglycerides are found in VLDL, which has five times as much triglyceride by weight as cholesterol. Therefore, the amount of cholesterol in VLDL can be calculated as triglycerides (mg/dL) divided by 5 or triglycerides (mmol/dL) divided by 2.2+-. For more than 50 years, most clinical laboratories have calculated the value of LDL cholesterol indirectly, according to the Friedewald equation [59; 60]: LDL (mg/dL) = total cholesterol (mg/dL) – HDL (mg/dL) – [triglycerides (mg/dL) / 5] Or, if the International System of Units is used, total LDL may be calculated as: LDL (mmol/dL) = total cholesterol (mmol/dL) – HDL (mmol/dL) – [triglycerides (mmol/dL) / 2.2] A modified Friedewald equation is also used and has been suggested to have a higher level of accuracy in calculating LDL values [61; 62]. This equation is: LDL (mg/dL) = [non-HDL cholesterol (mg/dL) x 0.9] – [triglycerides (mg/dL) x 0.1]
It is known that in hypertriglyceridemia, LDL calculated using the Friedewald equation can be unreliable, particularly at levels <70 mg/dL. The increased prevalence of high triglyceride states (e.g., diabetes, obesity) and the use of novel lipid lowering medications (e.g., proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors) have provided an impetus for finding improved methods for estimating LDL. Direct LDL assays are not standardized and can be even less accurate than the Friedewald equation. In one study of seven direct methods for measuring LDL, total assessment errors ranged from 13.3% to 13.5% across assays in healthy individuals and from -26.6% to 31.9% in individuals with known ASCVD or dyslipidemias. The National Cholesterol Education Program has a target total error goal of ≤13%, meaning that all seven direct assays failed standard accuracy goals [63; 64]. Several prior equations have attempted to improve upon the Friedewald equation, but most used the same fixed ratio between triglycerides and VLDL. In a study of more than 1.3 million fasting and nonfasting patients, Martin and colleagues derived and validated a novel equation that replaced the fixed ratio with one of 180 adaptable ratios based on the patient’s individual non-HDL and triglyceride values. The overall accuracy of the Martin/Hopkins approach compared with direct measurement was 92% for HDL and 85% for triglycerides. LDL estimation accuracy with the Martin/ Hopkins equation was 94%, compared with 77% with the Friedewald method [65]. The 2018 AHA/ACC guideline acknowledges the importance of accurate LDL estimation and recommends measuring LDL either directly or with an alternative method (e.g., the Martin/Hopkins equation) [24; 63].
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MDNE1526
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