1/19 Saturday Morning Class #18 Lp(a) and apoB
First some definitions
There are 2 kinds of apoB: apoB48 which is made by small intestine and apoB-100 made by the liver. ApoB48 and apoB100 come from the same gene, except one is 48% the size of the other, thus the name.
First some definitions
There are 2 kinds of apoB: apoB48 which is made by small intestine and apoB-100 made by the liver. ApoB48 and apoB100 come from the same gene, except one is 48% the size of the other, thus the name.
2/19 ApoB48 carries the lipid (fat in form of triglycerides) that one eats to the circulation and it goes to muscle for energy or liver for re-processing. The enzyme lipoprotein lipase (LPL) breaks down the TG into free fatty acids that go to the Krebs cycle for ATP energy
3/19 If one is missing both copies of LPL, one develops milky plasma- chylomicrons that cant be cleared. This causes acute pancreatitis. @IonisPharma has been working on a therapy to treat this by inhibiting ApoCIII which mediates LPL activity and chylomicron clearance
4/19 See photo of my pts' plasma after undergoing angiogram, the tube sat on benchtop for only 30 minutes during procedure. Note the chylomicrons all floated to the top. TG level was 12,000 mg/dL. One can imagine its not good to have large globs of fat circulating in your body 
5/19 ApoB-100 is primarily made by the liver. Each lipoprotein particle (chylomicron, VLDL, IDL, LDL, Lp(a)) has only 1 molecule of apoB – thus if you measure apoB, you get a summation of all the atherogenic particles
6/19 You can think of apoB as a “sponge” that sucks up lipid instead of water. It does this by having special combinations of amino acids that allow this.
7/19 Why do we need and other lipoproteins?. Because oil and water don’t mix. Lipoproteins transport lipids from the diet and from the liver to the cells in the body. When on apoB the lipids can dissolve in blood and be transported. By necessity, all mammals have lipoproteins.
8/19 ApoB-100 is huge, 4563 amino acids long. Lp(a) has one molecule of apo(a) which can be even larger than apoB. They are joined together by a disulfide bond (like conjoined twins) cysteine 4057 of apo(a) and cysteine 4326 of apoB-100. pubmed.ncbi.nlm.nih.gov/7592581/
9/19 Some math:
ApoB is presented in mg/dL. However, one can do some math gymnastics to understand the Lp(a)-apoB relationship for clinical care:
1-The molecular weight of apoB is 513,000 grams/mole. So one can convert mg/dL to nmol/L, so one can compare to moles of Lp(a).
ApoB is presented in mg/dL. However, one can do some math gymnastics to understand the Lp(a)-apoB relationship for clinical care:
1-The molecular weight of apoB is 513,000 grams/mole. So one can convert mg/dL to nmol/L, so one can compare to moles of Lp(a).
10/19 2-We talked about Avogadro's number before, the brilliance is that number of units in one mole of any substance (defined as its molecular weight in grams), equal to 6.02214076 × 10x23- one mole of apples and one mole of oranges has the same number of apples and oranges
11/19 3-So, if apoB is 100 mg/dL, then this equates to 1949 nmol/L
4-Lp(a) ranges from 0-~1000 nmol/L, most people have <75 nmol/L.
5-So, one can see here that there is a large excess of apoB relative to Lp(a) in most people.
4-Lp(a) ranges from 0-~1000 nmol/L, most people have <75 nmol/L.
5-So, one can see here that there is a large excess of apoB relative to Lp(a) in most people.
12/19 6-If Lp(a) is 300 nmol/L and apoB 900 nmol/L, there are 3x as many apoB particles, 300 stuck to Lp(a) and the rest are on VLDL/IDL/LDL. If apoB is 1500 and Lp(a) 50, then apoB is 30x in excess
13/19 What are clinical implications
1-Lp(a) has 3 mechanism of CVD risk; 1- the LDL component, 2- OxPL @OxPL_apoB, 3- anti-fibrinolytic effects
2-The correlation between apoB and Lp(a) is very weak usually r<0.1. If one removes the Lp(a)-apoB from it, there is no correlation
1-Lp(a) has 3 mechanism of CVD risk; 1- the LDL component, 2- OxPL @OxPL_apoB, 3- anti-fibrinolytic effects
2-The correlation between apoB and Lp(a) is very weak usually r<0.1. If one removes the Lp(a)-apoB from it, there is no correlation
14/19 3-If a patient has identical number of Lp(a) and LDL particles, Lp(a) has to be equally or higher risk, since LDL has little OxPL and no apo(a)
4-Lp(a) risk is independent of apoB100, likely because other components are not reflected in apoB pubmed.ncbi.nlm.nih.gov/33629108/
4-Lp(a) risk is independent of apoB100, likely because other components are not reflected in apoB pubmed.ncbi.nlm.nih.gov/33629108/
15/19 5-ApoB100 is not synonymous with LDL-C, since it includes the other lipoproteins
6-ApoB100 is generally the same (~80-90% of time) or better than LDL-C in risk prediction, the reason being it adds remnant chol and Lp(a) to the equation.
6-ApoB100 is generally the same (~80-90% of time) or better than LDL-C in risk prediction, the reason being it adds remnant chol and Lp(a) to the equation.
16/19 7-ApoB is most useful in people whose TGs are elevated, their LDL is relatively depleted of chol so one underestimates particle number. Also useful when Lp(a) is elevated and apoB will be higher than one can judge from LDL-C.
17/19 8-In a re-imagined world, apoB100 would be the metric of choice, but the lipid panel is dirt cheap, and also gives you TC, HDL and TG for lower price, so right now apoB is best used in the small subset of pts where it can tell you more than the lipid panel.
18/19 Quiz- 5 points:
How do you determine if a lipid of interest came for the diet or from the liver:
1-Measure LDL-C vs VLDL
2-Measure LPL and free fatty acids in muscle
3-Measure total apoB
4-Measure apoB48
How do you determine if a lipid of interest came for the diet or from the liver:
1-Measure LDL-C vs VLDL
2-Measure LPL and free fatty acids in muscle
3-Measure total apoB
4-Measure apoB48
19/19 bonus question:
True or false: The number of Lp(a) particles can never exceed the number of apoB-100 particles
True or false: The number of Lp(a) particles can never exceed the number of apoB-100 particles
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