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Simeon Margolis, M.D.I agree with you that the apoprotein stuff, (except for apo B, is not needed by this audience. I decided to be so complete becasue the drug profiles sontained so much pharmcokinetic information that certainly is never used by practiceing docs. Regarding the Fredrickson scheme. It is not used much BUT it is the simplest way to describe the various types of hyperlipidemia.
02-03-2011
- Standard lipid profile includes total cholesterol, TG, HDL cholesterol (HDL-C), and LDL cholesterol (LDL-C).
- Apolipoproteins and lipoprotein lipase activity can also be measured.
- Chylomicrons carry fat absorbed from the intestine.
- High LDL-C-("bad cholesterol") is the strongest lipid risk factor for cardiovascular disease.
- Low HDL-C ("good cholesterol) is also a strong risk factor for cardiovascular disease.
- High triglycerides (TG) are also associated with cardiovascular disease although less strongly than high LDL-C or low HDL-C.
- Severe hypertriglyceridemia is a cause of pancreatitis.
- The most important assay is a fasting lipid profile performed by a standard chemical assay, usually with autoanalyzer, which measures total cholesterol, TG, and HDL-C.
- Immunoassays can measure apoproteins A, B, C-II, C-III,and E as well as the 3 major isoforms of apo E.
- Chylomicrons can be detected by finding a white layer of fat at the top of serum refrigerated overnight.
- Obtain fasting lipid profile at the time of diagnosis of type 2 diabetes and at least annually during the course of treatment.
- Consider obtaining an apo B if LDL-C is still above target of 70 mg/d or the patient develops cardiovascular disease, to determine if more aggressive statin treatment or addition of niacin is needed because of persistently high levels of small, dense, atherogenic LDL particles; . (Pischon;Contois)
- The Fredrickson classification may be useful to distinguish different phenotypes of hyperlipoproteinemia, though the classification system itself is no longer commonly used. Major phenotypes are described below.
- Hyperchylomicronemia: characterized by very high fasting triglycerides (often > 1,000 mg/dl), which can be seen as a large band of chylomicrons in overnight refrigerated serum. The familial disorder is due to deficient lipoprotein lipase activity or apo CII, the activator of lipoprotein lipase. The types can be distinguished by measuring apo CII. Severe insulin deficiency can produce hyperchylomicronemia.
- Hypercholesterolemia (HCH): LDL-C is elevated. TG may be normal or high. LDL receptor deficiency is the major cause of familial hypercholesterolemia. Primary HCH can also result from other genetic defects. Other disorders and dietary excesses can also cause HCH.
- Familial combined hyperlipoproteinemia: elevated LDL-C and triglycerides and increased apoB. (Veerkamp)
- Dysbetalipoproteinemia: suspected by nearly equal elevations of cholesterol and TG. Confirmed by finding apo E2:E2 isoform pattern. (Kane)
- Familial hypertriglyceridemia: elevated VLDL-containing TG with normal or modest elevations in LDL-C.
- Mixed hypertriglyceridemia: elevated VLDL-containing TG and chylomicron-containing TG. In overnight refrigerated serum a layer of chylomicrons are on top of underlying turbid serum.
- Familial combined hyperlipidemia can be diagnosed by finding high levels of cholesterol, TG, and/or apo B in family members. Lipid abnormalities differ in members of the same family (Veerkamp). Acquired combined hyperlipidemia common in diabetes.
- It is important to identify patients with familial hypercholesterolemia, dysbetalipoproteinemia, and familial combined hyperlipidemia because of their especially high risk of CVD. Screening family members is indicated.
- The most common lipid disorder in type 2 diabetes is an elevation of both cholesterol and TG (mixed hyperlipidemia)
- LDL-C is not usually measured directly, but is estimated from the lipid profile by the following Friedewald equation (if triglycerides are below 400 mg/dL): LDL-C = total cholesterol - triglycerides/5- HDL-C.
- Non-HDL cholesterol is used when treating hypertriglyceridemia. It is calculated as follows: Non-HDL cholesterol = Total cholesterol - HDL-C.
- Target for LDL-C in type 2 diabetes is < 100 mg/dL, and in cases considered high risk, < 70 mg/dL Target for non-HDL cholesterol in type 2 diabetes is either <100 mg/dL or <130 mg/dL.
- Hypertriglyceridemia is almost always associated with low HDL-C and f an increased number of more atherogenic small dense LDL.
- Presence of chylomicrons may indicate a non-fasting sample.
- Risk of acute pancreatitis when triglycerides exceed 1000 mg/dL.
- LDL-C cannot be calculated accurately with the Friedewald equation when triglycerides exceed 400 mg/dL or in patients with dysbetalipoproteinemia; tests are available to directly measure LDL-C in these circumstances.
- When TG are very high, serum amylase and lipase usually cannot be used to make the diagnosis of acute pancreatitis.
- Worsening of glycemic control can lead to hyperchylomicronemia and the risk of acute pancreatitis.
- Triglycerides and HDL cholesterol can improve considerably with better glycemic control
- LDL varies less with exercise or glycemic control
- Lipid profile should be fasting since triglycerides can vary depending on recent food intake
- Cholesterol varies little between fed and fasted state unless TG are high
- HDL does not significantly depend on fasting status
- Non-HDL cholesterol, and especially apo B, may be better predictors of cardiovascular risk; changes in apo B provide an additional estimate of the effectiveness of lipid-lowering therapy . (Pischon;Contois)
- Apo B can determine the number of LDL particles and the presence of more atherogenic, small dense LDL.
- Other than apo B, special tests like lipoliprotein lipase activity and apoprotein measurements are largely of research interest and are rarely if ever needed for patient care. (Mora)
- Before initiating lipid-lowering therapy, baseline tests in patients with lipid abnormalities should include TSH and liver enzymes but not CK; however, CK must be obtained with complaints of either muscle pain or weakness
- Recent studies indicate that non-fasting triglycerides may be better predictors of cardiovascular risk than fasting triglycerides, but upper limits of normal values have not yet been established for non-fasting triglycerides. (Bansal;Nordestgaard)
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