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Lipoproteins I
Track 1 Lecture 2
| Question | Answer |
|---|---|
| What is the overall effect of soluble effect? | 1. increase bile acid formation in liver 2. decreases lipid absorption |
| soluble fiber | each gram fiber decreases total LDL-C by 1.5-2.7 mg/dL |
| Soluble fiber _________ the total and LDL-Cholesterol | decreases |
| What is the mechanism of soluble fibers | decreases the reabsorption of bile acids -> which increases hepatic conversion of cholesterol to bile acids -> leads to increase in LDL uptake by the liver |
| Lipoprotiens classes contan subclasses that differ in _______ | Particle Size |
| What did the cohort study show about particle size variability among the different LDL subclasses? | small LDL is associated w/ 4-fold increase in risk of IHD (ischemic heart disease) even if the men had a TC of < 3.8 mmol/L and a 6.5-fold increase of IH if the men had a TC of > 3.8 |
| Large prospective studies show that ____ LDL is NOT related to CAD risk | LARGe |
| The strongest association with CAD is ____ and ______ LDL | small, very small |
| Is distribution of LDL subclasses independent of Total Cholesterol? | Yes |
| The Medium LDL particle size is most abundant in _______ individuals | Healthy |
| The Small LDL particle size is associated with | reduced clearance greater entry into artery faster oxidation associated with metabolic syndrome/insulin resistance |
| In the cohort study, low/high LDL-C was not a significant factor in risk factor for CAD until | particle size (small/med) was taken into consideration than the p value was significant show risk increase and more so w/ higher LCL-C |
| What does measuring LDL-C fail to show? | The size of the particles abundance of the LDL particles |
| If you take two individuals and individual A has a lower LDL-small particles than individual B--which individual will have an increased risk of CVD? | Individual B |
| How are you able to capture the abundance of the LDL particles? | By noting the number of ApoB100 concentration |
| The LDL particle is unique | They have 1. only 1 apo B100/particle 2. Concentration of apo B100 relfects LDLD particle number |
| Increase in apoB100 | Increase in LDL particle number |
| Does the ApoB100 tell you about the particle size? | No. The concentration of ApoB100 does not tell you LDL particle size |
| Individuals with small LDL | also have an increased TG |
| Hypertriglyceridmeic | most likely to have small particles size of LDL-C |
| Phenotype B | individuals with an abundance of small LDL Particles |
| Who had phenotype B | men > 20 postmenopausal women CAD patients |
| LDL phenotype B is aka | Atherogenic Lipoprotein Phenotype (ALP) |
| ALP or Phenotype have | Increased TG Decreased HDL-C Increase in small, dense LDL particles |
| What factors associated with Phenotype B (ALP) increase your risk of CHD by 2-3-fold? | 1. Increase in small, dense LDL particles which is associated with other risk factors: a. tendency to increase adiposity b. insulin resistance = type 2 DM c. metabolic syndrome |
| Niacin | decreases TG levels and decreases the number of small LDL particles |
| Individuals are at risk of having a CHD independent of cholesterol level if they have an abundance of small LDL particles? T or F. | True |
| Determinants of Phenotype B | Heritability 40-75% Modifying Factors: diet & adiposity/insulin resistance Others Age: prevalence low in children Gender: men > women |
| Determinants of Phenotype B | Genetics Environment exacerbates it |
| Factors that affect expression of phenotype | 1. genetic predisposition 2. insulin resistance 3. adiposity 4. high carb diet |
| Abundance of TG | create LARGE VLDL ---> LPL will hydrolize the TG and form remnant particles---> remnant remain in the plasma longer |
| What happens to the remnants that remain in the plasma longer? | They get acted upon CETP--transfers cholesterol esters from 1 lipoprotein class to another--which will transfer cholesterol from LDL to remnant particles and there will be reciprocal transfer of TG to the LDL |
| What does the change in composition of the remnant make them more susceptible? | With an increase in cholesterol contact they are more likely to be acted upon by hepatic lipase as opposed to lipoprotein lipase |
| If one has a large quantity of hepatic TG what is triggered? | Pattern B--small LDL |
| large amount of hepatic TG | leads to large VLDL particles and eventually small LDL particles |
| In normally individuals the LDL has a _____ affinity to bind tot he LDL-R whereas the smaller LDL particles have ____ affinity to the LDL-receptor and just stay in the plasma longer--more prone to oxidation and are thus more atherogenic | higher reduced |
| Prevalence of ALP is related to _______ & _______. | dietary fat carbohydrate |
| Per research, phenotype B is inducible by | high carbohydrate and LOW-fat diet |
| If a patient has high cholesterol and low TG | this Phenotype B might might not be a problem |
| What populations are of concern in terms of CHD and phenotype B | Heavy individuals insulin resistance metabolic syndrome |
| Adiposity and phenotype B | As one increases their BMI they increase in % of phenotype B |
| Can weight decrease the % of phenotype B in individuals? | Yes. Weight loss to BMI < 25 promotes conversion to phenotype A in the majority of phenotype B individuals per 1 study |
| There are some individuals that are "hard-wired" that even with weight loss they still remain ____ | phenotype B |
| There are those that remained ______ and ________ in the study | overweight and phenotype B--they will following a caloric restriction but still DID not lose weight--might have a hard time oxidizing fat |
| What can reverse phenotype B (aka ALP)? | 1. decrease in carbohydrate intake 2. decrease in weight |
| Controversial finding in one study showed that a high fat (of diary products), low carb diet did _______ LDL-C but did NOT increase ______ particles but instead increased ______ particles | increase LDL-C, small, large |
| What did the meta-analysis show in regards to increase in saturated fat (in the context of a mixed diet) and increase in CVD? | There was NO association--this was similar for risk of stroke and SFA |
| There is strong support that saturated fat DOES raise LDL-C but not the ________ particle size of LDL | small |
| summary of information | 1. Both CHO restriction and weight loss decrease expression of ALP 2. SFA derived from dairy fat increases LDL-C by increasing large LDL but NOT small LDL |
| 43% of individuals express _____ w/ 60% CHO diet | ALP |
| Surrogate markers of small LDL particles when LDL particle size cannot be measured | 1. plasma TG levels 2. TG/HDL-C RATIO 3. Plasma ApoB Levels |
| Plasma TG Levels | > 200 = high probability that individuals have mostly SMALL LDL (85% are Pattern B) |
| What if the Plasma TG levels are <70? | High probability that individuals will have mostly LARGE LDL |
| What if the Plasma TG level is between 70-200 | Not accurate at predicting LDL phenotype |
| Plasma TG must be measured | during fasting |
| TG/HDL-Cholesterol Ratio | > 3.5-4.0 Can predict LDL subclass B w/ some accuracy < 4.0 does NOT accurately predict LDL phenotype |
| The TG/HDL-C Ration is NOT a good measure of | the concentration |
| Plasma Apolipoprotein B | > 80 mg/dL more strongly relates to concentration of small HDL |
| Plasma ApoB also provides a measure of | the # of circulating atherogenic lipoproteins |
| What is the recommendation in other country guidelines for the level of ApoB in high risk patients | < 90 mg/dL of ApoB |
| What is a reasonable way to assess small LDL when LDL particle size cannot be measured? | Combination of plasma TG, TG/HDL-C ration and plasma ApoB |
| ApoB is can tell you about the ________ of LDL particles | concentration |
| What are other novel markers of CHD risk | ApoB/A-I ratio |
| ApoB/A-I ratio | reflects the # of apoB-containing atherogenic lipoproteins relative to protective AI-containing lipoproteins |
| Is ApoB/ApoA-I superior to LDL-C/HDL-C ratio in predicting MI risk? | Yes |
| What ApoB/A-I ratio predicted MI risk in men? | >/= 0.9 |
| Are there laboratory tests that can be done to find out about particle size? | Yes |
| The standard lipid panel is recommended based on the ATPIII guidelines but have advanced lipoprotein tests been recommended yet in the US? | No |
| LDL particles recommended by the ADA and American College of Cardiology in | subjects at high risk for cardiometabolic d/o: obesity, IR, hyperglycemia, HTN, increase in TG, small dense LDL, decrease in HDL-C to better assess CHD risk and guide therapy toghether WITH LDL and non LDL-C |
| Lipoproteins are _________ in size and metabolism | heterogenous |
| LDL _____ strongly correlates with plasma and VLDL TG | particle size |
| What mediates the LDL particle size? | CETP and hepatic lipase |
| Small dense LDL are | LDL3 LDL4 |
| What sizes are associated with increase risk of CHD | small dense LDL |
| ALP (phenotype B) is more prevalent in _____. | men |
| Although it is less prevalent in women it increases when_________ | after menopause |
| What determines phenotype | genetics adiposity IR diet |
| What are "hard-wired" pattern B | patients that will continue to have small LDL even after weight loss and low CHO diet |
| Individuals w/ pattern can decrease their small LDL by | weight loss moderate restriction of CHO |
| When consuming high CHO diet what is critical | CHO quality: high fiber, minimize simple sugars |
| Low fat, high CHO diet may decrease LDL-C concentration reflecting a shit from large LDL to smaller LDL with NO change in particle amount, so that CV risk may NOT | decrease but actually incrase |
| Saturated fats derived from dairy foods increase | LDL-C by increase large LDL but NOT small LDL particles |
| Advanced Lipoprotein testing can be used to | 1. enhance accuracy of atherosclerosis risk prediction 2. enhance accuracy of outcome prediction 3. Assist in tx selection and dose adjustment 4. Counsel 1st degree relatives of pts w/ atheroschlerosis |
| Enhance accuracy of atherosclerosis risk prediction | Pattern B individuals have a 3-fold increase risk of CHD |
| Assist in tx selection and dose adjustment | 1. decrease small LDL or ApoB is associated w/ artiographic benefit in high risk pts 2. pattern B individuals respond w/ greater decrease small LDL and increase in LDL size to niacin than pattern A's |
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cwjlamh
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