Clinical Problems: Lipids Flashcards
_______ separation of lipoprotein particles is particularly useful for qualitative and semi- quantitative comparisons.
Electrophoretic separation of lipoprotein particles is particularly useful for qualitative and semi- quantitative comparisons.
Differences in density allow separation of the various lipoprotein particles by ________, but this method is cumbersome and expensive. For several decades, clinical labs have been using chemical ________ methods that take advantage of differences in particle size, charge, and apolipoprotein content. These precipitation procedures do not separate all the relevant lipoprotein fractions; instead, only _______ is cleanly separated from the other lipoproteins.
Differences in density allow separation of the various lipoprotein particles by ultracentrifugation, but this method is cumbersome and expensive. For several decades, clinical labs have been using chemical precipitation methods that take advantage of differences in particle size, charge, and apolipoprotein content. These precipitation procedures do not separate all the relevant lipoprotein fractions; instead, only HDL is cleanly separated from the other lipoproteins. (HDL is thus the only fraction for which cholesterol is measured directly, whereas LDL cholesterol is estimated).
Method for Estimating LDL-Cholesterol; 3 tasks.
- Determination of total plasma or serum cholesterol.
- Determination of cholesterol in a supernate after all lipoproteins other than HDL have been precipitated.
- Determination of total plasma or serum triglycerides.
Ratio of VLDL-cholesterol to triglyceride (on a mg/dL basis) is constant at about _ :_. Thus VLDL-cholesterol can be estimated from a triglyceride measurement.
Ratio of VLDL-cholesterol to triglyceride (on a mg/dL basis) is constant at about 1 : 5. Thus VLDL-cholesterol can be estimated from a triglyceride measurement.
TG/5 = VLDL
Friedewald formula: CLDL =
CLDL = CTOTAL — CHDL — (TRIGLYCERIDES / 5 )
CLDL = CTOTAL — CHDL — VLDL
C in front means cholesterol
HDL can be conveniently separated from all other lipoproteins and so HDL-cholesterol can be measured directly. If a measurement of total cholesterol is also available, LDL- cholesterol can then be determined by difference
Total Cholesterol / HDL ratio is reported on many lipid panels – a lower number indicates lower cardiovascular risk. The ratio of TC/HDL reflects the balance of two completely opposite processes: transport of cholesterol to peripheral tissues, with its subsequent uptake in arterial walls, and reverse transport to the liver.
3 factors that affect Lipid and LP Measurements:
- Reliability of laboratory (1 – 3%)
- Intra-individual biological variation (5%)
- Influence of fasting
Discuss the ACC/AHA 2013 Guidelines
Taken from systematic reviews and meta-analyses of RCTs
Four groups of individuals were identified, for whom an extensive body of RCT evidence demonstrated a reduction in atherosclerotic cardiovascular disease (ASCVD) events (including coronary heart disease, cardiovascular deaths, and fatal and nonfatal strokes) with a good margin of safety from statin therapy. Name the 4 statin groups.
- Individuals with clinical ASCVD (atherosclerotic cardiovascular disease = acute coronary syndromes, or a history of myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of atherosclerotic origin) without New York Heart Association (NYHA) class II-IV heart failure or receiving hemodialysis.
- Individuals with primary elevations of low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dl.
- Individuals 40-75 years of age with diabetes, and LDL-C 70-189 mg/dl without clinical ASCVD.
- Individuals without clinical ASCVD or diabetes, who are 40-75 years of age with LDL-C 70-189 mg/dl, and have an estimated 10-year ASCVD risk of 7.5% or higher.
NOTE: No recommendations are made to inform treatment decisions in selected individuals who are not included in the four statin benefit groups. In these individuals whose 10-year risk is 160 mg/dl, high- sensitivity C-reactive protein ≥2 mg/dl, coronary calcium score ≥300 Agatston units or ≥75th percentile for age, sex, ethnicity, and ankle-brachial index
Discuss how lifestyle modification is important therapeutically
Lifestyle modification (i.e., adhering to a heart healthy diet, regular exercise habits, avoidance of tobacco products, and maintenance of a healthy weight) remains a critical component of health promotion and ASCVD risk reduction, both prior to and in concert with the use of cholesterol-lowering drug therapies.
Discuss why treatment targets are no longer used
There is no evidence to support continued use of specific LDL-C and/or non–high-density lipoprotein cholesterol (non–HDL-C) treatment targets.
The appropriate intensity of statin therapy should be used to reduce risk in those most likely to benefit.
Nonstatin therapies, whether alone or in addition to statins, do not provide acceptable ASCVD risk reduction benefits compared to their potential for adverse effects in the routine prevention of ASCVD.
This guideline recommends use of the new Pooled Cohort Equations to estimate 10-year ASCVD risk in both white and black men and women. By more accurately identifying higher risk individuals for statin therapy, the guideline focuses statin therapy on those most likely to benefit. It also indicates, based on RCT data, those high-risk groups that may not benefit.
Discuss high intensity Statin therapy
High-intensity statin therapy is defined as a daily dose that lowers LDL-C by less than equal to 50% and moderate- intensity by 30% to less than 50%. All patients with ASCVD who are age less than equal to 75 years, as well as patients less than 75 years, should receive high-intensity statin therapy; or if not a candidate for high-intensity, should receive moderate-intensity statin therapy.
Those with an LDL-C ≥190 mg/dl should receive high-intensity or moderate-intensity statin therapy, if not a candidate for high-intensity statin therapy.
Addition of other cholesterol-lowering agents can be considered to further lower LDL-C. Diabetics with a 10-year ASCVD ≥7.5% should receive high-intensity statins and <7.5% moderate-intensity statin therapy. Persons 40-75 years with a ≥7.5% 10-year ASCVD risk should receive moderate- to high-intensity statin therapy.
What are not considered appropriate cholesterol treatment strategies anymore?
The following are no longer considered appropriate strategies: treat to target, lower is best.
The new guideline recommends: treat to level of ASCVD risk, based upon estimated 10-year or lifetime risk of ASCVD.
The guidelines provided no recommendations for initiating or discontinuing statins in NYHA class II-IV ischemic systolic heart failure patients or those on maintenance hemodialysis.
Discuss primary prevention in statin therapy
In primary prevention, the cholesterol guidelines recommend not only the risk calculation, but also the physician–patient review of the risk and the decision to take a statin. It is important to realize that the ASCVD risk calculator is heavily influenced by age.
A 65-year-old man and a 71-year-old woman with optimal risk factors have a >7.5% 10-year risk. This is where physician judgment, statin safety issues, and a consideration of patient preferences can inform this decision.
Prescription of a statin is not automatic, but part of a comprehensive approach to risk reduction that begins with the use of the ASCVD risk calculator and with the assumption that the physician is addressing each of the modifiable risk factors.
Discuss the factors that go into 10-year risk calculator.
Men vs women
Total cholesterol
Age
Smoker vs non-smoker
HDL
Systolic BP
Note that people with 10-year ASCVD risk of 7.5% have increased risk & may be indicated for Statin therapy!
