Lesson 6-6: Blood Cholesterol and Triglycerides (Estridge)

It is recommended that adults have cholesterol screening performed every:

5 years. - The patient should be fasting for 8 to 12 hours before blood collection for the test. - The screening should include total cholesterol, HDL and LDL cholesterol fractions (calculated or measured), and triglycerides. - If the patient is not fasting, only total cholesterol and HDL should be measured. - If this assay shows the total cholesterol result to be greater than 200 mg per dL or HDL less than 40 mg per dL a fasting lipoprotein profile should be ordered.

atherosclerosis

a form of arteriosclerosis in which lipids, calcium, cholesterol, and other substances deposit on the inner walls of the arteries

coronary heart disease (CHD)

a narrowing of the small blood vessels that supply blood to the heart; also called coronary artery disease

Total cholesterol, cholesterol fractions, and triglycerides are often included in:

a routine chemistry profile or are ordered as a lipid profile

Cholesterol Reference Values

- At birth, serum cholesterol ranges from about 50 mg per dL to 100 mg per dL. - At 1 month, the levels approach 100 to 230 mg per dL and remain at those levels until the age of 20 to 21 years.

LDL Methods​

- Beta-quantification: most common; combines ​ ultracentrifugation and chemical precipitation​ - Friedewald calculation: bypasses centrifugation; ​ commonly used in routine and sometimes research labs​ - Estimates the LDL​ Formula:​ LDL = Total Cholesterol - HDL - [Triglycerides/5]​ - Compact Analyzers​ - Mobile point-of-care testing systems​ - Can measure cholesterol, triglycerides, HDL ​ cholesterol, and glucose from a finger stick sample​

Sources of Cholesterol

- Cholesterol has two main sources: 1. Certain body tissues, especially the liver, synthesize cholesterol. - This is called endogenous cholesterol and is under genetic control. 2. Everyone consumes at least some cholesterol in their diet. - This dietary cholesterol is called exogenous cholesterol and is found in fats and fat-rich foods, such as red meat, egg yolks, and some seafood. - People who eat a rich, fatty diet can develop dangerously high blood cholesterol levels. - However, in some patients pathologically high cholesterol levels are due to genetic factors; dietary restrictions do not signicantly reduce these levels. - Cholesterol-lowering medications such as statin drugs are important alternatives for these patients.

Specimen Collection for Lipid Tests

- Cholesterol, cholesterol fractions and triglycerides should be measured on a fasting specimen. - The patient should be fasting for 8 to 12 hours before cholesterol tests; fasting for 12 hours is recommended before testing for triglycerides and lipid profiles.

Hyperlipoproteinemia​

- Diseases associated with elevated lipoprotein levels​ - Includes hypercholesterolemia, hypertriglyceridemia, and ​combined hyperlipidemia

Hypertriglyceridemia​

- Elevated triglyceride levels: high, 200 to 500 mg/dL; ​ very high, greater than 500 mg/dL​ - Due to either genetic abnormalities or hormonal ​ abnormalities

Using Cholesterol Levels to Determine the Heart Attack Risk Factor

- If the total cholesterol concentration is elevated in a patient, the HDL and LDL values can be used to determine the heart attack risk factor. - Other factors, such as smoking and level of exercise, also influence the risk. - When HDL is above the average value, it reduces the risk for MI, a type of heart attack, by as much as one-third.

Total Blood Cholesterol and Cholesterol Fractions

- It is important to know the levels of total cholesterol and the fractions of cholesterol. - The two fractions commonly measured are: 1. high-density lipoprotein (HDL) cholesterol 2. low-density lipo- protein (LDL) cholesterol. - HDL and LDL cholesterol levels are genetically determined to some extent.

Hypercholesterolemia​

- Lipid abnormality most closely linked to heart disease​ - Familial hypercholesterolemia (FH): genetic abnormality ​predisposing people to elevated cholesterol levels​ -------Homozygotes: rare (1:1 million); first heart attack in teens​ -------Heterozygotes: more common (1:500)

Hypolipoproteinemia

- Low levels of lipoproteins​ - Two forms: hypoalphalipoproteinemia and ​ hypobetalipoproteinemia​ - Can be caused by rare genetic conditions, or be a ​ sign of another disorder such as overactive thyroid,​ anemia, undernutrition, cancer, chronic infection,​ or impaired absorption of foods from the digestive ​ tract.

Lipoprotein Methods​

- Measure physical properties: density, size, charge​ - Methods: ultracentrifugation, electrophoretic separation, chemical precipitation, chromatographic, ​ immunochemical

Non-HDL Cholesterol​

- Reflects total cholesterol minus HDL-C​ LDL, VLDL, Lp(a)​ - Elevated non-HDL-C associated with ​ increased risk of CVD

Arteriosclerosis​

- Single leading cause of death and disability in U.S.​ - Caused by lipids, in form of esterified cholesterol, being ​deposited in artery walls, resulting in fatty streaks​ - Fatty streaks develop into plaques that can block blood flow.​ - Coronary heart disease​ - Clot formation​ ------Stroke​ ------Heart attack

Safety Precautions for Measuring Lipids

- Standard Precautions must be observed while performing cholesterol and triglyceride tests. Controls manufactured from human blood products should be handled as if potentially infectious. - The technician must wear appropriate personal protective equipment (PPE). - All contaminated materials must be discarded into appropriate biohazard containers. - Manufacturers' instructions must be carefully followed to prevent personal injury or instrument damage. - When tests are performed in screening situations such as in a mall, the same safety precautions must be observed that are required in medical facilities.

Triglyceride Reference Values

- The reference value for triglycerides is less than 150 mg per dL. - Values from 150 to 199 mg per dL are considered borderline high. - Values between 200 and 499 mg per dL are high. - Triglyceride values of 500 mg per dL and greater are called very high.

PERFORMING TESTS FOR CHOLESTEROL AND TRIGLYCERIDES

- The technology to measure total serum cholesterol has been available for decades, but efficient, easy methods for measuring HDL and LDL cholesterols have been available only since about 1980. - Before that time, cholesterol was measured using time consuming manual chemical methods that required hazardous chemicals. - Today's analyzers incorporate enzymatic methods for testing cholesterol, cholesterol fractions, and triglycerides. - These methods are simpler, safer, and faster than the chemical methods. - Measurement of triglycerides is a part of a lipid profile but is also offered separately in some screening situations. - The analysis can be performed on either venous or capillary blood. - Many point-of-care (POC) analyzers include triglyceride measurement in their menu of tests.

Quality Assessment

- The type of specimen required Q for lipid tests depends on the test to be performed. - The laboratory's standard operating procedure (SOP) manual should be followed to determine the appropriate specimen (serum, plasma, whole blood), test method and quality assessment procedures that must be performed. - Manufacturers of chemistry analyzers that perform lipid measurements provide calibrators and or controls for use with their instruments. - The controls are analyzed in the same manner as patient samples.

Cholestech LDX

- This System can perform a lipid profile, glucose determination, and other blood chemistries - The Cholestech LDX System can be used to screen for risk of coronary disease in POLs, POC sites, and corporate wellness programs or community health fairs. 1. A capillary blood sample is collected and added to the sample well of the test cassette. 2. Each cassette contains the reagents for a specific test or a group of tests, such as total cholesterol; total cholesterol and HDL; or total cholesterol, HDL, and triglycerides. 3. When a single cassette can perform multiple tests, portions of the sample are diverted into different test regions. 4. The test cassette is inserted into the analyzer and the test(s) are complete within minutes. 5. Test results are displayed on the digital screen or can be printed. - The instrument can also calculate the cardiac risk factor if the necessary tests have been performed.

Clinical Considerations for triglycerides

- Triglyceride levels have long been thought to be a good predictor for the presence of or development of coronary heart disease (CHD). - Levels greater than 200 mg per dL correlate with increased risk for CHD. - However, an increased value can also indicate cirrhosis, familial hyperlipoproteinemia, hypothyroidism, or poorly controlled diabetes, especially in type 2 diabetes patients. - Many factors other than lipid levels influence development of CHD and must be taken into consideration, such as hypertension, smoking, and family history.

TRIGLYCERIDES Structure and Function

- Triglycerides are the most common form of fat in the body and the major form of stored fat in the body. - Triglycerides also comprise the largest portion of fats in the diet. - The triglyceride molecule is composed of three chains of fatty acids combined with one molecule of glycerol. - Extra calories consumed are converted into triglycerides. - Between meals triglycerides are gradually released and metabolized in response to the energy needs of the body.

Pathology Associated with Increased Blood Cholesterol

- When the blood cholesterol levels remain elevated, it can contribute to atherosclerosis, a condition in which lipids and other substances accumulate on the inner walls of blood vessels, narrowing the vessel opening. - This is a leading cause of coronary heart disease (CHD). - These deposits (plaques) are especially likely to form on any damaged surface of a vessel wall. - The major portion of these deposits is made up of cholesterol, although other fats (lipids), calcium, and cells such as macrophages are also found in them. - Once these deposits form, their rough edges can cause blood clots to develop by activating platelets. - In addition, parts of the deposit can break off, become emboli and either damage the area in which they originate or travel to small vessels in vital organs such as the brain, heart, kidneys, or liver and cut off the blood supply to these organs. - The result can be a cerebrovascular event (stroke), myocardial infarction (MI), and or damage to other organs.

Lipid and Lipoprotein Population Distributions

- Women have, on average, higher HDL cholesterol levels but ​lower total cholesterol and triglyceride levels than men.​ - After menopause, no difference in total cholesterol​ - Total and LDL cholesterol and triglyceride levels all increase ​with age, in both men and women.​ - Total cholesterol, LDL cholesterol, and triglycerides are ​much lower in young children than in adults.​ - At puberty, boys' HDL cholesterol drops 20% to adult male ​levels, but girls' does not change.​ - Lower rates of LDL cholesterol and heart disease in Asians.

Structure and Biological Role of CHOLESTEROL

- a lipid sterol, is an important component of all body tissues. - is a major constituent of all mammalian cell membranes, except those in red blood cells. - Because lipids have limited solubility in water, they help the cell membrane control the flow of water-soluble substances in and out of the cell. - A relatively large amount of cholesterol is located in the skin, where it protects against the absorption of water-soluble substances. - It also aids in protecting against damaging chemical agents, such as acids, and excessive water evaporation from the skin. - Another major function of cholesterol is to serve as a precursor to bile salts and steroid hormones. - The sex hormones, adrenal steroids, and bile salts are synthesized from cholesterol in cells of the ovaries and testes adrenal glands, and liver, respectively.

Cholesterol testing is available is settings such as:

- health fairs, - pharmacies, or - blood donation centers. - In addition, over-the-counter (OTC) test kits are available that can estimate the blood cholesterol level and indicate if further testing is needed. - The continuing availability of free or inexpensive blood lipid testing is a responsible reaction to the increased awareness of the importance of controlling blood cholesterol and triglyceride levels for cardiac and overall health benefits.

The LDL:HDL ratio is used

- to calculate the heart attack risk factor. - As the LDL:HDL ratio increases, the risk for heart attack increases. - The calculated risk factor is often included with the laboratory results of cholesterol measurements. - A low risk factor number indicates less risk.

What are the functions of cholesterol in the body?

-helps the cell membrane to control the flow of substances soluble in water, in and out of the cell -protects against the absorption if water-soluble substances -protects against damaging chemical agents like acids -protects against excessive water evaporation from the skin -serves as a precursor to steroid hormones' and bile salts

- Examples of analyzers that perform cholesterol and triglyceride measurements include:

1. the Accutrend Plus (Roche Diagnostics), 2. the POINTE 180 (POINTE Scientific), and 3. the Cholestech LDX (Inverness Medical Innovations)

-For lipid analyzers that use reagent strips:

1. the liquid control is applied to a separate strip in the same manner as a patient sample and is then analyzed in the instrument. 2. This checks the reliability of the reagent strips, the function of the instrument, and the worker's technique. 3. If control results are not within acceptable limits, the patient specimens should not be analyzed until the problem is found and corrected. 4. Only personnel who have been properly trained on the instrument in use should be allowed to perform lipid testing and report results.

Explain the value of using an OTC cholesterol test. What classes of drugs can be used to lower LDL cholesterol? What are some side effects of these drugs?

An OTC cholesterol test can be valuable because a patient who otherwise would not go to the physician or health fair might purchase a kit for home use, and then see a physician if the test result indicates an elevated cholesterol level. Statin drugs, resins, and nicotine acid (niacin). Abnormal liver enzymes levels and breakdown of muscle tissue (rhabdomyolysis)

Most people have had ________ tests performed, know their __________ levels, and are aware of foods especially high in _________.

Cholesterol

Managing Blood Cholesterol​: Lifestyle changes​

Diet​ Exercise​ Identify other risk factors

Combined Hyperlipoproteinemia (CH)​

Elevated levels of serum total cholesterol and triglycerides​

Cholesterol Measurement​

Hexane extraction after hydrolysis with alcoholic KOH,​ followed by reaction with Liebermann-Burchard color reagent​ Acetic anhydride and sulfuric acid as reagents give ​ a green color in the presence of cholesterol.​ Current reference method GC-MS

Why are HDL and LDL cholesterol levels important?

Increased HDL cholesterol is desirable because it transports cholesterol to the liver where a portion is broken down and eliminated from the body as bile salts. Increased LDL cholesterol levels present a health risk because LDL carries cholesterol to the tissues to be deposited as fat and can contribute to the development of atherosclerosis.

Lp(a) Elevation​

Increased risk of CHD and cerebrovascular disease​

Lipoprotein (a) (Lp(a))

LDL-like particles​ Plasma levels of Lp(a) vary widely among individuals in population ​but remain relatively constant within a person

Cardiac risk factor =

LDL/HDL High number indicates high risk

Chylomicrons

Largest and least dense; diameters as large as 1,200 nm​ Produced by intestine; deliver dietary lipids to hepatic and ​ peripheral cells

Very-Low-Density Lipoproteins (VLDL)​

Produced by liver; major carriers of endogenous triglycerides ​ (formed within the liver)

Managing Blood Cholesterol​: Drugs

Statins (most common cholesterol lowering ​ medicine)​ Other​ Cholesterol lowering drugs can cause liver ​ enzymes to rise to abnormal levels, so persons​ on them should be monitored at regular intervals

How are the HDL and LDL cholesterol values used to calculate the heart disease risk factor?

The risk factor is the number obtained when the LDL value is divided by the HDL value. Higher risk factor numbers indicate increased risk for heart attack or coronary heart disease (CHD). as the HDL/LDL ratio increases, the threat for heart attack increases

Increased blood levels of what lipid other than blood cholesterol can be a predictor for increased risk of coronary heart disease?

Triglycerides

Discuss the function and importance of triglycerides.

Triglycerides are a storage form of fat found in adipose tissue and muscle. Extra fat calories consumed are converted into triglycerides. An elevated triglyceride level is considered to be a good predictor for the presence or development of CHD.

All Lipoproteins​

Typically spherical; diameters of 10 to 1,200 nm​ Composed of lipids and proteins; deliver fuel to peripheral cells

Triglyceride Measurement​

Useful in detecting metabolic disorders and CVD risk​ Uses an enzymatic reaction​ Reference method GC-MS

Cholesterol levels for adults are affected by:

age, diet, and gender. - In addition, studies have shown that cholesterol values increase 10% to 20% in the nonresting patient compared to the resting patient. - Estrogen seems to influence cholesterol levels, because in postmenopausal women the cholesterol level tends to increase.

What are the dangers of elevated blood cholesterol?

atherosclerosis which can lead to CHD, form blood clots which can cause a stroke, damage to organs or myocardial infarction

Organizations such as the American Heart Association and the National Cholesterol Education Program (NCEP) recommend that total cholesterol:

be kept below 200 mg per dL . - Total cholesterol of 240 mg per dL or above is considered to present a high risk for heart disease. - Cholesterol levels between 200 and 239 mg per dL are considered borderline. - There is no known cardiac risk associated with high HDL cholesterol levels.

Dyslipidemias

diseases associated with abnormal lipid concentrations

myocardial infarction (MI)

heart attack caused by obstruction of the blood supply to or within the heart

chylomicrons

lipoproteins made in the small intestine and released into the blood to transport exogenous (dietary) cholesterol and triglycerides from the small intestines to the liver and other tissues

HDL cholesterol

high-density lipoprotein fraction of blood cholesterol; good cholesterol - transports cholesterol from the tissues to the liver to be broken down, mostly into bile acids. - Because of this, HDL cholesterol is called good cholesterol. - Chylomicrons, lipoproteins made in the small intestine, transport cholesterol from the small intestines to the tissues after a meal. - The term chylomicron is derived from chylo, meaning milky, and micron, meaning small. - After a meal high in fats, the plasma can appear milky because of the presence of chylomicrons. - Smallest and the most dense; synthesized by the liver and ​the intestine​ - Capable of removing excess cholesterol from peripheral cells

Measurement of total blood cholesterol and the cholesterol fractions has assumed an important role:

in assessing risk for and management of coronary artery disease and other atherosclerotic conditions.

LDL cholesterol

low-density lipoprotein fraction of blood cholesterol; bad cholesterol - LDL also transports cholesterol to the tissues to be deposited as fat. Form as a result of lipolysis of VLDL​ Readily taken up by cells via LDL receptors in liver and ​ peripheral cells​ Significantly smaller than VLDLs; can infiltrate extracellular space

Some researchers now believe that an increased triglyceride value is not so much an indicator for CHD but is

often part of a condition called metabolic syndrome that is closely related to insulin resistance. - Associated with this syndrome are abdominal obesity, increased blood triglycerides, elevated blood pressure, elevated fasting glucose, and a low HDL value. - The presence of metabolic syndrome increases the risk for coronary artery disease.

exogenous

originating from the outside

endogenous

produced within; growing from within

triglycerides

the major storage form of lipids; lipid molecules formed from glycerol and fatty acids

What are the desirable levels of total cholesterol and LDL cholesterol recommended by the NCEP? Are recommended values the same as reference values?

total cholesterol must be kept below 200 mg/dL LDL must be kept below 100mg/dL, they are not the same as the reference values Recommended values are those determined by a national council to be best for good health. Reference values represent the values found in a sampling of the general population.