Chapter 8
Physical Activity and Dyslipidemia
“THEIR HEART IS AS FAT AS GREASE.”
P S A L M S 11 9 : 7 0
P-168
Cholesterol is a waxy substance found in all cell membranes, it is in the brain, nerves, muscle, skin,
liver, intestines and heart.
Cholesterol is need to produce many hormones, vit D, and the bile acids that help emulsify insoluble
lipids (from eating foods high in sat fat) so they can be used for cellular metabolism.
Because it is insoluble in blood, cholesterol also transports vit A & E which are also insoluble.
Too much cholesterol in the blood contributes to atherosclerosis, the disease that hardens and blocks
arteries and leads to CHD and ischemic stroke.
Hypercholesterolemia refers to total serum cholesterol that exceeds the population average of 200
mg/dl among adults.
Dyslipidemia refers to hypercholesterolemia or high triglycerides (a key energy store that includes fat)
or both, or low levels of HDL (HDL-C) the “good” cholesterol.
102.2 million America adults have total blood cholesterol levels of 200mg/dl and higher, which is
above recommended levels. Of these, 35.7 million have 240 mg/dl or higher which is high risk for
heart disease.
Physical activity is associated with lower blood lipids, decreased LDL-C (bad cholesterol) and
increased HDL-C---changes that can help explain part of the protective effect that physical
activity confers against CVD and mortality.
Lipoprotein fractions are very important—A low level of HDL-C (<40 mg/dl) is a major risk
factor for CHD.
In pharmacology, the fibrates are a class of amphipathic carboxylic acids. They are used for a
range of metabolic disorders, mainly hypercholesterolemia (high cholesterol), and are therefore
hypolipidemic agents.
High levels of LDL-C (>200 mg/dl) and triglycerides are also associated with a high risk of CHD.
Good cholesterol, bad cholesterol, saturated fat, and unsaturated fat -- sometimes it seems like you
need a program to keep track of all the fat players in the story of heart disease.
In some ways, triglycerides are the easiest to understand. Simply put, triglycerides are fat in the blood
and are used to provide energy to the body. If you have extra triglycerides, they are stored in different
places in case they are needed later. High triglyceride levels have been linked to a greater chance for
heart disease. Just what your triglyceride levels mean and how much lowering triglycerides reduces
heart disease risk is sometimes less clear.
What Are Triglycerides? They are the most abundant lipids in the human body. P-170.
Triglycerides are important to human life and are the main form of fat in the body. When you think of
fat developing and being stored in your hips or belly, you're thinking of triglycerides. Consider these
things:
Triglycerides are the end product of digesting and breaking down fats in meals. Some triglycerides are
made in the body from other energy sources such as carbohydrates.
What Are Normal and High Triglyceride Levels?
The National Cholesterol Education Program sets guidelines for triglyceride levels:
Normal triglycerides means there are less than 150 milligrams per deciliter (mg/dL).
Borderline high triglycerides = 150 to 199 mg/dL.
High triglycerides = 200 to 499 mg/dL.
Very high triglycerides = 500 mg/dL or higher.
High triglyceride levels may lead to heart disease, especially in people with low levels of "good"
cholesterol and high levels of "bad" cholesterol, and in people with type 2 diabetes. Experts
disagree, though, on just how bad of an effect high triglyceride levels by themselves have on the
heart.
Hyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia (British English) involves abnormally
elevated levels of any or all lipids and/or lipoproteins in the blood.[1] It is the most common form
of dyslipidemia (which also includes any decreased lipid levels).
Lipids (fat-soluble molecules) are transported in a protein capsule. The size of that capsule, or
lipoprotein, determines its density. The lipoprotein density and type of apolipoproteins it
contains determines the fate of the particle and its influence on metabolism.
Hyperlipidemias are divided in primary and secondary subtypes. Primary hyperlipidemia is
usually due to genetic causes (such as a mutation in a receptor protein), while secondary
hyperlipidemia arises due to other underlying causes such as diabetes. Lipid and lipoprotein
abnormalities are common in the general population, and are regarded as a modifiable risk
factor for cardiovascular disease due to their influence on atherosclerosis. In addition, some
forms may predispose to acute pancreatitis.
Health Readings
Total Cholesterol: (mg/dl): Optimal < 200; borderline high 200-239; high 240+.
LDL-C: (mg/dl): Optimal <; near optimal 100-129; borderline high 130-159; high 160-189; very
high 190+.
Triglycerides; (mg/dl); Normal <150; Borderline high 150-199; high 200-499; high 500+.
HDL-C: (mg/dl): Low <40; high 60+. Values are based on blood levels after fasting.
Low-density lipoprotein is the main transporter of cholesterol in the blood. High-density
lipoprotein removes cholesterol from extrahepatic (outside the liver) tissue by the process of
reverse cholesterol transport. P-171.
Both HDL (low) and LDL (high) cholesterol are risk factors for CAD.
Know Chart on page 169!
Magnitude of the Problem
P-169
What are lipoproteins? Cholesterol and other fats are not soluble so they are carried in the blood by binding
with proteins.
Chylomicrons are lipoprotein particles that consist of triglycerides (85-92%), phospholipids (6-12%),
cholesterol (1-3%) and proteins (1-2%).[1] They transport dietary lipids from the intestines to other locations
in the body. Chylomicrons are one of the five major groups of lipoproteins (chylomicrons, VLDL, IDL,
LDL, HDL) that enable fats and cholesterol to move within the water-based solution of the bloodstream.
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid
bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such
as choline; one exception to this rule is sphingomyelin, which is derived from sphingosine instead of
glycerol. The first phospholipid identified as such in biological tissues was lecithin, or phosphatidylcholine,
in the egg yolk, by Theodore Nicolas Gobley, a French chemist and pharmacist, in 1847.
HDL’s remove cholesterol from extrahepatic (outside the liver) tissue by Reverse Cholesterol Transport.
HDL Structure & Function
P-171
The majority of HDL is lecithin. Lecithin is a generic term to designate any group of yellow-brownish fatty
substances occurring in animal and plant tissues composed of phosphoric acid, choline, fatty acids, glycerol,
glycolipids, triglycerides, and phospholipids (e.g., phosphatidylcholine, phosphatidylethanolamine, and
phosphatidylinositol).
Lecithin was first isolated in 1846 by the French chemist and pharmacist Theodore Gobley.[1] In 1850 he named
the phosphatidylcholine léchithine.[2] Gobley originally isolated lecithin from egg yolk—λέκιθος (lekithos) is 'egg
yolk' in ancient Greek—and established the complete chemical formula of phosphatidylcholine in 1874;[3] in
between, he had demonstrated the presence of lecithin in a variety of biological matters, including venous blood,
bile, human brain tissue, fish eggs, fish roe, and chicken and sheep brain.
Lecithin can easily be extracted chemically (using hexane, ethanol, acetone, petroleum ether, benzene, etc.) or
mechanically. It is usually available from sources such as soy beans, eggs, milk, marine sources, rapeseed,
cottonseed, and sunflower. It has low solubility in water, but is an excellent emulsifier. In aqueous solution, its
phospholipids can form either liposomes, bilayer sheets, micelles, or lamellar structures, depending on hydration
and temperature. This results in a type of surfactant that usually is classified as amphipathic. Lecithin is sold as a
food supplement and for medical uses. In cooking, it is sometimes used as an emulsifier and to prevent sticking,
for example in nonstick cooking spray.
High-density lipoprotein (HDL) is one of the five major groups of lipoproteins, which, in order of
sizes, largest to smallest, are chylomicrons, VLDL, IDL, LDL, and HDL, which enable lipids (fats),
like cholesterol and triglycerides, to be transported within the water around cells, including the
bloodstream.
Even people with very low LDL levels are exposed to increased risk if their HDL levels are not
high enough
HDL1, HDL2 & HDL3: HDL molecules are classified according to increasing density into 3
subclasses or fractions. P-171.
Low levels of HDL are a stronger predictor of CHD than are elevated levels of LDL. P-176
Risk Factors
.
(P-172)
Only 1 in 500 people has the genetic form of hypercholesterolemia known as heterozygous familial type.
Less than 1 in a million have the homozygous version.
Zygosity is the degree of similarity of the alleles for a trait in an organism.
Most eukaryotes have two matching sets of chromosomes; that is, they are diploid. Diploid organisms have the same
genes on each of their two sets of homologous chromosomes, except that the sequences of these genes may differ between
the two chromosomes in a matching pair and that a few chromosomes may be mismatched as part of a sex-determination
system. If both alleles of a diploid organism are the same, the organism is homozygous for the trait. If they are different,
the organism is heterozygous for that trait. If one allele is missing, it is hemizygous, and, if both alleles are missing, it is
nullizygous.
Thus, almost everyone has some control over whether blood cholesterol level is explained by endogenous production by
the liver, dietary intake of cholesterol from meats, poultry, fish, seafood and dairy products explains most of the
fluctuation in each person’s serum cholesterol level.
Fruits veggies, nuts, grains and seeds have no cholesterol.
The average goal should be less than 300mg per day. The average though is 450 mg for men and 320 mg among women.
Although a large egg has 200 mg, eggs also contain lecithin, which limits absorption of dietary cholesterol.
P-172
Smoking, diabetes, obesity, ETOH, androgenic and anti-inflammatory steroids and emotional
stress also negatively influence blood lipid levels, especially increasing triglyceride and LDL-C
levels. Obesity and smoking reduce HDL-C. Total cholesterol, LDL-C and triglyceride levels are
elevated in people with diabetes but levels tend to normalize when blood glucose levels are
controlled.
Androgenic: A steroid hormone, such as testosterone or androsterone, that controls the
development and maintenance of masculine characteristics. Also called androgenic hormone.
P-173: Table 8.5—What Influences Lipoproteins? Sex, Age, % Body fat, Diet, Diabetes, ETOH,
Smoking, Steroids, Stress, Exercise.
Studies among people with CHD have shown that lowering blood cholesterol can reduce the risk
of dying from heart disease, having a nonfatal heart attack, and needing bypass surgery or
angioplasty.
Drug Treatment
When diet, activity and weight loss don’t lower high blood lipids, cholesterol drugs are the treatment of choice.
Drug therapy is necessary in some children and adolescents with hyperlipidemia—especially for those whose parents
have high cholesterol.
Statin drugs: Statins (or HMG-CoA reductase inhibitors) are a class of drugs used to lower cholesterol levels by
inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver.
Increased cholesterol levels have been associated with cardiovascular diseases,[1] and statins are therefore used in the
prevention of these diseases. Research has found that statins are most effective for treating cardiovascular disease (CVD)
as a secondary prevention strategy, with questionable benefit in those with elevated cholesterol levels but without
previous CVD.[2][3] Statins have rare but severe adverse effects, particularly muscle damage, and some doctors believe
they are overprescribed.
Statins typically reduce LDL-C by 50% and Ezetimibe, a selective cholesterol inhibitor added to statin therapy further
reduces total cholesterol by 16% and decreases LDL-C by 24% and increases HDL-C by 1.7%.
Statins also help CVD through their anti-inflammatory properties and by retarding atherogenesis.
Fibrates reduce the # of nonfatal heart attacks but does not improve all-cause mortality and are therefore indicated only
in those not tolerant to statins.
Low levels of HDL-C are a stronger predictor of CHD than are elevated levels of LDL-C.
Dyslipedemia Etiology and Physical Activity
P-177
Primary causes of dyslipidemia are single or polygene mutations that result in either overproduction or defective clearance of
triglycerides and LDL-C or in underproduction or excessive clearance of HDL-C.
Most cases of dyslipidemia are secondary to behavior or other medical conditions.
The most important secondary cause in developed nations is a sedentary lifestyle with excessive sat fat intake, cholesterol and trans fat.
Trans fat is the common name for unsaturated fat with trans-isomer (E-isomer) fatty acid(s). Because the term describes the configuration
of a double carbon–carbon bond, trans fats are sometimes monounsaturated or polyunsaturated, but never saturated. Trans fats exist in
nature and also occur during the processing of polyunsaturated fatty acids in food production. [1]
In humans, consumption of trans fats increases the risk of coronary heart disease[2][3] by raising levels of LDL cholesterol and lowering
levels of "good" HDL cholesterol.[4] There is an ongoing debate about a possible differentiation between trans fats of natural origin and
trans fats of man-made origin, but so far no scientific consensus has been found. Two Canadian studies, which received funding by the
Alberta Livestock and Meat Agency[5] and the Dairy Farmers of Canada,[6] have shown that the natural trans fat vaccenic acid, found in
beef and dairy products, may have an opposite health effect and could actually be beneficial compared to hydrogenated vegetable
shortening, or a mixture of pork lard and soy fat,[6] by lowering total and LDL cholesterol and triglyceride levels. [7][8][9] In lack of
recognized evidence and scientific agreement, nutritional authorities consider all trans fats as equally harmful for health [10][11][12] and
recommend that consumption of trans fats be reduced to trace amounts.
A 10% decrease in total blood cholesterol levels may result in a 20%-30% reduction in CHD.
P-179
For sedentary people, moderate physical activity such as brisk walking 8—15 miles a week for 6—9 months
increases HDL levels and lowers triglyceride levels. For recreational runners (15-60 miles per week) HDL levels
are higher in those who run faster, regardless of distance.
Exercise is advised along with a low fat, high fiber diet to lipid therapy.
Studies: P-179-186.
Aerobic exercise—P-181 &182.
Anaerobic exercise—P-181 & 187.
Postprandial lipemia, characterized by a rise in triglyceride-rich lipoproteins after eating, is a dynamic,
nonsteady-state condition in which humans spend the majority of time. There are several lines of evidence
suggesting that postprandial lipemia increases risk of atherogenesis. Clinical data show a correlation between
postprandial lipoproteins and the presence/progression of coronary artery disease and carotid intimal thickness
Strength of the Evidence
P-188
Temporal Sequence:
Strength of Association:
Consistency:
Dose Response:
Biological Plausibility:
Summary: High levels of total cholesterol, LDL and triglycerides and low HDL levels are
primary risk factors for developing CHD and atherosclerosis.\Weight loss, reduced fat and
cholesterol intake and statin drugs are frontline interventions for primary and secondary
prevention of dyslipidemia and physical activity is also advised.