Chapter 07 Physical Activity and Dyslipidemia. Hypercholesterolemia : is defined as levels of total...

Chapter 07

Physical Activity and Dyslipidemia


Hypercholesterolemia : is defined as levels of total serum cholesterol that exceed the population average of 200mg/dl among adults.

Dyslipidemia refers to hypercholesterolemia or high triglycerides (a key energy store that includes fat), or both, or low levels of high-density lipoprotein cholesterol (HDL-C, the “good” cholesterol).

An estimated 102.2 million American adults have total blood cholesterol levels of 200 mg/dl and higher, which is above desirable levels. Of these, 35.7 million have levels of 240 mg/dl or higher, which is considered high risk for heart disease (American Heart Association 2012).


Lipoprotein fractions which transport cholesterol, are better predictors of CHD risk than looking at total blood cholesterol levels alone.


Lipoproteins are cholesterol and other fats that are carried in the blood bound to protein because they are not soluble on water. Lipoproteins include triglycerides, chylomicrons, LDL-Cholesterol (LDL-C), and HDL-C. These molecules differ in their relative composition of cholesterol, lipids, phospholipids, and proteins.

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=1CFc2ehnDbhsJM&tbnid=7LH8a24Dk-XsPM:&ved=0CAUQjRw&url=http%3A%2F%2Fwww.sigmaaldrich.com%2Flife-science%2Fmetabolomics%2Fenzyme-explorer%2Flearning-center%2Fplasma-blood-protein%2Flipoprotein-function.html&ei=Ong-UZDYEIfS9QSw3YE4&bvm=bv.43287494,d.eWU&psig=AFQjCNHY7vBLyzxCcTmBL3Fd-VJMF3a7uQ&ust=1363134900912619


Dyslipidemia Total Cholesterol (mg/dl)

Optimal < 200; borderline 200-239; high >240

LDL-C (mg/dl) Optimal < 100; 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; very high

> 500

HDL-C Low < 40; high > 60

Values are based on blood levels after fasting.(source = National Cholesterol Education Program)


Dyslipidemia A low level of HDL-C is a major risk factor for CHD A high level of LDL-C and Triglycerides are risk

factors for CHD

Figure 8.1 HDL cholesterol and LDL cholesterol as risk factors for coronary artery disease.


Dyslipidemia – Magnitude of the Problem

Statistics show that nearly 36 million U.S. adults aged 20 years or older have high CHD and stroke risk because they have total cholesterol levels of 240 mg/dl or higher.

Another 66.5 million have borderline high levels between 200 and 240.

Ten percent of 12-19 yr olds have levels greater than 200 mg/dl

Approximately 18% of white adults have levels > 240 mg/dl

Nearly 43% of Mexican American men have elevated risk because they have LDL-C levels of 130 mg/dl or higher. The prevalence of low HDL-C is about half as great in black men compared to white and Mexican American men, and it is 40% and 80% higher among Mexican American women than in white and black women, respectively


Dyslipidemia – Magnitude of the Problem

Figure 8.2 shows the prevalence rates of high LDL-C and low HDL-C among Americans ages 20 and older by sex and selected racial and ethnic groups.

Age-adjusted prevalence of Americans age 20 and older with (a) LDL cholesterol of 130 mg/dl or higher and (b) HDL cholesterol of 40 mg/dl or lower, by race/ethnicity and sex. United States, 2006.


Dyslipidemia – Lipoproteins

Lipoproteins are cholesterol and other fats that are carried in the blood bound to protein because they are not soluble on water. Lipoproteins include triglycerides, chylomicrons, LDL-Cholesterol (LDL-C), and HDL-C. These molecules differ in their relative composition of cholesterol, lipids, phospholipids, and proteins.

They also differ in size and density such that higher concentrations of lipids are found in lipoprotein molecules that are larger and less dense (see figure 8.3 and table 8.4 in text).



Triglyceride and Chylomicrons “fat” molecule composed of three fatty acids attached to a

glycerol backbone. Fatty acids can be used for fuel and can be “cut” (lipolysis) from the glycerol backbone by lipoprotein lipase (LPL).

Triglycerides are transported from the intestines as chylomicrons. The action of LPL helps clear the chylomicrons from the circulation by releasing triglycerides during lipolysis. LPL found in the myocardial capillary endothelium, skeletal muscle and and adipose tissue.

Chylomicron remnants can be atherogenic, but LPL protects the endothelium from chylomicrons. Chylomicron remnants are then sent to the liver for re-esterification (rebuilding fats)



VLDL-C (Very Low Density Lipoprotein)

Responsible for transporting triglycerides synthesized by the liver to the adipose tissue for storage

After releasing some of the triglyceride content to adipose tissue VLDL-C becomes LDL-C in the circulation



LDL-C (Low Density Lipoprotein) Responsible for transporting cholesterol in

the blood HDL-C (High Density Lipoprotein)

Responsible for reverse cholesterol transport by removing cholesterol from the system and transporting it back to the liver

Reverse transport involves esterification and storage of cholesterol in the core of the HDL molecule by the enzyme lecithin:cholesterol acyltransferase (LCAT) and a cofactor protein named apolipoprotein A1 (or apo A1).



HDL-C (High Density Lipoprotein) Consists of a family of molecules that vary in

density from HDL1 to HDL3 (most abundant are HDL2 and HDL3)

The core diameter of the particle increases from HDL3 to HDL1. The core of HDL1 is about 50% larger than that of HDL3, and the cholesterol ester content and triglyceride content of HDL1 are three to four times greater than those of HDL3



HDL-C formation Secretion from the liver and small

intestine Hydrolyzed chylomicrons and VLDL In the Plasma (chemical reactions)

Additional information on HDL – reverse cholesterol Transport (FYI only)

http://www.youtube.com/watch?v=lh18qaShTZU

http://www.youtube.com/watch?v=lh18qaShTZU


Hypercholesterolemia – Risk Factors

Genetics accounts for 1 in 500 persons with hypercholesterolemia, thus most people can control blood cholesterol levels via behavioral choices

Seventy percent of the variation in blood cholesterol levels can be explained via liver production and dietary intake

Risk Factors are listed in Table 8.5, p 173, text, and next slide.


Hypercholesterolemia – Risk Factors

Cigarette smoking, diabetes mellitus, obesity, alcohol, androgenic and anti-inflammatory steroids, and emotional stress also negatively influence blood lipid levels, especially increasing triglyceride and LDL-C levels (Information in book on Drug treatment is FYI…)


Physical Activity and Lipoprotein Levels: The Evidence

Cross-Sectional Clinical and Population-Based Studies In cross-sectional comparisons of small clinical

samples, male and female endurance athletes of the same age had 20% to 30% higher levels of HDL-C than untrained peers, and a dose–response relationship was seen between more physical activity and greater HDL-C

Higher elevations in HDL-C found in those who ran longer distances on a weekly basis



Healthy, Nonsmoking Men There was an increase in HDL-C of about

0.3 mg/dl for each mile run. LDL-C and triglyceride levels were

positively associated with BMI and inversely correlated with the distance run per week, the frequency of exercise per week, and the duration of the exercise sessions



Marathon Study Leisure-time physical activity study Every 100 kcal expended at an intensity

> 7 kcal/min (moderate intensity exercise), was associated with a 2 mg/dl increase in HDL-C.

Higher intensity activity (9.5-12 kcal/min) was associated with lower levels of total cholesterol, and triglycerides.


Physical Activity and Lipoprotein Levels: The

Evidence Boston Area Health Study

MI survivors: Moderate to vigorous exercise was associated with elevations in HDL-C

Strong Heart Study American Indian Population: physical

activity was positively associated with levels of surface proteins (apo A1) found on HDL-C.



Evidence U.S. Work-Site Study

Men who spent 4-7 hours/week strength training had an odds ration (hypercholesterolemia) of 50% compared to non-lifters.



Evidence Aerobics Center Longitudinal Study

Did not find associations in muscular strength with total cholesterol or LDL-C reduction; and triglycerides were higher in stronger men, HDL-C was lower.

** Most of the people involved in the study were not on regular strength training programs, so other unknown factors common to inherent muscular strength and lipids, or other factors not controlled in the study, probably explain the findings.



Evidence Postmenopausal Study

Physical activity was positively associated with higher levels of HDL-C and HDL2 (modified HDL-C that has accumulated cholesterol)

There was a near linear relationship between frequency of sport activity and level of HDL2



Evidence Spanish Men

The association of physical activity with serum apo A protein was examined in 332 healthy Spanish men ages 20 to 60

The odds of having above-average levels of apo A of men who expended more than 300 kcal each day in leisure physical activity was less than 15% that of men who expended less than 300 kcal a day.

The results suggest that regular daily physical activity is helpful for controlling apo A protein levels in men who have a family history of CHD



Evidence Los Angeles Atherosclerosis Study The relation between physical activity, HDL-C,

and three year progression of carotid atherosclerosis, which can be estimated by intima media thickness of an artery, was examined in a cohort of 500 men and women 40 to 60 years of age initially without cardiovascular disease

Rates of increased intima media thickness (microns per year) measured by ultrasound in the common carotid arteries were 14.6, 10, and 5.8 in sedentary, moderately active, and highly active (aerobic activity 3.5 or more times per week) people, respectively.


Evidence Atherosclerosis Risk in Communities (ARIC) Study

The ARIC Study examined the longitudinal association of changes in physical activity with changes in plasma lipids and lipoproteins across nine years of follow-up in 8764 African American and white participants aged 45 to 64 at baseline

HDL-C increased by 3 to 4.9 mg/dl in all participants; LDL decreased by 4 to 10.6 mg/dl in women; total cholesterol decreased by 7.4 mg/dl in African American women; and triglycerides decreased by 9 to 12.9 mg/dl in white participants - for each increase in 180 MET min/wk. (45-60 min brisk walking)



EvidenceExercise Training Studies Summary: Exercise training led to

small but statistically significant reductions in total cholesterol, LDL-C, and triglycerides, and an increase in HDL-C.

See Meta-Analysis Summary on p. 183, text.



Evidence Washington University, St. Louis, Missouri Training of men with CAD increased VO2max by

30% and HDL-C by 11% while reducing plasma cholesterol by 8%, LDL-C by 9%, and triglycerides by 13%.

Changes in LDL-C and VO2max were inversely correlated (r = −0.73), while the changes in LDL-C and HDL-C each were correlated inversely with the levels measured before training.



Evidence Stanford, California

Improvements were found in HDL-C and reductions in LDL-C for those who ran over 8 miles/week. Findings were confounded by weight loss.

In men and women: diet plus exercise significantly reduces LDL-C.

Favorable effects of exercise are not independent of exercise. (however, exercise promoted the weight loss)


Evidence Premenopausal

Women Sedentary (24 week

walking program) Changes in HDL were not

associated with walking speed (fitness)

Study was confounded because of weight-loss program and because of the possible effects of estrogen on blood lipid levels. (Pre and post menopausal women used)



Evidence Postmenopausal Women

Exercise Training with and without estrogen replacement:

Exercise group 5% decrease in cholesterol, 10% decrease in LDL-C, 20% reduction in triglycerides, no reduction in HDL-C

Both the control group and exercise group with estrogen therapy showed 10% increase in HDL-C



Evidence African American Men with

Hypertension Greater changes in HDL-C (10%

increase) in men who exercised > 75% of max heart rate

Conclusions: low-to-moderate intensity exercise might not provide the stimulus to alter blood lipid levels in African American Men with Hypertension



Evidence HERTIAGE Family Study

Multiracial, young to old, study in men and women:

After controlling for age, change in fitness was unrelated to change in blood lipids, regardless of race

Changes in fat mass among men inversely related to changes in HDL-C and HDL2; in women positively correlated to LDL-C and the ratio of total cholesterol and HDL-C

These findings suggest the metabolic influences of physical activity on lipids depend more on energy expenditure or fat loss than on fitness change.



EvidenceStudies of Targeted Risk Reduction Interventions Through Defined Exercise (STRRIDE) Sedentary, overweight men (n = 49) and women

(n = 35) with mild-to-moderate dyslipidemia (either LDL-C of 130-190 mg/dl or HDL-C <40 mg/dl in men or <45 in women) were randomly assigned to participate for six months in a control group or for eight months in one of three exercise groups: 1) high; 2) low, and 3) low-moderate

Exercise training had no effect on total cholesterol or LDL-C levels. HDL-C was increased by 9.7% (4.3 mg/dl) after high amount–high-intensity exercise only. Triglycerides were decreased after exercise by 10% to 25% (13.1 to 51.6 mg/ dl) regardless of dose



EvidenceResistance Exercise Training Summary:

Clinical Studies found that resistance training lead to favorable changes in lipid levels.

Many of these studies had no control groups nor performed multiple sampling

Many studies did not control for diet, and when these factors were controlled, the effects of weight training seem to dissappear.



EvidenceResistance Exercise Training Men at Risk Study:

No Significant changes were reported in blood lipid profiles, and diet was controlled.

Other factors such as smoking, and alcohol use were not controlled in this study. Significant reductions were found in the U.S. Worksite Study that did control for these factors.



EvidenceResistance Exercise Training Premenopausal Women (14 wk

study): Exercise group (Strength training group)

had a decrease in total cholesterol, LDL-C, total to HDL-C ratio from 4.2-3.6. HDL-C and triglyceride levels were not changes



EvidenceObese Women Study Obese Women (12 wk study):

No significant change in blood lipid profiles accompanied no significant change in body fat

** Lipid levels were normal at the beginning of the study.


Strength of The Evidence Temporal Sequence

Studies have been limited to cross-sectional studies which lack the proper sequence to establish causality

However, a few prospective cohort studies support that physical activity increases HDL-C and reduces atherosclerosis.

Strength of the Association Exercise training increases HDL-C by 5%,

reduces LDL-C 5%, and triglycerides 4%. Population-based cross-sectional studies and a

limited number of prospective cohort studies have shown similar effects.

Strength of The Evidence

Consistency Results have been similar for men and women,

regardless of age Few studies have been conducted in minorities

Dose Response Based on the collective evidence, it appears that aerobic

exercise expending between about 1200 and 2400 kcal each week for at least 12 weeks and conducted at moderate or vigorous intensities yields favorable changes in lipoproteins.

There have not been enough randomized controlled trials comparing different intensities or amounts of physical activity to determine experimentally the dose response.

Best available evidence suggests that increases in HDL and decreases in triglycerides and LDL in people with dyslipidemia are dose dependent on total energy expenditure, more so than exercise intensity


Strength of The Evidence

Biological Plausibility Consistent findings are increases in HDL-C and

decreases in blood triglycerides. Triglycerides serve as fuel (especially with prolonged exercise) for exercise

Increases in LPL activity will mirror HDL-C activity because LPL activity will break down triglycerides for fuel (into Fatty Acids) thus, allowing HDL-C to move cholesterol back to the liver

Exercise may decrease the liver enzyme responsible for breaking apart HDL2, and increasing reverse cholesterol transport

FYI…See other enzymatic changes in Table 8.10, p.189


Summary

Weight loss, dietary intervention and pharmacological intervention are the primary methods recommended for resolving hyperlipidemia.

Exercise is recommend as a concurrent, secondary prevention/intervention method because of its effects on body mass and cholesterol metabolism.


END OF PRESENTATION

Chapter 07 Physical Activity and Dyslipidemia. Hypercholesterolemia : is defined as levels of total...

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