Introduction

The link between cholesterol and coronary heart disease (CHD) has been fairly well established through long-term studies of high levels of blood cholesterol and the incidence of CHD. High-density lipoprotein cholesterol (HDL-C) levels are inversely and independently associated with reduced risk of CHD (Neiman 1998). The risk of CHD increases by 2 to 3% for every 1.0 mg/dl decrease in HDL-C (Durstine & Haskell 1994). It is well established that a sedentary lifestyle contributes significantly to the development of CHD and that physical activity plays an important role in decreasing CHD mortality. Exercise training has been associated with increased concentrations of HDL-C, however, the amount of exercise necessary to significantly raise HDL-C levels has not been identified. Research in this area has provided inconsistent results, but has suggested that there may be an exercise threshold that must be met before significant changes in HDL-C are observed. Furthermore, a dose-response relationship between the amount of exercise performed and HDL-C has been suggested (Drygas et al. 2000).
Cholesterol
Cholesterol is a waxy, fat like substance found in all animal products (i.e., meats, dairy products and eggs). The body can make cholesterol in the liver and it can absorb cholesterol from the diet. Cholesterol is essential to the body and is used to build cell membranes, produce sex hormones, and form bile acids, which are necessary for the digestion of fats. It is essential that you have some cholesterol for optimal health; however, when blood levels are too high, some of the excess is deposited in the artery walls, increasing the risk for heart disease.
Lipoproteins
Cholesterol is a fat-soluble substance that is carried in the blood by special transporters called lipoproteins. Lipoproteins are an essential part of the complex transport system that exchanges lipids among the liver, the intestine, and peripheral tissues. The different types of lipoproteins are classified based on the thickness of the protein shell that surrounds the cholesterol. Four main classes of lipoproteins have been categorized: chylomicron, derived from the intestinal absorption of triglycerides; very low density lipoprotein (VLDL), made in the liver for the transport of triglycerides; low-density lipoprotein (LDL), a product of VLDL metabolism and the primary transporters of cholesterol; and high-density lipoprotein (HDL), involved in the reverse transport of cholesterol to the liver (Durstine & Haskell, 1994).

The role of LDL-cholesterol (LDL-C), sometimes called the “bad” or “lousy” cholesterol, is to transport cholesterol to various body cells and deposit excess cholesterol in the artery walls, increasing the risk of heart disease. LDL-C is a VLDL molecule with most of the triglyceride removed and almost all of the cholesterol remaining. A desirable level of LDL-C is below 130 mg/dl, with an optimal level of 100 mg/dl or less.

HDL-cholesterol (HDL-C), sometimes called the “good” or “healthy” cholesterol, is responsible for the transport of cholesterol from the blood and artery walls to the liver where it is converted to bile to be used for digestion or disposed of by the body. This “reverse cholesterol transport process” is believed to be helpful in preventing or reversing heart disease. HDL molecules have two main subclasses: HDL2 and HDL3 (Durstine & Haskell, 1994). The HDL3 molecule is synthesized in the liver and put into circulation to collect cholesterol. As the HDL3 molecule increases its cholesterol content, it becomes less dense and is classified as HDL2. HDL2 is then recycled in the liver and HDL3 is again released into circulation (Durstine & Haskell, 1994). When HDL-C levels are above 60 mg/dl the risk of heart disease is decreased. It is considered undesirable for HDL-C levels decrease below 35 mg/dl. Table 1 provides a cholesterol classification.

Potential Mechanism Involved in Exercise-Altered HDL-C levels
Regular participation in physical activity as well as a single exercise session can positively alter cholesterol metabolism (Durstine & Haskell, 1994). Exercise is involved in increasing the production and action of several enzymes that function to enhance the reverse cholesterol transport system (Durstine & Haskell 1994). The precise mechanisms are unclear, but evidence indicates that other factors including diet, body fat, weight loss, and hormone and enzyme activity interact with exercise to alter the rates of synthesis, transport and clearance of cholesterol from the blood (Durstine & Haskell 1994).

Exercise Intensity Threshold
Men
Data from exercise training studies and epidemiological studies support the existence of an exercise intensity threshold for increases in HDL-C levels. Although exercise studies specifically designed to define such a threshold have not been conducted, many studies give a general idea of the intensity threshold observed to favorably increase HDL-C levels. Several studies have suggested that the threshold for positive changes in HDL-C is an exercise intensity of 6 METs or more (21 ml/kg.min) (Leclerc 1985, Lakka & Salomen 1992). Leclerc and others (1985) also reported that there were no further improvements in HDL-C levels when exercise intensity increased above 6 METs. Stein et al. (1990) reported significant increases in HDL-C levels in men that exercised at or above 75% heart rate maximum (HRmax), 3 times a week for 12 weeks. No changes in HDL-C were reported in the subjects that exercised at 65% HRmax. The authors concluded that an intensity of 75% HRmax or above is necessary to increase HDL-C levels in men. In addition, Kokkinos and colleagues (1995) studied 2906 men and reported that increases in HDL-C levels occurred in men jogging at an exercise intensity of 10 to 11 minutes per mile. Although a specific exercise intensity threshold has not been defined, it appears that moderate intensity exercise is sufficient to raise HDL-C levels in men.

Women
Exercise training studies attempting to assess the role of exercise intensity on HDL-C in women are few and report conflicting results. Most of the research suggests that women (pre and postmenopausal) with low levels of HDL-C are more likely to respond positively to exercise training. Duncan et al. (1991) reported similar increases in HDL-C levels in women (29-40 years) following 24 weeks of walking (4.8 km/session), regardless of intensity. This finding suggests that moderate exercise will raise HDL-C levels as much as intense exercise. In addition, Spate-Douglas and Keyser (1999) reported that moderate-intensity training over a 12-week period was sufficient to improve the HDL-C profile, and high-intensity training appeared to be of no further advantage as long as training volume (total walking distance per week) was constant. Conversely, Santiago and others (1995 ) reported no changes in HDL-C levels in women following 40 weeks of endurance training similar to the program in Duncan’s study. However, the women in Santiago’s study had higher initial HDL-C levels than the women in Duncan’s study (65 vs. 55 mg/dl). These findings also support that women with lower levels of HDL-C are more likely to see increases in HDL-C with exercise training.

The research in postmenopausal women is also limited but provides positive results. Lindheim et al. (1994) reported increased HDL-C levels in postmenopausal women that exercised at 70% HRmax for 24 weeks and were on hormone replacement therapy (HRT). Interestingly, no increases in HDL-C levels were reported for the exercise only group. This finding suggests a synergistic relationship between exercise and HRT. Similarly, Seip and colleagues (1993) found significant increases in HDL-C levels in postmenopausal women following 9-12 months of endurance training at 80-90% HRmax. In addition, King et al. (1995) assessed the effects of high and low intensity exercise programs on HDL-C levels in sedentary women not receiving HRT. Although no significant increases in HDL-C were observed during year 1, by the end of year 2 subjects in both exercise groups showed small but significant increases in HDL-C levels. Interestingly, the increases were highest for subjects in the low-intensity group. The authors suggested that this was a result of exercising more days per week and concluded that frequency of participation may be particularly important for increasing HDL-C levels in women. The results of these studies suggest that habitual low to moderate intensity exercise may increase HDL-C levels in postmenopausal women with or without HRT.

Exercise Volume Threshold
Men
The volume or amount of exercise performed per week may also influence the magnitude of change in HDL-C levels. Most of the exercise training studies identify a weekly mileage threshold of 7 to 10 miles/week for significant increases in HDL-C. Wood and colleagues (1983) suggested that a threshold of running approximately 8 miles per week over a 1-year period is necessary to increases in HDL-C levels. In addition, Williams et al. (1982) reported that plasma concentrations of HDL-C generally did not begin to change until a threshold exercise level of 10 miles per week was maintained for at least 9 months. Kikkinos and others (1995a) reported significantly higher HDL-C levels in runners that averaged 7 to 10 miles per week. An additional study by Williams (1998) suggested that exercise volume is more important than exercise intensity. He reported that weekly mileage was more strongly correlated to HDL-C levels than exercise intensity. Interestingly, a higher volume of exercise provided significant increases in HDL-C in a shorter period of time. This indicates that there may be a relationship between exercise volume and the length of the training program. For non-runners a caloric expenditure above 1000 kcals per week has also been defined as a threshold dose of exercise to increase HDL-C levels (Drygas et al. 2000). These authors also noted that energy expenditure of &Mac179; 2000 kcals per week is associated with additional increases in HDL-C and that there may be a dose-response relationship between exercise and HDL-C levels.

Women
In women, the volume of exercise seems to be more important than the intensity of exercise for influencing HDL-C levels. Most studies suggest a large volume of exercise is necessary for significant HDL-C changes in women, however, the exercise volume threshold has not yet been defined. Generally, physically active women exhibit higher levels of HDL-C when compared to their sedentary counterparts (Kikkinos & Fernhall 1999). In a study by Kikkinos et al. (1995b) women who were categorized in a moderate and high fitness category, as assessed by an exercise tolerance test, exhibited higher HDL-C levels than those who were categorized in a low fitness category. Additionally, elevated HDL-C levels have been reported in women following a high-volume training program (Williams 1996, Williams 1998) but not for those in a low-volume training program (Brownell et al. 1982). Williams (1996) reported that HDL-C concentrations increased significantly in relation to the number of kilometers (km) run per week in premenopausal women and postmenopausal women, whether they were receiving HRT or not. He also noted substantial increases in HDL-C in women who ran more than 64 km/week (37 mile/wk) when compared to those who ran less than 48 km/wk (30 mile/wk). These findings also suggest a dose-response relationship between exercise and HDL-C levels.

In post-menopausal women, the research is limited and conflicting. Sunami et al. (1999) reported a positive correlation (r=.63) between the total weekly exercise duration and HDL-C levels. The post-menopausal women in the study exercised at 50% of VO2 max for 60 minutes two to four times a week. This finding suggests that moderate intensity exercise is sufficient to increase HDL-C levels in post-menopausal women as long as exercise duration and frequency are sufficient. In contrast, Ready et al. (1996) found that walking at 60% VO2 peak (VO2 peak is similar to VO2 max, but without all criteria met for a max test) for 60 minutes had no influence on HDL-C levels in post-menopausal women, regardless of frequency.

Conclusions
Most studies suggest that endurance exercise is positively associated with increases in HDL-C levels in men. However, in women the relationship between endurance exercise and HDL-C levels is less clear. The response of HDL-C levels will differ for each individual depending on the intensity, duration and frequency of exercise, the initial HDL-C level, and the length of the training period. There may be an exercise threshold for exercise intensity, weekly amount of exercise, and length of the training period, that must be met before changes in HDL-C are evident. This has yet to be acceptably elucidated.

Exercise Prescription
The aerobic exercise prescription should be individualized based on the health and/or fitness level of the client. The exercise prescription should be progressively introduced to individuals that are relatively sedentary and/or overweight. A general goal to work up to is a weekly caloric energy expenditure of &Mac179; 1000 kcals (Drygas et al. 2000).
Intensity & Duration of Exercise
The exercise prescription should involve continuous aerobic activities using large muscle groups. The exercise intensity should begin at a low to moderate level, depending on the fitness level of the client. As the client gains aerobic endurance intensity can be progressively increased. ACSM (1998) recommends an exercise intensity of 55-90% of maximal heart rate or 40-85% of heart rate reserve. The duration of activity will depend on the initial fitness level of the client and the client’s preferred exercise intensity. The exercise prescription should begin with approximately 20 minutes of continuous exercise and may progress up to 60 minutes (ACSM 1998).
Frequency
The optimal training frequency appears to be 3 to 5 times per week (ACSM 1998). If a dose-response relationship between exercise and physical activity exists, it appears that clients should strive to exercise 5-7 days per week.

Low-Density Lipoprotein Cholesterol
Low-density lipoproteins (LDL) are the primary transporters of cholesterol. LDLs are often called the “bad” or “lousy” cholesterol because their main function is to transport cholesterol to various body cells, including artery walls where LDLs release and deposit cholesterol. When LDL levels are elevated, cholesterol begins to accumulate in vessel walls and restrict blood flow. The liver contains specialized receptor sites that bind to LDL and remove them from circulation (Bishop & Aldana 1999). When LDL levels are elevated, all of the receptor sites are occupied, allowing other LDL molecules to circulate in the blood, depositing cholesterol. Delivery of cholesterol to various body cells is mediated by LDL receptor sites located on the surfaces of almost all cells (Durstine & Haskell 1994). Once LDL attaches to the receptor site, cholesterol is released and used to meet the metabolic needs of that cell (Durstine & Haskell 1994). When LDL-C enters an arterial wall it may be taken up and oxidized (biological breakdown of a substance) by the endothelial cells lining the arteries. The oxidation of LDL-C increases cell adherence to the endothelium. When an artery is injured white blood cells accumulate in the injured area as part of the inflammatory response. Growth factors, such as platelet-derived growth factor, increase the number of LDL receptors at the injury site, thereby increasing the deposition of cholesterol into the arterial wall (ACSM 1998). The accumulation of cells and cholesterol at the injury site create foam cells that are characteristic of atherosclerotic lesions. Foam cells accumulate on the artery wall and can eventually reduce blood flow through the artery (ACSM 1998).

References:
American College of Sports Medicine. 1998. ACSM’s Resource Manual for Guidelines for Exercise Testing and Prescription, Third edition. Baltimore: Lippincott Williams and Wilkins.
American Medical Association. 2001. “Executive summary of the third report of the National Cholesterol Education Program Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults. Journal of the American Medical Association. 285(19):2486-97.
Bishop J.G. & S.G. Aldana. 1999. Step Up to Wellness. Boston: Allyn & Bacon Publishing.
Brownell K.D., P.S. Bachorik & R.S. Ayerle. 1982. “Changes in plasma lipid and lipoprotein levels in men and women after a program of moderate exercise”. Circulation. 65(3):477-84.
Drygas W. et al. 2000. “Long term effects of different physical activity levels on coronary heart disease risk factors in middle-aged men”. International Journal of Sports Medicine. 21(4):235-41.
Duncan J.J., N.F. Gordon, & C.B. Scott. 1991. “Women walking for health and fitness. How much is enough?” Journal of the American Medical Association. 266(23):3295-9.
Dunn A.L. et al. 1999. “Comparison of lifestyle and structured interventions to increase physical activity and cardiorespiratory fitness: a randomized trial”. Journal of the American Medical Association. 281(4):327-34.
Durstine J.L. & W.L. Haskell. 1994. “Effects of exercise training on plasma lipids and lipoproteins”. Exercise and Sports Science Reviews. 22:477-522.
Katzmarzyk P.T. et al. 2001. “Changes in blood lipids consequent to aerobic exercise training related to changes in body fatness and aerobic fitness”. Metabolism 50(7);841-8.
Kikkinos P.F. et al. 1995a. “Miles run per week and high density lipoprotein cholesterol levels in healthy, middle-aged men. A dose-response relationship”. Archives of Internal Medicine. 155(4):415-20.
Kikkinos P.F. et al. 1995b. “Cardiorespiratory fitness and coronary heart disease risk factor association in women”. Journal of the American College of Cardiology. 26(2):358-64.
Kikkinos P.F. & B. Fernhall. 1999. “Physical activity and high density lipoprotein cholesterol levels”. Sports Medicine. 28(5):307-14.
King A.C. et al. 1995. “Varying intensities and formats of physical activity on participation rates, fitness and lipoproteins in men and women aged 50-65 years”. American Heart Journal. 91(10)2596-04.
Lakka T.A. & J.T. Salonen. 1992. “Physical activity and serum lipids: a cross-sectional population study in eastern Finnish men”. American Journal of Epidemiology. 136(7):806-18.Seip R.L. et al. 1993. “Exercise training decreases plasma cholesteryl ester transfer protein. Arteriosclerosis”. 13(9):1359-67.
Leclerc S. et al. 1985. “High density lipoprotein cholesterol, habitual physical activity and physical fitness”. Atherosclerosis. 57(1):43-51.
Lindheim S.R. et al. 1994. “The independent effects of exercise and estrogen on lipids and lipoproteins in postmenopausal women”. Obstetrics and Gynecology. 83(2):167-72.
Moll M.E. et al. 1979. “Cholesterol metabolism in non-obese women. Failure of physical conditioning to alter levels of high density lipoprotein cholesterol”. Atherosclerosis. 34(2):159-66.
Neiman, D.C. 1998. The Exercise Health Connection. Champaign, IL: Human Kinetics.
Ready A.E. et al. 1996. “Influence of walking volume on health benefits in women post-menopause”. Medicine and Science in Sport and Exercise. 28(9):1097-105.
Santiago, M.C., A.S. Leon & R.C. Serfass. 1995. “Failure of 40 weeks of brisk walking to alter blood lipids in normolipidemic women”. Canadian Journal of Applied Physiology. 20(4):417-28.
Spate-Douglass T. & R.E. Keyser. “Exercise intensity: its effect on the high-density lipoprotein profile”. Arch Phys Med Rehabil. 80(6):691-5.
Stein R.A. et al. 1990. “Effects of different exercise training intensities on lipoprotein cholesterol fractions in healthy middle aged men”. American Heart Journal. 119:277-83.
Sunami Y. et al. 1999. “Effects of low-intensity aerobic training on the high-density lipoprotein cholesterol concentration in healthy elderly subjects”. Metabolism. 48(8):984-9.
Williams P.T. et al. 1982. “The effects of running mileage and duration on plasma lipoprotein levels”. Journal of the American Medical Association. 247(19):2674-9.
Williams P.T. 1996. “High-density lipoprotein cholesterol and other risk factors for coronary heart disease in female runners”.334(20):1298-303.
Williams P.T. 1998. “Relationships of heart disease risk factors to exercise quantity and intensity”. Archives of Internal Medicine. 158(3):237-45.
Wood P.D. et al. 1983. “Increased exercise level and plasma lipoprotein concentrations: a one year randomized, controlled study in sedentary middle-aged men”. Metabolism. 32(1):31-9.
Wood P.D. et al. 1991. “The effects on plasma lipoproteins of a prudent weight-reducing diet, with or without exercise, in overweight men and women”. New England Journal of Medicine. 325(7):461-6.