OVERVIEW OF CHOLESTEROL Cholesterol is a waxy substance found throughout the body. It is needed for a number of body functions, including helping build cells and making vitamins and hormones (1,2). Cholesterol comes primarily from the liver and the foods we eat and is carried undissolved in the blood as lipoproteins, that is, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and triglycerides (TGs). Elevated levels of VLDLs, LDLs, and TGs in the blood are a major risk factor for the development of cardiovascular disease, which is the number one cause of death worldwide (2–4). PATHOPHYSIOLOGY OF ELEVATED LIPOPROTEINS Several terms are used to describe lipid disorders. Dyslipidemia refers to abnormal levels, low or high, of lipids in the blood. Hypercholesterolemia refers specifically to high LDL cholesterol, and hyperlipidemia is a more general term describing high cholesterol and/or TGs. Although the terms are sometimes used interchangeably, they each refer to a different type of lipid disorder. Of these, high LDL is most associated with the development of plaque within the blood vessels that may limit flow and develop into coronary artery disease (2). See Table 1 for descriptions of various types of cholesterol and Table 2 for normal values. TABLE 1. - Blood Cholesterol Descriptions •Total cholesterol (TC), the total amount of cholesterol in the blood. •High-density lipoprotein (HDL), often called “good” cholesterol, may decrease risk for heart disease and stroke. •Low-density lipoprotein (LDL), often called “bad” cholesterol. •Triglycerides (TG), another type of fat in the blood. •Very-low-density lipoprotein (VLDL), “bad” cholesterol, contains mostly triglycerides. High total cholesterol, LDLs, TGs, VLDLs, and low HDLs increases risk for cardiovascular disease (2,5). TABLE 2. - Blood Cholesterol Normal Values •Total cholesterol below 200 mg·dL−1. •HDL from 40 to 60 mg/dL, though higher is better. •LDL generally below 100 mg/dL. For people with heart or other vascular disease, it should be below 70 mg/dL. •Triglycerides below 150 mg/dL for adults and lower than 90 mg/dL for 10–19 year olds. •VLDL 2–30 mg/dL. Normal value ranges may vary slightly with different laboratories. These levels are a guideline. Some individuals may need treatment even if their lipids are at these levels, if they have risk factors or diseases such as coronary heart disease or stroke (1,5). High levels of LDL increase the probability of cholesterol infiltration into the spaces between the layers of the blood vessel wall. Once inside the wall, LDL particles accumulate, forming “foam cells” (referring to the high cholesterol load), which cause inflammation and plaque formation (6). Some of these plaques may become hard and calcified over time, leading to stiffened vessel walls (arteriosclerosis), contributing to hypertension. These plaques can be identified with a test known as coronary artery calcification scoring where the calcium in the plaque can be seen on imaging. Coronary artery calcification scores (Agatston score) range from 0 to 400, with lower scores indicating less risk. Scores above 100 are associated with the presence of moderate plaque burden and higher risk (7). Most total, or near total, blockages of blood vessels are of this calcified type and often are identified following a positive, symptom-limited cardiac stress test (8).Other plaques may not calcify completely and retain a liquid, lipid-rich core. These are referred to as “vulnerable plaques” and are the cause of most heart attacks. This type of plaque generally occupies less than 70% of the internal diameter of the blood vessel and is covered by a fibrous cap. Rupture of the fibrous cap exposes the blood to clotting agents within the plaque, causing clot formation, limiting blood flow past the clot, potentially causing the death (or infarction) of myocardial cells. These vulnerable plaques can be difficult to identify, and the use of a coronary artery angiogram to visualize the interior of blood vessels is used when symptoms or other testing suggest they may be present (9). It is estimated that more than 10% of Americans aged 20 and over have high cholesterol (3). The prevalence of dyslipidemia varies worldwide. Factors such as lifestyle, family history, diagnostic testing, and treatment contribute to this wide variation (3,10). Recent findings showed that there was no significant difference in high cholesterol in the United States between adult men (10.6%) and women (11.9%) (11). However, the difference in low HDLs was significant between U.S. adult men and women, 21.5%–6.6%, respectively (11). Overall, lifestyle, age, gender, and country/region seem to factor in the most regarding the prevalence of dyslipidemia (2,10). Risk factors for dyslipidemia include the following: Overweight/obesity Type 2 diabetes Diets high in saturated fats and trans fats Lack of exercise and physical activity Advanced age Smoking Gender (LDL, “bad cholesterol,” levels tend to increase in women during and after menopause) Family history (1,2). EFFECTS OF EXERCISE ON BLOOD LIPOPROTEINS Consistent aerobic exercise training has a measurable and meaningful beneficial effect on blood lipoproteins (12–14). Lowering of TGs is the most consistent effect exercise has on lipoproteins. The effect is magnified if accompanied by a plant-based diet and weight loss (12–15). Chronic aerobic exercise training increases hepatic HDL production, which affords protection against cardiovascular disease (15,16). HDL is increased with sustained aerobic exercise of 120 or more minutes or 900–1200 or more calories per week (12–14,16). The greater the exercise volume and caloric expenditure, the more likely an exerciser will achieve an increase in HDLs. In a cross-sectional analysis, HDLs increased in a linear fashion between 10 km and 40 km of running per week (17). The effect of exercise alone on reducing LDLs is less conclusive. Thus, the preferred approach to lowering LDL is to combine aerobic exercise with a plant-based diet and weight loss (12–15). It was recently demonstrated in 35 pairs of identical twins (active twins ran a mean of 63 km/week vs a mean of 7 km/week in the inactive twins) that low HDL cholesterol may be largely determined by genetic factors (18). Regular aerobic exercise is an essential lifestyle component for improving blood lipoproteins. The total amount of physical activity seems to be more important than the intensity (12–14). Cross-sectional studies have shown that lipids continue to improve across weekly running distances from 40 miles in a dose-response manner (13,17). Postprandial lipemia (PPL) refers to the rise in TG-rich lipoproteins (e.g., VLDLs) after a meal. The effect of exercise on PPL is significant and clinically meaningful (13,19). Individuals who regularly perform aerobic exercise typically display low levels of PPL (13,20). Aerobic exercise has been shown to reduce PPL in men with elevated TGs, even when performed 12 hours before a high-fat meal (13,19). Intermittent exercise in young men and women with normal lipoprotein levels also was shown to improve PPL significantly (13,21). Exercise that stimulates fat use as a substrate during and after the activity helps clear TGs from the blood. It is important to note that the favorable effect of endurance exercise on PPL seems to be a result of acute metabolic changes as opposed to chronic effects (13). This finding encourages daily aerobic exercise to treat elevated PPL. There have been few studies on resistance training (RT) and effects on lipoproteins, and the results are inconsistent (12,22). If weight loss is combined with aerobic and resistance exercise, lipoproteins are more likely to be improved after RT (12,13). Exercise training can improve lipoprotein profiles either directly (without weight loss) by increased lipoprotein enzymatic activity or indirectly (reduced body weight). When weight loss occurs in conjunction with exercise, TGs and LDL are usually lowered more and HDL is increased more (12,13). However, exercise training can significantly improve blood lipids even when there is minimal or no weight loss (12–14). Table 3 presents a summary of the effects of aerobic and combined aerobic with RT (CT). CT produced slightly greater decreases in TC and LDL than aerobic only, but the differences were not statistically significant (12). TABLE 3. - Summary of the Effects of Aerobic Exercise Training on Blood Lipoproteins Lipoprotein Aerobic Exercise Combined Traininga Total cholesterol Modest decrease independently Modest decrease independently LDL cholesterol Modest decrease independently Modest decrease independently HDL cholesterol Modest Increase independently Modest increase independently Triglycerides Decrease independently Decrease independently Very low-density lipoproteins Decrease independently Decrease independently Post Prandial Lipemia Decrease acutely and chronically Decrease acutely and chronically aCombined training involves resistance training and aerobic exercise. EXERCISE TESTING AND RECOMMENDATIONS Exercise testing is appropriate for medically cleared individuals with dyslipidemia (Bruce treadmill or 6-minute walk test), with caution for cardiovascular disease and comorbidities. Inactive individuals with symptoms or comorbidities need medical clearance (23). Because dyslipidemia often coexists with obesity, type 2 diabetes, hypertension, and metabolic syndrome, promoting energy expenditure and weight loss is key, while those without comorbidities may follow healthy adult guidelines (24). Exercise should be individualized, combining aerobic, resistance, and flexibility training, with moderate-intensity aerobic activity most days (250–300 minutes/week) and caution for vigorous exercise. High-intensity exercise may improve lipids, but unsupervised use is not recommended (25,26). Combined aerobic and RT is most effective, and stretching supports mobility in those with low functional fitness (27,28). See Table 4 for general exercise recommendations for individuals with dyslipidemia. TABLE 4. - General Exercise Recommendations for Individuals With Dyslipidemia Training Parameter Aerobic Training Resistance Training Frequency 5–7 days per week 2–3 nonconsecutive days per week Intensity 40%–75% HRR (RPE 11–14/20 or 4–7/10) 50%–70% 1-RM (progressively to 70%–85% 1-RM)OMNI-RES 5–6/10 (progressively increase to 7–8/10) Time 30 minutes (progressively to 60 minutes) per day 1–2 sets × 12–20 repetitions (progressively to 2–4 sets × 8–12 repetitions)8–12 exercises targeting the major muscle groups1–2 minutes rest between sets Type Low to moderate impact (treadmill- or free-walking, stationary cycling, and swimming) Bodyweight resistance, resistance bands, suspension training, manual resistance, basic stationary weight machines, and free weights (full body routine) 1-RM, one repetition maximum; HRR, heart rate reserve; OMNI-RES, OMNI-resistance exercise scale of perceived exertion PNF, proprioceptive neuromuscular facilitation; RPE, rating of perceived exertion (12,24). EXERCISE TRAINING CONSIDERATIONS Follow current exercise guidelines for individuals with dyslipidemia and cardiometabolic comorbidities (24). Older adults should follow age-specific recommendations (29). Use shorter aerobic bouts if 30–60 minute continuous sessions are not feasible (24). Unusual muscle soreness (myalgia) may occur in some patients receiving lipid-lowering medication and is generally benign; however, symptoms that interfere with activity, or abnormal results from routine blood tests, warrant medical evaluation (30). Monitor aerobic intensity via heart rate, rating of perceived exertion, and the talk test for safe, individualized training (31).
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