Life Extension

Deciding whether and how to treat elevated blood lipids hinges on a variety of factors, including overall cardiovascular risk and likelihood of adherence to dietary and lifestyle modification. People whose lipids are mildly elevated but are otherwise healthy may do well with dietary changes and initiation of an exercise regimen. On the other hand, people with high risk of cardiovascular disease (such as a history of cardiovascular events) may need to start on medication(s) in addition to changing their diet and exercising.

Dietary and Lifestyle Changes

Dietary modifications aim to reduce the intake and uptake of unhealthy fats such as saturated and trans fats and cholesterol from the diet. The inclusion of specific dietary compounds with cholesterol-lowering50 or cardioprotective properties may also reduce cardiovascular disease risk by several different mechanisms.

Diet is the most important aspect of a cholesterol management program. The American Heart Association and other experts recommend a diet that emphasizes51,52:

  • Fruits and vegetables
  • Whole grains
  • Nuts and legumes
  • Fish and skinless poultry, with limited amounts of red meat
  • Non-tropical vegetable oils, such as olive, sunflower, safflower, canola, and other oils low in saturated fat. Note that the American Heart Association does not recommend deep frying foods regardless of the type of oil used. They also do not recommend coconut oil, which is high in saturated fat.
  • Avoiding hydrogenated oils to reduce dietary trans fat
  • Reducing added sugar and sodium
  • Limiting daily alcohol consumption to no more than one drink for women and two drinks for men

In controlled clinical trials that replaced dietary saturated fat with polyunsaturated vegetable oils such as those listed above, cardiovascular disease was reduced by about 30%, which is roughly the degree of protection conferred by statin drugs. Substituting saturated fat for polyunsaturated vegetable oil lowers LDL cholesterol, which may in part explain the benefits observed. Observational trials have also found that higher intake of monounsaturated and polyunsaturated fats is associated with lower rates of death from cardiovascular disease or any cause. It should be noted that replacing saturated fat with refined carbohydrates and sugars has not been shown to reduce cardiovascular disease.53

Specific dietary approaches that are generally heart healthy are the Dietary Approaches to Stop Hypertension (DASH) diet and Mediterranean diet.

Caloric Restriction

Caloric restriction is the reduction of dietary calories (by up to 40%) while still maintaining good nutrition.54 Restricting energy intake slows down the body’s growth processes, causing it instead to focus on protective repair mechanisms; the overall effect is an improvement in several measures of health. Observational studies have tracked the effects of caloric restriction on lean, healthy individuals, and demonstrated that moderate restriction (22?30% decreases in caloric intake from normal levels) improves heart function and reduces markers of inflammation (C-reactive protein, tumor necrosis factor [TNF]), risk factors for cardiovascular disease (LDL cholesterol, triglycerides, blood pressure), and diabetes risk factors (fasting blood glucose, insulin levels).55-58 Preliminary results of the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) study, a long-term multicenter trial on the effects of calorie-restricted diets in healthy overweight volunteers,59 showed moderate calorie restriction can reduce several cardiovascular risk factors (LDL cholesterol, triglycerides, blood pressure, and C-reactive protein).60

More information is available in Life Extension's Caloric Restriction protocol.

Exercise

Exercise is a fundamental component of any lipid management strategy. The American Heart Association and American College of Cardiology recommend adults engage in at least 150 minutes of moderate-intensity activity or 75 minutes of high-intensity activity each week for the prevention of cardiovascular disease.61 Exercise helps raise HDL levels and boost the efficiency of reverse cholesterol transport, the process by which cholesterol is carried from the blood vessels back to the liver for excretion.62 A small study published in 2019 found exercise had a greater effect on cholesterol synthesis than calorie restriction.63 Exercise reduces LDL significantly when combined with a heart-healthy diet—much more so than a healthy diet without exercise.64

A meta-analysis of 37 studies found that exercise usually resulted in moderate-to-strong improvements in levels of total cholesterol, LDLs, triglycerides, and HDLs. This same analysis also found that exercise consistently improved glucose and insulin levels, which are often elevated in people with an unhealthy lipid profile.65 Both aerobic and anaerobic exercise have beneficial effects on blood lipids, so an exercise regimen that combines strength training (eg, weightlifting) and endurance training (eg, running, swimming) is suggested.66

Medications to Manage Blood Lipids

Reduction of total cholesterol and LDL cholesterol (and/or triglycerides) by drugs usually involves inhibiting cholesterol production in the body or preventing the absorption/reabsorption of cholesterol from the gut. When the availability of cholesterol to cells is reduced, they are forced to pull cholesterol from the blood (which is contained in LDL particles). This has the net effect of lowering LDL cholesterol. Therapies that increase the breakdown of fatty acids in the liver or lower the amount of VLDL in the blood (like fibrate drugs or high-dose niacin)67 also result in lower serum cholesterol levels. Often, complementary strategies (eg, statin to lower cholesterol production plus a bile acid sequestrant to lower cholesterol absorption) are combined to meet cholesterol-lowering goals.

Statins

Decreasing cellular cholesterol production is the most common strategy for reducing cardiovascular disease risk, with HMG-CoA reductase inhibitors (statins) being the most commonly prescribed cholesterol-lowering treatments. Statins inhibit the activity of the enzyme HMG-CoA reductase, a key enzyme in cholesterol synthesis. Since cholesterol levels in cells are tightly controlled (cholesterol is critical to many cellular functions), the shutdown of cellular cholesterol synthesis causes the cell to respond by increasing the activity of the LDL receptor on the cell surface, which has the net effect of pulling LDL particles out of the bloodstream and into the cell. Statins may also reduce CHD risk by other mechanisms, such as reducing inflammation.68

Statins may induce serious side effects in some individuals, the most common being muscle pain or weakness (myopathy). The prevalence of myopathy is fairly low in clinical trials (1.5?3.0%), but can be as high as 33% in community-based studies and may rise dramatically in statin users who are active (up to 75% in statin-treated athletes).69,70 Occasionally, statins may cause an elevation of the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). These enzymes can be monitored by doing a routine chemistry panel blood test. Additionally, by inhibiting HMG-CoA reductase (an enzyme not only required for the production of cholesterol, but other metabolites as well), statins may reduce levels of the critically important antioxidant molecule CoQ10.

Targeting Cholesterol Absorption

Lowering cholesterol absorption from the intestines reduces LDL cholesterol in a different fashion; by preventing uptake of intestinal cholesterol, cells respond by making more LDL receptor, which pulls LDL particles out of the bloodstream. Ezetimibe (Zetia) and bile acid sequestrants (colesevelam [Welchol], cholestyramine [Prevalite, Questran], colestipol [Colestid]) are two classes of prescription treatment that work in this fashion. Ezetimibe acts on the cells lining the intestines (enterocytes) to reduce their ability to take up cholesterol from the intestines. Ezetimibe, when added to a statin, has been shown to reduce cardiovascular events in high-risk patients and has been recommended as an alternative treatment in those who cannot take statins.71 Bile acid sequestrants bind to bile acids in the intestine, which reduces their ability to emulsify fats and cholesterol. This has the net effect of preventing intestinal cholesterol absorption. Bile acid sequestrants may also increase HDL production in the liver, which is usually inhibited by the reabsorption of bile acids.72

PCSK9 Inhibitors

The newest medications on the scene are agents that directly inhibit the enzyme PCSK9, effectively removing an inhibitor in the LDL receptor pathway. This means that more LDL receptors are free to grab LDL particles and remove them from the blood, thus potently lowering blood LDL concentrations. While highly effective in reducing LDL, the cost of PCSK9 inhibitors severely limits their use, but they are expected to become more affordable with time.73

Cholesterol

Figure 1: Steroid Biosynthesis Pathways7

Cholesterol is a wax-like steroid molecule that plays a critical role in metabolism. It is a major component of cellular membranes, where its concentration varies depending on cell type. For example, the lipid portion of the membrane of liver cells consists of about 17% cholesterol, while that of red blood cells consists of about 23%.8

The cholesterol in cell membranes serves two primary functions. First, it modulates the fluidity of membranes, allowing them to maintain their function over a wide range of temperatures. Second, it prevents leakage of ions by acting as a cellular insulator.8 (Ions are molecules used by cells to interact with their environment.) This effect is critical for the proper function of neuronal cells because the cholesterol-rich myelin sheath insulates neurons and allows them to transmit electrical impulses rapidly over long distances.

Cholesterol has other important roles in human metabolism. Cholesterol serves as a precursor to steroid hormones, which include the sex hormones (androgens and estrogens); mineral-corticoids,9 which control the balance of water and mineral excretion in the kidneys; and glucocorticoids, which control protein and carbohydrate metabolism, immune suppression, and inflammatory processes (Figure 1).7 Cholesterol is also the precursor to vitamin D. Finally, cholesterol provides the framework for the synthesis of bile acids, which emulsify dietary fats for absorption.

Triglycerides

Triglycerides are storage lipids that have a critical role in metabolism and energy utilization. They are molecular complexes of glycerol (glycerin) and three fatty acids.

While glucose is the preferred energy source for most cells, it is a bulky molecule that contains little energy for the amount of space it occupies. Glucose is primarily stored in the liver and muscles as glycogen. Fatty acids, on the other hand, when packaged as triglycerides, are denser sources of energy than carbohydrates, which make them superior for long-term energy storage (the average human can only store enough glucose in the liver for about 12 to 24 hours worth of energy without food, but can store enough fat to power the body for substantially longer).10

Lipoproteins: Blood Lipid Transporters

Lipids (cholesterol and fatty acids) are unable to move independently through the bloodstream, and so must be transported throughout the body as lipid-protein complexes called lipoproteins. Contained within these lipoproteins are one or more proteins, called apolipoproteins, which act as molecular "signals" to facilitate the movement of lipid-filled lipoproteins throughout the body. Lipoproteins can also carry fat-soluble nutrients, like coenzyme Q10 (CoQ10), vitamin E, and carotenoids, which protect the transported lipids from oxidative damage. Vitamin E and CoQ10 also help prevent the oxidative modification of LDL particles, which in turn protects the blood vessel lining from damage. This will be discussed in greater detail later in this protocol.

There are four main classes of lipoproteins, each with a different, important function11:

  • Chylomicrons are produced in the small intestines and deliver energy-rich dietary fats to muscles (for energy) or fat cells (for storage). They also deliver dietary cholesterol from the intestines to the liver.
  • Very low-density lipoproteins (VLDLs) take triglycerides, phospholipids, and cholesterol from the liver and transport them to fat cells.
  • Low-density lipoproteins (LDLs) carry cholesterol from the liver to cells that require it. In aging people, LDL often transports cholesterol to the linings of their arteries where it may not be needed.
  • High-density lipoproteins (HDLs) transport excess cholesterol (from cells, or other lipoproteins like chylomicrons or VLDLs) back to the liver, where it can be re-processed and/or excreted from the body as bile salts. HDL removes excess cholesterol from the arterial wall.

Among its myriad of functions, the liver has a central role in the distribution of cellular fuel throughout the body. Following a meal, and after its own requirements for glucose have been satisfied, the liver converts excess glucose and fatty acids into triglycerides for storage and packages them into VLDL particles for transit to fat cells. VLDLs travel from the liver to fat cells, where they transfer triglycerides/fatty acids to the cell for storage. VLDLs carry between 10% and 15% of the total cholesterol normally found in the blood.12

As VLDLs release their triglycerides to fat cells, their cholesterol content becomes proportionally higher (which also causes the VLDL particle to become smaller and denser). The loss of triglycerides causes the VLDL to transition to an LDL. The LDL particle, which averages about 45% cholesterol, is the primary particle for the transport of cholesterol from the liver to other cells of the body; about 60?70% of serum cholesterol is carried by LDL.12

During the VLDL to LDL transition, an apolipoprotein buried just below the surface of the VLDL, called ApoB-100, becomes exposed. ApoB-100 identifies the lipoprotein as an LDL particle to other cells. Cells which require cholesterol recognize ApoB-100 and capture the LDL, so the cholesterol it contains can be brought into the cell. Each LDL particle expresses exactly one ApoB-100 molecule, so measurement of Apo-B100 levels serves as a much more accurate indicator of LDL number than LDL cholesterol level.13

LDL particles are brought into cells via LDL receptors, and the more these receptors are active, the more LDL particles are removed from the blood resulting in a lower blood concentration of LDL.14 The enzyme PCSK9 (proprotein convertase subtilisin/kexin type 9) degrades the LDL receptor. PCSK9-inhibitor drugs that are antibodies against this enzyme have been developed, and they markedly lower LDL cholesterol.

Because of the correlation between elevated blood levels of cholesterol carried in LDL and the risk of heart disease, LDL is commonly referred to as the "bad cholesterol." LDL is, however, more than just cholesterol, and its contribution to disease risk involves more than just the cholesterol it carries.

All LDL particles are not created equal. In fact, LDL subfractions are divided into several classes based on size (diameter) and density, and are generally represented from largest to smallest in numerical order beginning with 1. The lower numbered classes are larger and more buoyant (less dense); size gradually decreases and density increases as the numbers progress. Smaller, denser LDLs are significantly more atherogenic for two reasons: they are much more susceptible to oxidation,15-17 and they pass from the bloodstream into the blood vessel wall much more efficiently than large, buoyant LDL particles.18 A more comprehensive lipid test, such as the NMR LipoProfile,6 allows for assessment of the size and density of LDL particles, a feature that increases the prognostic value and sets these advanced tests apart from conventional lipid tests. If an individual is found to have a greater number of small dense LDLs, they are said to express LDL pattern B and are at greater risk for heart disease than an individual with more large buoyant LDL particles, which is referred to as pattern A.

Lipoprotein(a), also called Lp(a), is a subclass of lipoprotein particles composed of LDL-like particles bound to another particle, called apolipoprotein(a). Lp(a) is a known marker of cardiovascular risk; that is, elevated levels correlate with greater risk for cardiovascular disease. Lp(a) levels are mostly determined by genetics (as opposed to diet and lifestyle as with other blood lipid markers). Generally, Lp(a) levels above 50 mg/dL (~125 nmol/L) are considered to indicate high cardiovascular risk, whereas levels below 30 mg/dL (~72 nmol/L) are associated with low risk.19

Lp(a) levels should be interpreted in the context of other cardiovascular and lipid risk markers, and family history of cardiovascular disease is an indication for measurement of Lp(a). As of mid-2019, no reliable data from randomized controlled trials have shown that targeting Lp(a) reduction with medication is an effective risk-reduction strategy. As of this writing, the only intervention available that appears promising for lowering Lp(a) is lipoprotein apheresis.20 Lipoprotein apheresis involves the removal of lipoproteins from the blood via a blood filtration process used only in people with very elevated blood lipids despite maximal lifestyle and drug therapy. Thus, Lp(a) is primarily useful as a marker for identifying people who might benefit from adopting a more intensive overall cardiovascular risk reduction strategy.

Nevertheless, some intriguing interventions that target Lp(a), such as antisense oligonucleotides, are currently under development and may represent a novel intervention if research progresses as hoped, but further studies are needed.5,21-23

HDLs are small, dense lipoprotein particles assembled in the liver. They carry about 20?30% of total serum cholesterol.12 Cholesterol carried in the HDL particle is called "good cholesterol," in reference to the protective effect HDL particles can have on cardiovascular disease risk. HDL particles can pick up cholesterol from other tissues and transport it back to the liver for re-processing and/or disposal as bile salts. HDL can also transport cholesterol to the testes, ovaries, and adrenals to serve as precursors to steroid hormones. HDLs are identified by their apolipoproteins ApoA-I and ApoA-II, which allow the particles to interact with cell surface receptors and other enzymes.

The movement of cholesterol from tissues to the liver for clearance, mediated by HDLs, is called reverse cholesterol transport. If the reverse cholesterol transport process is not functioning efficiently, lipids can build up in tissues such as the arterial wall. Thus, reverse cholesterol transport is critical for avoiding atherosclerosis.

Testosterone and Reverse Cholesterol Transport

Interestingly, a link has been observed between the male hormone testosterone and reverse cholesterol transport; that is, testosterone enhances reverse cholesterol transport. Though it is known that testosterone decreases levels of HDL, it also improves HDL function. This effect is mediated by a protein in the liver called scavenger receptor B1 that acts to stimulate cholesterol uptake for processing and disposal. Testosterone beneficially increases scavenger receptor B1.24 Testosterone also increases the activity of an enzyme called hepatic lipase, another facilitator of reverse cholesterol transport.25

Aging men experience a decline in testosterone levels, as well as an increase in heart disease risk, suggesting these phenomena may be related. Indeed, studies have shown that men with even slightly lower testosterone levels were over three times as likely to exhibit signs of early coronary artery disease.26 Men interested in learning more about the link between heart disease and declining testosterone levels and ways to boost testosterone naturally should read Life Extension's "Male Hormone Restoration" protocol.

Those with vascular disorders often manifesting as coronary artery disease should consider using a wide range of supplements, hormones and drugs to suppress the multiple risk factors involved in atherosclerosis progression. Healthy individuals should carefully follow blood test results to ascertain which nutrients are more important.

Inhibiting Cholesterol Synthesis

Inhibiting Absorption of Dietary Cholesterol

Enhancing Cholesterol Elimination

Inhibiting Oxidation and Glycation of LDL

Optimizing the Lipid Profile

Improving reverse cholesterol transport

In addition, the following blood testing resources may be helpful:

 

Deciding whether and how to treat elevated blood lipids hinges on a variety of factors, including overall cardiovascular risk and likelihood of adherence to dietary and lifestyle modification. People whose lipids are mildly elevated but are otherwise healthy may do well with dietary changes and initiation of an exercise regimen. On the other hand, people with high risk of cardiovascular disease (such as a history of cardiovascular events) may need to start on medication(s) in addition to changing their diet and exercising.

Dietary and Lifestyle Changes

Dietary modifications aim to reduce the intake and uptake of unhealthy fats such as saturated and trans fats and cholesterol from the diet. The inclusion of specific dietary compounds with cholesterol-lowering50 or cardioprotective properties may also reduce cardiovascular disease risk by several different mechanisms.

Diet is the most important aspect of a cholesterol management program. The American Heart Association and other experts recommend a diet that emphasizes51,52:

  • Fruits and vegetables
  • Whole grains
  • Nuts and legumes
  • Fish and skinless poultry, with limited amounts of red meat
  • Non-tropical vegetable oils, such as olive, sunflower, safflower, canola, and other oils low in saturated fat. Note that the American Heart Association does not recommend deep frying foods regardless of the type of oil used. They also do not recommend coconut oil, which is high in saturated fat.
  • Avoiding hydrogenated oils to reduce dietary trans fat
  • Reducing added sugar and sodium
  • Limiting daily alcohol consumption to no more than one drink for women and two drinks for men

In controlled clinical trials that replaced dietary saturated fat with polyunsaturated vegetable oils such as those listed above, cardiovascular disease was reduced by about 30%, which is roughly the degree of protection conferred by statin drugs. Substituting saturated fat for polyunsaturated vegetable oil lowers LDL cholesterol, which may in part explain the benefits observed. Observational trials have also found that higher intake of monounsaturated and polyunsaturated fats is associated with lower rates of death from cardiovascular disease or any cause. It should be noted that replacing saturated fat with refined carbohydrates and sugars has not been shown to reduce cardiovascular disease.53

Specific dietary approaches that are generally heart healthy are the Dietary Approaches to Stop Hypertension (DASH) diet and Mediterranean diet.

Caloric Restriction

Caloric restriction is the reduction of dietary calories (by up to 40%) while still maintaining good nutrition.54 Restricting energy intake slows down the body’s growth processes, causing it instead to focus on protective repair mechanisms; the overall effect is an improvement in several measures of health. Observational studies have tracked the effects of caloric restriction on lean, healthy individuals, and demonstrated that moderate restriction (22?30% decreases in caloric intake from normal levels) improves heart function and reduces markers of inflammation (C-reactive protein, tumor necrosis factor [TNF]), risk factors for cardiovascular disease (LDL cholesterol, triglycerides, blood pressure), and diabetes risk factors (fasting blood glucose, insulin levels).55-58 Preliminary results of the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) study, a long-term multicenter trial on the effects of calorie-restricted diets in healthy overweight volunteers,59 showed moderate calorie restriction can reduce several cardiovascular risk factors (LDL cholesterol, triglycerides, blood pressure, and C-reactive protein).60

More information is available in Life Extension's Caloric Restriction protocol.

Exercise

Exercise is a fundamental component of any lipid management strategy. The American Heart Association and American College of Cardiology recommend adults engage in at least 150 minutes of moderate-intensity activity or 75 minutes of high-intensity activity each week for the prevention of cardiovascular disease.61 Exercise helps raise HDL levels and boost the efficiency of reverse cholesterol transport, the process by which cholesterol is carried from the blood vessels back to the liver for excretion.62 A small study published in 2019 found exercise had a greater effect on cholesterol synthesis than calorie restriction.63 Exercise reduces LDL significantly when combined with a heart-healthy diet—much more so than a healthy diet without exercise.64

A meta-analysis of 37 studies found that exercise usually resulted in moderate-to-strong improvements in levels of total cholesterol, LDLs, triglycerides, and HDLs. This same analysis also found that exercise consistently improved glucose and insulin levels, which are often elevated in people with an unhealthy lipid profile.65 Both aerobic and anaerobic exercise have beneficial effects on blood lipids, so an exercise regimen that combines strength training (eg, weightlifting) and endurance training (eg, running, swimming) is suggested.66

Medications to Manage Blood Lipids

Reduction of total cholesterol and LDL cholesterol (and/or triglycerides) by drugs usually involves inhibiting cholesterol production in the body or preventing the absorption/reabsorption of cholesterol from the gut. When the availability of cholesterol to cells is reduced, they are forced to pull cholesterol from the blood (which is contained in LDL particles). This has the net effect of lowering LDL cholesterol. Therapies that increase the breakdown of fatty acids in the liver or lower the amount of VLDL in the blood (like fibrate drugs or high-dose niacin)67 also result in lower serum cholesterol levels. Often, complementary strategies (eg, statin to lower cholesterol production plus a bile acid sequestrant to lower cholesterol absorption) are combined to meet cholesterol-lowering goals.

Statins

Decreasing cellular cholesterol production is the most common strategy for reducing cardiovascular disease risk, with HMG-CoA reductase inhibitors (statins) being the most commonly prescribed cholesterol-lowering treatments. Statins inhibit the activity of the enzyme HMG-CoA reductase, a key enzyme in cholesterol synthesis. Since cholesterol levels in cells are tightly controlled (cholesterol is critical to many cellular functions), the shutdown of cellular cholesterol synthesis causes the cell to respond by increasing the activity of the LDL receptor on the cell surface, which has the net effect of pulling LDL particles out of the bloodstream and into the cell. Statins may also reduce CHD risk by other mechanisms, such as reducing inflammation.68

Statins may induce serious side effects in some individuals, the most common being muscle pain or weakness (myopathy). The prevalence of myopathy is fairly low in clinical trials (1.5?3.0%), but can be as high as 33% in community-based studies and may rise dramatically in statin users who are active (up to 75% in statin-treated athletes).69,70 Occasionally, statins may cause an elevation of the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). These enzymes can be monitored by doing a routine chemistry panel blood test. Additionally, by inhibiting HMG-CoA reductase (an enzyme not only required for the production of cholesterol, but other metabolites as well), statins may reduce levels of the critically important antioxidant molecule CoQ10.

Targeting Cholesterol Absorption

Lowering cholesterol absorption from the intestines reduces LDL cholesterol in a different fashion; by preventing uptake of intestinal cholesterol, cells respond by making more LDL receptor, which pulls LDL particles out of the bloodstream. Ezetimibe (Zetia) and bile acid sequestrants (colesevelam [Welchol], cholestyramine [Prevalite, Questran], colestipol [Colestid]) are two classes of prescription treatment that work in this fashion. Ezetimibe acts on the cells lining the intestines (enterocytes) to reduce their ability to take up cholesterol from the intestines. Ezetimibe, when added to a statin, has been shown to reduce cardiovascular events in high-risk patients and has been recommended as an alternative treatment in those who cannot take statins.71 Bile acid sequestrants bind to bile acids in the intestine, which reduces their ability to emulsify fats and cholesterol. This has the net effect of preventing intestinal cholesterol absorption. Bile acid sequestrants may also increase HDL production in the liver, which is usually inhibited by the reabsorption of bile acids.72

PCSK9 Inhibitors

The newest medications on the scene are agents that directly inhibit the enzyme PCSK9, effectively removing an inhibitor in the LDL receptor pathway. This means that more LDL receptors are free to grab LDL particles and remove them from the blood, thus potently lowering blood LDL concentrations. While highly effective in reducing LDL, the cost of PCSK9 inhibitors severely limits their use, but they are expected to become more affordable with time.73

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