About this course:
This learning activity aims to increase the nurse's knowledge of the disease process of hyperlipidemia, risk factors, and management of the affected individual.
This learning activity aims to increase the nurse's knowledge of the disease process of hyperlipidemia, risk factors, and management of the affected individual.
This learning activity is designed to allow learners to:
explain the functions of the liver as it relates to cholesterol production and processing
identify diagnostic tests used in cholesterol assessment
identify modifiable and non-modifiable risk factors in hyperlipidemia
discuss the dietary implications concerning cholesterol management
analyze the pharmacological treatment of hyperlipidemia
interpret the American Heart Association (AHA) guidelines for the management of hyperlipidemia
Different terms are used to identify an abnormal level of specific lipids, or fats, in the blood (Martinez-Hervas & Ascaso, 2019; McCance & Huether, 2019):
Hyperlipidemia is a condition characterized by high levels of lipids, or fats, in the blood. Hyperlipidemia indicates a high level of low-density lipoprotein (LDL) cholesterol and triglycerides. This high level of lipoproteins in the blood results in fat deposits in the heart, liver, and muscle.
Hypercholesterolemia is a specific sub-type of hyperlipidemia. With hypercholesterolemia, an individual has high LDL cholesterol or low high-density lipoprotein (HDL) cholesterol. Triglycerides levels are normal with hypercholesterolemia.
The prevalence of hyperlipidemia is a concern in the US. In the US alone, approximately 94 million people over the age of 20 have a total cholesterol level above 200 mg/dL, and about 28 million individuals have a total cholesterol level above 240 mg/dL. Of the patients who could benefit from cholesterol treatment, only 54.5% (47 million) of individuals are currently being treated. In the US, between 2015 and 2018, 17% of individuals over 20 had an HDL cholesterol level below 40 mg/dL. One in three adults has an elevated LDL blood level. Increased cholesterol levels do not just affect adults; 7% of children and adolescents ages 6-19 years have high total cholesterol levels in the US. Gender and ethnic or racial background affect the prevalence of high total cholesterol levels. Among men, Hispanics have the highest prevalence of total cholesterol over 240 mg/dL at 13%, followed by Non-Hispanic Asians at 11.3%, Non-Hispanic Whites at 10.9%, and Non-Hispanic Blacks at 10.6%. Among women, Non-Hispanic Whites have the highest prevalence of total cholesterol over 240 mg/dL at 14.8%, followed by Non-Hispanic Blacks and Non-Hispanic Asians at 10.3%, and Hispanics at 9.0%. For most individuals, hyperlipidemia is a silent disease without symptoms. Therefore, many do not know there is a problem until their cholesterol level is checked by a healthcare professional (HCP). Hyperlipidemia is a concern for HCPs since it raises an individual's risk for heart disease, the leading cause of death, and stroke, the fifth leading cause of death in the US (Centers for Disease Control and Prevention [CDC], 2021; Karr, 2017).
Cholesterol is a molecule that contributes to the formation of cell membranes and is a vital component in synthesizing vitamin D and steroid hormones, including estradiol, testosterone, aldosterone, and cortisol. Cholesterol is also
...purchase below to continue the course
High consumption of dietary saturated fats increases LDL levels in the blood and can lead to hypercholesterolemia. Since blood is primarily composed of water, fat and cholesterol must bind with lipoproteins to travel through the bloodstream. LDL cholesterol refers to lipoproteins high in cholesterol, and HDL cholesterol contains a smaller amount of cholesterol. HDL cholesterol is often referred to as "good" cholesterol since it helps remove other forms of cholesterol from the bloodstream and returns the excess to the liver, where it is broken down and excreted in the bile. LDL cholesterol is known as 'bad' cholesterol since it can build up along the walls of blood vessels, narrowing the vessel (see Figure 1 below). When there is more LDL cholesterol in the body than needed, excess cholesterol accumulates in the arteries, resulting in atherosclerosis, as depicted in Figure 2 below. If a clot forms, it can become stuck in the narrow vessel, leading to myocardial infarction or stroke (Marcel & Engelke, 2018b; McCance & Huether, 2019).
Guidelines recommend that HCPs utilize a risk calculator to determine a patient's 10-year risk for developing heart disease. One such calculator is the Atherosclerotic Cardiovascular Disease (ASCVD) Risk Estimator Plus, developed by the ACC. This calculator estimates a patient's 10-year ASCVD risk, determines the impact of various interventions on overall risk, reassesses ASCVD risk over time during follow-up visits, and provides the HCP with resources to facilitate discussions with patients regarding ASCVD risk and risk-lowering interventions. Data required to assess risk accurately include the patient's age, sex, race, systolic and diastolic blood pressure, total cholesterol, HDL cholesterol, and LDL cholesterol. The risk estimator also considers whether the patient has a diagnosis of diabetes, their smoking status, and medication therapy, including hypertension treatment, use of statins, and acetylsalicylic acid (aspirin). Many modifiable and non-modifiable factors increase a patient's risk of developing hyperlipidemia and subsequently ASCVD, heart attack, or stroke (ACC, n.d.).
Smoking and vaping damage the blood vessels and increase the risk of plaque buildup. It also reduces the amount of HDL cholesterol in the blood, effectively lowering the amount of cholesterol carried back to the liver to be flushed from the body. High levels of HDL cholesterol in the blood protect against heart disease. A smoker is 2 to 4 times more likely to develop heart disease than a nonsmoker. The risk is even greater if the individual has other risk factors or has been already diagnosed with hyperlipidemia as smoking and vaping compounds risk (CDC, 2020; National Heart, Lung, and Blood Institute [NHLBI], 2022; Nursing in Practice, 2016). Some of the benefits of smoking cessation occur quickly, while others occur over time (US Department of Health and Human Services [HHS], 2020):
Within 20 minutes of quitting, blood pressure and heart rate recover from the nicotine-induced spike.
Once a patient quits smoking, a rapid increase in HDL cholesterol concentrations occurs in less than three weeks.
Within three months of quitting, the blood circulation and lung function improve.
Within a year of quitting, the risk of heart disease is half that of a smoker.
After 10 years of smoking cessation, the risk of developing cardiovascular disease decreased by 33%.
This highlights that some, at least, of the adverse effects of smoking appear to be reversible upon quitting, emphasizing the need to encourage smokers to quit.
A patient with non-insulin-dependent diabetes mellitus (NIDDM) has an increased risk of developing hyperlipidemia. NIDDM lowers the amount of HDL cholesterol and raises LDL cholesterol levels in the blood. This combination elevates the risk of heart disease and stroke. Individuals with NIDDM are twice as likely to have heart disease or suffer a stroke than adults without NIDDM (CDC, 2020; National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK], 2021).
Obesity is linked to higher triglyceride and LDL cholesterol levels and lower HDL cholesterol levels. Obesity increases the risk of heart disease. A patient losing 5%-10% of their total body weight can positively affect blood cholesterol levels and decrease their hyperlipidemia and heart disease risk. Even for a patient with a healthy overall weight, excessive belly fat raises the risk of heart disease. Excessive belly fat is a waist measurement of over 40 inches for males and 35 inches for females (CDC, 2020).
Many other medical conditions can negatively affect cholesterol and increase a patient's risk of hyperlipidemia, heart disease, heart attack, and stroke, including:
chronic kidney disease
polycystic ovarian syndrome (PCOS)
lupus erythematosus (NHLBI, 2022)
There are also medications used to treat unrelated conditions that can raise LDL cholesterol or lower HDL cholesterol, including:
anti-arrhythmia drugs such as amiodarone (Pacerone)
beta-blockers such as sotalol (Betapace)
thiazide diuretics such as hydrochlorothiazide (HydroDiuril)
immunosuppressant drugs such as cyclosporine (Neoral)
retinoids such as tretinoin (Retin-A)
steroids such as prednisone (Deltasone; NHLBI, 2022)
Some patients may have a predisposition to hyperlipidemia due to family history. Familial hypercholesterolemia (FH) is a genetic disorder caused by a defect on chromosome 19. FH affects approximately 1 million people in the US. This disorder is autosomal dominant, meaning it only takes an abnormal gene from one parent for their child to be affected by the disease. The effects are much more severe when the affected gene is inherited from both parents, yielding homozygous familial hypercholesterolemia (HoFH). FH causes LDL cholesterol and total cholesterol to be extremely high; however, triglyceride levels are unaffected. Patients with untreated homozygous FH can have a total cholesterol and LDL level greater than 600 mg/dL. Patients with untreated heterozygous FH have an LDL level greater than 250 mg/dL. In patients younger than 20, an LDL level greater than 200 mg/dL is highly suggestive of heterozygous FH. The condition is present from birth and can lead to early-onset heart disease, with many affected individuals experiencing heart attacks at a young age (CDC, 2020; July, 2021; National Human Genome Research Institute [NHGRI], 2013). Symptoms of FH include:
tendonitis or arthralgias
cutaneous, planar, tuberous, and tendon xanthomas
a murmur of aortic stenosis (July, 2021; NHGRI, 2013)
Familial combined hyperlipidemia is an autosomal dominant disorder inherited by patients from their parents. Like FH, familial combined hyperlipidemia increases LDL cholesterol and total cholesterol levels and decreases HDL cholesterol; however, it also increases triglycerides. Familial combined hyperlipidemia affects 1% of the population. In the early years, patients may be asymptomatic; however, when symptoms appear, they mimic those seen with FH without xanthomas or xanthelasmas (Sweeney, 2021).
Often, a family history of hyperlipidemia is not related to genetics but lifestyle. Family members often share behaviors, lifestyle choices, and environments that can result in similar health concerns, including hyperlipidemia and heart disease. Ethnicity also plays a role in an individual's cholesterol levels. People of South Asian origin often have more harmful LDL cholesterol types and fewer protective HDL cholesterol types compared to people of European descent. People of South Asia descent may also have a worse LDL-to-HDL cholesterol ratio and triglyceride level that cannot be explained by changes in the typical daily diet (CDC, 2020; Nursing in Practice, 2016).
Age and Gender
Hyperlipidemia can affect patients of all ages; however, it is more common in individuals over 40 due to an age-related decline in liver function. As the liver becomes less efficient, higher LDL cholesterol levels are not effectively removed from the blood. This eventually leads to increased cholesterol levels, dyslipidemia, and an increased risk of heart disease, heart attack, and stroke. Until age 55 (or until menopause), women tend to have lower LDL cholesterol levels and higher HDL cholesterol levels than men due to the cardiovascular-protective effects of estrogen (CDC, 2020).
Living a sedentary lifestyle leads to decreased HDL cholesterol. When there is less HDL cholesterol in the blood, LDL cholesterol is less likely to be efficiently removed and returned to the liver. Not engaging in regular physical activity can also increase weight gain and lead to hyperlipidemia (Grundy et al., 2019). It is recommended that patients engage in the following amounts and types of physical activity to prevent hyperlipidemia (HHS, 2018):
Individuals should get at least 150 minutes of moderate aerobic activity, 75 minutes a week of vigorous aerobic activity, or a combination of moderate and vigorous activity. Moderate aerobic exercises include brisk walking, biking, swimming, and mowing. Vigorous aerobic exercise includes activities such as running, heavy yard work, and aerobic dancing.
Individuals are advised to complete strength training exercises for all major muscle groups at least twice weekly. Examples include lifting free weights, using weight machines or resistance bands, and rock climbing. The goal is to do a single set of exercises addressing each muscle group with enough weight or resistance to cause muscle fatigue after 12 to 15 repetitions.
Exercise should occur throughout the week. If the goal is to lose weight, moderate aerobic activity must be increased to 300 minutes or more a week to offset the caloric intake. All exercise programs and changes to physical activity levels should occur under the direction of an HCP to minimize the risk of injury or adverse effects, such as a heart attack.
Heart-healthy lifestyle changes include dietary changes to lower cholesterol foods. The top five most effective and well-studied diets to reduce cholesterol include the Mediterranean diet, the DASH diet, the Therapeutic Lifestyle Changes (TLC) diet, a vegetarian diet, and a vegan diet (Patino, 2021). For more information, see the NursingCE course Diets Decoded.
The TLC diet was created by the National Institute of Health's (NIH) National Cholesterol Education Program to reduce cholesterol through dietary modifications. The recommendations of this diet include eating healthier fats, limiting foods high in cholesterol, increasing fiber intake, limiting salt and alcohol intake, and increasing the intake of fruits, vegetables, and fish high in omega-3 fatty acids. If the only goal of starting the TLC diet is lowering LDL cholesterol, men are advised to limit their intake to 2,500 calories per day, and women are encouraged to limit their intake to 1,800 calories per day. If LDL cholesterol levels have not decreased after following the diet for six weeks, it is recommended that 2 grams of plant stanols and sterols and 10-25 grams of soluble fiber daily are added to the diet (US News & World Report, n.d.).
Some general dietary changes included in most heart-healthy diets include the following (US Department of Agriculture [USDA], 2020; Yu et al., 2018):
Reducing saturated fats can reduce blood levels of LDL cholesterol. Saturated fats raise LDL cholesterol levels more than any other dietary factor. Less than 25% to 35% of total daily calories consumed should come from dietary fats, with less than 7% from saturated fat. Saturated fats appear in most meats, dairy products, chocolate, baked goods, and deep-fried and processed foods. See Table 3 for the recommended maximum amount of fat per daily caloric intake.
Eliminate trans fats or partially hydrogenated vegetable oil, as it is commonly referred to on food labels, entirely from the diet. Trans fats can raise LDL cholesterol and lower HDL cholesterol in the blood. Trans fats are commonly found in foods made with hydrogenated oils and fats, including margarine, crackers, store-bought cookies and cakes, and french fries. The US Food and Drug Administration (FDA) had initially mandated that all food products be free of partially hydrogenated vegetable oils by 2021; however, a 1-year extension was granted, moving the deadline to 2022.
Limit the intake of cholesterol to under 200 mg per day. Foods high in cholesterol include organ meats, egg yolks, shrimp, and whole-milk dairy products.
Eating foods rich in omega-3 fatty acids has heart-healthy benefits. Although omega-3 fatty acids do not directly affect LDL cholesterol levels, they can increase HDL cholesterol levels. They also decrease blood pressure and reduce the risk of blood clots, inflammation, and heart attack. Omega-3 fatty acids are found in salmon, mackerel, herring, walnuts, and flaxseeds. According to several recommendations, fish should be incorporated into the diet at least twice weekly.
Increasing soluble fiber can reduce cholesterol absorption through the digestive tract into the bloodstream. Soluble fiber is found in oatmeal, kidney beans, lentils, chickpeas, black-eyed peas, lima beans, Brussels sprouts, apples, bananas, and oranges.
Adding whey protein as a dietary supplement lowers LDL cholesterol, total cholesterol, and blood pressure. Whey protein is found in dairy products and may account for the benefits of consuming dairy.
Only consume alcohol in moderation. Alcohol intake increases daily caloric totals and may lead to weight gain. Excessive alcohol intake can also increase blood pressure and triglyceride levels, elevating the risk of developing heart disease. Moderate alcohol intake can increase HDL cholesterol levels; however, the evidence is not strong enough to encourage anyone to incorporate alcohol into their diet that does not already do so. Women should limit alcohol intake to no more than a single alcoholic drink per day, and men should limit alcohol intake to no more than two alcoholic drinks per day. One drink is considered a 5 oz glass of wine, a 12 oz beer, or 1.5 oz of 40% distilled spirits.
Increasing the intake of fruits and vegetables can increase cholesterol-lowering compounds known as plant stanols or sterols, which are discussed later. Sterols and stanols decrease cholesterol levels by affecting absorption in the digestive tract like soluble fiber.
Stress has physiological effects, causing veins to rupture and serum cholesterol levels to rise. Stress is related to the production of higher levels of LDL cholesterol. Scandinavian researchers enrolled more than 40,000 workers in a study of workplace stress and cholesterol and found a direct link between persistently high-stress levels and greater production of LDL cholesterol. However, the participants' diets were not assessed, and only one marker was used for measuring stress levels. Other evidence points to the effects of chronic stress on cholesterol levels. Animals such as zebras have episodic periods of stress, which their systems can deal with; humans are more likely to suffer prolonged chronic periods of anxiety and stress, which leads to cell damage and cholesterol production. If three risk factors are present—smoking, high blood cholesterol, and a family history of heart disease—the risk of heart disease increases tenfold (Nursing in Practice, 2016).
Researchers have shown that both too much and too little sleep can negatively impact cholesterol levels. Sleep duration is closely associated with serum lipid and lipoprotein levels for both males and females. Other research studies confirm this finding and have shown that snoring is associated with lower HDL cholesterol. This could be due to other factors like obesity and stress, as it is difficult to separate all possible confounders. Another study suggested that shortened sleep makes people eat a diet higher in saturated fats and are less inclined to exercise. A lack of sleep also heightens stress and general anxiety levels, which also links to increased LDL cholesterol levels (Nursing in Practice, 2016).
When discussing cholesterol, HCPs need to take a lifespan approach. Due to the potentially dangerous effects of lifetime exposure to high cholesterol, particularly LDL, the 2018 Guideline on the Management of Blood Cholesterol indicates that HCPs should consider selective screenings of children as young as two with a family history of early heart disease, heart attack, stroke, or high cholesterol. For children without known risk factors, it is recommended that cholesterol be tested between the ages of 9 and 11 and then again between ages 17 and 21. This early testing can help HCPs identify and correct high cholesterol levels early through lifestyle modifications, thereby decreasing the long-term risks associated with hyperlipidemia (Davidson & Pulipati, 2021; Grundy et al., 2019).
The AHA recommends that all adults ages 20-45 have their cholesterol checked every 4-6 years if they are considered low risk. Recommending cholesterol monitoring of younger patients prompts HCPs to consider cholesterol screening and cardiovascular health more often for young adults. Young adults with risk factors for hyperlipidemia may often already show the first stages of atherosclerosis. After age 40, the HCP should use a risk assessment tool, as described below, to calculate the 10-year risk of having a heart attack or stroke. Men ages 45-65 and women ages 55-65 should have their cholesterol checked every 1-2 years, depending on risk level. After age 65, all patients should have their cholesterol checked annually (Davidson & Pulipati, 2021; Grundy et al., 2019; NHLBI, 2022).
A lipid panel or lipid profile is a laboratory test used to measure the amount of cholesterol and triglycerides in a patient's blood. The patient should fast and not eat or drink anything but water for 9 to 12 hours before laboratory collection for this type of testing. A complete lipid profile measures the levels of different fats in the blood, including total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides. The reference ranges for components of a lipid profile test according to age and sex are outlined in Table 1 (Corbett & Banks, 2019).
The AHA and American College of Cardiology (ACC) recommend that HCPs focus on reducing LDL levels from the patient's baseline and then progressively decreasing total LDL into the targeted range. Table 2 below outlines the risk categories for each type of cholesterol and triglycerides (ACC, n.d.; Grundy et al., 2019).
Lipoprotein-a or Lp(a) can also gauge a patient's risk of developing cardiovascular disease. This test is not included in the standard lipid profile and must be ordered separately by the HCP. An individual's Lp(a) level ishereditary and determined mainly by genetic history. Lp(a) is often completed for patients with a family history of early heart disease, heart attack, or stroke or who are unsure about their family history. High levels of Lp(a) indicate that the patient is at an increased risk of developing cardiovascular disease despite cholesterol results that are within the normal ranges. If the results are elevated, initiation of a statin is indicated to prevent cardiovascular disease (NHLBI, 2022).
The AHA guidelines have included using coronary artery calcium (CAC) measurement when the risk of ASCVD is uncertain in patients ages 40-75. CAC involves using a CT scan to take cross-sectional images of the blood vessels surrounding the heart. These images show whether calcified plaque buildup is present. Measurements of plaque buildup can help HCPs determine which patients are most at risk for heart disease before symptoms appear. The test results yield a risk score called the Agatston score, which indicates the total area of calcium located within the vessels and measures the density of the calcium deposits. When calcium is present, the higher the Agatston score, the higher the patient's risk for developing heart disease. A score of zero indicates that no calcium is present in the heart vessels. A score of 1-99 suggests calcium is beginning to accumulate in the blood vessels. A score of 100-300 indicates moderate plaque deposits are present, and the patient is at a relatively high risk of heart attack or heart disease over the next 3-5 years. For these patients, medication intervention is indicated. A score greater than 300 indicates severe heart disease and a high risk of a heart attack. CAC testing should not be used on everyone but is recommended for patients with a risk score in the intermediate range (Grundy et al., 2019; Gupta et al., 2022).
AHA Management Guidelines
Cholesterol management is viewed as a shared endeavor between patients and their HCP. HCPs should ensure patients understand the implications of hyperlipidemia and the healthcare plan specific to them. The main goal of cholesterol-lowering treatment and lifestyle modifications is to lower the LDL level enough to reduce the risk of developing heart disease or having a heart attack. The following ten recommendations appear in the 2018 ACC/AHA Guideline on the Management of Blood Cholesterol (Grundy et al., 2019):
For all individuals, emphasize a heart-healthy lifestyle across the lifespan. A healthy lifestyle reduces ASCVD risk at all ages. For younger individuals, a healthy lifestyle can reduce the development of risk factors and is the foundation of ASCVD risk reduction. For young adults 20 to 39 years of age, an assessment of lifetime risk facilitates the clinician-patient risk discussion (see point 6 below) and emphasizes intensive lifestyle efforts. Across all age groups, lifestyle therapy is the primary intervention for metabolic syndrome.
For patients with clinical ASCVD, reduce LDL cholesterol with high-intensity statin therapy or maximally tolerated statin therapy. The more LDL cholesterol is reduced on statin therapy, the more significant the subsequent risk reduction will be. Use a maximally tolerated statin to lower LDL cholesterol levels by ≥50%.
In very high-risk ASCVD, use an LDL threshold of 70 mg/dL (1.8 mmol/L) to consider the addition of non-statins to statin therapy. Very high risk includes a history of multiple major ASCVD events or a major ASCVD event and multiple high-risk conditions. For very high-risk ASCVD patients, adding ezetimibe (Zetia) to maximally tolerated statin therapy is reasonable when the LDL level remains ≥70 mg/dL (≥1.8 mmol/L). For patients at very high risk whose LDL level remains ≥70 mg/dL (≥1.8 mmol/L) on a maximally tolerated statin and ezetimibe (Zetia) therapy, adding a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor is reasonable. However, this step's long-term safety (>3 years) is uncertain, and cost-effectiveness is low.
For patients with severe primary hypercholesterolemia (LDL level ≥190 mg/dL [≥4.9 mmol/L]), without calculating 10-year ASCVD risk, begin high-intensity statin therapy. Adding ezetimibe (Zetia) is reasonable if the LDL level remains ≥100 mg/dL (≥2.6 mmol/L). If the LDL level on a statin plus ezetimibe (Zetia) remains ≥100 mg/dL (≥2.6 mmol/L) and the patient has multiple factors that increase subsequent risk of ASCVD events, a PCSK9 inhibitor may be considered. However, the long-term safety (>3 years) and economic value are uncertain.
For patients 40 to 75 years of age with diabetes mellitus and LDL ≥70 mg/dL (≥1.8 mmol/L), start moderate-intensity statin therapy without calculating the 10-year ASCVD risk. For patients with diabetes mellitus at higher risk, especially those with multiple risk factors or those 50 to 75 years of age, it is reasonable to use a high-intensity statin to reduce the LDL level by ≥50%.
For adults, 40 to 75 years of age, evaluated for primary ASCVD prevention, have a clinician-patient risk discussion before starting statin therapy. The risk discussion should include a review of significant risk factors (e.g., cigarette smoking, elevated blood pressure, LDL cholesterol level, hemoglobin A1C if indicated, and calculated 10-year risk of ASCVD), the presence of risk-enhancing factors (see No. 8) the potential benefits of lifestyle and statin therapies, the potential for adverse effects and drug-drug interactions, consideration of costs of statin therapy, and patient preferences and values in shared decision-making.
For adults, 40 to 75 years of age without diabetes mellitus and with LDL levels ≥70 mg/dL (≥1.8 mmol/L) at a 10-year ASCVD risk of ≥7.5%, start a moderate-intensity statin if a discussion of treatment options suggests statin therapy. Risk-enhancing factors favor statin therapy (see point 8). If the risk status is uncertain, consider using CAC to improve specificity (see point 9). If statins are indicated, reduce LDL levels by ≥30%; if the 10-year risk is ≥20%, lower LDL levels by ≥50%.
For adults ages 40 to 75 years without diabetes mellitus and a 10-year risk of 7.5% to 19.9% (intermediate risk), risk-enhancing factors favor the initiation of statin therapy (see point 7). Risk-enhancing factors include a family history of premature ASCVD; persistently elevated LDL levels ≥160 mg/dL (≥4.1 mmol/L); metabolic syndrome; chronic kidney disease; history of preeclampsia or early menopause (age <40 years); chronic inflammatory disorders (e.g., rheumatoid arthritis, psoriasis, or chronic HIV); high-risk ethnicity (e.g., South Asian); persistent elevations of triglycerides ≥175 mg/dL (≥1.97 mmol/L); and, if measured in selected individuals, apolipoprotein B ≥130 mg/dL, high-sensitivity C-reactive protein ≥2.0 mg/L, ankle-brachial index <0.9, and lipoprotein (a) ≥50 mg/dL or 125 nmol/L, especially at higher values of lipoprotein (a). Risk-enhancing factors may favor statin therapy for patients at a 10-year risk of 5-7.5% (borderline risk).
For adults 40 to 75 years old without diabetes mellitus, with LDL levels ≥70 mg/dL to 189 mg/dL (≥1.8-4.9 mmol/L), and a 10-year ASCVD risk of ≥7.5% to 19.9%, consider measuring CAC if a decision about statin therapy is uncertain. If CAC is zero, treatment with statin therapy may be withheld or delayed, except for cigarette smokers, those with diabetes mellitus, and those with a strong family history of premature ASCVD. A CAC score of 1 to 99 favors statin therapy, especially in those ≥55 years of age. For any patient, if the CAC score is ≥100 Agatston units or ≥75th percentile, statin therapy is indicated unless otherwise deferred by the outcome of clinician-patient risk discussion.
Assess adherence and percentage response to LDL-lowering medications and lifestyle changes with repeat lipid measurement 4 to 12 weeks after statin initiation or dose adjustment, repeated every 3 to 12 months as needed. Define lifestyle and statin therapy responses by percentage reductions in LDL levels compared to baseline. For ASCVD patients at very high risk, triggers for adding nonstatin drug therapy are defined by threshold LDL levels ≥70 mg/dL (≥1.8 mmol/L) on maximal statin therapy (see point 3 above).
The present guidelines continue to emphasize the importance of a clinician-patient risk discussion. For those with a 10-year ASCVD risk of ≥7.5%, it is recommended that discussion occur before a statin prescription is written. As suggested in the ACC/AHA cholesterol guidelines, this frank discussion should consider whether ASCVD risk factors have been addressed, evaluate whether an optimal lifestyle has been implemented, and review the potential for statin benefit versus the potential for adverse outcomes effects and drug-drug interactions. Then, based on individual characteristics and including an informed patient preference in shared decision-making, a risk decision about treatment can be made (Grundy et al., 2019).
LDL Cholesterol-Lowering Treatment
Statins inhibit cholesterol synthesis in the liver by blocking the protein HMG-CoA reductase from making cholesterol. As a result, liver cells try to compensate for low cholesterol by synthesizing more LDL receptors on the cell surface to increase LDL uptake from the blood. Statins are the most common pharmacologic treatment used to treat hyperlipidemia in people 10 years old or older. In very high-risk situations, a statin may be used for patients younger than 10 years old (Karr, 2017; NHLBI, 2022).
Examples of statins include atorvastatin (Lipitor), fluvastatin (Lescol and Lescol XL), lovastatin (Altoprev), pitavastatin (Livalo), pravastatin (Pravachol), rosuvastatin (Crestor), and simvastatin (Zocor). Statins may increase the risk of diabetes for patients who have already been diagnosed with prediabetes, are overweight, or suffer from metabolic syndrome. Statins may also cause abnormal results on liver enzyme tests; however, actual liver damage is rare. Other adverse effects include myopathy (muscle damage) and hepatotoxicity. Statins are contraindicated in patients with a history of chronic liver disease or cirrhosis and pregnant patients (Burchum & Rosenthal, 2019; Karr, 2017; NHLBI, 2022).
The AHA divides statin therapy into three categories: high-intensity, moderate-intensity, and low-intensity. High-intensity statins lower LDL cholesterol levels by more than 50%, moderate-intensity statins reduce LDL cholesterol levels by 30%-49%, and low-intensity statins lower LDL cholesterol levels by less than 30%. High-intensity statins include atorvastatin (Lipitor) and rosuvastatin (Crestor). Moderate-intensity statins include simvastatin (Zocor), pravastatin (Pravachol), lovastatin (Altoprev), fluvastatin XL (Lescol XL), and pitavastatin (Livalo). Low-intensity statins include low doses of simvastatin (Zocor), pravastatin (Pravachol), and fluvastatin (Lescol; Grundy et al., 2019).
Ezetimibe (Zetia) is a unique drug used to reduce cholesterol. Like statins, ezetimibe (Zetia) should not be used for patients under the age of 10. Ezetimibe (Zetia) acts on the small intestine cells to inhibit the absorption of dietary cholesterol. It does not inhibit cholesterol synthesis in the liver or increase bile acid excretion. Ezetimibe (Zetia) can be used alone or in combination with a statin. It is used to treat familial hypercholesterolemia when treatment with a statin is ineffective. Adverse effects include myopathy, rhabdomyolysis, hepatitis, pancreatitis, and thrombocytopenia (Burchum & Rosenthal, 2019).
Bile-acid sequestrants reduce LDL cholesterol and were the first-line treatment for hyperlipidemia in the past. Currently, they are used for patients who do not tolerate statins or whose cholesterol levels are not responding to statin therapy alone. Bile-acid sequestrants lower LDL cholesterol by increasing LDL receptors on hepatocytes. Once administered, these agents bind with bile acids in the intestines and form an insoluble complex, preventing the bile acids' reabsorption. This accelerated excretion of bile acids creates a demand for increased synthesis of LDL cholesterol by the liver, which prompts liver cells to increase their capacity for LDL uptake. Examples of bile-acid sequestrants include cholestyramine (Questran, Prevalite), colesevelam (Welchol), and colestipol (Colestid). Adverse effects are limited to the digestive system since bile-acid sequestrants cannot be absorbed and include constipation, bloating, indigestion, and nausea (Burchum & Rosenthal, 2019; Karr, 2017).
Bempedoic Acid (Nexletol)
Bempedoic acid (Nexletol) is a newer drug that works similarly to statins, except instead of inhibiting HMG CoA reductase, bempedoic acid (Nexletol) inhibits ATP-citrate lyase (ACL). It is less likely to cause myopathy since it is converted to its active form in the liver and not in the muscles. When combined with a statin, it can reduce LDL cholesterol significantly. Adverse effects of bempedoic acid (Nexletol) include hyperuricemia, tendon rupture, respiratory tract infection, back pain, abdominal pain, anemia, and elevated liver enzymes (Tibuakuu et al., 2020).
PCSK9 inhibitors lower LDL cholesterol by decreasing the destruction of LDL receptors in the liver, which helps remove and clear LDL cholesterol from the blood. They are administered subcutaneously every 2-4 weeks. PCSK9 inhibitors are often used in conjunction with a statin for patients at a high risk of heart attack and stroke or those with familial hypercholesterolemia. Examples include evolocumab (Repatha) and alirocumab (Praluent). Localized side effects include itching, pain, and inflammation at the injection site (Karr, 2017; NHLBI, 2022).
Fibric Acid Derivatives (Fibrates)
Fibrates are the most effective drugs available for lowering triglyceride levels. In addition to lowering triglyceride levels, fibrates can also increase HDL cholesterol levels. Fibrates have little to no effect on LDL cholesterol. Fibrates work by reducing the very-low-density lipoproteins (VLDLs) produced by the liver. They also increase the removal of triglycerides from the blood. Examples of fibrates include gemfibrozil (Lopid), fenofibrate (Tricor), and fenofibric acid (Trilipix). Adverse effects include rash, nausea, abdominal pain, and diarrhea. Gallstones, myopathy, and liver injury have also been reported (Burchum & Rosenthal, 2019; Karr, 2017).
Nicotinic Acid (Niacin)
Nicotinic acid (Niacin) decreases LDL cholesterol and triglycerides and raises HDL cholesterol. The primary action of nicotinic acid (Niacin) is to reduce the production of VLDLs. LDL cholesterol is a byproduct of VLDL degradation; therefore, reducing VLDL causes a decrease in LDL cholesterol. The primary mechanism by which nicotinic acid (Niacin) reduces VLDL is by inhibiting lipolysis in adipose tissue. Although nicotinic acid (Niacin) is effective, it causes various undesirable side effects, including intense flushing, nausea, vomiting, and diarrhea. Intense flushing of the face, neck, and ears affects most patients who take the medication and can be uncomfortable (Burchum & Rosenthal, 2019; Karr, 2017).
Omega-3 Fatty Acids
Icosapent ethyl (Vascepa) is used as an adjunct therapy with statins to reduce the risk of myocardial infarction, stroke, and unstable angina in patients with hyperlipidemia. Icosapent ethyl (Vascepa) is also indicated as an adjunct to dietary measures to reduce triglyceride levels in patients with severe hypertriglyceridemia (triglyceride level >500 mg/dL). Adverse effects include peripheral edema, myalgia, constipation, gout, and atrial fibrillation (Amarin, 2022).
Familial Hypercholesterolemia Treatment
Some patients with familial hypercholesterolemia may benefit from lipoprotein apheresis to lower their blood cholesterol levels. Lipoprotein apheresis is a dialysis-like process in which a filtering machine removes LDL cholesterol from the blood, and the remainder of the blood is returned to the patient (NHLBI, 2022).
Lomitapide (Juxtapid) is a microsomal triglyceride transfer protein inhibitor used with dietary modifications to reduce the amount of LDL cholesterol and total cholesterol in patients with HoFH. It works by inhibiting the microsomal triglyceride transfer protein (MTTP), which is necessary for VLDL assembly and excretion in the liver. Adverse effects include diarrhea, nausea, vomiting, constipation, bloating, and weight loss. Lomitapide (Juxtapid) may cause severe hepatoxicity. Due to this, patients should be advised not to drink alcohol while taking lomitapide (Juxtapid). Due to the severity of hepatotoxicity, the FDA approved a program called Juxtapid REMS. All prescriptions for lomitapide (Juxtapid) must be written by a registered HCP with the Juxtapid REMS program and filled at an approved pharmacy (Karr, 2017).
Herbs and Supplements
Stanols and Sterols
Incorporating foods and dietary supplements containing added plant stanols or sterols is an option in conventional treatment for high cholesterol levels. The evidence for the effectiveness of the supplements is less extensive than the evidence for foods containing stanols or sterols. Still, studies show that stanol or sterol supplements taken with meals can reduce cholesterol levels. Some foods and dietary supplements that contain stanols or sterols are permitted to carry a health claim, approved by the FDA, stating that they may reduce the risk of heart disease when consumed in recommended doses. Examples of plant stanols and sterols include certain vegetable oils (e.g., canola oil), nuts (e.g., walnuts), certain fruits, most beans, and vegetables. They are also found in cholesterol-lowering types of margarine, which are commonly advertised as "buttery spreads" (Burchum & Rosenthal, 2019; National Center for Complementary and Integrative Health [NCCIH], 2019).
Flaxseed supplements, including whole flaxseeds and flaxseed lignans, but not flaxseed oil, have been shown to lower cholesterol levels. A 2015 randomized control study with 110 participants found that milled flaxseed lowered total cholesterol and LDL cholesterol in patients with significant cardiovascular disease. Flaxseed and supplements are well tolerated and confer minimal side effects when used in small amounts. Since flaxseed is a fiber supplement, it should be taken with a full glass of water to prevent constipation (NCCIH, 2019).
A 2016 meta-analysis and review of 39 randomized controlled trials found that 10% of patients who took garlic supplements for more than two months saw a reduction in total cholesterol and LDL cholesterol. Garlic is safe with minimal adverse effects, including breath and body odor, pyrosis (heartburn), and dyspepsia (upset stomach; NCCIH, 2019).
Red Yeast Rice
Some red yeast rice contains a substantial amount of monacolin K, which is chemically identical to lovastatin (Altoprev). Consequently, these types of red yeast rice can have the same LDL cholesterol-lowering effects; however, it also has the same adverse effects and drug interactions as lovastatin (Altoprev). The FDA has determined that red yeast rice containing more than a trace amount of monacolin K is unapproved and cannot legally be sold as a dietary supplement. Red yeast rice may also be contaminated with citrinin, which can cause kidney disease (NCCIH, 2019).
Oats and Oat Bran
Consistent long-term dietary intake of oats or oat bran can decrease cholesterol levels. A 2014 systematic review showed that oat consumption could reduce the risk of cardiovascular disease and lower serum cholesterol levels. This was especially true for individuals with hypercholesterolemia. These findings were consistent with the results of a 1992 meta-analysis. Oats are well tolerated but may have the side effects of intestinal gas and bloating (NCCIH, 2019).
Amarin. (2022). Vascepa. https://vascepahcp.com/
American College of Cardiology. (n.d.). ASCVD risk estimator plus. Retrieved May 3, 2022, from https://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/calculate/estimate
Burchum, J., & Rosenthal, L. (2019). Lehne’s pharmacology for nursing care (10th ed). Elsevier.
CCCOnline. (n.d.). Progression of atherosclerosis [Image]. Retrieved May 3, 2022, from https://pressbooks.ccconline.org/bio106/chapter/cardiovascular-homeostasis/
Centers for Disease Control and Prevention. (2020). Knowing your risk for high cholesterol. https://www.cdc.gov/cholesterol/risk_factors.htm
Centers for Disease Control and Prevention. (2021). High cholesterol facts. US Department of Health and Human Services. https://www.cdc.gov/cholesterol/facts.htm
Corbett, J. V., & Banks, A. D. (2019). Laboratory tests and diagnostic procedures with nursing diagnoses (9th ed.). Pearson.
Davidson, M. H., & Pulipati, V. P. (2021). Overview of lipid metabolism. In Merck Manual Professional Version. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/lipid-disorders/overview-of-lipid-metabolism
Grundy, S. M., Stone, N. J., Bailey, A. L., Beam, C., Birtcher, K. K., Blumenthal, R. S., Braun, L. T., de Ferranti, S., Faiella-Tommasino, J., Forman, D. E., Goldberg, R., Heidenreich, P. A., Hlatky, M. A., Jones, D. W., Lloyd-Jones, D., Lopez-Pajares, N., Ndumele, C. E., Orringer, C. E., Peralta., C. E., … Yeboah, J. (2019). 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: A report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation, 139, e1082-e1143. https://doi.org/10.1161/CIR.0000000000000625
Gupta, A., Bera, K., Kikano, E., Pierce, J. D., Gan, J., Rajdev, M., Ciancibello, L. M., Gupta, A., Rajagopalan, S., Gilkeson, R. C. (2022). Coronary artery calcium scoring: Current status and future directions. RadioGraphics. Advance online publication. https://doi.org/10.1148/rg.210122
July, M. (2021). Familial hypercholesterolemia. https://emedicine.medscape.com/article/121298-overview
Karr, S. (2017). Epidemiology and management of hyperlipidemia. The American Journal of Managed Care, 23(9), S139-S148. https://www.ajmc.com/view/epidemiology-and-management-of-hyperlipidemia-article
Le Van Thao. (2012). Cholesterol [Image]. https://www.flickr.com/photos/thaotyphucom/7123261417
Marcel, C., & Engelke, Z. (2018a). Cholesterol. Nursing Reference Center. https://research.ebscomedical.com/eds/detail?db=nup&an=T706835
Marcel, C., Engelke, Z. (2018b). Dietary saturated fat and cholesterol: Risk for coronary artery disease. Nursing Reference Center. https://research.ebscomedical.com/eds/detail?db=nup&an=T706607
Martinez-Hervas, S., & Ascaso, J. F. (2019). Hypercholesterolemia. In I. Huhtaniemi & L. Martini (Eds.), Encyclopedia of endocrine diseases (2nd ed., Vol. 1, pp. 320-326). Elsevier. https://doi.org/10.1016/B978-0-12-801238-3.65340-0
Mayo Clinic Laboratories. (2022). Test definition: LPSC. https://www.mayocliniclabs.com/api/sitecore/TestCatalog/DownloadTestCatalog?testId=8053
McCance, K. L., & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in adults and children (8th ed.). Elsevier.
MedlinePlus. (2021). How to lower cholesterol with diet. https://medlineplus.gov/howtolowercholesterolwithdiet.html
National Center for Complementary and Integrative Health. (2019). High cholesterol and natural products: what the science says. https://www.nccih.nih.gov/health/providers/digest/high-cholesterol-and-natural-products-science
National Heart, Lung, and Blood Institute. (2022). Blood cholesterol diagnosis. National Institutes of Health. https://www.nhlbi.nih.gov/health/blood-cholesterol/diagnosis
National Human Genome Research Institute. (2013). About familial hypercholesterolemia. https://www.genome.gov/Genetic-Disorders/Familial-Hypercholesterolemia
National Institute of Diabetes and Digestive and Kidney Diseases. (2021). Diabetes, heart disease, and stroke. https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/heart-disease-stroke
Nursing in Practice (2016). Cholesterol-lowering. https://www.nursinginpractice.com/cpd/cholesterol-lowering/
Patino, E. (2021). 5 diets that can help lower cholesterol. https://www.everydayhealth.com/heart-health/special-diets-that-help-lower-cholesterol/
Sweeney, M. E. (2021). What is familial combined hyperlipidemia? https://www.medscape.com/answers/126568-15809/what-is-familial-combined-hyperlipidemia
Tibuakuu, M., Blumenthal, R. S., & Martin, S. S. (2020). Bempedoic acid for LEL-C lowering: What do we know. https://www.acc.org/latest-in-cardiology/articles/2020/08/10/08/21/bempedoic-acid-for-ldl-c-lowering
US Department of Agriculture. (2020). Dietary guidelines for Americans, 2020-2025 (9th ed.). https://www.dietaryguidelines.gov/sites/default/files/2021-03/Dietary_Guidelines_for_Americans-2020-2025.pdf
US Department of Health and Human Services. (2018). Physical activity guidelines for Americans (2nd ed.). https://health.gov/sites/default/files/2019-09/Physical_Activity_Guidelines_2nd_edition.pdf
US Department of Health and Human Services. (2020). Smoking cessation: A report of the surgeon general. https://www.ncbi.nlm.nih.gov/books/NBK555591/
US News & World Report. (n.d.). TLC diet. Retrieved May 6, 2022, from https://health.usnews.com/best-diet/tlc-diet
Yu, E., Malik, V. S., & Hu, F. B. (2018). Cardiovascular disease prevention by diet modification: JACC health promotion series. Journal of the American College of Cardiology, 72(8), 914-926. https://doi.org/10.1016/j.jacc.2018.02.085