- An elevated level of cholesterol carried by circulating apolipoprotein (apo) B containing lipoproteins (non-high-density lipoprotein cholesterol [non-HDL-C] and low-density lipoprotein cholesterol [LDL-C], termed atherogenic cholesterol) is a root cause of atherosclerosis, the key underlying process contributing to most clinical atherosclerotic cardiovascular disease (ASCVD) events.
- Reducing elevated levels of atherogenic cholesterol will lower ASCVD risk in proportion to the extent that atherogenic cholesterol is reduced.
- The intensity of risk-reduction therapy should generally be adjusted to the patient’s absolute risk for an ASCVD event (see Table 1).
- Atherosclerosis is a process that often begins early in life and progresses for decades before resulting in a clinical ASCVD event. Therefore, both intermediate-term and long-term/lifetime risk should be considered when assessing the potential benefits and hazards of risk-reduction therapies.
- For patients in whom lipid-lowering drug therapy is indicated, statin treatment is the primary modality for reducing ASCVD risk.
- Treatment goals and periodic monitoring of atherogenic cholesterol levels (non-HDLC and LDL-C) are important tools in the implementation of a successful treatment strategy. These aid the clinician in assessing the adequacy of treatment and facilitate active participation by the patient through feedback and reinforcement of the beneficial effects of lifestyle and pharmaceutical therapies.
- Non-lipid ASCVD risk factors should also be managed appropriately, particularly high blood pressure, cigarette smoking, and diabetes mellitus.
- NLA Dyslipidemia – Part II represents a continuation of NLA Dyslipidemia – Part I a providing patient-centered, evidence-graded recommendations for the management of specific aspects of dyslipidemia.
a Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 1. Lipid 2014; 8:473–88.
Table 1. Criteria for ASCVD Risk Assessment, Treatment Goals for Atherogenic Cholesterol, and Levels at Which to Consider Drug Therapy
|Qualityb||Type of Evidence|
a This was the system used in the new American Heart Association/American College of Cardiology cholesterol guidelines that were published in the 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults Report from the Panel members appointed to the Eighth Joint National Committee. Permission to reuse table granted by the American Medical Association.
b The evidence quality rating system used in this guideline was developed by the National Heart, Lung and Blood Institutes (NHLBI's) Evidence-Based Methodology Lead (with Input from NHLBI staff, external methodology team, and guideline panels and work groups) for use by all the NHLBI cardiovascular disease guideline panels and work groups during this project. As a result, it includes the evidence quality rating for many types of studies, including studies that were not used in this guideline. Additional details regarding the evidence quality rating system are available in the online Supplement.
|Gradec||Strength of Recommendation|
There is high certainty based on the evidence that the net benefitd is substantial.
There is moderate certainty based on the evidence that the net benefit is moderate to substantial, or there is high certainty that the net benefit is moderate.
There is at least moderate certainty based on the evidence that there is a small net benefit.
There is at least moderate certainty based on the evidence that it has no net benefit or that the risks/harms outweigh benefits.
There is insufficient evidence or evidence is unclear or conflicting, but this is what the expert panel recommends.
|N||No recommendation for or against|
c The system was adapted as a hybrid of the National Heart Lung and Blood Institute’s (NHLBI) rating system (NHLBI cardiovascular-based methodology) used in the new American Heart Association/American College of Cardiology cholesterol guidelines and adapted from the original GRADE system of evidence rating.
d Net benefit is defined as benefits minus risks/harms of the service/intervention.
Chart 1. Nutritional Recommendations
|The NLA Expert Panel supports a cardioprotective eating pattern for the management of dyslipidemia and overall cardiovascular health that includes <7% of energy from saturated fat, with minimal intake of trans fatty acids to lower levels of atherogenic cholesterol (LDL-C and non- HDL-C).||A||Moderate|
|The cardioprotective eating pattern should limit cholesterol intake to <200 mg per day to lower levels of atherogenic cholesterol (LDL-C and non-HDL-C).||B||Moderate|
|There are individuals who are hyper-responders to dietary cholesterol because of genetic or other reasons. For known or suspected hyper-responders, further reduction in dietary cholesterol beyond the <200 mg/day that is recommended as part of the cardioprotective eating pattern for the management of dyslipidemia may be considered. Consumption of very low intakes of dietary cholesterol (near 0 mg/day) may be helpful for such individuals.||B||Low|
The NLA Expert Panel recommends any of the following healthy dietary patterns, including an emphasis on a variety of plant foods and lean sources of protein for managing dyslipidemia: DASH, USDA (healthy U.S.-style), AHA, Mediterranean-style, and vegetarian/vegan. However, the dietary pattern should be individualized based on the patient’s specific dyslipidemia. Also, patients’ cultural and food preferences are important for guiding food selection to maximize dietary adherence. Nutritional counseling and follow-up/monitoring by a registered dietitian nutritionist is recommended whenever possible to individualize a patient’s dietary pattern. Nutrition therapy should be included in those with other medical conditions, including diabetes.
|If alcohol is consumed as part of a healthy dietary pattern, this should be in moderation (≤7 drinks per week for women and ≤14 drinks per week for men, consumed in a non-binge pattern). One drink is equivalent to 12 oz. beer, 5 oz. wine, or 1.5 oz. distilled spirits.||A||Moderate|
|Dietary saturated fat may be partially replaced with unsaturated fats (mono- and polyunsaturated fats), as well as proteins, to reach a goal of <7% of energy from saturated fats. This can be achieved, in part, by incorporating foods high in unsaturated fats, such as liquid vegetable oils and vegetable oil spreads, nuts and seeds, as well as lean protein foods, such as legumes, seafood, lean meats, and non- or low-fat dairy products, into the diet as replacements for foods high in saturated fats.||A||Moderate|
Weight loss of 5-10% body weight is generally recommended for overweight or obese individuals to lower atherogenic lipoprotein lipids and improve other ASCVD risk factors. A variety of dietary approaches can be implemented for weight loss. Any dietary approach will result in weight loss if energy intake is reduced. An energy-reduced healthy dietary pattern that meets nutrient needs is recommended for patients who are overweight or obese. Several healthy dietary patterns, such as the Mediterranean- style, DASH, USDA, and vegetarian diets, can be tailored to personal and cultural food preferences and appropriate calorie needs for weight control.
|Eating patterns that contain a moderate quantity of carbohydrate, lower glycemic index and load, and higher protein, have been associated with modest benefits for weight loss and maintenance.||Low|
|Plant sterols and stanols (~2 g/day) are recommended for cholesterol lowering, as well as viscous fibers (5–10 g/day or even greater, if acceptable to the patient), as adjuncts to other lifestyle changes. However, individuals with phytosterolemia (sitosterolemia) should avoid foods that are fortified with stanols and sterols.||B||Moderate|
|For patients with TG levels ≥150 mg/dL, lifestyle therapy is indicated, including weight loss if overweight or obese, physical activity, and restriction of alcohol, sugars and refined starches. Partial replacement of sugars and refined starches with a combination of unsaturated fats, proteins, and high-fiber foods may help to reduce TG and non-HDL- C concentrations.||A||Moderate|
|For patients with TG levels ≥1000 mg/dL (and selected patients with TG 500–999 mg/dL), a low-fat diet (<15% of energy) and alcohol abstinence are recommended initially to minimize chylomicronemia. In patients with hypertriglyceridemia and diabetes, dietary carbohydrate should not be substantially increased to avoid worsening glycemia when reducing fat intake. Medium chain TG oil may be used as a source of energy that will not induce chylomicron production. For patients without lipoprotein lipase deficiency, dietary fat may be liberalized with monitoring of the TG response once the TG concentration is <500 mg/dL.||B||Moderate|
|Therapeutic dosages of EPA + DHA for TG reduction are 2.0–4.0 g/day. Use of these dosages of long-chain omega-3 fatty acids for TG-lowering should be done only under the supervision of a qualified clinician. Clinicians are encouraged to educate patients on the importance of the amount of EPA + DHA in each capsule of dietary supplement or prescription products, and to take the appropriate number of capsules daily to achieve therapeutic levels. At present, prescription forms of EPA and EPA + DHA concentrates are indicated only for treatment of very high TG (≥500 mg/dL) to reduce the risk of pancreatitis.||B||Moderate|
|For primary and secondary prevention of ASCVD, consuming ≥2 servings/week of fish/seafood (preferably oily) is recommended. One serving is equal to 3.5–4 oz. and should ideally not be prepared using deep-frying.||A||Moderate|
|For patients with known ASCVD, suggestive, but not conclusive, evidence from RCTs is available for a benefit of long-chain omega-3 fatty acid supplementation at ~1 g/day EPA + DHA on cardiac mortality, but not non-fatal ASCVD events. EPA + DHA supplements may be considered for such patients, especially those who do not consume the recommended intakes of EPA + DHA from dietary sources.||Low|
For patients with heart failure, 1 g/day of EPA + DHA is recommended as an adjunct to heart failure therapy.
An alpha linonelic acid intake of 0.6–1.2% of energy is recommended.
|Consumption of at least three 1-oz. equivalent servings per day of fiber-rich whole grains is recommended.||A||Moderate|
|Consumption of ≥ 4 servings/week (1 oz. per serving) of nuts (including the legume, peanuts) is recommended, because nut consumption has been consistently associated with reduced ASCVD risk. Nuts may be included in the diet as a protein food and as a source of healthy fat (predominantly unsaturated fatty acids).||A||Moderate|
|Soy protein foods are one source of plant protein, among others (e.g., nuts, legumes), that may be used as a substitute for protein foods high in saturated fat as part of a cardioprotective eating pattern.||B||Moderate|
|Nutrition education/MNT by a registered dietitian nutritionist with follow-up and monitoring are recommended to promote long-term dietary adherence. Clinicians should, when feasible, refer patients to a registered dietitian nutritionist for MNT to individualize a cardioprotective dietary pattern and promote successful lifestyle modifications.||A||Moderate|
Table 3. Predicted Effects of Macronutrient Replacement of Dietary Saturated Fatty Acids with PUFA, MUFA, and Carbohydrate on Lipoprotein Lipids Based on Results from Controlled Feeding Trialsa
Chart 2. Exercise/Physical Activity Recommendations
|The recommended minimal quantity of exercise for supporting cardiovascular health and improving the lipid profile (lowering TG and sometimes raising HDL-C) is 150 min per week of moderate to higher intensity aerobic activity. This level of physical activity is consistent with public health recommendations.||A||High|
|To enhance the effects on TG and HDL-C, and produce reductions in LDL-C, as well as loss of body fat and weight, ≥2000 kcal per week of energy expenditure (generally 200 to 300 min per week) of moderate or higher intensity physical activity is recommended.||B||Moderate|
|Resistance exercise is also recommended to play a supportive role in maintaining strength, balance, and bone density.||B||Moderate|
Chart 3. Patient Adherence
|The provider should assess adherence to both lifestyle and atherogenic cholesterol-lowering medications at every patient encounter.||E||Low|
|A multidisciplinary health care team (such as the patient’s primary health care provider; nurses; nurse practitioners; pharmacists; physician assistants; registered dietitian nutritionists, including certified diabetes educators in some practices; exercise specialists; social workers; community health workers; and licensed professional counselors, psychologists, and health educators) is desirable to identify medication non-adherence and to facilitate strategies to improve adherence by helping patients overcome real (or perceived) barriers to adherence.||E||Low|
|The multi-faceted approach should be employed by clinicians to improve medication adherence, including:||E||Low|
Chart 4. Team-Based Collaborative Care
|Health care teams for optimal lipid and ASCVD risk management may include, where available: the patient; the patient’s primary health care provider; nurses; nurse practitioners; pharmacists; physician assistants; registered dietitian nutritionists, including certified diabetes educators in some practices; exercise specialists; social workers; community health workers; and licensed professional counselors, psychologists, and health educators.||A||High|
|Health care team members should coordinate care support among various team members, use evidence-based guidelines/recommendations for dyslipidemia management, establish a structured plan for monitoring patient progress, and provide patients with a variety of tools and resources to improve their own care.||A||High|
|Team-based collaborative care may be incorporated into the Patient Centered Medical Home as a strategy to address shortfalls in patient health care quality, access, continuity, and cost.||E||Low|
- Currently, TG is not a specific target for therapy except when levels are ≥500 mg/dL.
- When the TG concentration is ≥500 mg/dL, and especially if ≥1000 mg/dL, reducing risk of pancreatitis by lowering of TG to <500 mg/dL becomes the primary goal of therapy.
- Presently, prescription EPA and EPA + DHA concentrates, which have been approved in ethyl ester and carboxylic acid forms, are indicated for the treatment of very high TG (≥500 mg/dL).
- Fibrate drugs can reduce TG and non-HDL-C in patients with mixed dyslipidemia, and are considered a first-line choice for patients with severe hypertriglyceridemia (TG ≥500 mg/dL).
Table 4. Evaluation of Hypertriglyceridemia
Figure 1. Clinical Algorithm for Screening and Management of Elevated TG
a Adapted from Miller M, et al. Circulation. 2011;123:2292-2333.
b Special consideration for patients with initial TG ≥1000 mg/dL and chylomicronemia: recheck lipids in 2 weeks. When TG <500 mg/dL, diet may gradually be liberalized with monitoring.
c In addition to added sugars, some foods and beverages that are high in naturally occurring sugars, e.g., honey and fruit juices, should be limited.
Table 5. Nutrition Therapy for Very High TG (≥500 mg/dL)/Chylomicron Clearing
|Temporarily limit total fat to 10–15% calories (typically 20–40 g/day) during chylomicron clearing|
|Avoid refined starches and partially replace with high fiber, whole grain foods.|
|Avoid added sugars, limit fruit, no fruit juice or sugary beverages.|
|Spread calories and carbohydrates evenly through the day.|
|Limit calories if weight loss is indicated.|
|If extra calories are needed, add medium chain triglyceride oil and increase gradually.|
|Exercise 30–60 min most days.|
|Adjust diabetes medications as appropriate to maintain glycemic control.|
|Once chylomicron particles have been cleared and triglycerides are <500 mg/dL, gradually advance dietary fat to tolerance.|