2025 AACE共识声明：成人血脂异常的管理流程（更新版）

共识心血管内科· 血脂管理 · 2025

Introduction

Management of dyslipidemia is key to reducing atherosclerotic cardiovascular disease(ASCVD) and triglyceride(TG)-induced pancreatitis risk. The global impact of ASCVD is high, with more than half a billion people affected.1 The prevalence of CVD varies by race/ethnicity and social determinants of health.2 In 2025, AACE published an update of the 2017 Guidelines for Management of Dyslipidemia and Prevention of Cardiovascular Disease, providing evidence-based recommendations for the pharmacologic man-agement of adults with dyslipidemia by multidisciplinary care teams.3 As a companion to the guideline, AACE subsequently developed this algorithm as an update of the previous iteration published in 2020.4 This updated algorithm provides visual guid-ance for the management of adults with dyslipidemia to help cli-nicians navigate the complexities of screening, diagnostic testing,and treatment of lipid disorders. While differences in prevalence,access to care, and lack of diverse representation in clinical trials were discussed in detail in the 2025 AACE Clinical Practice Guideline for Pharmacologic Management of Adults with Dyslipidemia, ${}^{3}$ op-tions in clinical management for different groups of individuals and locations were also considered in the visual guidance and supporting text below.

A multidisciplinary task force with representatives from AACE and several international co-sponsoring organizations(Canadian Cardiovascular Society, European Association for the Study of Dia-betes, and the Latin American Academy for the Study of Lipids and Cardiometabolic Risk) were appointed to determine the scope and breadth of the algorithm and the areas in need of updated guidance.Searches were conducted by a methodology fellow to identify peer-reviewed literature in response to specific questions from the task force.Clinical practice guidelines and systematic reviews of sufficient quality were prioritized followed by randomized controlled trials and observational studies. Where data were limited or unavailable,the task force used their judgment and expertise. The process for updating the algorithm involved multiple task force meetings be-tween January 2024 and February 2025. Smaller groups focused on specific sections, which were then brought to the complete task force for discussion and review. A proportion of algorithm task force members overlapped with the 2025 dyslipidemia clinical practice guideline to ensure continuity and content alignment.

This 2025 algorithm emphasizes lifestyle modification, the importance of managing atherosclerotic risk factors, and provides a framework regarding pharmacologic choices for the treatment of individuals with dyslipidemia, in alignment with the 2025 AACE Clinical Practice Guideline on Management of Adults with Dyspli-demia.3 The task force acknowledged that health care disparities and lack of access to newer medications remain significant bar-riers. In addition, task force members included information on new topics such as the management of dyslipidemia in special populations and genetic dyslipidemias.

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hypertriglyceridemia in pregnant and lactating individuals; and(11) FDA-approved medications for dyslipidemia.

Conclusions: This 2025 dyslipidemia algorithm update aligns with the 2025 AACE Clinical Practice Guideline for Pharmacologic Management of Adults with Dyslipidemia and other recent AACE guidance.The algorithm is also in agreement with guidance provided by the other international bodies represented within this task force.This update emphasizes ASCVD risk assessment, addresses pancreatitis risk,and highlights individualized pharmacotherapy.The algorithm includes considerations on health equity,cost effectiveness, and the benefits and harms of different management options.

The algorithm is divided into specific sections with graphics that outline the guiding principles of person-centered management(Algorithm Fig. 1), appropriate evaluation and ASCVD risk assess-ment(Algorithm Figs. 2 and 3), lifestyle modifications specific for individuals with dyslipidemia(Algorithm Fig. 4), risk-stratified treatment of low-density lipoprotein cholesterol(LDL-C) and statin-associated muscle symptoms(SAMS)(Algorithm Figs. 5 and 6), and treatment of adults with hypertriglyceridemia(HTG)(Algorithm Fig.7). In addition, the algorithm provides new sections for the management of special populations and adults who are pregnant or lactating(Algorithm Figs. 8-10). Finally, a summary of current medications for adults with dyslipidemia that are approved by the U.S. Food and Drug Administration(FDA) is provided(Algorithm Fig. 11). Specific clinical considerations, key informa-tion, and evidence-based guidance are provided in the narrative for each section to aid the reader in using the visual algorithms.

Guiding Principles of Algorithm

Guiding principles are provided to highlight the foundation for patient-centered management of adults with dyslipidemia(Algorithm Fig.1).

Cardiovascular Risk Assessment and Testing for Dyslipidemia

For primary ASCVD prevention, AACE recommends that adults with dyslipidemia be assessed using a validated risk assessment tool(Algorithm Fig. 2). In addition, we recommend that all in-dividuals(primary and secondary prevention) should be coun-seled on enduring lifestyle changes to address lipid and nonlipid ASCVD risk factors.

Adults with ASCVD do not need risk assessment since they are already considered to be at high risk and should receive treatment for secondary prevention. Adults>40 years of age(or younger if additional ASCVD risk factors are present) with diabetes, familial hypercholesterolemia(FH) diagnosis, HIV, metabolic syndrome,metabolic dysfunction-associated steatotic liver disease(MASLD),chronic kidney disease(CKD), and chronic inflammatory diseases may be considered at moderate to high risk for ASCVD and should be managed accordingly.4-9 MASLD deserves particular attention because despite its high prevalence worldwide10 and its strong association with ASCVD mortality,11 it is still underdiagnosed.12

For most adults, the routine use of nontraditional risk markers including coronary artery calcium(CAC) score, apolipoprotein B(ApoB), and lipoprotein a(Lp[a]) does not provide meaningful improvement in risk prediction.3 However, special consideration that incorporates costs and benefits may be given to the use of these markers and potentially to genetic testing in young adults with a family history of premature ASCVD. While not evaluated in the 2025 AACE dyslipidemia guideline, 2- and 3-dimensional ca-rotid and femoral ultrasonography has been observed to provide

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Guiding Principles for Patient-Centered Management of Dyslipidemia

•Assess risk of ASCVD and pancreatitis in individuals with hypertriglyceridemia,especially when TG≥885 mg/dL(10 mmol/L).

●Assess and address underlying causes of dyslipidemia including dietary and lifestyle factors,co-morbidities,medications,and genetics(where applicable).

•Engage with individuals and caregivers about the importance of diet, physical activity,and adoption of healthy lifestyle patterns with considerations for access to healthy food and safe spaces for physical activity.

● Where pharmacotherapy is indicated, use shared decision-making to assess risk and benefits as well as goals of therapy.

● Use caution in prescribing medications for certain populations for which there is limited evidence, especially for individuals who are pregnant or lactating.

•Develop management plans that incorporate individual preferences and values, adhere to health equity principles,and are culturally sensitive. Considerations should include medication availability,fordability,and access to health care services.

● To improve adherence, discuss the treatment rationale and need of long-term therapy with individuals and caregivers.

Algorithm Figure 1-Guiding Principles

Algorithm Fig.1. Guiding principles for management of adults with dyslipidemia.

Risk Assessment and Testing for Dyslipidemia

●Emphasize life-long adoption of healthy lifestyle changes(diet,exercise,stress reduction,restful sleep,avoidance of tobacco,and a healthy body weight)

●Treat all cardiometabolic risk factors in an integrated manner

The following individuals should be considered at moderate to high risk for ASCVD events:Presence of clinical ASCVD,FH,diabetes over 40 years of age(or younger if additional ASCVD risk factors),HIV,metabolic syndrome, MASLD, and chronic inflammatory disease.

For primary prevention, use a validated risk assessment calculator to determine risk of future ASCVD risk. Emphasize healthy life-style modifications to all.

Low risk(7.5%)

Focus on lifestyle interventions

Example Risk Assessment Tools or Calculators*

1.PCE 10-year risk calculator-https://tools.acc.org/ascvd-risk-estimator-plus/#/calculate-estimate/

2. PREVENT risk calculator-https://professional.1/em/nen/nen/nem/nen/nem/nen/nem/s

3. Framham risk score-https://www.mdcalc.com/calc/36/

4. SCORE& SCORE2-OP-https://www.escard.org/Education/for(Famplimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimimim

<BeginOfPara>6. QRISK-https://qrrk.org/

Intermediate risk(7.5-20%)

● Consider additional risk enhancers

● Engage in shared decision-making regarding treatment

Additional risk. Additional Testing: ${}^{b}$ enhances:● CAC score/ or 2D-3D● Family history● Cardiomatolic ultrasound ultrasound individuals. May be considered to disease● TG/Non-HDL● ApoB ● ks

TG/Non-HDL TG. ApoB

● CKD

High risk(20%)

Recommend pharmacotherapy

a Percent risk refers to risk of future ASCVD-related events.Tock points vary across assessment tools. Currently there is no evidence to support the preferential use of any particular risk calculator.

B cument evidence does not show meaningful improvement in prediction of ASCVD risk with the addition of non-traditional risk factors(i.e.CAC score,ApoB or Lpa| to the risk model for most individuals. May be considered to disify risk for individuals at intermediate risk(2025 AACE

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small improvements in risk assessment and remains an option for additional risk assessment.13-15

ASCVD risk assessment is critical in the management of adults with dyslipidemia. It allows for the prevention of ASCVD and the definition of individualized treatment goals which include shared decision making and promote risk behavior modification. Once a 10-year ASCVD risk is estimated, individuals are classified as fall-ing within a low(<7.5%), intermediate(7.5-20%), or high(>20%)risk category.The main treatment recommendation for individuals at low risk is lifestyle intervention that includes diet and physical activity modifications(See Algorithm Fig.4 below). Pharmacologic lipid management is not recommended for individuals at low risk for ASCVD. In individuals whose lipid levels are not at goal, shared decision making on pharmacologic intervention, with discussion of risks and absolute benefits, is recommended.3

For individuals at high risk, pharmacologic therapy should be added to lifestyle interventions(Algorithm Fig. 5). For individuals at intermediate risk, clinicians should discuss benefits and harms of treatment options(See Algorithm Fig. 5 below). AACE recommends an LDL-C treatment target of<70 mg/dL for individuals with ASCVD or at increased risk of ASCVD including those with diabetes mellitus.3 Some individuals at intermediate risk may benefit from additional testing for risk enhancers to aid in shared decision making. However,these tests have limited evidence to support wide adoption, and many individuals may have barriers with access.3

There are several risk assessment tools available for use, and while all these share core risk factors, they all also have subtle differences. Risk category cut points may differ across assessment tools. Currently, there is no evidence to support the preferential use of any particular risk calculator. Clinicians should recognize the limitations of risk calculators as they may not have been validated in all populations and may not appropriately account for diversity and risk related to current or previous health conditions.3 There are some tools that are preferred in specific regions of the world.Regardless of the tool used, risks and benefits, as well as harms of treatment compared with no treatment should be discussed with the individual and/or caregivers to underscore the importance of both lifestyle changes and pharmacologic treatment.

Tools and algorithms used to estimate ASCVD risk include ${}^{16}$ :

● Pooled Cohort Equations ASCVD Risk Calculator: Estimates the 10-year and lifetime risk of cardiovascular disease(https://tools.acc.org/ascvd-risk-estimator-plus/#!/calculate/estimate/).

● PREVENT Calculator: Designed to estimate the 10-and 30-year ASCVD risk for individuals 30-79 years of age. Includes ZIP code as a measure of social deprivation index in lieu of race(https://professional.heart.org/en/guidelines-and-statements/prevent-calculator).

● Framingham Risk Score: Estimates 10-year cardiovascular risk based on data from the Framingham Heart Study(https://www.mdcalc.mcalc/38/framingham-risk-score-hard-coronary-heart-disease).

● SCORE2 and SCORE2-OP: Provides risk estimates based on Eu-ropean populations, particularly informative for individuals>79 years of age(https://www.escardio.org/Education/Practice-Tools/CVD-prevention-toolbox/SCORE-Risk-Charts).

● PAHO Cardiovascular Risk Calculator: Developed to estimate the risk of developing ASCVD within the next 10 years among Latin American and Caribbean populations(https://www.paho.org/en/hearts-americas/cardiovascular-risk-calculator-app).

● QRISK: Developed using large data sets within the UK National Health Service, it estimates 10-year CVD risk for people 25 to 84 years of age(including those with T2DM). There is also a life-time risk calculator(https://qrisk.org/ or https://www.qrisk.org/lifetime/index.php).

Identifying Genetic Dyslipidemias

In all individuals at initial assessment, an elevated LDL-C is defined as>160 mg/dL, an elevated TG(fasting) as>150 mg/dL,and a low high-density lipoprotein cholesterol(HDL-C) is defined as<45 mg/dL for men and<55 mg/dL for women. The Identifying Genetic Dyslipidemia Algorithm(Algorithm Fig. 3) starts with the observation of an extreme clinical finding(ie, tendon xanthomas)or a lipid profile where these values are significantly abnormal. The most common monogenic condition is FH, signified by an eleva-tion of LDL-C at the 95th percentile or higher, caused by reduced receptor-mediated clearance of circulating LDL. Note that suspi-cion for FH should be considered when the LDL-C is at the 95th percentile or higher. ${}^{17}$ Heterozygous FH has an estimated world-wide prevalence of 1:250.18

Familial Hypercholesterolemia, Xenosterolemia/Sitosterolemia, and Cerebrotendinous Xanthomatisation

Observing an LDL-C>190 mg/dL(>4.9 mmol/L) in adulthood should prompt consideration of heterozygous FH, even though most dyslipidemias with LDL-C elevated to this level are not FH.19 The presence of tendon xanthomas with drastically raised LDL-C has been considered pathognomonic for FH. However, as genetic testing becomes more accessible and less costly, it is increasingly being incorporated into the evaluation of individuals with FH and their direct family members(cascade testing). Experts recommend that both genetic and phenotypic diagnoses be pursued when possible given that the two approaches may be complementary and may influence treatment decisions.18,20 Importantly, to avoid unnecessary genetic testing, secondary causes of hypercholester-olemia should be first excluded and the probability of a diagnosis of FH examined with the use of a likelihood scoring system such as the Dutch Lipid Clinic Networks algorithm,21 the Welsh Scoring system,22 the Simon Roome Register criteria,23 or the U.S.(Make Early Diagnosis to Prevent Early Deaths[MEDPED]) Diagnostic Criteria for FH.24

The presence of tendon xanthomas with much less extreme LDL-C levels should prompt consideration of sitosterolemia or cerebrotendinous xanthomatosis, which are respectively caused by biallelic pathogenic variants in ABCG5 or ABCG8 and CYP27A1.Sitostolemeria/xenosterolemia is further associated with a ten-dency for macrothromobycytopenia and valvular heart disease,while cerebrotendinous xanthomatosis is associated with a variety of neurologic signs and symptoms.25,26 Diagnostic biochemical testing with measurements of plasma plant sterols or bile alcohols,respectively, is available for both suspected genetic disorders.27

A DNA test sample is usually derived from whole blood and sent to a dedicated genetic testing laboratory to screen for pathogenic variants in LDLR,APOB,PCSK9(gain-of-function),LDLRAP1,ABCG5/G8, LPA, and APOB by gene sequencing. More than 95% of detected causal variants in FH are found in the LDLR and APOB genes and the rest are rare. ${}^{18}$ The information of positively identified cases can be used for cascade testing tests of family members to facilitate early-in-life cholesterol lowering for the prevention of ASCVD.20 Many genetic testing laboratories can also provide a result for polygenic hyper-cholesterolemia. Of all cases submitted for FH genetic testing, the most common response is a high polygenic score for elevated LDL-C,which is associated with a lower cardiovascular risk than mono-genic FH but a higher risk than the general population. ${}^{28}$

Hypobetaliporproteinemia and Abetalipoproteinemia

Secondary causes for extremely low LDL-C(<39 mg/dL or<1 mmol/L) far outnumber monogenic causes. Most cases of

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Identifying Genetic Dyslipidemias

||High LDL-C 190 mg/dL (4.9 mmol/L)|Low LDL-C 199 mg/dL (1.0 mmol/L)|High TG 885 mg/dL (10 mmol/L)|High TG and TC 530 mg/dL for TG and 230 mg/dL for total cholesterol(6 mmol/L for both)|Extreme HDL-C 8 mg/dL(0.2 mmol/L) or 116 mg/dL(63 mmol/L)| |---|---|---|---|---|---| |Clinical assessment|Xanthomas,*atherosclerosis, Family history Likelihood scoring: ● Dutch Lipid Clinic ● Simon Broome ● Welsh|Fat intolerance, hepatostatosis, blood film for acanthocytes, fat soluble vitamin deficiencies|Eruptive xanthomas, panceatitis hadefinitioes, lipemia retinals|Tubero-eruptive xanthomas, Apo B(120 mg/dL, TG: Apo B(10:1 TC: Apo B:6:2:1|Corneal arcconal opacities, xanthomas, renal impairment, peripheral neuropathy, enlarged orange tonsils, blood film| |Secondary factors (genetic testing needed only if lipid abnormality persists after adjustment of secondary factors)|Diet, excessive alcohol, anabolic steroid use, hypothyroidism,anorexia nervosa, liver disease, nephrotic syndrome, (consider especially if historic LDL-C>155 mg/dL (4 mmol/L)|Lipid-lowering therapy, cachexia,malnutrition,malsublation, chronic liver disease, chronic pancreatitis, cystic fibrosis,end stage renal disease|Excessive alcohol, obesity, poor glycemic control,lipodystrophy, nephrotic syndrome, retinody, atypical anti-lypsychotics,glucocorticoids, estrogens and beta-blockers|Recent weight gain, new T2D, new medication, hypothyroid male sex, change in hormone status|Drugs(fibrates,TZDs, anti-epileptics, estrogens, niacin), pesticide exposure, excessive alcohol| |Genetic test|LDLR,APOB,PCSK9, LDLRAP1,ABCG5/G8,LIPA, APOE.LDL-C polygenic score|MTTP,APOB,PCSK9, ANGPT3,S1R8|LPL,PGIHPB1,APOA5, APOC2,LMF1|APOF E2/2 genotype; rarely APOE dominant variant|Low HDL-C: ABCA1, LCAT, APOA1 High HDL-C: CETP SCARB1, LIPC,LIPG,APOC3| |Condition|Familial or polygenic hypercholesterolemia, sitsterolemia, LIPA-deficiency|Hypobetalipoproteinemia|Familial chylomicronemia, multifactorial chylomicronemia|Dysbetalipoproteinemia|Tangier,LCAT deficiency, Fish-eye disease| |Follow up||Specialist endocrine or lipid clinic management(see narrative for treatment options)||||

Specialist endocrine or lipid clinic management(see narrative for treatment options)

a See narrative for additional conditions with xanthomas, such as sisterochemia and cerebroternidous xanthatomosis, and with hepatostatosis, namely lysosomal acid lipase deficiency.

$$\text{ COPYRIGHTS 2025 A.MAY.}\text{ By not reproduced in any form without express written permission from Elwever on behalf of A.Vit. https://doi.org/1016/2025.07.041 to request copyright permission.}$$

Algorithm Fig. 3. Identifying genetic dyslipidemas.

ACE.

hypobetalipoproteinemia are asymptomatic and will be discov-sclerotic disease has not been reported as an issue in individuals with hypobetalipoproteinemia as they age. Cases of hypo-betalipoproteinemia could warrant genetic testing of MTTP, APOB(heterozygous truncating variants), PSCK9(heterozygous loss-of-function variants), ANGPTL3, and SARIB. Most cases of abetalipo-proteinemia(due to biallelic variants in MTTP) are clinically obvious in infancy(fat-soluble vitamin malabsorption) but may also be considered when acanthocytosis, retinitis pigmentosa,hepatic steatosis, or abnormally low LDL-C levels are noted.

Severe Hypertriglyceridemia

The definition of severe HTG differs mostly according to area of practice, with SI-based jurisdictions defining severe HTG as a TG level>10 mm/L and those using conventional units as TG>1000 mg/dL.29 When TG levels are in this range, the clearance of TG is significantly impaired, and chylomicron particles accumulate in circulation, leading to an increased risk of pancreatitis. 30,31 The risk of pancreatitis increases with rising TG levels, reaching~5%when TG are>1000 mg/dL and 10% to 20% when>2000 mg/dL.32 Severe HTG is overwhelmingly dominated by secondary causes and polygenic predisposition(ie, multifactorial chylomicronemia syndrome[MCS], formerly Frederickson type V hyper-lipoproteinemia), which would not require genetic testing. Typical cases with familial chylomicronemia syndrome(FCS; previously called Frederickson type I hyperlipoproteinemia) present in childhood or young adulthood with grossly lipidemic plasma and frequently with abdominal pain/pancreatitis. In such cases a strict low-fat diet will reduce TG levels but rarely normalize them.

Monogenic severe HTG is autosomal recessive and therefore not always observed as a trait in a family with the exception of consanguineous situations. The raised TG concentration is always dependent on a clearance defect, with lipoprotein lipase(LPL)being the major lipolytic enzyme responsible for removing TG from blood. Algorithms for determining FCS probabilities are available.30,31 Furthermore, some therapies approved by the FDA are now available for treatment of FCS33 and others may be available in the near future for FCS and MCS. A common reason to pursue genetic testing with the suspicion of FCS would be the observation of otherwise unexplained acute pancreatitis in the setting of severe HTG. Genetic testing panels include LPL, GPIHBP1,APOA5, APOC2, and LMF1; biallelic pathogenic variants are diag-nostic for FCS while single heterozygous variants are inconsis-tently seen in MCS.

Dysbetalipoproteinemia

Dysbetalipoproteinemia should be suspected if there is a near-equimolar rise in TG and total cholesterol. Simultaneous observa-tion of tuberoerutive xanthomas on elbows, knees, or back of the hands is pathogenomonic. Typical for this condition is that it can fluctuate between a seemingly normal lipid profile and extreme elevations of both cholesterol and TG. At times of extreme TG and cholesterol elevations there is often an identifiable precipitant,such as weight gain, persistent hyperglycemia in individuals with diabetes, or a new medication. A close inspection of the lipid profile would reveal a surprisingly low plasma Apo B concentration and high ratios of TG and total cholesterol to Apo B.34 The condition is almost exclusively seen on a genetic background of APOE E2/2. This genotype is found in~1% of most populations, but the dysbetalli-poproteinemia is only found in<5% of APOE E2/2 individuals. A

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genetic test showing homozygosity for the APOE E2/2 variant together with a typical lipid profile is diagnostic for the condition.Dysbetaliproproteinemis is exquisitely responsive to fibrate treat-ment and an immediate response to a fibrate would support an exjuvantibus diagnosis.

Extreme High-Density Lipoprotein Cholesterol(HDL-C)

The genetic syndromes causing extremely low HDL-C are rare and often discovered in connection with investigations of other manifestations, such as eye disease, red blood cell abnormalities,neuropathy, or kidney disease. Nongenetic causes of very low HDL-C include renal disease, low estrogen states, hyperandrogenemic states, and paradoxical response to fibrates or thiazolidineiones or their combination.36 The most common cause of low HDL-C from a genetic disorder is a pathogenic variant in ABCA1, where heterozygous carriers have HDL-C which are typically<50th percentile of normal in the absence of HTG. Tangier disease, with biallelic pathogenic variants in ABCA1(autosomal recessive) lead to HDL-C levels which are<5th percentile. LCAT deficiency and fish-eye disease result from biallelic variants in LCAT and are associated with low HDL-C but also proteinuria and corneal opa-cification, which should alert the clinician to this rare disease.Investigations of genetic causes of such syndromes are highly specialized and are often performed in a research setting, but these are increasingly used in practice.

Most cases of extremely raised HDL-C levels(>90th percentile)are secondary to excessive alcohol intake, antilepileptic treatment,niacin, pharmacologic use of estrogens, or exposure to pesticides.Genetic causes of extremely high HDL-C are rare and either caused by CETP deficiency or deficiency in the lipolytic enzymes that remove TG from HDL, ie hepatic lipase(LIPC) or endothelial lipase(LIPG). Although rare variants in CETP, LIPC, and LIPG underlie high

HDL-C, and the phenotype sometimes has a polygenic basis, there are usually limited clinical consequences.

Specific Lifestyle Recommendations for Adults with Dyslipidemia

General Advice

The effective management of dyslipidemia includes consump-tion of a diet focused on whole, unprocessed foods, such as fruits,vegetables, nuts, whole grains, legumes, lean proteins(such as fish and chicken), and low-fat dairy products(Algorithm Fig. 4).Incorporating nontropical plant oils like olive, canola, and sun-flower oils is advised, whereas tropical oils are to be avoided, as they are typically high in saturated fats and may contain trans fats,if hydrogenated. The addition of stanols in the diet(2 g/day) has been shown to reduce LDL-C levels, but there are no available outcome trials demonstrating a reduction in ASCVD events.37,38 Certain foods rich in saturated or trans fats should be minimized or avoided, including bacon, sausage, salami, deli meats, red meat,and fried or deep-fried foods. Refined grains and sugary food and drinks are low in fiber and promote weight gain which may indi-rectly impact lipid levels and therefore are not recommended. As part of other general guidance to reduce ASCVD risk, individuals without HTG who choose to consume alcohol should do so in moderation, limiting the units of alcohol and the number of days when alcohol is consumed.39,40 Excess consumption of alcohol can increase the risk of other chronic conditions and ASCVD risk.40

Dietary patterns such as the Mediterranean diet, the Dietary Approaches to Stop Hypertension(DASH), and healthful plant-based diets incorporate essential dietary principles discussed above and have been shown to be of benefit in the prevention of ASCVD events.5 Low-carbohydrate and very low-carbohydrate

Specific Lifestyle Recommendations for Adults with Dyslipidemia

|General Evidence-Based Advice|| |---|---| |Consumer|Limit/Avoid| ||Foods| ||●Fruit,nuts,vegetables,| ||●Ultra-processed foods| ||●Red meat| ||● Low fat dairy| ||● Non-tropical oils such as| |olive oil|●Fried/deep fried food| ||● Alcohol(limit/avoid/ eliminate) ● Large portions| ||● Dietary Patterns| |● Mediterranean diet|| |. DASH diet|| ||● Healthful plant-based diet|

|Hypertriglyceridemia|Hypertriglyceridemia|Hypertriglyceridemia|Hypertriglyceridemia|| |---|---|---|---|---| |Triglycerides|150-499 mg/dL (1.7-5.6 mmol/L)|500-884 mg/dL (5.6-9.9 mmol/L)|2885 mg/dL(10 mmol/L)|| |Triglycerides|150-499 mg/dL (1.7-5.6 mmol/L)|$\uparrow\uparrow$|$\uparrow\uparrow\uparrow$|| |Pancreatitis risk|Pancreatitis risk|||| |Treatment priority|Treatment priority|Prioritize pancreatitis risk+address CVD risk||| |Treatment priority|Treatment priority|||| |Treat underlying medical conditions|Diabetes| Overweight/obesity/Alcohol Use Dis|||| |Intenify medications known to increase triglycerides|Avoid and alternatives|||| |Identify诱terricides|Identify诱terricides|Eliminate eliminate|Eliminate eliminate|| |Required Dietary Management|Fat content Type of fat|~30% of calories fat|~30% of calories fat|20-30 g fat/day| |Required Dietary Management|Fat content Type of fat|Limit/avoid Limited/avoid rans saturated/trans fat|• Avoid saturated& trans fats If chronic: MCTs and fat-soluble vitamins|| ||Carbohydrates|foods and drinks| Eat fiber-rich foods||| |Dietary interventions:|Alcohol|Limit/avoid eliminate|Eliminate||

|Hypercholesterolemia| |---| |Treatment priority:Cardiovascular disease| |Treat underlying medical conditions(i.e hypothyroidism, altenatives to medications nephromic syndrome,etc.)| |Dietary interventions: Limit saturated/ trans fats $\cdot$ Increase fiber-rich foods|

COPYRIGHTS 2025 AACE. May not be reproduced in any form without express written permission from Elsevier on behalf of AACE Visit https://dolorg/10.1016/j.ppraee.2025.07.014 to request copyright permission. Algorithm Figure 4-Lifestyle Recommendations AACE.

Algorithm Fig.4. Specific lifestyle recommendations for adults with dyslipidemia.

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diets, such as ketogenic or pale diets, have variable impact on lipid levels depending on whether saturated or unsaturated fats replace the carbohydrates being restricted41; evidence on ASCVD outcomes from these dietary patterns is currently lacking.

Hypercholesterolemia

For all adults, managing hypercholesterolemia effectively in-volves addressing underlying health conditions that may increase LDL-C and selecting diet patterns to support healthy cholesterol levels and reduce ASCVD risk(Algorithm Fig. 4). Likewise, medi-cations known to increase LDL-C should be avoided where possible.29,42,43

Hypertriglyceridemia

The plasma TG concentration varies substantially within a per-son and recently consumed foods will have a significant influence.It is therefore helpful to base recommendations on more than one determination and ideally measure fasting TG levels at least once.Addressing underlying causes for HTG is key to the treatment of these individuals. A review of medications that may contribute to HTG is warranted.44 Lifestyle interventions aimed at correcting underlying medical conditions such as obesity44 and persistent hyperglycemia in individuals with diabetes will reduce plasma TG(Algorithm Fig. 4). In addition, individuals should be counseled to limit or completely avoid(depending on the severity of their HTG)alcohol and sugary drink intake.45 Dietary nonadherence is the most common cause of persistent high TG and necessary dietary lifestyle changes should be emphasized at all clinic visits.

HTG is linked to an increased risk of ASCVD.46 In instances of mild/moderate HTG(TG 150-499 mg/dL or 1.7-5.6 mmol/L), the treatment priority is to reduce ASCVD risk; in that sense, LDL-C must be the primary target based on the person's individual risk. It is important to emphasize that the TG-carrying particles in this range are predominantly derived from very low-density lipopro-tein(hepatic origin) or their remnants and focuses attention on the metabolic pathways that impact increased very low-density lipo-protein secretion and/or clearance issues. Individuals should be counseled to limit alcohol and sugary drink intake and minimize a high glycemic food intake.45 Diabetes and insulin resistance are frequent associations with TGs in this range and their control should be optimized.5 In individuals with mild/moderate HTG, it is recommended to limit dietary fat intake to no more than a third of calories consumed and with a further limitation on the type of fat,i.e. saturated and trans fatty acids should be restricted. Individuals should be counseled to limit alcohol and sugary drinks.

For individuals with fasting TG levels in the 500 to 884 mg/dL range(5.6-9.9 mmol/L), ASCVD prevention remains a priority, but attention should be given to the reduction of TG levels to decrease the individual's risk of HTG-induced acute pancreatitis. This is particularly true when TG levels reach the 885 to 1000 mg/dL(10-11.3 mmol/L) threshold. At these extreme TG levels, the primary focus shifts to the prevention of HTG-induced pancreatitis. Elim-inating underlying causes for HTG remains critical. An immediate reduction in dietary fat intake is imperative. By doing so, the load of postprandial TG will be decreased with less competition in overall plasma TG clearance. Alcohol should be avoided in in-dividuals with TG≥500 mg/dL(5.6 mmol/L).

At TG≥885 mg/dL(10 mmol/L), the risk of pancreatitis rises substantially and will require a severe restriction in dietary fat intake.47-49 There should be an immediate restriction in dietary fat intake<15 to 20 grams per day, but this is often challenging to implement and will require professional dietetic support. If this degree of reduction in dietary fat intake is needed to chronically

maintain TGs<885 mg/dL(10 mmol/L), and it is proving difficult to maintain adequate calorie intake, medium-chain TGs(MCT) and essential fatty acid supplements can be added to the diet to avoid nutritional deficiencies. Effective implementation of lifestyle measures aimed at lowering TG will have a very noticeable effect in a short space of time(days to weeks). 50 It should be noted that most adults with TG levels≥885 to 1000 mg/dL present with the polygenic form of the chylomicronemia syndrome(MCS) and retain partial or full PL activity. These individuals will be able to maintain TG levels<250 mg/dL by effectively addressing second-ary factors, a moderate restriction of dietary fat(25-30% calories from fat, ideally≤40-50 grams of fat/day) and the use of TG-lowering medications. Diets with fat content of<15 to 20 grams of fat per day are needed in individuals with persisting chylomicro-nemia who have FCS or a refractory form of MCS. Engaging in-dividuals in decision making by acknowledging the difficulties of dietary fat restriction while accounting for their individual increased risk of pancreatitis will help attain the TG goals.

Targeting LDL-C with Pharmacologic Therapy for ASCVD Prevention

When managing lyslipidemia with pharmacologic therapy to lower ASCVD risk (Algorithm Fig. 5), it is important to determine whether the approach involves primary or secondary prevention;the latter involves individuals with known clinical ASCVD. For secondary prevention, LDL-C lowering is standard of care. 3,4,51,52 Some primary prevention categories include individuals at mod-erate to high ASCVD risk, who also warrant LDL-C-lowering therapy. These individuals include those suspected to have FH,those with persistently elevated LDL-C levels(>190 mg/dL or>4.9 mmol/L), as well as adults over the age of 40(or at a younger age if additional ASCVD risk factors are present) with diabetes, HIV,metabolic syndrome, MASLD, CKD, and chronic inflammatory diseases.4-9 For other individuals in the primary prevention cate-gory,AACE recommends the use of a validated risk assessment tool to estimate future ASCVD risk and to discuss the risks and benefits of pharmacotherapy with individuals using shared decision making.3

Moderate- to high-intensity statin therapy is recommended for individuals without known ASCVD but who are considered to be at high risk, whereas high-intensity statins are indicated for sec-ondary prevention. In some individuals with diabetes who are at high risk, whereas highiating statins at a younger age might be advisable. The addition of ezetimibe to statin therapy should be considered if the LDL-C target is not met. There may be a need for treatment intensification using proprotein convertase subtilisin/nexite type 9(PCSK9) monoclonal antibodies(mAbs) or other therapies based on individualized response if the LDL-C target is not met after initial treatment.3 While not addressed in the 2025 AACE dyslipidemia guideline, early initiation of a combination therapy of a statin with ezetimibe is likely to be more successful at intensive lipid-lowering and achieving LDL-C goal than high-dose statin alone, an approach that may benefit individuals presenting with a recent acute cardiovascular event, who may require intensive LDL-C lowering.53-55 For individuals at elevated risk or with known ASCVD, AACE suggests targeting LDL-C levels below 70 mg/L(1.8 mmol/L).3 As detailed in the 2025 guideline, there is limited evidence to support treatment goals of<55 mg/dL(1.4 mmol/L) for most individuals.3,56,57 There are different treatment targets recommended by different specialty organizations(American College of Cardiology/American Heart Association,European Society for Cardiology/European Atherosclerosis Soci-ety,9 Canadian Cardiovascular Society,8 etc), but targets should be individualized to the extent possible with some individuals

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Targeting LDL-Cholesterol with Pharmacologic Therapy for ASCVD Prevention in Adults

![Primary Prevention\nCounsel on lifestyle modifications that reduce ASCVD risk\nSecondary Prevention (Clinical ASCVD)\nAssess ASCVD risk*\nControl by 10b /T 2Db\nMetabolic syndrome/ MASLD\nPersistent\nLDL-C≥ 190 mg/dL\nHigh-intensity statin d\nLow risk\nIntermediate risk\nLow risk\nConsider moderate- to high-intensity statin\nConsider moderate- to high-intensity statin\nConsider add-on therapy: bempedoic acid, PCSK9-based therapy, or bile acid resins\nPCSK9-based therapy, or bile acid resins\nIf LDL-C above goal or continues to have CV events, add ezetimibe\nACE suggests treating individuals with ASCVD or increased risk of ASCVD or an LDL-C target of 70 mg/dL. Potential impacts from polypharmacy and the increased costs with certain medications should be considered when determining appropriate treatment goals. ${}^{*}$ \nHigh intensity Statin\nACE4 suggests treating individuals with ASCVD or increased risk of ASCVD or an LDL-C target of 70 mg/dL. Potential impacts from polypharmacy and the increased costs with certain medications should be considered when determining appropriate treatment goals. ${}^{*}$ \nHigh intensity Statin\nAvatorvastatin 40-80 mg\nAvatorvastatin 10-20 mg\nAsvivastatin 20-40 mg\nResovastatin 20-40 mg\nFluvastatin XL 80 mg\nFluvastatin 40 mg BID\nPravastatin 40-80 mg\na Use a validated risk tool(see full list in text). Family history of premature coronary disease carries increased ASCVD risk individuals fall in the intermediate or high-risk categories depending on overall risk. Current evidence does not show meaningful improvement in prediction of ASCVD risk with the addition of non-traditional risk factors (he.h.cSR,CAC score, ApoB,Or Lpla) to the risk model (see 2025 AACE Dyslipidemia Guideline)\na Use a validated risk tool(see full list in text). Family history of premature coronary disease carries increased ASCVD risk individuals fall in the intermediate or high-risk categories depending on overall risk. Current evidence does not show meaningful improvement in prediction of ASCVD risk with the addition of non-traditional risk factors (he.h.cSR,CAC score, ApoB,Or Lpla) to the risk model (see 2025 AACE Dyslipidemia Guideline) c\na Use a validated risk tool(see full list in text). Family history of premature coronary disease carries increased ASCVD risk individuals fall in the intermediate or high-risk categories depending on overall risk. Current evidence does not show meaningful improvement in prediction of ASCVD risk with the addition of non-traditional risk factors (he.h.cSR,CAC score, ApoB,Or Lpla) to the risk model (see 2025 AACE dyslipidemia Guideline) c\nACE4\nACE 10b /T 2052 AACE\nConsider moderate- to high-intensity statin\nConsider add-on therapy: bempedoic acid, PCSK9-based therapy, or bile acid resins\nPCSK9-based therapy, or bile acid resins\nConsider not all add-on agents have evidence for reducing ASCVD risk. Use shared decision-making to discuss benefits and harms of the individual therapies. ${}^{*}$ \nACE 10b /T 2052 AACE\nACE 10b /T 2052 AACE\nACE 10b /T 2052 AACE\nACE 10b /T 2052 AACE\nACE 10b /T 2052 AACE\nACE 10b /T 2052 AACE\nACE 10b /T 2052 AACE\nACE 10b /T 2052 AACE\nACE 10b /T 2052 AACE\nACE 10b /T 2052 AACE\nACE 10b /T 2052 AICE\nACE 10b /T 2052 AICE\nACE 10b /T 2052 AICE\nACE 10b /T 2052 AICE\nACE 10b /T 2052 AICE\nACE 10b /T 2052 AICE\nACE 10b /T 2052 AICE\nACE 10b /T 2052 AICE\nACE 10b /T 2052 AICE\nACE 10b /T 2052 AICE\nACE 10b /T 2052 AICE\nACE 10b /T 2052 AICE\nACE 10b /T 2052 AICE\nACE 10b /T 2052 AICE\nACE 10b /T 2052 AICE\nACE 10b /T 2052\n](2/aj0YEe4oUhYkBdfpda0fYP/figure1d59475e32524da186ef07fc2ed03e9a_0_3.png) choosing lower treatment goals based on risk. When creating personalized treatment plans, it is important to consider factors such as polypharmacy and medication costs.

Cardiovascular outcome trials have shown combination therapy involving statins, along with ezetimibe et or PCSK9 inhibitors, pro-vides further LDL-C lowering in adults with ASCVD or at increased risk for ASCVD, supporting the intensification of therapy to reach LDL-C goals.56,58,59 For individuals with dyslipidemia on maximally tolerated statins, and with ASCVD or high ASCVD risk who fail to attain their LDL-C target(ie, LDL-C<70 mg/dL or 1.8 mmol/L),adding ezetimibe as the next step is suggested to optimize their treatment regimen. If further LDL-C reduction is needed, consider adding bepedoic acid(BA) or a PCSK9 inhibitor.

Approach to Statin-Associated Muscle Symptoms(SAMS in Adults)

For most individuals, statins are safe and well tolerated, and the benefits of therapy clearly outweigh the risk for adverse effects,including the potential development of diabetes. A subset of in-dividuals may experience SAMS or statin intolerance(Algorithm Fig.6).

SAMS are characterized by muscle complaints such as myalgia,weakness, or tenderness after starting statins, which improve or resolve after dose reduction or discontinuation. To confirm SAMS,a trial of at least 2 different statins, including one at the lowest approved dose, is recommended.60 While observational studies and clinical practice suggest an incidence of SAMS between 5% and 25%, placebo-controlled trials report much lower rates.60 Addressing and correcting underlying conditions, such as vitamin D deficiency or persistent hypothyroidism, may help minimize the risk of SAMS before initiating statin therapy or effectively resolve the symptoms if individuals have already initiated therapy

Clinicians should also be aware of the increased risk resulting from common drug interactions(Algorithm Fig. 6), substance use dis-orders,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,62,6

After ruling out secondary causes, the next step in managing SAMS depends on symptom severity. For mild symptoms, clini-cians may consider challenging with a lower statin dose or a hydrophilic statin(which may have a lower incidence of myop-athy), along with cautious dose up-titration. Alternative strategies,such as less frequent dosing(e.g. 1-3 times per week) or substi-tution of nonstatin lipid-lowering medications, may also alleviate symptoms.63 If a rechallenge fails or the LDL-C remains above target levels, nonstinherapies should be considered.

For moderate to severe symptoms, it is advisable to check creatine kinase(CK) levels. If CK levels are elevated but remain<3 times the upper limit of normal(ULN), individuals may be managed similarly to those with mild symptoms as detailed above.However, in more severe cases where CK levels are>5 times the ULN, in the presence of rhabdomyolysis(a rare condition,approximately 1 in 10 000 individuals), or in the extremely rare case of statin-associated autoimmune myopathy, statin therapy should be immediately discontinued.64,65 After appropriate treat-ment, non-statin therapies should be explored. For CK elevations between 3 and 5 times the ULN, evidence is limited. Clinicians may choose to challenge individuals with a lower dose or switch to a different statin or opt for non-statin therapy after shared decision making with the patient.

For individuals with statin intolerance who either have known ASCVD or are at high risk for ASCVD, treatment with PSCK9 inhibitors or with BA was shown to lower the risk of patient-important out-comes. ${}^{3,56,66}$ Shared decision making is recommended when dis-cussing the benefits and harms of individual therapies.

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![Approach to Statin-Associated Muscle Symptoms in Adults\nDefinition: One or more muscular complaints(myalgia, weakness, tenderness) improved or resolved after dose\nSource Systems in Adults\nEvaluate risk factors: Age(older adults), race/ethnicity (Asian), vitamin D deficiency, hypothyroidion, CKD, genetics\n● Evaluate substance use and medication interactions\n● Consider statin type and dose\nEvaluate risk factors: Age(older adults), race/ethnicity (Asian), vitamin D deficiency, hypothyroidion, CKD, genetics\n● Evaluate substance use and medication interactions\nCK:5 ULN\n● Discontinue\nCorrect underlying contributors\n●(e.g. vitamin D deficiency/ cyclocine/ hypothyroidism, CCK-3 ULN)\n●(g.e. vitamin D deficiency/ hydrocyndium, CCK-3 ULN)\nhypothyroidism, drug-drug interactions etc.)\nNormal/mild elevation\n(CK-3 ULN)\nAdd/start non-statin therapy\n(ezetimibe, bemopedic acid, PCSK9-based\n(ethyl and/ol) bile acid resins)\nConsider rechallenge with other statin, or lower dose\nIf actin-rechallenge fails\nClinical\nand how the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the follow\n](2/aj0YEe4oUhYkBdfpda0fYP/figure5e47653cb3fe42e8a157755246f60340_0_2.png) a Warden BA,Glujon,Kovacz A,Duham JA,Jones K,Lix D.Liobson A,Duell PJ,Bassment and management of statin-associated muscle symptoms(SAMS)

A 3. A critical perspective from the National Lipid Association. J Clin Lipidol. 2023 Jan-Feb:719-39: doi:10.1016/j.2022.09.001

Adapted from H-Handelsen Y,Jollinger PS,Quin LDK,Conseas Statement by the American Association of Clinical Endocrinologists and American College of Inducorino orology on the Management of

$$\text{ CopyrightO2 2025 ACE. May not be reproduced in any form without express written permission from Elsevier on behalf of AZE. Vritd on/loclig. 2010/16/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/06/1/0

Algorithm Fig. 6. Approach to statin-associated muscle symptoms in adults.

Management of Adults with Hypertriglyceridemia

The approach to a patient with HTG involves clinical assess-ment, ruling out secondary causes, lifestyle intervention, and medical treatment to reduce the risks of CVD and pancreatitis(Algorithm Fig. 7).29 When fasting TG levels are elevated, ie,>150 mg/dL(1.7 mmol/L), a fasting lipid profile is recommended.There are frequently contributory secondary causes, the most common being T2D.67 Clinical assessment should primarily focus on detecting or ruling out characteristic features of severe HTG,including those found in individuals with chylomicronemia syn-dromes or dysbetaliprotemopenia.29,68 Addressing the secondary causes-dietary factors, medications, and/or medical conditions such as T2D or obesity-will often normalize TG and are critical to the treatment of HTG, even when severe.29,67

If TG levels are between 500 and 884 mg/dl(5.6-9.9 mmol/L),there is increasing concern for metabolic deterioration predis.pres-posing the patient to the development of acute pancreatitis. 69 Secondary causes should be addressed, diets modified(Algorithm Fig. 3), and fibrates/omega-3 fatty acids initiated if levels do not improve. In a patient with a history of HTG-associated pancreatitis or an individual whose fasting TG levels remain>885 mg/dL(10 mmol/L) on repeat fasting lipid profiling, without an obvious and treatable secondary cause(including nonadherence to dietary re-strictions), treatment to protect against future pancreatitis epi-sodes must be considered.29,49 The first-line treatment in the in cases includes a low-fat diet, plus strong consideration for use of a fibrate.29,49 Omega-3 fatty acids are also a consideration, although are somewhat less efficacious. Persistent or refractory HTG would warrant referral to a lipidologist and possibly DNA analysis to rule out FCS. Also, access to new investigational therapies for severe HTG can be explored through a specialty clinic. ${}^{29,70-72}$ For

individuals with confirmed FCS, clinicians may consider use of FDA-approved apolipoprotein CIII inhibitors.33

For those with mild to moderate HTG(TG 150-499 mg/dL; 1.7-5.6 mmol/L), the primary concern is excess ASCVD risk, and the primary target must be LDL-C. This may also expand to individuals with TG in the 500 to 884 mg/dL(5.6-9.9 mmol/L) range in whom the presence of a heterogenic lipoproteins predisposes them to ASCVD.29,49,68 CVD risk factors-hypertension, smoking, diabetes,and chronic stress-should be managed concurrently.49,68 If ASCVD risk is high or intermediate, medications with proven cardiovascular benefit, such as statins, ezetimide, and eicosa-pentenoic acid monotherapy(icosapentyl ethyl) are preferred.29,49 Because LDL-C may be impossible to determine in an individual treated with statins with persistently elevated TG,non-HDL-C and/or ao B are alternative tests for treatment thresholds and for monitoring the effects of therapy.29,67 If ASCVD risk is low, lifestyle advice should be recommended with periodic lipid monitoring every 12 to 24 months.29,67 Statin treatment can be considered as the individual's situation evolves. Consideration of TG-lowering therapy for individuals with a history of severe HTG-associated pancreatitis must be individualized. Mild to moderate TG elevation in these individuals is a predictor of future risk of severe HTG and pancreatitis. 29,68

Management of Dyslipidemia in Special Populations

As outlined in several of the slides, there are current or previous medical conditions that put individuals at higher risk for ASCVD or ones that impact treatment options. Considerations for risk assessment and treatment for adults in these and additional spe-cial populations are outlined below(Algorithm Figs.8-10).

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Management of Adults with Hypertriclyceridemia(HTG)

![Management of Adults with Hypertricyseridemia (HTG)\nIn all individuals with HTG\nAddress or manage 2° causes:\n>150 mg/dL or>1.7 mmol/L:\n● Alcohol use\n● Diabetes with persistent\n● Medications\n● Clinical assessment and fasting lipids\n●Nausea, vomiting, failure to thrive, abdominal pain,\nhyperglycemia\n● rejection drugs, anti-\n● Address 2° causes\npancreatitis risk;\n● Obesity\nhypersstolic syndrome,\npsychotics,etc.\n● Lifestyle intervention: diet, weight loss\n●Optimize cardiovascular risk factors\nDystabelipoproteinemia\n● Polylipemic plasma\n● Mortality disease\n● Systemic lupus erythematosus\n● Tubero-eruptive xanthomas, palmar crease xanthomas\n● Hypothyroidism\n● Cushing's Syndrome\n● Premature atherosclerosis\nTG288 mg/dL or z10 mmol/L*\nTO 688 mg/dL\nGol: Pancreatitis prophylaxis | Rx: low fat diet, fibrate and/or omega-3 FA\nGoal: CVD risk reduction| Evaluate: global cardiovascular risk\nHow to evaluate: global cardiovascular risk\nReassess in 8-12 weeks b\nHigh/intermediate\nLow\nPersistent TG 885 mg/dL or\nTG 150-884 mg/dL\nStart statin; monitor:LDI-C\nbehavior changes\nor non-HDL-C or Apo B\nConsider:\n● DNA testing for FCS°\n● Lipidologist referral\nLDL-C target attained?\na If TG are in the 500-884 mg/dL range, there is increasing concern for metabolic deterioration predisposing an\nindividual to pancreatitis.A low-fat diet and fibrates/omega-3 FA should be added if levels do not improve.\na If TG are in the 500-884 mg/dL range, there is increasing concern for metabolic deterioration predisposing an\nof individual to pancreatitis.A low-fat diet and fibrates/omega-3 FA should be added if levels do not improve.\nYes; consider icosapert ethyl for\nTG 150-500 mg/dL(1.7-5.6 mmol/L)\nALPHIRGIRD by onelath of ACE. Vait https://dolor/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10\n](2/aj0YEe4oUhYkBdfpda0fYP/figure9711ecc61f4e4f91b80f3887358bff54_0_3.png) Algorithm Fig. 7. Management of adults with hypertricydersidemia

Older Adults

More than 80% of ASCVD deaths occur in individuals 65 years of age and older.73 Older adults face higher risks of recurrent myocardial infarction, stroke, and death, highlighting a heavy ASCVD burden. The strongest evidence for cholesterol-lowering benefits in older adults comes from secondary pre-vention studies. Large randomized controlled trials(RCTs)demonstrate significant reductions in all-cause mortality and major coronary heart disease events with statin use.74-78 Though several primary prevention trials have shown that sta-tins cause significant risk reduction in ASCVD events in in-dividuals 65 years of age and older, data on statin effectiveness for primary prevention beyond 75 years of age are limited,particularly in individuals without diabetes.79-81

Statin therapy should involve shared decision making,considering polypharmacy, frailty, comorbidities, and side effects Algorithm Fig.8). Competing risks and life expectancy are crucial for older adults. Muscle-related side effects do not appear to be more common in these individuals at higher doses.82 However,when muscle symptoms occur, strategies like dose reduction,agent switching, or interval dosing may help. In individuals taking other medications metabolized by the CYP450 system, pravastatin or rosuvatin(partially metabolized by CYP450) are preferred.83 For older individuals with ASCVD or at increased risk for ASCVD, ezetimbe and PCSK9 inhibitors, may be added to statin therapy if the LDL-C goal is not reached with statin therapy alone.3-5,84 However, data regarding the safety and efficacy of these drugs in older adults are currently limited. Evi-dence is also scant on treatment approaches for ASCVD preven-tion in elderly individuals with HTG; clinicians should follow available adult evidence-based guidelines(see section on HTG above).3,5,8

Adults Receiving Gender-Affirming Care

Specific concerns for adults receiving gender-affirming care includes whether the use of hormone therapies will alter the ASCVD risk of individuals who affirm a gender different to the biological sex. As in the general population, most individuals receiving gender-affirming care fall into the primary prevention category and need only to have conventional risk factors assessed(Algorithm Fig.8).The use of HRT may cause small changes in lipid levels.85,86 There are no prospective high-quality studies to form a robust opinion on whether these changes will lead to an increase in ASCVD.87,88 Risk assessment must be nuanced as high-risk be-haviors, including continued use of tobacco products, may in-crease ASCVD risk significantly. In 2022, transgender individuals represented 2% of new HIV diagnoses, with transgender women accounting for the majority of diagnosis of HIV.89 HIV increases the risk of ASCVD, and statin use may be indicated at a higher rate for transgender women. For assessment of risk in individuals receiving gender-affirming care, particularly hormone therapy,cinicians may use conventional risk calculators for both sex at birth and patient self-identified gender and then use the highest risk for shared decision making about the use of pharmacologic

Adults Living with HIV

People living with HIV have a higher risk of acute coronary syndromes and unfavorable post-event outcomes than those without HIV.90,91 Factors explaining their increased cardiovascular risk and the early occurrence of ASCVD include, in addition to traditional risk factors such as smoking, low-grade inflammation,immune activation, and the dysmetabolic effects associated with antiretroviral therapy(ART).

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Management of Special Populations with Dyslipidemia

![Older Adults(70y)\nTrans widid by Adults with Auto immune Disorders\nOldts and Widots who are Childhoods Cancer Survivors\nAdults who are Transpant Recipients\nCounsel on lifestyle changes recommended for all groups\nPrimary Prevention\nCaution with use of ASCVD risk calculators developed for general population\nAscods in an independent risk factor\nASCVD Risk calculated with both\nAscodically high risk for ASCVD\nAscodically abnormality in\nand benefit from statin use\nAscodically high risk due to be at high ASCVD risk due to systemic inflammation\nAscodically abnormality in\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inflammation\nAscodically abnormality in inf\n](2/aj0YEe4oUhYkBdfpda0fYP/figure66297a694ed6466ba00faf00b0fd8e32_0_3.png) Algorithm Fig.8. Management of special populations with dyslipidemia.

Adults with HIV should receive appropriate lifestyle counseling(Algorithm Fig.8), including smoking cessation. Given the variable effects of antiretroviral agents on lipids and their drug-drug in-teractions, prescribing physicians should work closely with an infectious disease specialist to choose ART that achieves effective viral control while minimizing the adverse metabolic effects of these medications, including dyslipidemia. Information on the effects of specific antiretroviral drugs on lipid metabolism and specific statin-ART adverse interactions is available,92,93 and should be incorporated into decision making, particularly if a statin other than pitavastatin is being entertained and/or if high-intensity statin is indicated because of underlying ASCVD or a high ASCVD risk estimate. Individuals should receive close monitoring where there may be potential drug-drug interactions and re-evaluation any time ART changes are made.

In persons under 40 years of age, primary prevention de-cisions should be individualized.92 Pitavastatin is preferred over other statins in persons with HIV infection who are found to be at low/moderate ASCVD risk on traditional risk calculators. Pit-avastatin effectively decreases ASCVD events ${}^{94}$ and avoids the risk of adverse interactions with ART since it is metabolized via glucuronidation.95 Rosuvastatin(≤10 mg/day) is a good alter-native and atorvastatin(≤10-20 mg/day) may be used with certain antiretroviral drugs. Pravastatin should not be prescribed in individuals on darunavir but is otherwise safe, although its LDL-C lowering effect is more modest compared with rosuvas-tatin. Simvastatin and lowastatin are contraindicated with pro-tease inhibitors or cobicistat.93 Rosuvastatin at 20 mg per day is a high-intensity statin option with decreased risk of interactions with ART medications. Input from a lipidologist and pharmacist is particularly valuable when initiating therapy to ensure that lipid targets are met and that drug interactions are avoided.

Ezetimibe, BA, or PCSK9 inhibitors may be considered if LDL-C targets have not been achieved on statins alone or if statin therapy is not tolerated(Algorithm Fig. 5). In individuals with HIV and HTG, prescription-grade omega-3 fatty acids or a fibrate(not gemfibrozil) may be prescribed, as indicated in the general adult population(Algorithm Fig. 7) since they do not result in adverse interactions with ART.

Adults with Autoimmune Disorders

Chronic inflammation or autoimmune disease should be considered as a risk-enhancing factor for ASCVD. Individuals with psoriatic arthritis(PA), rheumatoid arthritis(RA), systemic lupus erythematosus(SLE), and inflammatory myopathies require care-ful ASCVD risk assessment because of increased risks linked to chronic inflammation. Individuals with psoriasis and RA, irre-spective of disease severity, may be considered at increased ASCVD risk.96-98 In RA, studies show that statins significantly lower all-cause mortality and reduce the progression of atherosclerosis.96-98 Large prospective trials with statin therapy in SLE are lacking;smaller studies(the Lupus Atherosclerosis Prevention Study and Atherosclerosis Prevention in Pediatric Lupus Erythematosus studies) did not show benefit in terms of progression of subclinical measures of atherosclerosis. ${}^{99,100}$ Post hoc analysis of the Treating to New Targets and Incremental Decrease in End Points Through Aggressive Lipid Lowering trials show a similar decrease in event rates in individuals with and without psoriasis when statin was used for secondary prevention.101 A meta-analysis of mostly non-randomized studies involving 148 722 individuals with autoim-mune conditions, including SLE,RA,and T1D, showed that statin use for primary prevention was associated with lower risks of mortality and cardiovascular events.102 Despite limited studies, an

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aggressive approach combining lifestyle and statin therapy is advisable for primary prevention in autoimmune conditions because of the heightened ASCVD risk in these individuals and low side-effect profiles of statins. Small observational studies have shown that moderate- to high-intensity statins may be tolerated by some individuals with immune myopathies.103 However, PCSK9 inhibitors who are considered first-line therapy in certain cases,including those who are symptomatic.

Adults who are Childhood Cancer Survivors

Adult survivors of childhood cancer, in particular those with acute leukemia who received total body irradiation and stem cell transplantation, are at high risk of dyslipidemia, T2D, and osteo-porosis.105-107 The most typical lipid change observed in these individuals is a pattern of low HDL-C and HTG. It is likely caused by systemic features including sarcopenia and lipodystrophy affecting lipid and glucose metabolism.108 Dual X-ray absorpti-ometry will quantify lean body mass and reveal level of sarcope-nia,fat distribution, and bone mineral density.

Interventions based on physical activity have been shown effective in improving the ASCVD risk factor profile.109,110 Such interventions improve metabolic control but will not reverse abnormal fat distribution. A number of case series suggest raised ASCVD risk, but evidence for ASCVD outcomes is sparse.111,112 Because of the multiple ASCVD risk factors associated,105 and recent data documenting accelerated aging and increased CVD risk among childhood cancer survivors,113 it would seem prudent to have a low threshold for lipid-lowering treatment. Signs of short stature and low lean mass should be considered in relation to statin doses.

Adults who are Transplant Recipients

Individuals who have undergone whole organ transplantation have an increased prevalence of dyslipidemia and are at increased risk of ASCVD. They should receive lifestyle counseling and phar-macologic therapy accordingly. Underlying causes for dyslipidemia and possible side effects related to drug-drug interactions should be considered when discussing treatment options(Algorithm Figs. 6 and 8).9,114 Drug-drug interactions include statins and some immunosuppressive agents like cyclosporine and tacrolimus that are metabolized by the same CYP enzymes. Similarly, fibrates should be used with caution because of their interaction with cyclosporine. ${}^{9}$

While there is limited information, particularly for ASCVD outcomes, the use of statins has been reported in several RCTs and observational studies after kidney and heart transplants.115-118 Small decreases in major adverse cardiovascular events and all-cause mortality were observed with the use of statins for kidney and heart transplant; however, event rates and participant numbers are small in available systematic reviews. No differences were seen in renal function or cardiac myopathy, although 1 re-view observed an increase in rhabmyolysis.116

The use of PCSK9 inhibitors has not been extensively evaluated in individuals after organ transplant. A systematic review of 6 studies(97 individuals) saw no serious adverse drug reactions and stable coronary plaque thickness after heart transplant.119 A case series of 12 individuals treated with either PCSK9 mAb after kid-ney transplant showed safety and tolerability with these medica-tions. In addition, no impacts on therapeutic ranges of immunosuppressive agents were observed.120 Based on the limited information available, the task force agrees with the Eu-ropean Society of Cardiology guidelines that statins should be

considered first-line treatment options with consideration for ezetimbe alone or PCSK9 mAb for individuals who are statin-intolerant(Algorithm Fig. 8). ${}^{9}$ However, more trials for lipid-lowering agents are needed to support the management of dysli-pidemia in adults who receive organ transplants.

Management of Hypercholesterolemia in Pregnant and Lactating Individuals

Hypercholesterolemia management during pregnancy requires both the evaluation of the individual's cardiovascular risk and consideration of treatment effects on embryonic and fetal devel-opment(Algorithm Fig. 9). Information on the effects of choles-terol-lowering medications on pregnancy outcomes is limited. In individuals at very high risk of ASCVD, such as those with homo-zygous FH or with severe heterozygous FH and/or a history of underlying ASCVD who are on cholesterol-lowering drugs, a pre-conception discussion with multidisciplinary input regarding the risks and benefits of available treatment options is recommended.Shared decision making should involve the individual, maternal-fetal medicine/obstetrics, and lipidology and cardiology special-ists. In individuals with homozygous FH, an assessment of coro-nary status and severity of aortic stenosis is necessary.Preconception genetic counseling may be advisable for individuals with FH who are contemplating pregnancy.

A lipid profile before pregnancy or when pregnancy is first identified will inform the treatment plan. If dyslipidemia is newly diagnosed, exclusion of secondary causes is necessary. Adherence to a healthy lifestyle with dietary modifications that reduce intake of saturated and trans stats is recommended. Physical activity may need to be adjusted according to pregnancy status.121

Statin use among adults of reproductive age has increased. In 2021, the FDA removed its strongest warning against the use of statins in pregnancy considering that these medications may help reduce serious or potentially fatal events in a small group of high-risk pregnant individuals, including those with FH and/or a history of previous cardiovascular events.122 However, they clarify that statins should be discontinued in most individuals during preg-nancy and not prescribed during lactation.

The first case series documenting the potential teratogenic ef-fect of statins in humans was published in 2004.123 This series reported 70 cases of statin exposure with evaluable birth out-comes, almost all within the first trimester of pregnancy. Adverse outcomes were reported in 30 cases(including 22 structural de-fects and 5 fetal deaths). No adverse outcomes were observed in 20 cases involving pravastatin use, a finding attributed to its hydro-philic properties and low tissue penetration.124 Two small pro-spective randomized trials examining the use of pravastatin for the prevention of pre-eclampsia in the second trimester of preg-nancy125,126 and a large trial that randomized 543 women to pravastatin in the thimester127 did not find an increase in adverse pregnancy outcomes in pravastatin-treated individuals when compared with those taking a placebo. Available systematic reviews and meta-analyses evaluating statin exposure and preg-nancy outcomes are limited by the paucity of data and based mostly on observational studies. Primary studies may have recall and selection bias, rely on drug dispensing or database linkage,and/or have unaddress confounders. Increased risk in overall congenital abnormalities has not been observed. However, there may be an increased risk of cardiac anomalies in addition to an increased risk of spontaneous abortion. ${}^{128-130}$ The differential ef-fect of statins on pregnancy outcomes based on lipophilicity re-mains to be established.130 In view of the limited evidence and

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Management of Hypercholesterolemia in Pregnant and Lactating Individuals

|Hypercholesterolemia|Hypercholesterolemia|Hypercholesterolemia|Hypercholesterolemia|Hypercholesterolemia|Hypercholesterolemia| |---|---|---|---|---|---| |||Preconception|1st Trimester|2nd and 3rd Trimester|Lactation| |TREATMENT OPTIONS: Shared decision-making and multidisciplinary input is essential|||||| |Obtain a baseline lipid profile|||If not done during preconception visit||| |Recommend healthy lifestyle|||||| |Statins to be stopped,4 weeks before conception unless individual is at very high risk(ASCVD/HoFH), desires pregnancy and would like to continue despite potential risk to fetus.|||||| |Request input from maternal-fetal medicine and cardiology.|||||| |Bile acid monotherapy(i.e, colesveemal) may be started/continued(if no HTG). Prescribe fat-soluble vitamins.|√|||√|| |Ezetimibe,niacin,bempedeic acid, and PCSK9 inhibitors(evolocumab,alirocumab,and inclisiran) should be stopped,4 weeks prior to conception|$\checkmark$|||$\checkmark$|| |Individuals with HoFH or HeFH at very high risk or|$\checkmark$||||| |with CVD may continue/consider LDL apheresis|$\checkmark$||||$\checkmark$|

Algorithm Fig. 9. Management of hypercholesterolemia in individuals who are pregnant or lactating.

signals of concern with first trimester use, it is recommended that statins be stopped at least 4 weeks before conception that they be avoided during pregnancy unless the patient's ASCVD risk is very high. In the latter case, statins should be held during the first trimester when the risk of teratogenicity is the highest. If LDL apheresis is available, it may be continued or initiated in in-dividuals with severe hypercholesterolemia and/or ASCVD once statins are discontinued.

Bile acid sequestrants are safe during pregnancy but should be avoided in individuals with HTG121; their cholesterol-lowering effect is modest. Ezetimbe blocks the intestinal absorption of sterols and potentiates the LDL-C-lowering effect of statins. There are insufficient data to support its use in pregnancy.121 The car-diovascular benefits of niacin are questionable, and it crosses the placenta. Its use in pregnancy should be avoided. ${}^{121}$ PCSK9 mAbs cross the placenta more readily as pregnancy progresses. ${}^{131,132}$ A recent Mendelian randomization study modeling fetal LDL-C-lowering through PCSK9 drug targets showed higher odds of fetal malformations. ${}^{133}$ Until future information proves that PCSK9 mAbs are safe in pregnancy, it is recommended that their use be held at least 4 weeks before conception. Lack of outcome data on the embryo-fetal effects of BA and incislar preclude their use in pregnancy. However, incislar is a liver-directed small-interfering RNA molecule that targets PCSK9 mRNA and is undetectable in circulation 48 hours after administration,134 providing months of effective LDL-C lowering ${}^{135}$ and making its use in the preconcep-tion period attractive. Further research confirming the safety of this approach for the treatment of hypercholesterolemia during pregnancy is awaited.

Management of Hypertriglyceridemia in Pregnant and Lactating Individuals

In pregnancy, the goal for management of HTG is preventing TG-induced pancreatitis, a rare but feared complication of dyslipidemia associated with adverse maternal and fetal outcomes, including death(Algorithm Fig.10).136-138 TG levels increase during pregnancy more than 3-fold, a change that mirrors the gestational rise of es-trogen levels.139 The risk of TG-induced pancreatitis is highest during the third trimester of pregnancy when estrogen levels peak and the counter-regulatory effect of placental hormones leads to the development of an insulin-resistant state.139,140 Insulin resistance diminishes lipoprotein lipase activity and promotes excess pro-duction of TG-rich lipoproteins by the liver.

The best approach to avoid the occurrence of TG-induced pancreatitis is prevention. A baseline TG level should be obtained at preconception, and if not obtained then, as early as possible during the first trimester of pregnancy. If fasting TG levels are> 150 mg/dL(1.7 mmol/dL) in the nonpregnant patient or≥250 mg/dL(2.8 mmol/L) during pregnancy, a search for secondary causes of HTG should ensue. Diabetes, obesity, and alcohol commonly un-derlie HTG and must be appropriately managed, ideally in the preconception period, with alcohol discontinuation if applicable.Medications that increase TG levels should be discontinued when possible. Individuals with HTG planning pregnancy should implement healthy lifestyle modifications that will improve TG levels, changes that they will need to sustain and maximize while pregnant to keep their plasma levels below the 500 mg/dL(5.6 mmol/L) range. All TG-lowering medications, except for omega-3

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Management of Hypertriglyceridemia in Pregnant and Lactating Individuals

Hypertriglyceridemia(All Secondary Causes Optimally Minaged)Risk of pancreatitis a$$++\rightarrow+++$$$$++\rightarrow++++$$$$+3^{rd}\rightarrow++++$$$$+$$++→Pre-conception 1st Trimester 2nd Trimester 3rd Trimester Lactation Check lipid profile:If TG 250 mg/dL(2.8 mmol/L) or● If TG 250 mg/dL(2.8 mmol/L) or patient at risk: Monthly monitoring: or patient at risk: Monthly monitoring: dietary adherence of high TG● If TG 250 mg/dL(5.6 mmol/L): further dietary fat restriction and start further dietary fat restriction and start omega-3 FA pharmacotherapy TREATMENT OPTIONS: Shared decision-making and multidisciplinary input are essential Achieve and maintain excellent diabetes control, if applicable,prior to and during pregnancy.Avoid alcohol and medications known to cause HTG.Strict dietary fat restriction of 20-40 g/day depending on HTG severity;20 gTG:285 mg/dL(10 mmol/L)Add medium chain TG oils for calorie supplementation if fats<20 g in diet. Avoid simple sugars. Supplement fat soluble vitamins and essential fatty acids.May continue/start omega-3FA if TG>500 mg/dL(2.8 mmol/L)as applicable,4 weeks prior to conception Avoidest funcortes bine and niacin$$\text{ exceptional circumstances} b$$fibrate, and niacin If TG 285 mg/dL(10 mmol/L)● Consider hospital admission to optimize and support dietary fat restriction to-20 g/day Start/continue 0-3FA; may consider fibrate in 2nd 3rd inextrerexti nptional circumstances b● Consider plasmapheresis if TG remain x1,000-2,000 mg/dL(11.2-22.4mmol/L) on strict dietary fat restriction+omega 3FA acenatents:● NPO status is mandatory when TG:750 mg/dL(8.4 mmol/L may initiate very-low fat diet(-20 g/fat/day)● Insulin infusion if patient has diabetes Consider plasmapheresis if TG remain x1,000-2,000 mg/dL(11.2-22.4mmol/L) and on omega-3FA The risk of acute pancreatitis increases in the second and third trimesters and then decreases positrons a tip or its very low-fat diet(<20 g/fat/day).In subulin infusion if patient has diabetes Consider plasmapheresis if TG remain x1,000-2,000 mg/dL(11.2-22.4mmol/L) and on omega-3FA AACE 2005-2075-2076-2075-2076-2076-2077-2076-2077-2077 AACE 2005-2075-2076-2075-2076-2077-2077-2077-2077 AICE 2005-2075-2076-2075-2076-2077-2077-2077-2077-2077-2077-2077-2077-2077-2077-2077-2077-2077-2077-2077-2077-2077-2

Algorithm Fig. 10. Management of hypertrigherlyceridemia in individuals who are pregnant or lactating.

fatty acids, will need to be discontinued at least 4 weeks before conception; fibrates may be restarted only under exceptional cir-cumstances during the second or third trimesters of preg-nancy.45,136 A dietary pattern such as that of a Mediterranean diet,rich in plants and legumes, fish and olive oil, and low in simple sugars and saturated fats is recommended, with fat restriction depending on TG levels.136,139 Physical activity to support weight management and enhance insulin response is encouraged.139

If TG levels immediately before or during pregnancy are≥250 mg/dL(2.8 mmol/L) or if there is a known history of HTG, lipid levels should be monitored monthly48 and dietary adherence emphasized and supported. If TG levels are<250 mg/dL(2.8 mmol/L) in a low-risk patient in the first trimester of pregnancy, it may not be necessary to check retc PG levels until the start of the third trimester. Any time during pregnancy that TG levels rise above 250 mg/dL(2.8 mmol/L), a search for and management of secondary causes should ensue, including the onset of gestational diabetes. With TG≥500 mg/dL(5.6 mmol/L), strict dietary fat re-striction becomes a priority with referral to a dietician for guid-ance on how to implement meal plans that limit fats to no more than 20 to 40 grams per day. ${}^{136}$ These meals should provide adequate calories, lipid-soluble vitamins, and essential fatty acids,particularly when TGs are higher(≥885-1000 mg/dL or 10-11.3 mmol/L) and more aggressive fat restriction is necessary(≤20 g/day).136,141 Supplementation with medium chain triglycerides can help address caloric needs and do not add to the chylomicron load.136,141

When TG levels are≥500 mg/dL(5.6 mmol/L), TG levels should be followed weekly and response to dietary management

continuously assessed. If TG levels remain above 500 mg/dL(5.6 mmol/L) despite dietary fat restriction and omega-3 FA treatment(prescription grade) in an individual who is pregnant, a brief hospitalization to optimize and support dietary management,including dietary fat restriction under medical observation, may be necessary. Dietary intervention is essential for the management of individuals with severe HTG.141,142 If an individual is in the second or third trimester, some would consider fibrate use, while others would not initiate fibrates unless TGs are≥1000 mg(11.3 mmol/L) and other options, including plasmapheresis, are un-available.48,139 Case reports have been published documenting fibrate use with no observable teratogenic or developmental ef-fects.143-146 A retrospective cohort study with 260 fibrate expo-lures during the first trimester of pregnancy did not find increased teratogenicity unless exposure was>60 days.147 Given the paucity of evidence, fibrates should not be used except in exceptional cases during pregnancy. Caution must be exercised and include shared decision making with the patient and maternal-fetal/obstetric input. It must be acknowledged that the effect of fibrates on TG levels is not immediate and that in individuals with FCS fibrates may not result in TG lowering.148

The risk of pancreatitis is very high when TG levels reach 885 to 1000 mg/dL(10-11.3 mmol/L) and imminent when approaching 2000 mg/dL(22.6 mmol/L).48,136 Supervised dietary management in the hospital setting with<20 grams of fat is recom-mended.48,136,143 Parental nutrition without lipid infusion or with controlled amounts of lipids, as TG levels allow, may be used to support the mother's nutritional status and prevent the risk of low birthweight or premature birth.136,143,149-151 Plasmapheresis is

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an alternative for the management of chylomicronemia in preg-nancy; it effectively and quickly reduces TG levels. Because of its invasive nature, plasmapheresis is usually limited to the man-agement of refractory chylomicronemia in pregnancy when there is imminent risk of pancreatitis and as a bridge to delivery.Plasmapheresis usually requires multiple sessions and may result in complications. If initiated to prevent pancreatitis, use of plas-mapheresis should be limited to HTG in the chylomicronemia range(≥1000 mg/dL or 11.3 mmol/L) and discontinuing sessions when TG fall to<400 mg/dL(4.5 mmol/L).48,136,149 The use of parental nutrition or plasmapheresis in gestational HTG in in-dividuals without pancreatitis should be individualized.

In the individual presenting with HTG-induced pancreatitis, it is critical that a fast be implemented. This approach will clear chylomicrons from circulation. If the individual has diabetes, in-sulin infusion at a starting rate of 0.1 unit per kilogram per hour and intravenous fluids with glucose to maintain euglycemia may be added to the fast. Insulin helps activate lipoprotein lipase and enhances TG clearance. Plasmapheresis is a therapeutic alternative in the management of TG-ing pancreatitis during pregnancy,particularly if TG levels are≥2000 mg/dL(22.6 mmol/L) or if pancreatitis is severe.152,153 Prospective studies in TG-induced pancreatitis documenting benefits from plasmapheresis are lack-ing; there does not appear to be a mortality benefit[152,153] but a small observational study in pregnancy suggests that it may reduce length of hospitalization.154 Consideration may be given to intravenous fluids with glucose to provide calories or to parenteral nutrition(lipid-deplete or with low fat content as TG levels allow)to support the nutritional needs of the mother and fetus while fasting is in place.149-151 In HTG-induced pancreatitis, oral intake

$$\text{ may be restituted once TGs are}<750 mg/ dL(8.5 mmol/L)\text{ with}$$adherence to strict dietary fat restrictions(≤20 g fat/day) that may be further relaxed(30-40 g/day) when TG decline to<500 mg/dL(5.6 mmol/L).

Summary of FDA-Approved Medications for Dyslipidemia

While appropriate nutrition and physical activity are essential to management of dyslipidemia, pharmacotherapy is needed for many to lower the risk for ASCVD or pancreatitis. The table of“FDA-Approved Medications for Dyslipidemia” summarizes cur-rent FDA-approved medications for adults with hypercholester-olemia and HTG(Algorithm Fig.11) that are used most frequently in practice. Not included in the table are medications that are currently approved only for treatment of rare forms of genetic dyslipidemia, such as homozygous FH and FCS. Information on dosing, route of administration, observed ASCVD benefit, potential side effects, and contraindications are provided. To review the evidence for these medications, clinicians should consult recent AACE guidance documents including the 2025 AACE Guideline for Pharmacologic Management of Adults with Dyslipidemia. ${}^{3,5,7}$

Review Process

Drafts is constants statement were reviewed and approved by all task for force members, the AACE Clinical Practice Guidelines Oversight Committee, the AACE Board of Directors, and peer reviewers for Endocrine Practice. In addition, co-sponsoring

FDA-Approved Medications for Dyslipidemiaa

||Mechanism of Action|Delivery|Dose|Evidence of ASCVD Benefit& Benefit|Adverse effects|Cautions/Contraindications|Cost d| |---|---|---|---|---|---|---|---| |Statins|$$\text{ HMG-CoA Reductase inhibitors,}$$ up-regulate LDL-R expression,and increase LDL clearance|Oral|Varies(see LDL-C treatment slide for doing)|$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$|Myalgias/ myopathy|Individuals who are pregnant/ breastfeeding, or with moderate to severe hepatic function impairment|$| |Ezetimibe|Inhibits cholesterol absorption via NPCL1|Oral|10 mg once daily|$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$|Mild diarrhea|Individuals who are pregnant/ breastfeeding, or with moderate to severe hepatic impairment|$| |Bile acid sequestrants|Block enterohepolic recirculation of bile acids decreasing cholesterol availability, increasing LDL-R expression and LDL-C clearance|Oral|Coleovskal 625 mg tab: 3 tab bid or 6 tab once daily OR 3.75g powder for suspension once daily + Choleystramine 4.24 g powder for suspension in 2 to 4 divided doses|$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$|Contation, HTG|Individuals with history of bowel obstruction,triglycerides,300 mg/dL. Must be dosed 2h or 4h after dosing of other oral medications|$| |Aliarocumab|Human monoclonal Ab that binds PCSK9, interfering with LDL-R degradation, thereby increasing LDL-C clearance|SC|75-150 mg every 2 weeks or 300 mg monthly|$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$|Injection site the reaction,flu-like symptoms|$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$|$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$| |Inclisrinol*|Small interfering RNA that inhibits synthesis of PCSK9, interfering with LDL-R degradation, thereby increasing LDL-C clearance|SC|284 mg once, again at 3 months and then every 6 months|n/a||Individuals who are pregnant/ breastfeeding or are allergic to medication or product ingredients|$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ $| |Bempedic Acid|Inhibits adenosine triphosphate-citrate lyase activity, reducing hepatic cholesterol synthesis, increasing LDL-R expression and LDL-C clearance|Oral|180 mg once daily|$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \end{array}$$|Hyperuremia, gout,tendon, toward rupture||$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$| |EPA/IPE|Reduction|Oral|2 g twice daily with meals|$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \end{array}$$|Hemorrhage,atrial flutter/fibrillation|Individuals who are allergic to medication or product ingredients|$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$| |Fibrates|Activate PPAR with increased lipoprotein|Oral|Various class members and daily doses|+/-|Skin rash,dearhea|Individuals who are pregnant, breastfeeding, or with moderate-severe hepatic dysfunction--caution when combining gemibrozil with certain statins|$|

2005 A. Cincine Clinical Practice Guideline for the Pharmacological Management of Actuis Dyspidemia 2025; AACE 2022 Comprehensive Diabetes Care Partl: 2020 AACE Dysdipemia A ginteria Aglir 2020 AICE 2020

c. Most frequently reported adverse which may result in stopping and medication

c. Approximate relative cost by indicated x. expact cost vary based on region/location, insurance coverage, and pharmacy benefits.

e.f. Use a fibres of tiser in abstract to severe hyperinegialidea. Berichhe Heihage.2022. A modern approach to modern adipemia. Endlence Rev.43(4):61-653.

COPYRIGHT@2025 ACE.MAY are not reproduced in a form without express written as permission from behalf of AACE. Vol https://doi.org/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/10.1016/1

Algorithm Figure 11-Medication Table

Algorithm Fig.11. FDA-approved medications for dyslipidemia.

S.B. Patel, LM. Delbazar, S. Afteren et al.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGY

2025

Algorithm for Management of Adults with Dyslipidemia

Algorithm Title Page

SB.Patel,L.M.Balataraz,S.frenren et al.

Algorithm for Management of Adults with Dyslipidemia

1. Guiding Principles for Management of Adults with Dyslipidemia

2.Risk Assessment and Testing for Dyslipidemia

3.Identifying Genetic Dyslipidemias

4. Specific Lifestyle Recommendations for Adults with Dyslipidemia

5.Targeting LDL-Cholesterol with Pharmacologic Therapy for ASCVD Prevention in Adults

6. Approach to Statin-Associated Muscle-Symptoms in Adults

7.Management of Adults with Hypertriglyceridemia

8.Management of Special Populations with Dyslipidemia

9.Management of Hypercholesterolemia in Individuals who are Pregnant or Lactating

10.Management of Hypertriglyceridemia in Individuals who are Pregnant or Lactating

11.FDA-Approved Medications for Dyslipidemia

Abbreviations:AACE,American Association of Clinical Endocrinology; ApoB.apolipoprotein B:ApoC,apolipoprotein C;ASCVD,atherosclerotic cardiovascular disease;BA,bempedolic acid;CAC,coronary artery calcium;CKD,chronic kidney disease;CVD,cardiovascular disease;EPA,eicosapentaenoic acid;FCS,familial chylomicronemia syndrome;FDA,U.S.Food and Drug Administration;FH,familial hypocholesterolemia:HDL,high-density lipoprotein;HeFH,heterozygous familial hypercholesterolemia;hsCRP,high-sensitivity C-reactive protein;IPE,icosapent ethyl;LCAT,Lecithin cholesterol acyltransferase;LDL-C,low-density lipoprotein cholesterol;Lp(a),lipoprotein a;MASLD,metabolic dysfunction-associated steatotic liver disease;MCT,medium chain triglycerides;ML,myocardial infarction; PCSKproprotein convertase subtilisin/kexin type9:T1D,type1 diabetes mellitus:T2D,type 2 diabetes mellitus:TC,total cholesterol;TG,triglyceride;TZD,thiazolidinediones

S.B.Pacel,L.M.Balatazar,S.Afren et al.

Guiding Principles for Patient-Centered Management of Dyslipidemia

●Assess risk of ASCVD and pancreatitis in individuals with hypertriglyceridemia, especially when TG≥885 mg/dL(10 mmol/L).

●Assess and address underlying causes of dyslipidemia including dietary and lifestyle factors,co-morbidities,medications,and genetics(where applicable).

● Engage with individuals and caregivers about the importance of diet, physical activity,and adoption of healthy lifestyle patterns with considerations for access to healthy food and safe spaces for physical activity.

● Where pharmacotherapy is indicated, use shared decision-making to assess risk and benefits as well as goals of therapy.

● Use caution in prescribing medications for certain populations for which there is limited evidence, especially for individuals who are pregnant or lactating.

●Develop management plans that incorporate individual preferences and values, adhere to health equity principles,and are culturally sensitive. Considerations should include medication availability,affordability,and access to health care services.

● To improve adherence, discuss the treatment rationale and need of long-term therapy with individuals and caregivers.

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Risk Assessment and Testing for Dyslipidemia

•Emphasize life-long adoption of healthy lifestyle changes(diet,exercise,stress reduction,restful sleep,avoidance of tobacco,and a healthy body weight)

● Treat all cardiometabolic risk factors in an integrated manner

For primary prevention, use a validated risk assessment calculator to determine risk of future ASCVD risk.Emphasize healthy life-style modifications to all.

Low risk(7.5%)

Intermediate risk(7.5-20%)

High risk(20%)

Focus on lifestyle interventions

● Consider additional risk enhancers

Recommend pharmacotherapy

•Engage in shared decision-making regarding treatment

Example Risk Assessment Tools or Calculators a

1.PCE10-year risk calculator-https://tools.acc.org/ascvd-risk-estimator-plus/#/calculate/estimate/

2. PREVENT risk calculator-https://professional.heart.org/en/guidelines-and-statements/prevent-calculator

3. Framingham risk score-https://www.mdalc.com/calc/38-framingham-risk-score-hard-coronary-heart-disease

4. SCORE2 & SCORE2-OP-https://www.escardio.org/Education/Practice-Tools/CVD-prevention-toolbox/SCORE-Risk-Charts

5. PAHO HEARTS Cardiovascular Risk Calculator https://www.paho.org/en/hearts-americas/cardiovascular-risk calculator-app

6.QRISK-https://qrisk.org/

Additional risk enhancers:

● Family history

● Cardiometabolic disease

Additional Testing:B

CAC score/ or 2D-3D

•Carotid and femoral

ultrasound

●Lp(a)

• ApoB

·hsCRP

ApoB

Algorithm Figure 2-Risk Assessment

S.B.Pater,LM,Balazar,S.A/freen et al.

ARTICLE IN PRESS

AACE

Follow up Specialist endocrine or lipid clinic management(see narrative for treatment options)

a See narrative for additional conditions with xanthomas, such as sitosterolemia and corebrotendinous xanthomatosis, and with hepatosteatosis, namely lysosomal acid lipase deficiency.

COPYRIGHT©2025 AACE. May not be reproduced in any form without express written permission from Elsevier on behalf of AACE. Visit https://doi.org/10.1016/j.eprac.2025.07.014 to request copyright permission.

Endocrine Practice xx(xxx) xxx

S.B.Parter,L.M.L.Bebatarz,S.Aprent al.

![General Evidence-Based Advice\nConsume\n Limit/Avoid\n Foods\n● Fruit,nuts, vegetables, whole grains, and legumes\n● Fish and chicken\n● Low fat dairy\n● Non-tropical oils such as olive oil\n● Dietary patterns\n● Mediterranean diet\n● Dash diet\n● Healthful plant-based diet\nHypercholesterolemia\nTreatment priority: Cardiovascular disease\nTreat underlying medical\nconditions (i.e hypothyroidism, nephrotic syndrome, etc.)\nDietary interventions: Limit saturated /trans fats ● Increase fiber-rich foods\n](2/aj0YEe4oUhYkBdfpda0fYP/figure1d92cb5873364961b273369c0d3c2595_0_2.png) |Hypertriglyceridemia|Hypertriglyceridemia|Hypertriglyceridemia|Hypertriglyceridemia|| |---|---|---|---|---| |Triglycerides|Triglycerides|150-499 mg/dL (1.7-5.6 mmol/L)|500-884 mg/dL (5.6-9.9 mmol/L)|| |Pancreatitis risk|Pancreatitis risk|$\rightarrow\uparrow\uparrow$|$\uparrow\uparrow\uparrow$|| |Treatment priority|Treatment priority|Prioritize CVD risk+address pancreatitis risk|Prioritize pancreatitis risk+address CVD risk|| |Treat underlying medical conditions|Diabetes | Overweight/obesity/Alcohol Use Disorder/etc|||| |Identify medications known to increase triglycerides|Consider alternatives|Avoid and eliminate||| |Required Dietary|Fat content|~30% of calories as fat|20-30 g fat/day|<15-20 g fat/day| |Required Dietary|Type of fat|Limit saturated/ trans fat|● Avoid saturated& trans fats ● If chronic:MCTs and fat-soluble vitamins|| |Carbohydrates Limit/avoid suged foods and drinks | Eat fiber-rich foods||||| |Alcohol|Alcohol|Avoid and eliminate|Avoid and eliminate||

COPYRIGHT@ 2025 AACE. May not be reproduced in any form without express written permission from Elsevier on behalf of AACE. Visit https://dol.org/10.1016/j.eprac.2025.07.014 to request copyright permission. Algorithm Figure 4-Lifestyle Recommendations

S.B. Patel, LM. Belaudazar, S. Afteren et al.

Targeting LDL-Cholesterol with Pharmacologic Therapy for ASCVD Prevention in Adults

![Primary Prevention\nCounsel on lifestyle modifications that reduce ASCVD risk\nSecondary Prevention (Clinical ASCVD)\nSecondary Prevention (Clinical ASCVD)\nAssess ASCVD risk*\nLow risk\nLow risk\nIf LDL-C above goal or continues to have CV (t4.9 mmol/L) c\nConsider moderate-tive statin\nConsider moderate-tive statin\nConsider add-on therapy: bempedoic acid, PCSK9-based therapy, or bile acid resins\nPCSK9-based therapy, or bile acid resin\nNote: Not all add-on agents have evidence for reducing ASCVD risk. Use shared decision-making to discuss benefits and harms and harms of the individual therapies.*\n](2/aj0YEe4oUhYkBdfpda0fYP/figurec22d874d47a94f3f9bf51b0e83f24cf0_0_3.png) AACE suggests treating individuals with ASCVD or increased risk of ASCVD to an LDL-C target of 70 mg/d.Lot potential impacts from polypharmacy and the increased costs with certain earnings and risks of harms of the individual therapies.*

|High Intensity Statin|Rosuvatin 5-10 mg|Atorvatin 10-20 mg|Moderate-intensity Statin|Simvastatin 20-40 mg|Pitavastatin 2-4 mg| |---|---|---|---|---|---| |Atorvastatin 40-80 mg|Fluvastatin XL 80 mg|Fluvastatin XL 80 mg|Pravastatin 40-80 mg|Lovastatin 40 mg|Lovastatin 40 mg|

a Use a validated risk tool(see full list of fun history of premature coronary disease carries increased ASCVD Eii, he HS CRP, CAPC score, ApoB, or Ltp(a) to the risk model(see 2025 AACE Dysdipemia Guideline)

Individual with diabetes and age 40 or younger if ASCVD risk factors are present with electronic production factors. See the narrative for additional details on familial hypercholesteromia(HF).Cotvign whether the oleid LDL-Ctrend is genetic or acquired, and exclude secondary causes, including dietary factors. See the narrative for accordance 10.1016/1027.014 to request copyright permission.

![Approach to Statin-Associated Muscle Symptoms in Adults\n Definition: One or more muscular complaints (myalgia, weakness, tenderness) improved or resolved after dose reduction/discontinuation. Minimum of 2 statin-treatment attempts(including 21 at the lowest approved dose), a\n Definition: One or more muscular complaints (myalgia, weakness, tenderness) improved or resolved after dose reduction/discontinuation. Minimum of 2 statin-treatment attempts(including 21 at the lowest approved dose), a\n Use shared decision-making to discuss benefits and harms of the individual therapies\n Consider rechallenge with other statin, or lower dose (including alternate-day dosing)\n](2/aj0YEe4oUhYkBdfpda0fYP/figure1ff0ca1886a843639a295df4f5869918_0_2.png) a Warden BA, Guyton Jr,R.Kovacs AC,Durham JA,Jones LK,Dixon Dlin,Jacobson TA,Dueli PB,Assessment and management of statin-assembly of muscle symptoms(SAMS);

b Aclinical perspective from the National Lipid Association.J Clin Lipidol.2023 Jan-Feb;17(10:19-39. doi:10.1016/j.jacl.2022.09.001

c Adapted from Handelsman Y,Jellinger PS,Guerrin CK,et al.Consensus Statement by the American Association of Endocrinology on the Management of Dysdipideria and Prevention of Cardiovascular Disease Algorithm-2020 Executive Summary.Endor Pract.2020/26/10.1186-1224.20/10.1016/10.1000.2025.07.014 to request copyright permission.

CapyRiGHT©2025 AACE May not be reproduced in any form without express written permission from Elsevier on behalf of AACE. Visit https://dol.org/10.1016/j.eprac.2025.07.014 to request copyright permission.

S.B. Patel, LM. Beladaar, S. After en

Management of Adults with Hypertriglyceridemia(HTG)

![#Management of Adults with Hypertriglyceridemia (HTG)\nIn all individuals with HTG\n>150 mg/dL or $>1.7 mmol/L$ \nClinical assessment: Hylomicronemia syndromes (familial and multifactoral)\n● Nausea, vomiting, failure to thrive, abdominal pain, pancreatitis risk;\n● Nausea, vomiting, failure to thrive, abdominal pain, pancreatitis risk;\n● Nausea, vomiting, failure to thrive, abdominal pain, pancreatitis risk;\n● Nausea, vomiting, failure to thrive, abdominal pain, pancreatitis risk;\n● Nausea, vomiting, failure to thrive, abdominal pain, pancreatitis risk;\n● Nausea, vomiting, failure to thrive, individual, and may be able to achieve the same dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics\n\nTo Changeatitis prophylaxis | Rx: low fat diet, fibrate and/or omega-3 FA\nProgress in 8-12 weeks b\nTo start& statin; monitor LDL-C\nTo start& statin; monitor LDL-C or non-HDL-C or Apo B\nReassess in 8-12 weeks b\nTo Search in 8-12 weeks b\nTo start& statin; monitor LDL-C or non-HDL-C or Apo B\nYes; consider icosapent ethyl for TG 150 - 500 mg/dL (1.7 - 5.6 mmol/L)\nTo follow LDL-C algorithm\nADF\nArchitecture xx (x/x) Exslier on behalf of AACE, Visit https://dolorg/10.1016/j.expracy/2025.07/014 to request copyright permission.\nTo start& statin; monitor LDL-C or non-HDL-C or Apo B\nLD-L-C target attained? \nYes; consider icosapent ethyl for TG 150 - 500 mg/dL (1.7 - 5.6 mmol/L)\nTo follow LDL-C algorithm\nAACE\n52.04\n Postline, JEXE1000\n\n\n](2/aj0YEe4oUhYkBdfpda0fYP/figure0a8fb56e29e2467fb5b90dd70f6dda8b_0_4.png) 25

S.B.Pater,LM,Belbazar,S.Arenet al.

![Management of Special Populations with Dyslipidemia\nOlder Adults (70y)\nCounsel on lifestyle changes recommended for all groups\nAcge is an independent risk factor\nGreater impact of lipid-lowering on ASCVD, but consider co-morbidity and life expectancy\nexpectancy\n● Trans women have lower risk than matched cis men\n● Trans men have similar risks as cis women\n● Early Upatinson of ASCVD\n● Death of high-quality studies\n● Mar. 2005\n● Exsecting in SCSy\n● Defect and high-roratory studies\n● May use or resystatin\n● Low and high-roratory studies\n● Consider evaluative impact and therapy\n● Consider evaluative impact and high\n● Ace is an independent risk factor\n● Interferent of ASCVD\n● Adults living with HIV\n● Homar perfusion of ASCVD\n● Homar perfusion of ASCVD\n● Homar pertainable results in\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effect, may be a\n● Homer effec\n](2/aj0YEe4oUhYkBdfpda0fYP/figurec827a64996724c16b135ba5ce9a0a21e_0_3.png) S.B. Patel, LM. Belauzao, S. Aften

Management of Hypercholesterolemia in Pregnant and Lactating Individuals

|Hypercholesterolemia|Hypercholesterolemia|Hypercholesterolemia|Hypercholesterolemia|Hypercholesterolemia| |---|---|---|---|---| |Management Plan|Preconception|1st Trimester|2nd and 3rd Trimester|Lactation| |TREATMENT OPTIONS: Shared decision-making and multidisciplinary input is essential||||| |Obtain a baseline lipid profile|√|If not done during preconception visit||| |Recommend healthy lifestyle||||| |Statins to be stopped>4 weeks before conception unless individual is at very high risk(ASCDV/HoFH), desires pregnancy and would like to continue despite potential risk to fetus|x||Statins should generally be avoided.May be considered for very high-risk individuals.|Avoid statins as they are found in breastmilk| |Bile acid monotherapy(i.e, colesevelam) may be started/continued(if no HTG). Prescribe fat-soluble vitamins.|√|√|√|$\checkmark$| |Ezetimibe,niacin,bempedoic acid,and PCSK9 inhibitors (evolocumab,alirocumab,and inclisiran) should be stopped 4 weeks prior to conception|√|$\times$|$\times$|$\times$| |Individuals with HoFH or HeFH at very high risk or with CVD may continue/consider LDL apheresis|√|||AACE|

S.B.Patel,L.M.Lm.Balazar,5.Afrenet al.

Management of Hypertriglyceridemia in Pregnant and Lactating Individuals

|Hypertriglyceridemia(All Secondary Causes Optimally Managed)|||| |---|---|---|---| |Risk of pancreatitis a|++→+++|+++→++++|+++→+| |Pre-conception|1st Trimester 2nd Trimester|3rd Trimester|Lactation| |Obtain a baseline lipid profile if at risk or if history of high TG|Check lipid profile: 2stary monolari patient at risk: Monthly monitoring; dietary adherence ● If TG $\geq$ 500 mg/dL(5.6 mmol/L): further dietary fat restriction and start omomega-3 FA pharmacotherapy|Check lipid profile: ● If TG $\geq$ 500 mg/dL(2.8 mmol/L) or patient at risk: Monthly monitoring; dietary adherence ● If TG $\geq$ 500 mg/dL(5.6 mmol/L): further dietary fat restriction and and pharmacotherapy|if TG during pregnancy;V500 mg/dL,recheck levels at 3-7 days postpartum| |TREATMENT OPTIONS: Shared decision-making and multidisciplinary input are essential Achieve and maintain excellent diabetes control, if applicable, prior to and during pregnancy is known to cause HTG. 2|||| |Strict dietary fat restriction of 20-40 g/day depending on HTG severity: 20 g if TG $\geq$ 885 mg/dL(10 mmol/L) Add medium chain TG oils for calorie supplementation if fats20 g in diet. Avoid simple sugars. Supplement fat soluble vitamins and essential fatty acids.|||| |May continue/start omega-3 FA if TG>500 mg/ dL(2.5 mmol/L) despite dietary fat restriction|||| |Discontinue statin, fibrate and niacin, if applicable,2 4 weeks prior to conception|May consider fibrate in 2nd or 3rd trimester in exceptional circumstances b|Avoid statin, fibrate, and niacin|| |IFTOB85 mg/dL(10 mmol/L): ● Consider hospital admission to optimize and support dietary fat restriction to<20 g/day|||| |- Start/continue omega-3-FA; may consider fibrate in 2nd or 3rd trimester in 2000-2,000 mg/dL(11.2-22.4 mmol/L) on strict dietary fat restriction+omega-3FA|||| |- Consider plasmapheresis if TG remain 21|mg/dL(<8.4 mmol/L may initiate very-low fat diet(<20 g fat/day)||| |●NPO status is mandatory; when TG.750 mg/dL(<8.4 mmol/L may initiate very-low fat diet(<20 g fat/day)|||| |●Insulin infusion if patient has diabetes|||| |●Consider plasmapheresis if TG remain 21|0000-2,000 mg/dL(11.2-22.4 mmol/L) and on omega-3FA||| |●Consider plasmapheresis if TG remain 21|0,000,000 mg/dL(11.2-22.4 mmol/L) and on omega-3FA|||

S.B.Patel,L.M.Bladrazaz,S.Afrenet al.

FDA-Approved Medications for Dyslipidemiaa

||Mechanism of Action|Delivery|Dose|Evidence of ASCVD Benefitb|Adverse Effectsc|Cautions/Contraindications|Costd| |---|---|---|---|---|---|---|---| |Statins|HMG-CoA ReductaseInhibitors, up-regulate LDL-R expression,and increase LDL clearance|Oral|Varies (see LDL-CTreatment slide for dosing)|++|Myalgias/ myopathy|Individuals who are pregnant/ breastfeeding, or with moderate to severe hepatic function impairment|$| |Ezetimibe|Inhibits cholesterol absorption via NPCIL1|Oral|10 mg once daily|++|Mild diarrhea|Individuals who are pregnant/ breastfeeding, or with moderate to severe hepatic impairment|$| |Bile acid sequestrants|Block enterohepatic recirculation of bile acids decreasing cholesterol availability, increasing LDL-R expression and LDL-C clearance|Oral|● Colesevelam 625 mg tab:3 tab bid or 6 tab once daily OR3.75g powder for suspension once daily ● Cholestryamine 4-24 g powdeer for suspension in 2 to 4 divided doses|+|Constipation, HTG|Individuals with history of bowel obstruction,triglycerides;300 mg/dL. Must be dosed 2h or 4h after dosing of other oral medications|$ $\$ $$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$| |Alirocumab|Human monoclonal Ab that binds PCSK9, interfering with LDL-R degradation, thereby increasing LDL-C clearance|SC|75-150 mg every 2 weeks or 300 mg monthly|++|Injection site reactions,flu-like symptoms|$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$|$\ $$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$| |Evolumabc|Human monoclonal Ab that binds PCSK9, interfering with LDL-R degradation, thereby increasing LDL-C clearance|SC|75-150 mg every 2 weeks or 300 mg monthly|++|Injection site reactions,flu-like symptoms|$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$|140 mg every 2 weeks or 420 mg monthly| |Inclisiran®|Small interfering RNA that inhibits synthesis of PCSK9, interfering with LDL-R degradation, thereby increasing LDL-C clearance|SC|284 mg once,again at 3 months and then every 6 months|++|Injection site reactions,flu-like symptoms|$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$|| |Bempedoic Acid|Inhibits adenosine triphosphate-citrate lyase activity,reducing hepatic cholesterol synthesis, increasing LDL-R expression and LDL-C clearance|Oral|180 mg once daily|$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$||Hyperuricemia, gout,tendon rupture|$ $\$| |EPA/IPE|Reduction in hepatic production of VLDL, activation of lipoprotein lipase|Oral|2 g twice daily with meals|$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$|$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \end{array}$$|Individuals who are allergic to medication or product ingredients|$ $\$| |Fibrates|Activate PPAR with increased lipoprotein lipase activity and hepatic and fatty acid oxidation and lowering of VLDL production|Oral|Various class members and daily doses|+/-|Skin rash,|individuals who are pregnant, breastfeeding, or with moderate-severe hepatic dysfunction--caution when combining gemfibrozil with certain statins|$ $$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$|

a.Not listed: Medications approved for treatment of rare forms of genetic dyslipidemia(see narrative)

b.2025 AACE Clinical Practice Guideline for the Pharmacological Management of Adults with Dyslipidemia. 2025; AACE 2022 Comprehensive Diabetes Care Plan; 2020 AACE Dyslipidemia Algorithm

c.Most frequently reported adverse which may result in stopping/adjusting medication

d.Approximate relative cost indicated by$,exact cost will vary based on region/location,insurance coverage,and pharmacy benefits).

e.Available only by injection at a healthcare facility.

f. Use of fibrates is limited to treatment of severe hypertriglyceridemia. Berberich and Hegele.2022.A modern approach to dyslipidemia. Endo Rev.43(4):611-653.COPYRIGHT@2025.ACE May not be reproduced in any form without express written permission from Elsevier on behalf of AACE. Valk https://dol.org/10.1016/japrac.2025.07.014 to request copyright permission.

Algorithm Figure 11-Medication Table

S.B. Patel, L.M. Belalcazar, S. Aforeen et al.

Endocrine Practice xxx(xxxx) xxx

organizations provided review prior to endorsement of the document.

Panel Composition

This consensus statement was developed by an international group of credential medical professionals in the fields of endo-crinology, lipidology, and diabetology. The task force was empaneled in accordance with the AACE Conflict of Interest and Diversity,Equity,and Inclusion policies and included members of AACE and co-sponsoring organizations.

Disclosures

Disclosures were obtained, reviewed, and managed according to the AACE Conflicts of Interest Policy updated in 2023(https://pro.aace.com/about/aace-conflicts-interests-policy). See Appendix A for the full list of disclosures.

Acknowledgments

The task force is grateful for the contribution and framework provided by the authors of the 2020 committee. The task force also thanks the AACE CPG Oversight Committee, Co-sponsoring orga-nizations, and all those of the 2020 committee, Co-sponsoring orga-nizations.

Funding

The algorithm for the management of adults with dyslipidemia was developed with financial support from AACE. AACE received no outside funding for the development of this guidance docu-ment. All members who served on this AACE task force completed the work electronically and met via video conference. Volunteer authors received no remuneration for their participation in the development of this guidance document.

Document Retirement Date: October 2030

AACE reviews and updates or retires its guidance documents five years following publication or sooner if significant scientific developments or change in public policy occurs.

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表 1
	High LDL-C 190 mg/dL (4.9 mmol/L)	Low LDL-C 199 mg/dL (1.0 mmol/L)	High TG 885 mg/dL (10 mmol/L)	High TG and TC 530 mg/dL for TG and 230 mg/dL for total cholesterol(6 mmol/L for both)	Extreme HDL-C 8 mg/dL(0.2 mmol/L) or 116 mg/dL(63 mmol/L)
Clinical assessment	Xanthomas,*atherosclerosis, Family history Likelihood scoring: ● Dutch Lipid Clinic ● Simon Broome ● Welsh	Fat intolerance, hepatostatosis, blood film for acanthocytes, fat soluble vitamin deficiencies	Eruptive xanthomas, panceatitis hadefinitioes, lipemia retinals	Tubero-eruptive xanthomas, Apo B(120 mg/dL, TG: Apo B(10:1 TC: Apo B:6:2:1	Corneal arcconal opacities, xanthomas, renal impairment, peripheral neuropathy, enlarged orange tonsils, blood film
Secondary factors (genetic testing needed only if lipid abnormality persists after adjustment of secondary factors)	Diet, excessive alcohol, anabolic steroid use, hypothyroidism,anorexia nervosa, liver disease, nephrotic syndrome, (consider especially if historic LDL-C>155 mg/dL (4 mmol/L)	Lipid-lowering therapy, cachexia,malnutrition,malsublation, chronic liver disease, chronic pancreatitis, cystic fibrosis,end stage renal disease	Excessive alcohol, obesity, poor glycemic control,lipodystrophy, nephrotic syndrome, retinody, atypical anti-lypsychotics,glucocorticoids, estrogens and beta-blockers	Recent weight gain, new T2D, new medication, hypothyroid male sex, change in hormone status	Drugs(fibrates,TZDs, anti-epileptics, estrogens, niacin), pesticide exposure, excessive alcohol
Genetic test	LDLR,APOB,PCSK9, LDLRAP1,ABCG5/G8,LIPA, APOE.LDL-C polygenic score	MTTP,APOB,PCSK9, ANGPT3,S1R8	LPL,PGIHPB1,APOA5, APOC2,LMF1	APOF E2/2 genotype; rarely APOE dominant variant	Low HDL-C: ABCA1, LCAT, APOA1 High HDL-C: CETP SCARB1, LIPC,LIPG,APOC3
Condition	Familial or polygenic hypercholesterolemia, sitsterolemia, LIPA-deficiency	Hypobetalipoproteinemia	Familial chylomicronemia, multifactorial chylomicronemia	Dysbetalipoproteinemia	Tangier,LCAT deficiency, Fish-eye disease
Follow up		Specialist endocrine or lipid clinic management(see narrative for treatment options)

表 2
General Evidence-Based Advice
Consumer	Limit/Avoid
	Foods
	●Fruit,nuts,vegetables,
	●Ultra-processed foods
	●Red meat
	● Low fat dairy
	● Non-tropical oils such as
olive oil	●Fried/deep fried food
	● Alcohol(limit/avoid/ eliminate) ● Large portions
	● Dietary Patterns
● Mediterranean diet
. DASH diet
	● Healthful plant-based diet

表 3
Hypertriglyceridemia	Hypertriglyceridemia	Hypertriglyceridemia	Hypertriglyceridemia
Triglycerides	150-499 mg/dL (1.7-5.6 mmol/L)	500-884 mg/dL (5.6-9.9 mmol/L)	2885 mg/dL(10 mmol/L)
Triglycerides	150-499 mg/dL (1.7-5.6 mmol/L)	$\uparrow\uparrow$	$\uparrow\uparrow\uparrow$
Pancreatitis risk	Pancreatitis risk
Treatment priority	Treatment priority	Prioritize pancreatitis risk+address CVD risk
Treatment priority	Treatment priority
Treat underlying medical conditions	Diabetes	Overweight/obesity/Alcohol Use Dis
Intenify medications known to increase triglycerides	Avoid and alternatives
Identify诱terricides	Identify诱terricides	Eliminate eliminate	Eliminate eliminate
Required Dietary Management	Fat content Type of fat	~30% of calories fat	~30% of calories fat	20-30 g fat/day
Required Dietary Management	Fat content Type of fat	Limit/avoid Limited/avoid rans saturated/trans fat	• Avoid saturated& trans fats If chronic: MCTs and fat-soluble vitamins
	Carbohydrates	foods and drinks	Eat fiber-rich foods
Dietary interventions:	Alcohol	Limit/avoid eliminate	Eliminate

表 4
Hypercholesterolemia
Treatment priority:Cardiovascular disease
Treat underlying medical conditions(i.e hypothyroidism, altenatives to medications nephromic syndrome,etc.)
Dietary interventions: Limit saturated/ trans fats $\cdot$ Increase fiber-rich foods

表 5
Hypercholesterolemia	Hypercholesterolemia	Hypercholesterolemia	Hypercholesterolemia	Hypercholesterolemia	Hypercholesterolemia
		Preconception	1st Trimester	2nd and 3rd Trimester	Lactation
TREATMENT OPTIONS: Shared decision-making and multidisciplinary input is essential
Obtain a baseline lipid profile			If not done during preconception visit
Recommend healthy lifestyle
Statins to be stopped,4 weeks before conception unless individual is at very high risk(ASCVD/HoFH), desires pregnancy and would like to continue despite potential risk to fetus.
Request input from maternal-fetal medicine and cardiology.
Bile acid monotherapy(i.e, colesveemal) may be started/continued(if no HTG). Prescribe fat-soluble vitamins.	√			√
Ezetimibe,niacin,bempedeic acid, and PCSK9 inhibitors(evolocumab,alirocumab,and inclisiran) should be stopped,4 weeks prior to conception	$\checkmark$			$\checkmark$
Individuals with HoFH or HeFH at very high risk or	$\checkmark$
with CVD may continue/consider LDL apheresis	$\checkmark$				$\checkmark$

表 6
	Mechanism of Action	Delivery	Dose	Evidence of ASCVD Benefit& Benefit	Adverse effects	Cautions/Contraindications	Cost d
Statins	$$\text{ HMG-CoA Reductase inhibitors,}$$ up-regulate LDL-R expression,and increase LDL clearance	Oral	Varies(see LDL-C treatment slide for doing)	$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$	Myalgias/ myopathy	Individuals who are pregnant/ breastfeeding, or with moderate to severe hepatic function impairment	$
Ezetimibe	Inhibits cholesterol absorption via NPCL1	Oral	10 mg once daily	$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$	Mild diarrhea	Individuals who are pregnant/ breastfeeding, or with moderate to severe hepatic impairment	$
Bile acid sequestrants	Block enterohepolic recirculation of bile acids decreasing cholesterol availability, increasing LDL-R expression and LDL-C clearance	Oral	Coleovskal 625 mg tab: 3 tab bid or 6 tab once daily OR 3.75g powder for suspension once daily + Choleystramine 4.24 g powder for suspension in 2 to 4 divided doses	$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$	Contation, HTG	Individuals with history of bowel obstruction,triglycerides,300 mg/dL. Must be dosed 2h or 4h after dosing of other oral medications	$
Aliarocumab	Human monoclonal Ab that binds PCSK9, interfering with LDL-R degradation, thereby increasing LDL-C clearance	SC	75-150 mg every 2 weeks or 300 mg monthly	$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$	Injection site the reaction,flu-like symptoms	$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$	$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$
Inclisrinol*	Small interfering RNA that inhibits synthesis of PCSK9, interfering with LDL-R degradation, thereby increasing LDL-C clearance	SC	284 mg once, again at 3 months and then every 6 months	n/a		Individuals who are pregnant/ breastfeeding or are allergic to medication or product ingredients	$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \\ $
Bempedic Acid	Inhibits adenosine triphosphate-citrate lyase activity, reducing hepatic cholesterol synthesis, increasing LDL-R expression and LDL-C clearance	Oral	180 mg once daily	$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \end{array}$$	Hyperuremia, gout,tendon, toward rupture		$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$
EPA/IPE	Reduction	Oral	2 g twice daily with meals	$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \end{array}$$	Hemorrhage,atrial flutter/fibrillation	Individuals who are allergic to medication or product ingredients	$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$
Fibrates	Activate PPAR with increased lipoprotein	Oral	Various class members and daily doses	+/-	Skin rash,dearhea	Individuals who are pregnant, breastfeeding, or with moderate-severe hepatic dysfunction--caution when combining gemibrozil with certain statins	$

表 7
Hypertriglyceridemia	Hypertriglyceridemia	Hypertriglyceridemia	Hypertriglyceridemia
Triglycerides	Triglycerides	150-499 mg/dL (1.7-5.6 mmol/L)	500-884 mg/dL (5.6-9.9 mmol/L)
Pancreatitis risk	Pancreatitis risk	$\rightarrow\uparrow\uparrow$	$\uparrow\uparrow\uparrow$
Treatment priority	Treatment priority	Prioritize CVD risk+address pancreatitis risk	Prioritize pancreatitis risk+address CVD risk
Treat underlying medical conditions	Diabetes	Overweight/obesity/Alcohol Use Disorder/etc
Identify medications known to increase triglycerides	Consider alternatives	Avoid and eliminate
Required Dietary	Fat content	~30% of calories as fat	20-30 g fat/day	<15-20 g fat/day
Required Dietary	Type of fat	Limit saturated/ trans fat	● Avoid saturated& trans fats ● If chronic:MCTs and fat-soluble vitamins
Carbohydrates Limit/avoid suged foods and drinks	Eat fiber-rich foods
Alcohol	Alcohol	Avoid and eliminate	Avoid and eliminate

表 8
High Intensity Statin	Rosuvatin 5-10 mg	Atorvatin 10-20 mg	Moderate-intensity Statin	Simvastatin 20-40 mg	Pitavastatin 2-4 mg
Atorvastatin 40-80 mg	Fluvastatin XL 80 mg	Fluvastatin XL 80 mg	Pravastatin 40-80 mg	Lovastatin 40 mg	Lovastatin 40 mg

表 9
Hypercholesterolemia	Hypercholesterolemia	Hypercholesterolemia	Hypercholesterolemia	Hypercholesterolemia
Management Plan	Preconception	1st Trimester	2nd and 3rd Trimester	Lactation
TREATMENT OPTIONS: Shared decision-making and multidisciplinary input is essential
Obtain a baseline lipid profile	√	If not done during preconception visit
Recommend healthy lifestyle
Statins to be stopped>4 weeks before conception unless individual is at very high risk(ASCDV/HoFH), desires pregnancy and would like to continue despite potential risk to fetus	x		Statins should generally be avoided.May be considered for very high-risk individuals.	Avoid statins as they are found in breastmilk
Bile acid monotherapy(i.e, colesevelam) may be started/continued(if no HTG). Prescribe fat-soluble vitamins.	√	√	√	$\checkmark$
Ezetimibe,niacin,bempedoic acid,and PCSK9 inhibitors (evolocumab,alirocumab,and inclisiran) should be stopped 4 weeks prior to conception	√	$\times$	$\times$	$\times$
Individuals with HoFH or HeFH at very high risk or with CVD may continue/consider LDL apheresis	√			AACE

表 10
Hypertriglyceridemia(All Secondary Causes Optimally Managed)
Risk of pancreatitis a	++→+++	+++→++++	+++→+
Pre-conception	1st Trimester 2nd Trimester	3rd Trimester	Lactation
Obtain a baseline lipid profile if at risk or if history of high TG	Check lipid profile: 2stary monolari patient at risk: Monthly monitoring; dietary adherence ● If TG $\geq$ 500 mg/dL(5.6 mmol/L): further dietary fat restriction and start omomega-3 FA pharmacotherapy	Check lipid profile: ● If TG $\geq$ 500 mg/dL(2.8 mmol/L) or patient at risk: Monthly monitoring; dietary adherence ● If TG $\geq$ 500 mg/dL(5.6 mmol/L): further dietary fat restriction and and pharmacotherapy	if TG during pregnancy;V500 mg/dL,recheck levels at 3-7 days postpartum
TREATMENT OPTIONS: Shared decision-making and multidisciplinary input are essential Achieve and maintain excellent diabetes control, if applicable, prior to and during pregnancy is known to cause HTG. 2
Strict dietary fat restriction of 20-40 g/day depending on HTG severity: 20 g if TG $\geq$ 885 mg/dL(10 mmol/L) Add medium chain TG oils for calorie supplementation if fats20 g in diet. Avoid simple sugars. Supplement fat soluble vitamins and essential fatty acids.
May continue/start omega-3 FA if TG>500 mg/ dL(2.5 mmol/L) despite dietary fat restriction
Discontinue statin, fibrate and niacin, if applicable,2 4 weeks prior to conception	May consider fibrate in 2nd or 3rd trimester in exceptional circumstances b	Avoid statin, fibrate, and niacin
IFTOB85 mg/dL(10 mmol/L): ● Consider hospital admission to optimize and support dietary fat restriction to<20 g/day
- Start/continue omega-3-FA; may consider fibrate in 2nd or 3rd trimester in 2000-2,000 mg/dL(11.2-22.4 mmol/L) on strict dietary fat restriction+omega-3FA
- Consider plasmapheresis if TG remain 21	mg/dL(<8.4 mmol/L may initiate very-low fat diet(<20 g fat/day)
●NPO status is mandatory; when TG.750 mg/dL(<8.4 mmol/L may initiate very-low fat diet(<20 g fat/day)
●Insulin infusion if patient has diabetes
●Consider plasmapheresis if TG remain 21	0000-2,000 mg/dL(11.2-22.4 mmol/L) and on omega-3FA
●Consider plasmapheresis if TG remain 21	0,000,000 mg/dL(11.2-22.4 mmol/L) and on omega-3FA

表 11
	Mechanism of Action	Delivery	Dose	Evidence of ASCVD Benefitb	Adverse Effectsc	Cautions/Contraindications	Costd
Statins	HMG-CoA ReductaseInhibitors, up-regulate LDL-R expression,and increase LDL clearance	Oral	Varies (see LDL-CTreatment slide for dosing)	++	Myalgias/ myopathy	Individuals who are pregnant/ breastfeeding, or with moderate to severe hepatic function impairment	$
Ezetimibe	Inhibits cholesterol absorption via NPCIL1	Oral	10 mg once daily	++	Mild diarrhea	Individuals who are pregnant/ breastfeeding, or with moderate to severe hepatic impairment	$
Bile acid sequestrants	Block enterohepatic recirculation of bile acids decreasing cholesterol availability, increasing LDL-R expression and LDL-C clearance	Oral	● Colesevelam 625 mg tab:3 tab bid or 6 tab once daily OR3.75g powder for suspension once daily ● Cholestryamine 4-24 g powdeer for suspension in 2 to 4 divided doses	+	Constipation, HTG	Individuals with history of bowel obstruction,triglycerides;300 mg/dL. Must be dosed 2h or 4h after dosing of other oral medications	$ $\$ $$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$
Alirocumab	Human monoclonal Ab that binds PCSK9, interfering with LDL-R degradation, thereby increasing LDL-C clearance	SC	75-150 mg every 2 weeks or 300 mg monthly	++	Injection site reactions,flu-like symptoms	$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$	$\ $$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$
Evolumabc	Human monoclonal Ab that binds PCSK9, interfering with LDL-R degradation, thereby increasing LDL-C clearance	SC	75-150 mg every 2 weeks or 300 mg monthly	++	Injection site reactions,flu-like symptoms	$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$	140 mg every 2 weeks or 420 mg monthly
Inclisiran®	Small interfering RNA that inhibits synthesis of PCSK9, interfering with LDL-R degradation, thereby increasing LDL-C clearance	SC	284 mg once,again at 3 months and then every 6 months	++	Injection site reactions,flu-like symptoms	$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$
Bempedoic Acid	Inhibits adenosine triphosphate-citrate lyase activity,reducing hepatic cholesterol synthesis, increasing LDL-R expression and LDL-C clearance	Oral	180 mg once daily	$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$		Hyperuricemia, gout,tendon rupture	$ $\$
EPA/IPE	Reduction in hepatic production of VLDL, activation of lipoprotein lipase	Oral	2 g twice daily with meals	$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$	$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \end{array}$$	Individuals who are allergic to medication or product ingredients	$ $\$
Fibrates	Activate PPAR with increased lipoprotein lipase activity and hepatic and fatty acid oxidation and lowering of VLDL production	Oral	Various class members and daily doses	+/-	Skin rash,	individuals who are pregnant, breastfeeding, or with moderate-severe hepatic dysfunction--caution when combining gemfibrozil with certain statins	$ $$$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \\ \\ \end{array}$$

图示：Primary Prevention Counsel on lifestyle modifications that reduce ASCVD risk Secondary Prevention (Clinical ASCVD) Assess ASCVD risk* Control by 10b /T 2Db Metabolic syndrome/ MASLD Persistent LDL-C≥ 190 mg/dL High-intensity statin d Low risk Intermediate risk Low risk Consider moderate- to high-intensity statin Consider moderate- to high-intensity statin Consider add-on therapy: bempedoic acid, PCSK9-based therapy, or bile acid resins PCSK9-based therapy, or bile acid resins If LDL-C above goal or continues to have CV events, add ezetimibe ACE suggests treating individuals with ASCVD or increased risk of ASCVD or an LDL-C target of 70 mg/dL. Potential impacts from polypharmacy and the increased costs with certain medications should be considered when determining appropriate treatment goals. ${}^{*}$ High intensity Statin ACE4 suggests treating individuals with ASCVD or increased risk of ASCVD or an LDL-C target of 70 mg/dL. Potential impacts from polypharmacy and the increased costs with certain medications should be considered when determining appropriate treatment goals. ${}^{*}$ High intensity Statin Avatorvastatin 40-80 mg Avatorvastatin 10-20 mg Asvivastatin 20-40 mg Resovastatin 20-40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg BID Pravastatin 40-80 mg a Use a validated risk tool(see full list in text). Family history of premature coronary disease carries increased ASCVD risk individuals fall in the intermediate or high-risk categories depending on overall risk. Current evidence does not show meaningful improvement in prediction of ASCVD risk with the addition of non-traditional risk factors (he.h.cSR,CAC score, ApoB,Or Lpla) to the risk model (see 2025 AACE Dyslipidemia Guideline) a Use a validated risk tool(see full list in text). Family history of premature coronary disease carries increased ASCVD risk individuals fall in the intermediate or high-risk categories depending on overall risk. Current evidence does not show meaningful improvement in prediction of ASCVD risk with the addition of non-traditional risk factors (he.h.cSR,CAC score, ApoB,Or Lpla) to the risk model (see 2025 AACE Dyslipidemia Guideline) c a Use a validated risk tool(see full list in text). Family history of premature coronary disease carries increased ASCVD risk individuals fall in the intermediate or high-risk categories depending on overall risk. Current evidence does not show meaningful improvement in prediction of ASCVD risk with the addition of non-traditional risk factors (he.h.cSR,CAC score, ApoB,Or Lpla) to the risk model (see 2025 AACE dyslipidemia Guideline) c ACE4 ACE 10b /T 2052 AACE Consider moderate- to high-intensity statin Consider add-on therapy: bempedoic acid, PCSK9-based therapy, or bile acid resins PCSK9-based therapy, or bile acid resins Consider not all add-on agents have evidence for reducing ASCVD risk. Use shared decision-making to discuss benefits and harms of the individual therapies. ${}^{*}$ ACE 10b /T 2052 AACE ACE 10b /T 2052 AACE ACE 10b /T 2052 AACE ACE 10b /T 2052 AACE ACE 10b /T 2052 AACE ACE 10b /T 2052 AACE ACE 10b /T 2052 AACE ACE 10b /T 2052 AACE ACE 10b /T 2052 AACE ACE 10b /T 2052 AACE ACE 10b /T 2052 AICE ACE 10b /T 2052 AICE ACE 10b /T 2052 AICE ACE 10b /T 2052 AICE ACE 10b /T 2052 AICE ACE 10b /T 2052 AICE ACE 10b /T 2052 AICE ACE 10b /T 2052 AICE ACE 10b /T 2052 AICE ACE 10b /T 2052 AICE ACE 10b /T 2052 AICE ACE 10b /T 2052 AICE ACE 10b /T 2052 AICE ACE 10b /T 2052 AICE ACE 10b /T 2052 AICE ACE 10b /T 2052

图示：Approach to Statin-Associated Muscle Symptoms in Adults Definition: One or more muscular complaints(myalgia, weakness, tenderness) improved or resolved after dose Source Systems in Adults Evaluate risk factors: Age(older adults), race/ethnicity (Asian), vitamin D deficiency, hypothyroidion, CKD, genetics ● Evaluate substance use and medication interactions ● Consider statin type and dose Evaluate risk factors: Age(older adults), race/ethnicity (Asian), vitamin D deficiency, hypothyroidion, CKD, genetics ● Evaluate substance use and medication interactions CK:5 ULN ● Discontinue Correct underlying contributors ●(e.g. vitamin D deficiency/ cyclocine/ hypothyroidism, CCK-3 ULN) ●(g.e. vitamin D deficiency/ hydrocyndium, CCK-3 ULN) hypothyroidism, drug-drug interactions etc.) Normal/mild elevation (CK-3 ULN) Add/start non-statin therapy (ezetimibe, bemopedic acid, PCSK9-based (ethyl and/ol) bile acid resins) Consider rechallenge with other statin, or lower dose If actin-rechallenge fails Clinical and how the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the following of the follow

图示：Management of Adults with Hypertricyseridemia (HTG) In all individuals with HTG Address or manage 2° causes: >150 mg/dL or>1.7 mmol/L: ● Alcohol use ● Diabetes with persistent ● Medications ● Clinical assessment and fasting lipids ●Nausea, vomiting, failure to thrive, abdominal pain, hyperglycemia ● rejection drugs, anti- ● Address 2° causes pancreatitis risk; ● Obesity hypersstolic syndrome, psychotics,etc. ● Lifestyle intervention: diet, weight loss ●Optimize cardiovascular risk factors Dystabelipoproteinemia ● Polylipemic plasma ● Mortality disease ● Systemic lupus erythematosus ● Tubero-eruptive xanthomas, palmar crease xanthomas ● Hypothyroidism ● Cushing's Syndrome ● Premature atherosclerosis TG288 mg/dL or z10 mmol/L* TO 688 mg/dL Gol: Pancreatitis prophylaxis | Rx: low fat diet, fibrate and/or omega-3 FA Goal: CVD risk reduction| Evaluate: global cardiovascular risk How to evaluate: global cardiovascular risk Reassess in 8-12 weeks b High/intermediate Low Persistent TG 885 mg/dL or TG 150-884 mg/dL Start statin; monitor:LDI-C behavior changes or non-HDL-C or Apo B Consider: ● DNA testing for FCS° ● Lipidologist referral LDL-C target attained? a If TG are in the 500-884 mg/dL range, there is increasing concern for metabolic deterioration predisposing an individual to pancreatitis.A low-fat diet and fibrates/omega-3 FA should be added if levels do not improve. a If TG are in the 500-884 mg/dL range, there is increasing concern for metabolic deterioration predisposing an of individual to pancreatitis.A low-fat diet and fibrates/omega-3 FA should be added if levels do not improve. Yes; consider icosapert ethyl for TG 150-500 mg/dL(1.7-5.6 mmol/L) ALPHIRGIRD by onelath of ACE. Vait https://dolor/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10/10

图示：Older Adults(70y) Trans widid by Adults with Auto immune Disorders Oldts and Widots who are Childhoods Cancer Survivors Adults who are Transpant Recipients Counsel on lifestyle changes recommended for all groups Primary Prevention Caution with use of ASCVD risk calculators developed for general population Ascods in an independent risk factor ASCVD Risk calculated with both Ascodically high risk for ASCVD Ascodically abnormality in and benefit from statin use Ascodically high risk due to be at high ASCVD risk due to systemic inflammation Ascodically abnormality in Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inflammation Ascodically abnormality in inf

图示：General Evidence-Based Advice Consume Limit/Avoid Foods ● Fruit,nuts, vegetables, whole grains, and legumes ● Fish and chicken ● Low fat dairy ● Non-tropical oils such as olive oil ● Dietary patterns ● Mediterranean diet ● Dash diet ● Healthful plant-based diet Hypercholesterolemia Treatment priority: Cardiovascular disease Treat underlying medical conditions (i.e hypothyroidism, nephrotic syndrome, etc.) Dietary interventions: Limit saturated /trans fats ● Increase fiber-rich foods

图示：Primary Prevention Counsel on lifestyle modifications that reduce ASCVD risk Secondary Prevention (Clinical ASCVD) Secondary Prevention (Clinical ASCVD) Assess ASCVD risk* Low risk Low risk If LDL-C above goal or continues to have CV (t4.9 mmol/L) c Consider moderate-tive statin Consider moderate-tive statin Consider add-on therapy: bempedoic acid, PCSK9-based therapy, or bile acid resins PCSK9-based therapy, or bile acid resin Note: Not all add-on agents have evidence for reducing ASCVD risk. Use shared decision-making to discuss benefits and harms and harms of the individual therapies.*

图示：Approach to Statin-Associated Muscle Symptoms in Adults Definition: One or more muscular complaints (myalgia, weakness, tenderness) improved or resolved after dose reduction/discontinuation. Minimum of 2 statin-treatment attempts(including 21 at the lowest approved dose), a Definition: One or more muscular complaints (myalgia, weakness, tenderness) improved or resolved after dose reduction/discontinuation. Minimum of 2 statin-treatment attempts(including 21 at the lowest approved dose), a Use shared decision-making to discuss benefits and harms of the individual therapies Consider rechallenge with other statin, or lower dose (including alternate-day dosing)

图示：#Management of Adults with Hypertriglyceridemia (HTG) In all individuals with HTG >150 mg/dL or $>1.7 mmol/L$ Clinical assessment: Hylomicronemia syndromes (familial and multifactoral) ● Nausea, vomiting, failure to thrive, abdominal pain, pancreatitis risk; ● Nausea, vomiting, failure to thrive, abdominal pain, pancreatitis risk; ● Nausea, vomiting, failure to thrive, abdominal pain, pancreatitis risk; ● Nausea, vomiting, failure to thrive, abdominal pain, pancreatitis risk; ● Nausea, vomiting, failure to thrive, abdominal pain, pancreatitis risk; ● Nausea, vomiting, failure to thrive, individual, and may be able to achieve the same dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics and dynamics To Changeatitis prophylaxis | Rx: low fat diet, fibrate and/or omega-3 FA Progress in 8-12 weeks b To start& statin; monitor LDL-C To start& statin; monitor LDL-C or non-HDL-C or Apo B Reassess in 8-12 weeks b To Search in 8-12 weeks b To start& statin; monitor LDL-C or non-HDL-C or Apo B Yes; consider icosapent ethyl for TG 150 - 500 mg/dL (1.7 - 5.6 mmol/L) To follow LDL-C algorithm ADF Architecture xx (x/x) Exslier on behalf of AACE, Visit https://dolorg/10.1016/j.expracy/2025.07/014 to request copyright permission. To start& statin; monitor LDL-C or non-HDL-C or Apo B LD-L-C target attained? Yes; consider icosapent ethyl for TG 150 - 500 mg/dL (1.7 - 5.6 mmol/L) To follow LDL-C algorithm AACE 52.04 Postline, JEXE1000

图示：Management of Special Populations with Dyslipidemia Older Adults (70y) Counsel on lifestyle changes recommended for all groups Acge is an independent risk factor Greater impact of lipid-lowering on ASCVD, but consider co-morbidity and life expectancy expectancy ● Trans women have lower risk than matched cis men ● Trans men have similar risks as cis women ● Early Upatinson of ASCVD ● Death of high-quality studies ● Mar. 2005 ● Exsecting in SCSy ● Defect and high-roratory studies ● May use or resystatin ● Low and high-roratory studies ● Consider evaluative impact and therapy ● Consider evaluative impact and high ● Ace is an independent risk factor ● Interferent of ASCVD ● Adults living with HIV ● Homar perfusion of ASCVD ● Homar perfusion of ASCVD ● Homar pertainable results in ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effect, may be a ● Homer effec

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2025 AACE共识声明：成人血脂异常的管理流程（更新版）. 2025.