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Hypercholesterolemia

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General Information

Description

  • condition characterized by elevated serum levels of total cholesterol, low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol1,2,3
  • this topic deals with nonfamilial forms of hypercholesterolemia; see also Familial hypercholesterolemia

Also called

  • dyslipidemia (broader term for abnormal amounts of fat or cholesterol in the blood)
  • hypercholesterolemia may also be called
    • hypercholesterolaemia
    • pure hypercholesterolemia
    • Fredrickson Type IIa hyperlipoproteinemia
    • hyperbetalipoproteinemia
    • group A hyperlipidemia
    • low-density lipoprotein hyperlipoproteinemia
  • mixed hypercholesterolemia (hypercholesterolemia with hypertriglyceridemia) may also be called
    • broad-betalipoproteinemia
    • floating-betalipoproteinemia
    • Fredrickson Type IIb hyperlipoproteinemia
    • Fredrickson Type III hyperlipoproteinemia
    • hypercholesterolemia with endogenous hyperglyceridemia
    • hyperbetalipoproteinemia with prebetalipoproteinemia
    • combined hyperlipidemia

Types

  • Table 1. Fredrickson Classification of Dyslipidemias*
    PhenotypeLipoproteins(s) Elevated Serum Cholesterol Level Serum Triglyceride LevelAtherogenicity
    IChylomicronsNormal to mildly increasedVery severely increasedNone
    IIaLDLModerately increasedNormalSevere
    IIbLDL and VLDLModerately increasedModerately increasedSevere
    IIIIDLModerately increasedSeverely increasedSevere
    IVVLDLNormal to mildly increasedModerately increasedMild to Moderate
    VVLDL and chylomicronsNormal to mildly increasedVery severely increasedMild to Moderate

    Abbreviations: HDL, high-density lipoprotein; IDL,
                                        intermediate-density lipoprotein; LDL, low-density lipoprotein;
                                        VLDL, very-low-density lipoprotein.

    * HDL cholesterol levels not considered.

    Reference -
                                        14262568Circulation 1965 Mar;31:321
    OpenInNew

                                  

References

General references used

  1. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002 Dec 17;106(25):3143-421OpenInNewPDFPictureAsPdf or at NHLBI 2002 Sep PDFPictureAsPdf, editorial can be found in Circulation 2002 Dec 17;106(25):3140OpenInNew
  2. Grundy SM, Cleeman JI, Merz CN, et al; National Heart, Lung, and Blood Institute, American College of Cardiology Foundation, American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004 Jul 13;110(2):227-39OpenInNewfull-textOpenInNew, correction can be found in Circulation 2004 Aug 10;110(6):763
  3. National Institute for Health and Care Excellence (NICE). Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. NICE 2014 Jul:CG181OpenInNewPDFPictureAsPdf, summary can be found in BMJ 2014 Jul 17;349:g4356OpenInNew
  4. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 Nov 8 early onlineOpenInNew
  5. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S49-73OpenInNew or in J Am Coll Cardiol 2014 Jul 1;63(25 Pt B):2935OpenInNewfull-textOpenInNew (correction can be found in J Am Coll Cardiol 2014 Jul 1;63(25 Pt B):3026), commentary can be found in Mayo Clin Proc 2014 Jun;89(6):722OpenInNew
  6. Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S76-99OpenInNew or in J Am Coll Cardiol 2014 Jul 1;63(25 Pt B):2960OpenInNewPDFPictureAsPdf
  7. Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J. 2016 Oct 14;37(39):2999-3058OpenInNew

Recommendation grading systems used

  • Canadian Cardiovascular Society (CCS) uses Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system
    • strength of recommendations
      • Strong recommendation - high confidence that desirable effects of recommendation outweigh undesirable effects
      • Conditional recommendation - less confidence that desirable effects of recommendation probably outweigh undesirable effects, or benefits and harms are finely balanced, or appreciable uncertainty
    • quality of evidence
      • High - further research very unlikely to change confidence in estimate of effect
      • Moderate - further research likely to have important impact on confidence in estimate of effect and may change estimate
      • Low - further research very likely to have important impact on confidence in estimate of effect and likely to change estimate
      • Very low - any estimate of effect very uncertain
    • Reference - 2016 CCS guideline on management of dyslipidemia for prevention of cardiovascular disease in adults (27712954Can J Cardiol 2016 Nov;32(11):1263OpenInNew)
  • American College of Cardiology/American Heart Association (ACC/AHA) grading system for recommendations
    • classifications of recommendations
      • Class I - procedure or treatment should be performed or administered
      • Class IIa - reasonable to perform procedure or administer treatment, but additional studies with focused objectives needed
      • Class IIb - procedure or treatment may be considered; additional studies with broad objectives needed, additional registry data would be useful
      • Class III - procedure or treatment should not be performed or administered because it is not helpful or may be harmful
        • Class III ratings may be subclassified as Class III No Benefit or Class III Harm
    • levels of evidence
      • Level A - data derived from multiple randomized clinical trials or meta-analyses
      • Level B - data derived from single randomized trial or nonrandomized studies
      • Level C - only expert opinion, case studies, or standard of care
  • American College of Cardiology/American Heart Association (ACC/AHA) grading system for recommendations
    • classifications of recommendations
      • Class I - procedure or treatment should be performed or administered
      • Class IIa - reasonable to perform procedure or administer treatment, but additional studies with focused objectives needed
      • Class IIb - procedure or treatment may be considered; additional studies with broad objectives needed, additional registry data would be useful
      • Class III - procedure or treatment should not be performed or administered because it is not helpful or may be harmful
        • Class III ratings may be subclassified as Class III No Benefit or Class III Harm
    • levels of evidence
      • Level A - high-quality evidence from > 1 randomized controlled trial or meta-analysis of high-quality randomized controlled trials
      • Level B-R - moderate-quality evidence from ≥ 1 randomized controlled trial or meta-analysis of moderate-quality randomized controlled trials
      • Level B-NR - moderate-quality evidence from ≥ 1 well-designed nonrandomized trial, observational studies, or registry studies, or meta-analysis of such studies
      • Level C-LD - randomized or nonrandomized studies with methodological limitations or meta-analyses of such studies
      • Level C-EO - consensus of expert opinion based on clinical experience
  • European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) grading system for recommendations
    • classes of recommendations
      • Class I - evidence and/or general agreement that given treatment or procedure is beneficial, useful, and effective
      • Class II - conflicting evidence and/or divergence of opinion about usefulness/efficacy of given treatment or procedure
        • Class IIa - weight of evidence/opinion in favor of usefulness/efficacy
        • Class IIb - usefulness/efficacy less well established by evidence/opinion
      • Class III - evidence or general agreement that given treatment or procedure is not useful/effective, and in some cases may be harmful
    • levels of evidence
      • Level A - data derived from multiple randomized clinical trials or meta-analyses
      • Level B - data derived from single randomized clinical trial or large nonrandomized studies
      • Level C - consensus of opinion of experts and/or small studies, retrospective studies, registries
  • United States Preventive Services Task Force (USPSTF) grades of recommendation (June 2007 to June 2012)
    • Grade A - USPSTF recommends the service with high certainty of substantial net benefit
    • Grade B - USPSTF recommends the service with high certainty of moderate net benefit or moderate certainty of moderate-to-substantial net benefit
    • Grade C - clinicians may provide the service to select patients depending on individual circumstances; however, only small benefit is likely for most individuals without signs or symptoms
    • Grade D - USPSTF recommends against providing the service with moderate-to-high certainty of no net benefit or harms outweighing benefits
    • Grade I - insufficient evidence to assess balance of benefits and harms
    • Reference - USPSTF Grade DefinitionsOpenInNew

Synthesized Recommendation Grading System for DynaMed

  • DynaMed systematically monitors clinical evidence to continuously provide a synthesis of the most valid relevant evidence to support clinical decision-making (see 7-Step Evidence-Based MethodologyOpenInNew).
  • Guideline recommendations summarized in the body of a DynaMed topic are provided with the recommendation grading system used in the original guideline(s), and allow DynaMed users to quickly see where guidelines agree and where guidelines differ from each other and from the current evidence.
  • In DynaMed (DM), we synthesize the current evidence, current guidelines from leading authorities, and clinical expertise to provide recommendations to support clinical decision-making in the Overview & Recommendations section.
  • We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE)OpenInNew to classify synthesized recommendations as Strong or Weak.
    • Strong recommendations are used when, based on the available evidence, clinicians (without conflicts of interest) consistently have a high degree of confidence that the desirable consequences (health benefits, decreased costs and burdens) outweigh the undesirable consequences (harms, costs, burdens).
    • Weak recommendations are used when, based on the available evidence, clinicians believe that desirable and undesirable consequences are finely balanced, or appreciable uncertainty exists about the magnitude of expected consequences (benefits and harms). Weak recommendations are used when clinicians disagree in judgments of relative benefit and harm, or have limited confidence in their judgments. Weak recommendations are also used when the range of patient values and preferences suggests that informed patients are likely to make different choices.
  • DynaMed (DM) synthesized recommendations (in the Overview & Recommendations section) are determined with a systematic methodology:
    • Recommendations are initially drafted by clinical editors (including ≥ 1 with methodological expertise and ≥ 1 with content domain expertise) aware of the best current evidence for benefits and harms, and the recommendations from guidelines.
    • Recommendations are phrased to match the strength of recommendation. Strong recommendations use "should do" phrasing, or phrasing implying an expectation to perform the recommended action for most patients. Weak recommendations use "consider" or "suggested" phrasing.
    • Recommendations are explicitly labeled as Strong recommendations or Weak recommendations when a qualified group has explicitly deliberated on making such a recommendation. Group deliberation may occur during guideline development. When group deliberation occurs through DynaMed-initiated groups:
      • Clinical questions will be formulated using the PICO (Population, Intervention, Comparison, Outcome) framework for all outcomes of interest specific to the recommendation to be developed.
      • Systematic searches will be conducted for any clinical questions where systematic searches were not already completed through DynaMed content development.
      • Evidence will be summarized for recommendation panel review including for each outcome, the relative importance of the outcome, the estimated effects comparing intervention and comparison, the sample size, and the overall quality rating for the body of evidence.
      • Recommendation panel members will be selected to include at least 3 members that together have sufficient clinical expertise for the subject(s) pertinent to the recommendation, methodological expertise for the evidence being considered, and experience with guideline development.
      • All recommendation panel members must disclose any potential conflicts of interest (professional, intellectual, and financial), and will not be included for the specific panel if a significant conflict exists for the recommendation in question.
      • Panel members will make Strong recommendations if and only if there is consistent agreement in a high confidence in the likelihood that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. Panel members will make Weak recommendations if there is limited confidence (or inconsistent assessment or dissenting opinions) that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. No recommendation will be made if there is insufficient confidence to make a recommendation.
      • All steps in this process (including evidence summaries which were shared with the panel, and identification of panel members) will be transparent and accessible in support of the recommendation.
    • Recommendations are verified by ≥ 1 editor with methodological expertise, not involved in recommendation drafting or development, with explicit confirmation that Strong recommendations are adequately supported.
    • Recommendations are published only after consensus is established with agreement in phrasing and strength of recommendation by all editors.
    • If consensus cannot be reached then the recommendation can be published with a notation of "dissenting commentary" and the dissenting commentary is included in the topic details.
    • If recommendations are questioned during peer review or post publication by a qualified individual, or reevaluation is warranted based on new information detected through systematic literature surveillance, the recommendation is subject to additional internal review.

DynaMed Editorial Process

Special acknowledgements

  • DynaMed topics are written and edited through the collaborative efforts of the above individuals. Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice. Recommendations Editors are actively involved in development and/or evaluation of guidelines.
  • Editorial Team role definitions
    Topic Editors define the scope and focus of each topic by formulating a set of clinical questions and suggesting important guidelines, clinical trials, and other data to be addressed within each topic. Topic Editors also serve as consultants for the internal DynaMed Editorial Team during the writing and editing process, and review the final topic drafts prior to publication.
    Section Editors have similar responsibilities to Topic Editors but have a broader role that includes the review of multiple topics, oversight of Topic Editors, and systematic surveillance of the medical literature.
    Recommendations Editors provide explicit review of DynaMed Overview and Recommendations sections to ensure that all recommendations are sound, supported, and evidence-based. This process is described in "Synthesized Recommendation Grading."
    Deputy Editors are employees of DynaMed and oversee DynaMed internal publishing groups. Each is responsible for all content published within that group, including supervising topic development at all stages of the writing and editing process, final review of all topics prior to publication, and direction of an internal team.

How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):

  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T114250, Hypercholesterolemia; [updated 2018 Dec 03, cited place cited date here]. Available from https://www.dynamed.com/topics/dmp~AN~T114250. Registration and login required.
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    Overview and Recommendations

    • Background

    • Evaluation

    • Management

  • Related Summaries

  • KeyboardArrowRight

    General Information

    • Description

    • Also called

    • Types

  • KeyboardArrowRight

    Epidemiology

    • Incidence/Prevalence

    • Likely risk factors

    • Possible risk factors

    • Associated conditions

  • KeyboardArrowRight

    Etiology and Pathogenesis

    • Causes

    • Pathogenesis

  • History and Physical

  • KeyboardArrowRight

    Diagnosis

    • Making the diagnosis

    • Differential diagnosis

    • Testing overview

    • KeyboardArrowRight

      Blood tests

      • Lipid profile

      • LDL cholesterol calculation

      • Other lipid parameters

      • Non-lipid blood tests

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    Management

    • Management overview

    • KeyboardArrowRight

      Recommendations including risk assessment

      • American College of Cardiology/American Heart Association (ACC/AHA) 2018 guidelines

      • European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) 2016 guidelines

      • National Institute for Care Excellence (NICE) 2014 guidelines (United Kingdom)

      • Choosing Wisely recommendations

      • Other risk assessment tools

    • Diet

    • Activity

    • Counseling

    • KeyboardArrowRight

      Medications

      • General information

      • Statins

      • KeyboardArrowRight

        Niacin

        • Prescribing information

        • Efficacy for cardiovascular disease risk reduction

      • KeyboardArrowRight

        Ezetimibe

        • Prescribing information

        • Efficacy overview (ezetimibe)

        • Efficacy for clinical outcomes

        • Efficacy for carotid artery intima-media thickness

        • Efficacy for improving dyslipidemia

        • Adverse events (ezetimibe)

      • KeyboardArrowRight

        PCSK9 inhibitors

        • General information

        • Evolocumab

        • Alirocumab

        • Bococizumab

        • Inclisiran

      • Bile acid-binding resins

      • ATP citrate lyase inhibitors

      • Herbs and dietary supplements

    • Surgery and procedures

    • Consultation and referral

    • Combination of lifestyle interventions

    • Follow-up

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    Complications and Prognosis

    • Prognosis

  • KeyboardArrowRight

    Prevention and Screening

    • Screening

  • KeyboardArrowRight

    Quality Improvement

    • Choosing Wisely

    • Choosing Wisely Australia

    • Physician Quality Reporting System Quality Measures

  • KeyboardArrowRight

    Guidelines and Resources

    • KeyboardArrowRight

      Guidelines

      • Guideline comparison

      • United States guidelines

      • United Kingdom guidelines

      • Canadian guidelines

      • European guidelines

      • Asian guidelines

      • Australian and New Zealand guidelines

      • African guidelines

    • Review articles

    • MEDLINE search

  • Patient Information

  • KeyboardArrowRight

    ICD Codes

    • ICD-10 codes

  • KeyboardArrowRight

    References

    • General references used

    • Recommendation grading systems used

    • Synthesized Recommendation Grading System for DynaMed

    • DynaMed Editorial Process

    • Special acknowledgements

    • How to cite

Topic Editor
Fatima Cody Stanford MD, MPH, MPA, FAAP, FACP, FTOS
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Affiliations

Adult and Pediatric Obesity Medicine Physician, Massachusetts General Hospital; Massachusetts, United States

Conflicts of Interest

Dr. Stanford declares no relevant financial conflicts of interest.

Recommendations Editor
Zbys Fedorowicz MSc, DPH, BDS, LDSRCS
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Affiliations

Director of Bahrain Branch of the United Kingdom Cochrane Center, The Cochrane Collaboration; Awali, Bahrain

Conflicts of Interest

Dr. Fedorowicz declares no relevant financial conflicts of interest.

Deputy Editor
Peter Oettgen MD
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Affiliations

Editor in Chief, DynaMed; Cardiologist, Beth Israel Deaconess Medical Center; Massachusetts, United States; Associate Professor of Medicine, Harvard Medical School; Massachusetts, United States

Conflicts of Interest

Dr. Oettgen declares no relevant financial conflicts of interest.

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