Summary
Definition
History and exam
Key diagnostic factors
- family history of early onset of coronary heart disease or dyslipidemia in first-degree relatives
- history of cardiovascular disease
- consumption of saturated fats and trans-fatty acids
- excess body weight (especially abdominal obesity)
- xanthelasmas
- tendinous xanthomas
Other diagnostic factors
- arcus cornealis with onset before the age of 45 years
- tuberous xanthomas
Risk factors
- insulin resistance and type 2 diabetes mellitus
- excess body weight (body mass index >25 kg/m²)
- cigarette smoking
- hypothyroidism
- cholestatic liver disease
- nephrotic syndrome
- use of certain medications
Diagnostic tests
1st tests to order
- lipid profile
- serum thyroid-stimulating hormone (TSH)
- lipoprotein(a)
Tests to consider
- genetic testing
Treatment algorithm
with clinical ASCVD: very high risk
with clinical ASCVD: not very high risk and age ≤75 years
with clinical ASCVD: not very high risk and age >75 years
without clinical ASCVD: LDL-C ≥190 mg/dL without diabetes mellitus (age 20-75 years)
without clinical ASCVD: LDL-C ≥160 mg/dL without diabetes mellitus (age 20-39 years)
without clinical ASCVD: LDL-C 70-189 mg/dL without diabetes mellitus (age 40-75 years)
without clinical ASCVD: LDL-C 70-189 mg/dL without diabetes mellitus (age >75 years)
without clinical ASCVD: with diabetes mellitus and risk enhancers (age 20-39 years)
without clinical ASCVD: with diabetes mellitus, 10-year ASCVD predicted risk <7.5% and no risk factors (age 40-75 years)
without clinical ASCVD: with diabetes mellitus, 10-year ASCVD predicted risk ≥7.5% and risk enhancers (age 40-75 years)
without clinical ASCVD: with diabetes mellitus (age >75 years)
familial hypercholesterolemia
Contributors
Authors
Thorsten Leucker, MD, PhD
Assistant Professor of Medicine
Division of Cardiology, Department of Medicine
Johns Hopkins University School of Medicine
Baltimore
MD
Disclosures
TL has received grant funding for his university from Amgen and Merck.
Richard A. Ferraro, MD
Cardiovascular Disease Fellow
Division of Cardiology, Department of Medicine
Johns Hopkins University School of Medicine
Baltimore
MD
Disclosures
RAF declares that he has no competing interests.
Acknowledgements
Dr Thorsten Leucker and Dr Richard A. Ferraro would like to gratefully acknowledge Dr Seth S. Martin, Dr Rhanderson Cardoso, Dr Raul D. Santos, Dr Martin Engelhardt, and Dr Michael Miller, the previous contributors to this topic.
Disclosures
SSM has received honoraria from the American College of Cardiology for educational activities. SSM is listed as a co-inventor on a pending patent filed by Johns Hopkins University for a novel method of LDL-cholesterol estimation. SSM received a charitable gift for the VLDL big data project from the David and June Trone Family Foundation, and has also received research support from the PJ Schafer Cardiovascular Research Fund, American Heart Association, Aetna Foundation, iHealth, Stanford MedX/Nokia, Google, and Apple. SSM has acted as a consultant for Abbott Nutrition, Pressed Juicery, Quest Diagnostics, Sanofi/Regeneron, Amgen, Novo Nordisk, Esperian, Akcea, and the Pew Institute. RC declares that he has no competing interests. RDS has received honoraria for consulting, speaker activities and research from Astra Zeneca, Amgen, Akcea, Biolab, Esperion, Kowa, Pfizer, Merck, Novo-Nordisk, and Sanofi/Regeneron. ME declares that he has no competing interests. MM has received research grant support and honoraria for lectures from AstraZeneca, Merck-Schering Plough, and Pfizer. MM has received consulting fees from Pfizer, Merck-Schering Plough, and Roche.
Peer reviewers
Mahi Lakshmi Ashwath, MD
Assistant Professor of Medicine
Noninvasive Cardiology
MetroHealth Campus
Case Western Reserve University
Cleveland
OH
Disclosures
MLA declares that he has no competing interests.
Deepak Bhatnagar, TD MBBS PhD FRCP FRCPI FRCPath
Consultant/Senior Lecturer in Diabetes & Metabolism
The Royal Oldham Hospital & University of Manchester Cardiovascular Research Group Diabetes Centre
Royal Oldham Hospital
Oldham
UK
Disclosures
DB declares that he has no competing interests.
References
Key articles
Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020 Jan 1;41(1):111-88.Full text Abstract
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. Circulation. 2019 Jun 18;139(25):e1082-143.Full text Abstract
National Institute of Health and Care Excellence (UK). Cardiovascular disease: risk assessment and reduction, including lipid modification. Dec 2023 [internet publication].Full text
Expert Dyslipidemia Panel of the International Atherosclerosis Society Panel members. An International Atherosclerosis Society position paper: global recommendations for the management of dyslipidemia - full report. J Clin Lipidol. 2014 Jan-Feb;8(1):29-60.Full text Abstract
Writing Committee; Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2022 ACC Expert Consensus Decision Pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022 Oct 4;80(14):1366-418.Full text Abstract
Cholesterol Treatment Trialists' (CTT) Collaboration; Fulcher J, O'Connell R, Voysey M, et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet. 2015 Apr 11;385(9976):1397-405. Abstract
Grundy SM, Cleeman JI, Mertz 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):227-39.Full text Abstract
Reference articles
A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.
Differentials
- Obstructive liver disease
- Nephrotic syndrome
- Chronic renal insufficiency
More DifferentialsGuidelines
- Consensus statement on homozygous familial hypercholesterolaemia: new treatments and clinical guidance
- Cardiovascular disease: risk assessment and reduction, including lipid modification
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High cholesterol
High cholesterol: questions to ask your doctor
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Cardiovascular Risk Assessment in Men (10-year, patient information, Framingham 2008)
Cardiovascular Risk Assessment in Women (10-year, patient information, Framingham 2008)
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