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 investigations
1st investigations to order
- lipid profile
- serum thyroid-stimulating hormone (TSH)
- lipoprotein(a)
Investigations 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 and no risk factors (age 40-75 years)
without clinical ASCVD: with diabetes mellitus and multiple risk factors (age 40-75 years)
without clinical ASCVD: with diabetes mellitus (age >75 years)
severe familial hypercholesterolemia
Contributors
Authors
Seth S. Martin, MD, MHS

Associate Professor of Medicine/Cardiology
Director
Lipid Clinic
Ciccarone Center for the Prevention of Cardiovascular Disease
Division of Cardiology, Department of Medicine
Johns Hopkins University School of Medicine
Baltimore
MD
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, he 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.
Rhanderson Cardoso, MD

Cardiovascular Fellow
Pollin Prevention Fellow
Ciccarone Center for the Prevention of Cardiovascular Disease
Division of Cardiology, Department of Medicine
Johns Hopkins University School of Medicine
Baltimore
MD
Disclosures
RC declares that he has no competing interests.
Acknowledgements
Dr Seth S. Martin and Dr Rhanderson Cardoso would like to gratefully acknowledge Dr Raul D. Santos, Dr Martin Engelhardt and Dr Michael Miller, the previous contributors to this topic.
Disclosures
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.
Differentials
- Obstructive liver disease
- Nephrotic syndrome
- Chronic renal insufficiency
More DifferentialsGuidelines
- Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the management of dyslipidemia and prevention of cardiovascular disease algorithm – 2020 executive summary
- VA/DoD clinical practice guideline for the management of dyslipidemia for cardiovascular risk reduction
More GuidelinesPatient leaflets
High cholesterol
High cholesterol: questions to ask your doctor
More Patient leafletsCalculators
Cardiovascular Risk Assessment in Men (10-year, patient information, Framingham 2008)
Cardiovascular Risk Assessment in Women (10-year, patient information, Framingham 2008)
More CalculatorsLog in or subscribe to access all of BMJ Best Practice
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