Hypercholesterolemia

Last reviewed: May 2019

Last updated: April 2018

Summary

Elevation of total cholesterol and/or low-density lipoprotein (LDL)-cholesterol or non-high-density lipoprotein (HDL)-cholesterol (defined as the subtraction of HDL-cholesterol from total cholesterol) in the blood, is also often referred to as dyslipidemia, to encompass the fact that it might be accompanied by a decrease in HDL-cholesterol or an increase in triglycerides.

Usually symptomatically quiescent until significant degrees of atherosclerosis have occurred.

Complications include myocardial infarction, ischemic cardiomyopathy, sudden death, ischemic stroke, erectile dysfunction, peripheral vascular disease, and acute limb ischemia.

Risk factors for secondary hypercholesterolemia in industrialized populations include a sedentary lifestyle and a diet characterized by the excessive consumption of saturated fats, trans-fatty acids, and cholesterol. Other associations include diabetes, excess body weight mainly in the abdominal region, hypothyroidism, nephrotic syndrome, and cholestatic liver disease. Low HDL-cholesterol levels are associated with smoking and abdominal obesity.

Diagnosed by fasting lipid profile, consisting of measurements of total cholesterol, LDL (estimated or direct), HDL, and triglycerides. Non-HDL-cholesterol is calculated by the subtraction of HDL-cholesterol from total cholesterol.

Treated with lifestyle modifications such as dietary changes, exercise, and smoking cessation, as well as pharmacologic intervention with statin therapy, supported by the use of niacin, bile acid sequestrants, or cholesterol absorption inhibitors (ezetimibe).

Definition

Hypercholesterolemia, an elevation of total cholesterol (TC) and/or low-density lipoprotein (LDL)-cholesterol or non-HDL-cholesterol (defined as the subtraction of high-density lipoprotein (HDL)-cholesterol from total cholesterol) in the blood, is also often referred to as dyslipidemia, to encompass the fact that it might be accompanied by a decrease in HDL-cholesterol or an increase in triglycerides. Dyslipidemia is classified as serum TC, LDL-cholesterol, triglyceride, apolipoprotein B (apoB), or lipoprotein (a) concentrations above the 90th percentile, or HDL-cholesterol or apolipoprotein A-I concentrations below the 10th percentile for the general population.

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

Full details

Other diagnostic factors

arcus corneae with onset before the age of 45 years
tuberous xanthomas

Full details

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

Full details

Diagnostic investigations

1st investigations to order

lipid profile
serum thyroid-stimulating hormone (TSH)

Full details

Treatment algorithm

ACUTE

with clinical atherosclerotic cardiovascular disease (CVD) ≤75 years

with clinical atherosclerotic cardiovascular disease (CVD) >75 years

without clinical atherosclerotic cardiovascular disease (CVD): LDL-cholesterol ≥190 mg/dL

without clinical atherosclerotic cardiovascular disease (CVD): LDL-cholesterol 70-189 mg/dL: 40-75 years with diabetes mellitus

without clinical atherosclerotic cardiovascular disease (CVD): LDL-cholesterol 70-189 mg/dL: 40-75 years without diabetes mellitus

without clinical atherosclerotic cardiovascular disease (CVD): LDL-cholesterol <190 mg/dL: <40 or >75 years

without clinical atherosclerotic cardiovascular disease (CVD): isolated low HDL-cholesterol

ONGOING

less than anticipated therapeutic response to statin therapy

statin apparently not tolerated

statin-intolerance proven or in need of additional LDL-cholesterol lowering after maximum tolerated statin therapy

homozygous familial hypercholesterolemia

Contributors

Authors VIEW ALL 

Raul D. Santos, MD, PhD, MSc

Associate Professor of Medicine

Director Lipid Clinic Heart Institute (InCor)

University of Sao Paulo Medical School Hospital

Scientific Advisor

Hospital Israelita Albert Einstein

Sao Paulo

Brazil

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.

Seth S. Martin, MD, MHS

Assistant Professor of Medicine/Cardiology

Associate Director

Lipid Clinic

Ciccarone Center for the Prevention of Heart Disease

Johns Hopkins University School of Medicine

Baltimore

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 Trone Foundation. SSM has received research support from the PJ Schafer Cardiovascular Research Fund, American Heart Association, Aetna Foundation, Google, and Apple. SSM has acted as a consultant for Abbott Nutrition, Pressed Juicery, Quest Diagnostics, Sanofi/Regeneron, Amgen, and the Pew Institute.

Acknowledgements

Dr Raul D. Santos and Dr Seth S. Martin would like to gratefully acknowledge Dr Martin Engelhardt and Dr Michael Miller, the previous contributors to this topic. 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 VIEW ALL 

Mahi Lakshmi Ashwath, MD

Assistant Professor of Medicine

Noninvasive Cardiology

MetroHealth Campus

Case Western Reserve University

Cleveland

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

Disclosures

DB declares that he has no competing interests.

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Hypercholesterolemia

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Treatment algorithm

with clinical atherosclerotic cardiovascular disease (CVD) ≤75 years

with clinical atherosclerotic cardiovascular disease (CVD) >75 years

without clinical atherosclerotic cardiovascular disease (CVD): LDL-cholesterol ≥190 mg/dL

without clinical atherosclerotic cardiovascular disease (CVD): LDL-cholesterol 70-189 mg/dL: 40-75 years with diabetes mellitus

without clinical atherosclerotic cardiovascular disease (CVD): LDL-cholesterol 70-189 mg/dL: 40-75 years without diabetes mellitus

without clinical atherosclerotic cardiovascular disease (CVD): LDL-cholesterol <190 mg/dL: <40 or >75 years

without clinical atherosclerotic cardiovascular disease (CVD): isolated low HDL-cholesterol

less than anticipated therapeutic response to statin therapy

statin apparently not tolerated

statin-intolerance proven or in need of additional LDL-cholesterol lowering after maximum tolerated statin therapy

homozygous familial hypercholesterolemia

Contributors

Authors VIEW ALL 

Raul D. Santos, MD, PhD, MSc

Disclosures

Seth S. Martin, MD, MHS

Disclosures

Acknowledgements

Peer reviewers VIEW ALL 

Mahi Lakshmi Ashwath, MD

Disclosures

Deepak Bhatnagar, TD MBBS PhD FRCP FRCPI FRCPath

Disclosures

Differentials

Guidelines

Patient leaflets

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