What is the approach to evaluating hypercholesterolemia (high cholesterol)?

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Last updated: March 9, 2025View editorial policy

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From the Guidelines

High cholesterol is best evaluated through a comprehensive lipid panel blood test, with LDL-C as the primary target for treatment, and the goal of treatment is to achieve an LDL-C level of < 1.8 mmol/L (70 mg/dL) in patients at very high CV risk, or a reduction of at least 50% if the baseline LDL-C is between 1.8 and 3.5 mmol/L (70 and 135 mg/dL) 1.

Evaluation Approach

The evaluation of hypercholesterolemia involves a comprehensive lipid panel blood test, which measures total cholesterol, LDL (bad) cholesterol, HDL (good) cholesterol, and triglycerides.

  • The test can be done after fasting for 9-12 hours, but nonfasting samples can also be used for risk assessment in primary prevention and for assessment of baseline LDL-C levels before the initiation of a statin in primary and secondary prevention 1.
  • Normal values are: total cholesterol below 200 mg/dL, LDL below 100 mg/dL, HDL above 40 mg/dL for men and above 50 mg/dL for women, and triglycerides below 150 mg/dL.

Risk Assessment

The results of the lipid panel are considered alongside other risk factors like age, family history, smoking status, blood pressure, and diabetes to calculate the overall cardiovascular risk using tools like the ASCVD Risk Calculator.

  • Additional tests may include non-HDL cholesterol, apolipoprotein B, or advanced lipid testing for unclear cases.
  • Regular monitoring is important, with testing recommended every 4-6 years for healthy adults and more frequently for those with elevated levels or on cholesterol-lowering medications.

Treatment Goals

The goal of treatment is to achieve an LDL-C level of < 1.8 mmol/L (70 mg/dL) in patients at very high CV risk, or a reduction of at least 50% if the baseline LDL-C is between 1.8 and 3.5 mmol/L (70 and 135 mg/dL) 1.

  • A statin is the usual first-line treatment to reach the LDL-C goal and should be used up to the highest recommended dose or highest tolerable dose to reach the goal.
  • High-dose statins should be given early after admission in all acute coronary syndrome patients without contraindication or a history of intolerance, regardless of initial LDL-C values.

From the FDA Drug Label

Therapy with lipid-altering agents should be a component of multiple risk factor intervention in those individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Treatment should begin and continue with dietary therapy specific for the type of hyperlipoproteinemia determined prior to initiation of drug therapy Prior to initiating therapy with cholestyramine resin, secondary causes of hypercholesterolemia (e.g., poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinemias, obstructive liver disease, other drug therapy, alcoholism), should be excluded and a lipid profile performed to assess Total cholesterol, HDL-C and triglycerides (TG). The NCEP treatment guidelines are summarized below. Definite Atherosclerotic Disease* Two or More Other Risk Factors† LDL-Cholesterol mg/dL (mmol/L) Initiation Level Goal No No ≥ 190 (4.9) < 160 (< 4. 1) No Yes ≥ 160 (4.1) < 130 (< 3.4) Yes Yes or No ≥ 130 (3.4) ≤ 100 (≤ ‑2. 6)

The approach to evaluating hypercholesterolemia involves:

  • Dietary therapy as the initial treatment
  • Exclusion of secondary causes of hypercholesterolemia
  • Lipid profile assessment to determine Total cholesterol, HDL-C, and triglycerides (TG)
  • Use of NCEP treatment guidelines to determine initiation and goal levels for LDL-Cholesterol
  • Consideration of definite atherosclerotic disease and other risk factors in determining treatment goals 2

From the Research

Evaluating Hypercholesterolemia

The approach to evaluating hypercholesterolemia involves assessing various lipid markers, including:

  • Total cholesterol
  • High-density lipoprotein (HDL)-cholesterol (HDL-C)
  • Low-density lipoprotein (LDL) cholesterol (LDL-C)
  • Triglyceride 3, 4 These markers are used to predict the risk of vascular disease and atherosclerotic cardiovascular disease (ASCVD) 5.

Lipid Panel

A new lipid panel has been proposed for the assessment of dysfunctional HDL and lipoprotein-related atherosclerotic cardiovascular disease, which includes the measurement of:

  • Lipid peroxide
  • Triglyceride contents within HDL particles 3

Treatment Targets

Different guidelines recommend various treatment targets, including:

  • LDL-C levels
  • HDL-C levels
  • Lifetime risk assessment
  • Numerical treatment targets based on level of risk 6

Treatment Options

Available treatment options for hypercholesterolemia include:

  • Statins
  • Ezetimibe
  • Bile acid sequestrants
  • Fibrates
  • Fish oil
  • Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors
  • Apolipoprotein A-100 (Apo B-100) antisense
  • Microsomal triglyceride transfer protein (MTP) inhibitor 4, 5, 6, 7

Special Considerations

Certain patient populations require special consideration, including:

  • Patients with familial hypercholesterolemia
  • Patients with renal insufficiency
  • Young patients with hyperlipidemia
  • Patients with statin-related myopathies 4, 5, 7

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Dyslipidemia management update.

Current opinion in pharmacology, 2017

Research

An Evidence-Based Guide to Cholesterol-Lowering Guidelines.

The Canadian journal of cardiology, 2017

Research

Familial hypercholesterolemia.

Cardiology clinics, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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