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Quick Reference
  • Optimal: <100 mg/dL
  • Near/Above Optimal: 100-129 mg/dL
  • Borderline High: 130-159 mg/dL
  • High: 160-189 mg/dL
  • Very High: ≥190 mg/dL
  • Primary Use: PRIMARY TARGET for cholesterol-lowering therapy and cardiovascular risk reduction
  • Sample Type: Serum or plasma (fasting preferred for calculated LDL)
  • Key Point: Lower is better - no "too low" threshold established in statin trials; LDL <70 mg/dL for very high-risk patients

Test Description

What is LDL Cholesterol?

Low-density lipoprotein (LDL) cholesterol, commonly called "bad cholesterol," is the major cholesterol-carrying lipoprotein in blood. LDL particles transport cholesterol from the liver to peripheral tissues, where it is used for cell membrane synthesis, hormone production, and other vital functions.

Why is LDL Called "Bad Cholesterol"?

LDL earns its "bad" reputation because elevated levels directly cause atherosclerosis - the buildup of cholesterol-laden plaques in arterial walls. This process underlies most cardiovascular diseases:

  • Coronary artery disease (CAD): Leading cause of myocardial infarction
  • Cerebrovascular disease: Carotid artery stenosis causing stroke
  • Peripheral arterial disease (PAD): Claudication and limb ischemia
  • Aortic disease: Aneurysm formation and atherosclerotic disease

Mechanism of Atherosclerosis

LDL drives atherosclerosis through a multi-step process:

  • Step 1 - LDL penetration: LDL particles cross endothelial barrier and accumulate in arterial intima (subendothelial space)
  • Step 2 - Oxidation: Trapped LDL becomes oxidized by reactive oxygen species, creating oxidized LDL (oxLDL)
  • Step 3 - Inflammation: OxLDL is highly inflammatory, attracting monocytes that differentiate into macrophages
  • Step 4 - Foam cell formation: Macrophages engulf oxLDL via scavenger receptors, becoming lipid-laden "foam cells"
  • Step 5 - Plaque development: Foam cells accumulate, die, and release cholesterol, forming necrotic core covered by fibrous cap
  • Step 6 - Complications: Plaques can rupture (causing acute MI or stroke), progressively narrow arteries (causing angina or claudication), or calcify
Key Concept - LDL Causality: Decades of randomized controlled trials prove that lowering LDL reduces cardiovascular events proportionally. For every 38-40 mg/dL reduction in LDL, relative risk of major cardiovascular events decreases by approximately 20-25%. This relationship is consistent across all baseline LDL levels - "lower is better."

How is LDL Cholesterol Measured?

LDL can be determined by two methods:

Calculated LDL (Friedewald Equation):

Friedewald Equation:
LDL = Total Cholesterol - HDL - (Triglycerides ÷ 5)

Limitations:
  • Requires fasting sample (triglycerides affected by meals)
  • Invalid when triglycerides ≥400 mg/dL (VLDL estimation becomes inaccurate)
  • Less accurate when triglycerides 200-399 mg/dL
  • May underestimate LDL when triglycerides are elevated

Direct LDL Measurement:

  • Method: Direct enzymatic or immunologic assays that selectively measure LDL
  • Advantages: Can be performed on non-fasting samples; valid even when triglycerides >400 mg/dL; more accurate in hypertriglyceridemia
  • Cost: Slightly more expensive than calculated LDL
  • When to use: Triglycerides ≥400 mg/dL (required), non-fasting samples, hypertriglyceridemia

Alternative Markers

  • ApoB (Apolipoprotein B): Measures number of atherogenic particles; each LDL particle has one ApoB molecule; may be superior to LDL-C for risk prediction
  • LDL particle number (LDL-P): Measured by NMR or ion mobility; counts actual number of LDL particles regardless of cholesterol content
  • Small dense LDL: More atherogenic subtype; not routinely measured but associated with metabolic syndrome and diabetes
Normal Ranges

LDL cholesterol is classified by cardiovascular risk rather than "normal vs. abnormal." The NCEP ATP III established these categories, though current guidelines focus more on absolute risk assessment.

Swipe to see more
Category LDL Cholesterol Clinical Meaning
Optimal <100 mg/dL Ideal for cardiovascular health
Near/Above Optimal 100-129 mg/dL Acceptable for low-risk individuals; target for some moderate-risk patients
Borderline High 130-159 mg/dL Consider therapy based on overall cardiovascular risk
High 160-189 mg/dL Strong consideration for lipid-lowering therapy
Very High ≥190 mg/dL Likely genetic; high-intensity statin recommended regardless of risk score

Risk-Based LDL Goals (Traditional Approach)

While current guidelines emphasize statin intensity rather than specific LDL targets, understanding traditional goals remains clinically useful:

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Risk Category Traditional LDL Goal Definition
Very High Risk <70 mg/dL Established ASCVD, diabetes + ASCVD, ACS
High Risk <100 mg/dL CHD or CHD risk equivalent (diabetes, 10-year risk >20%)
Moderate Risk <130 mg/dL 2+ risk factors, 10-year risk 10-20%
Low Risk <160 mg/dL 0-1 risk factor
2018 ACC/AHA Guidelines: Current guidelines focus on statin intensity (high vs. moderate vs. low) and percent LDL reduction rather than absolute LDL targets. However, many clinicians still use LDL goals, and guidelines suggest considering additional therapy (ezetimibe, PCSK9 inhibitors) if LDL remains ≥70 mg/dL in very high-risk patients despite maximum tolerated statin.
Clinical Significance

Elevated LDL Cholesterol

High LDL is the primary modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD). Causes and associations include:

Primary (Genetic) Causes

  • Familial hypercholesterolemia (FH): Autosomal dominant LDL receptor mutations; heterozygotes have LDL 190-400 mg/dL, homozygotes >400-1000 mg/dL; premature CAD (men <55, women <60); physical findings include tendon xanthomas, xanthelasmas, corneal arcus
  • Familial defective apoB-100: Defective apolipoprotein B prevents LDL binding to receptors; similar phenotype to heterozygous FH
  • Polygenic hypercholesterolemia: Multiple genetic variants causing moderate LDL elevation (160-200 mg/dL)
  • Familial combined hyperlipidemia: Elevated LDL and triglycerides; most common genetic lipid disorder (1:100 people)

Secondary Causes

  • Hypothyroidism: Decreased LDL receptor expression; check TSH in all new hyperlipidemia
  • Nephrotic syndrome: Urinary protein loss triggers hepatic lipoprotein overproduction
  • Cholestasis: Impaired bile acid synthesis reduces cholesterol excretion
  • Diabetes mellitus: Insulin resistance alters lipid metabolism; typically increases triglycerides and small dense LDL
  • Obesity: Increases VLDL production and conversion to LDL
  • Medications: Thiazide diuretics, cyclosporine, anabolic steroids, protease inhibitors, corticosteroids

Lifestyle Factors

  • Saturated fat intake: Primary dietary driver of LDL elevation (found in red meat, full-fat dairy, tropical oils)
  • Trans fats: Raise LDL and lower HDL (partially hydrogenated oils; banned in many countries)
  • Dietary cholesterol: Modest effect (body compensates by reducing synthesis)
  • Obesity and sedentary lifestyle: Contribute to metabolic syndrome and elevated LDL

Low LDL Cholesterol

Very low LDL (<40 mg/dL) is uncommon and usually results from:

  • Statin therapy: Especially high-intensity statins or combination therapy (statin + ezetimibe + PCSK9 inhibitor)
  • Malnutrition/malabsorption: Inadequate dietary intake or intestinal disease
  • Severe liver disease: Reduced lipoprotein synthesis
  • Hyperthyroidism: Increased LDL receptor activity and catabolism
  • Abetalipoproteinemia: Rare genetic disorder; cannot produce apoB-containing lipoproteins
  • Hypobetalipoproteinemia: Genetic defect causing low LDL (<50 mg/dL)
Is Low LDL Harmful? No lower threshold for LDL safety has been identified in randomized trials. Patients achieving LDL <30 mg/dL with PCSK9 inhibitors show continued cardiovascular benefit without increased adverse effects. However, very low LDL from malnutrition or severe illness indicates underlying pathology requiring evaluation.
Interpretation Guidelines

2018 ACC/AHA Cholesterol Management Guidelines

Current approach stratifies patients into four statin benefit groups:

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Benefit Group Criteria Recommended Therapy
Clinical ASCVD Prior MI, ACS, stroke, TIA, PAD, coronary revascularization High-intensity statin (target ≥50% LDL reduction)
If LDL ≥70 mg/dL on max statin: add ezetimibe
If LDL ≥70 mg/dL on statin+ezetimibe: consider PCSK9 inhibitor
Severe Hypercholesterolemia LDL ≥190 mg/dL (likely FH) High-intensity statin regardless of risk score
Often requires combination therapy
Screen family members
Diabetes (40-75 years) Type 1 or 2 diabetes, LDL 70-189 mg/dL Moderate-intensity statin (target 30-49% LDL reduction)
High-intensity if 10-year ASCVD risk ≥20% or multiple risk factors
Primary Prevention No diabetes or ASCVD, LDL 70-189 mg/dL, age 40-75 Calculate 10-year ASCVD risk
If ≥7.5%: moderate to high-intensity statin
If 5-7.5%: consider statin + risk discussion
If <5%: emphasize lifestyle

Statin Intensity Definitions

Swipe to see more
Intensity Expected LDL Reduction Examples
High-Intensity ≥50% Atorvastatin 40-80 mg, Rosuvastatin 20-40 mg
Moderate-Intensity 30-49% Atorvastatin 10-20 mg, Rosuvastatin 5-10 mg, Simvastatin 20-40 mg, Pravastatin 40-80 mg
Low-Intensity <30% Simvastatin 10 mg, Pravastatin 10-20 mg, Lovastatin 20 mg

ACC/AHA ASCVD Risk Calculator

The Pooled Cohort Equations estimate 10-year risk of first atherosclerotic cardiovascular event (MI, stroke, or cardiovascular death) using:

  • Age, sex, race (African American vs. other)
  • Total cholesterol and HDL cholesterol
  • Systolic blood pressure and antihypertensive treatment status
  • Diabetes mellitus
  • Current smoking

Risk Categories:

  • <5%: Low risk - lifestyle modifications primary approach
  • 5-7.4%: Borderline risk - consider statin if risk enhancers present
  • 7.5-19.9%: Intermediate risk - moderate to high-intensity statin recommended
  • ≥20%: High risk - high-intensity statin recommended
Risk Enhancers: Consider these factors when deciding on statin therapy in borderline or intermediate risk patients:
  • Family history of premature ASCVD (men <55, women <65)
  • Chronic kidney disease (eGFR <60 mL/min/1.73m²)
  • Metabolic syndrome
  • Chronic inflammatory conditions (RA, psoriasis, HIV)
  • High-risk ethnic groups (South Asian)
  • Elevated triglycerides (≥175 mg/dL persistently)
  • Elevated high-sensitivity CRP (≥2.0 mg/L)
  • Elevated Lp(a) (>50 mg/dL)
  • Elevated ApoB (≥130 mg/dL)
  • Ankle-brachial index <0.9
  • Coronary artery calcium (CAC) score ≥100 or ≥75th percentile for age/sex

Non-Statin Therapy

When statins are insufficient or not tolerated:

  • Ezetimibe: Reduces LDL 15-20% by blocking intestinal cholesterol absorption; add to statin if LDL goal not met
  • PCSK9 inhibitors (evolocumab, alirocumab): Reduce LDL 50-60%; expensive; reserved for very high-risk patients with LDL ≥70 mg/dL despite max therapy or statin intolerance
  • Bempedoic acid: Reduces LDL ~18%; option for statin-intolerant patients
  • Bile acid sequestrants: Reduce LDL 15-30%; GI side effects limit use
  • Inclisiran: Long-acting siRNA targeting PCSK9; reduces LDL ~50% with twice-yearly dosing
Interfering Factors

Factors That Increase LDL

  • Dietary: Saturated fats (red meat, full-fat dairy, butter, coconut oil, palm oil), trans fats (partially hydrogenated oils)
  • Medications: Thiazide diuretics, beta-blockers, cyclosporine, tacrolimus, anabolic steroids, protease inhibitors, corticosteroids
  • Hormonal: Progestins, pregnancy (physiologic increase)
  • Medical conditions: Hypothyroidism, nephrotic syndrome, cholestasis, diabetes, obesity, metabolic syndrome
  • Genetic: Familial hypercholesterolemia, familial defective apoB-100, polygenic hypercholesterolemia

Factors That Decrease LDL

  • Medications: Statins (20-60% reduction), ezetimibe (15-20%), PCSK9 inhibitors (50-60%), bempedoic acid (~18%), bile acid sequestrants (15-30%), niacin (10-25%)
  • Dietary: Soluble fiber (oats, beans, psyllium), plant sterols/stanols, soy protein, omega-3 fatty acids, reduced saturated fat intake
  • Lifestyle: Weight loss (5-10% weight loss can reduce LDL 5-8%), regular aerobic exercise
  • Medical conditions: Hyperthyroidism, malabsorption, severe liver disease, malnutrition
  • Acute illness: LDL drops 10-40% during acute MI, infection, surgery, trauma (not a true reduction; reflects stress response)

Analytical Considerations

  • Friedewald equation limitations: Invalid when triglycerides ≥400 mg/dL; less accurate when triglycerides 200-399 mg/dL; requires fasting sample
  • Non-fasting samples: If using Friedewald equation, non-fasting sample may overestimate LDL due to elevated postprandial triglycerides; direct LDL measurement preferred for non-fasting
  • Biological variation: LDL varies ±8-10% day-to-day; obtain 2-3 measurements before treatment decisions
  • Seasonal variation: LDL may be 3-5% higher in winter
  • Recent illness: Wait 6-8 weeks after acute illness, surgery, or trauma for accurate baseline
Clinical Pearls
Clinical Pearl
"Lower is better, no threshold identified": Every 38-40 mg/dL reduction in LDL reduces cardiovascular events by ~20-25%. This relationship holds regardless of baseline LDL - benefit extends even when LDL is reduced to <30 mg/dL. No safety concerns with very low LDL in statin trials.
Clinical Pearl
LDL is PRIMARY target of therapy: While total cholesterol, HDL, and triglycerides matter, LDL is the main focus of lipid-lowering therapy. Current guidelines recommend statin intensity based on LDL reduction goals (high-intensity = ≥50% reduction).
Clinical Pearl
LDL <70 mg/dL for very high-risk patients: Patients with established ASCVD, especially with recent events or multiple risk factors, benefit from LDL <70 mg/dL. Some guidelines suggest <55 mg/dL for very high-risk patients. If not achieved with maximum tolerated statin, add ezetimibe, then consider PCSK9 inhibitor.
Triglycerides ≥400 mg/dL? Use direct LDL: Friedewald equation becomes invalid when triglycerides ≥400 mg/dL. Must use direct LDL measurement or non-HDL cholesterol (Total Chol - HDL) as target. Non-HDL goal is typically LDL goal + 30 mg/dL.
Clinical Pearl
Screen for familial hypercholesterolemia: If LDL ≥190 mg/dL, especially with family history of premature CAD, tendon xanthomas, or corneal arcus, suspect FH. These patients need aggressive treatment and cascade family screening. FH affects 1:250 people but is vastly underdiagnosed.
Clinical Pearl
Particle size matters: Small, dense LDL particles are more atherogenic than large, buoyant LDL. Patients with metabolic syndrome, diabetes, or high triglycerides typically have more small dense LDL even if LDL-C is normal. This is why non-HDL and apoB may be better risk markers in these patients.
Check LDL 4-12 weeks after starting statin: Assess response and adherence. If high-intensity statin doesn't achieve ≥50% reduction or LDL remains high, consider: poor adherence, inadequate dose, statin metabolism issues (CYP3A4 interactions), or need for combination therapy.
Clinical Pearl
Don't check lipids during acute illness: LDL drops 10-40% during acute MI, infection, surgery, or trauma. If LDL measured during hospitalization for ACS is elevated, it's VERY elevated at baseline. Wait 6-8 weeks after acute event for accurate baseline unless you're starting statin anyway (which you should in ACS).
Clinical Pearl
Statin benefit is largely LDL-independent: While statins work primarily by lowering LDL, they also have "pleiotropic" anti-inflammatory effects. However, the cardiovascular benefit is proportional to LDL lowering - the more LDL drops, the greater the benefit.
Hypothyroidism mimics familial hypercholesterolemia: Always check TSH in patients with unexplained hypercholesterolemia, especially if symptoms suggest hypothyroidism. Treating hypothyroidism may normalize lipids without need for statins.
ApoB may be superior to LDL-C: Apolipoprotein B measures the number of atherogenic particles (LDL, VLDL, IDL, Lp(a)). Each particle has one ApoB. ApoB >130 mg/dL indicates high risk even if LDL-C appears normal. Useful in metabolic syndrome, diabetes, and high triglycerides where LDL-C may underestimate risk.
References
  1. Kratz, A., Ferraro, M., Sluss, P. M., & Lewandrowski, K. B. (2004). Laboratory reference values. New England Journal of Medicine, 351, 1548-1564.
  2. Lee, M. (Ed.). (2009). Basic skills in interpreting laboratory data. Ashp.
  3. Farinde, A. (2021). Lab values, normal adult: Laboratory reference ranges in healthy adults. Medscape. https://emedicine.medscape.com/article/2172316-overview?form=fpf
  4. Nickson, C. (n.d.). Critical Care Compendium. Life in the Fast Lane • LITFL. https://litfl.com/ccc-critical-care-compendium/
  5. Farkas, Josh MD. (2015). Table of Contents - EMCrit Project. EMCrit Project. https://emcrit.org/ibcc/toc/
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