cholesterol LDL in serum

Genetics

• variations in NPC1L1 that inhibit its function that lower plasma LDL cholesterol levels & a reduce the risk of coronary artery disease
• gene mutations* for familial hypercholesterolemia in < 2% of patients with LDL cholesterol level > 190 mg/dL

* genetic testing for familial hypercholesterolemia

• LDLR gene mutations
• APOB gene+LDLR gene mutations
• APOB+LDLR+PCSK9 gene mutations

Indications

• dyslipidemia
• cardiovascular disease
  • coronary artery disease
  • cerebrovascular disease
  • peripheral artery disease
• cardiovascular risk factors
  • diabetes mellitus
  • hypertension
  • chronic renal failure
• general health screening (health maintenance)
  • see lipid panel for screening intervals
• primary utility of serum LDL cholesterol is identifying patients who will benefit from statin therapy & to assess response to statin therapy

Reference interval

mg/dL -> mmol/L, multiply by 0.0259

risk	LDL cholesterol
high-risk	> 160 mg/dL (< 4.14 mmol/L)
borderline	130 - 159 mg/dL (3.37 - 4.12 mmol/L)
desirable	< 130 mg/dL (< 3.37 mmol/L)
vasculopathy*	< 100 mg/dL (< 2.50 mmol/L)
intensive control	< 70 mg/dL (< 1.8 mmol/L)

* vasculopathy = CAD, diabetes, ischemic stroke target LDL for high risk patients with coronary artery disease (CAD) has been lowered to 70 mg/dL. (NCEP)

Clinical significance

• an LDL/HDL ratio of > 4 predicts increased risk of CAD, lowering of total cholesterol & LDL cholesterol to levels within NCEP guidelines reduces coronary artery disease related deaths in men & women
• benefits in the young & the elderly have not yet been demonstrated (20 > age > 65).
• LDL cholesterol not associated cardiovascular disease in elderly > 75 years
• low cholesterol absorption efficiency in elderly predicts all-cause mortality
• cholesterol synthesis diminishes in elderly, but does not predict mortality
• frailty & poor health decrease LDL cholesterol
• high LDL cholesterol associated with lower mortality in most people over 60 years of age
• high LDL cholesterol not associated with increased mortality in women > 68 years of age
• LDL cholesterol > 160 mg/dL associated with increased mortality in low-risk patients
• LDL cholesterol has a U-shaped association with all-cause mortality
  • all-cause mortality was lowest at an LDL cholesterol level of 140 mg/dL
  • U-shaped association with all-cause mortality not apparent in statin users
• LDL-cholesterol-lowering with statins, ezetimibe, or PCSK9 inhibitors significantly lowers risk for vascular events in adults of all ages
• 7% of adults have LDL cholesterol level > 190 mg/dL
• patients with LDL cholesterol > 190 mg/dL should be
  • treated with a high-intensity statin
    • atorvastatin 40-80 mg QD, rosuvastatin 20-40 mg QD
  • evaluated for familial hypercholesterolemia, & secondary causes of hyperlipidemia including glucocorticoid use, diabetes mellitus, & hypothroidism
• higher LDL cholesterol associated with diminished risk of type 2 diabetes
• for patients on a PCSK9 inhibitor, estimate LDL-cholesterol with Martin/Hopkins estimation

intensive lipid-lowering therapy to very low LDL cholesterol

• intensive lipid-lowering therapy to very low LDL cholesterol levels is not associated with diminished mortality
• intensive lipid-lowering therapy of LDL cholesterol to < 70 mg/dL slows atherosclerotic plaque progression assessed by CT angiography
• adding evolocumab & ezetimibe to a statin in high-risk patients with LDL cholesterol < 70 mg/dL further decreases risk of cardiovascular event (21% for 39 mg/dL decrease in LDL cholesterol)
• AHA states that intensive lipid lowering therapy does not adversely affect risk of cognitive impairment or dementia or hemorrhagic stroke, but admits there is some disagreement in the literature & stops short in its abstract of expressing this claim in terms of numbers
• lowering serum LDL cholesterol to < 25-35 mg/dL with with evolocumab does not adversely affect cognitive function within 5 years

Increases

• hypothyroidism
• poorly controlled diabetes mellitus
• nephrotic syndrome
• medications:
  • glucocorticoids
  • diuretics
  • amiodarone

Decreases

• poor health

Procedure

LDL-cholesterol is generally calculated from measurements of total cholesterol, HDL-cholesterol & triglycerides obtained from a lipid panel & the assumption that the VLDL-cholesterol is equal to 1/5 of the triglyceride concentration, using the formula:

[[[A144160|LDL]]-chol] = [total chol] - [HDL-chol] - [[[A18141|triglycerides]]/5]

This equation works well for triglycerides < 400 mg/dL in the absence of dysbetalipoproteinemia.

The lipoprotein LDL may be measured directly using lipoprotein electrophoresis or determined from apolipoprotein B measurement.

Management

• high-dose statin (atorvastatin 40 mg QD) for patients with known cardiovascular disease
  • dose to achieve > 50% reduction in LDL cholesterol
  • add ezetimibe as needed & then a PCSK9 inhibitor for high-risk patients with LDL cholesterol > 70 mg/dL
    • mortality risks decrease as statin doses increase
    • no benefit in lowering LDL cholesterol below 70 mg/dL
• for LDL cholesterol > 190 mg/dL, high-intensity maximally tolerated statin
  • ezetimibe as needed
• moderate intensity statin for patients with diabetes mellitus without cardiovascular disease & LDL cholesterol > 70 mg/dL
• check LDL cholesterol 1-3 months after treatment change

Comparative biology

• CRISPR knock out of the PCSK9 gene in the livers of mice increases LDL receptors & reduces plasma LDL cholesterol without observable adverse effects

More general terms

• cholesterol LDL in body fluid

More specific terms

• cholesterol LDL-1 in serum
• cholesterol LDL-2 in serum
• cholesterol LDL-3 in serum
• cholesterol LDL-4 in serum

Additional terms

• cholesterol LDL in serum calculated
• LDL triglycerides in serum/plasma
• low density lipoprotein (LDL, beta-lipoprotein)

Component of

• lipid panel (fasting lipid panel, FLP)
• cholesterol LDL/apolipoprotein B in serum/plasma
• apolipoprotein B/LDL cholesterol in serum/plasma
• cholesterol LDL/cholesterol HDL in serum/plasma
• cholesterol total/cholesterol LDL in serum/plasma
• cholesterol LDL/cholesterol total in serum/plasma

Patient information

LDL & VLDL cholesterol in serum patient information