What does total cholesterol measure?

What Total Cholesterol Measures

Total cholesterol is a composite measurement that includes both LDL cholesterol (low-density lipoprotein) and HDL cholesterol (high-density lipoprotein), making it a convenient but potentially misleading single metric for cardiovascular risk assessment. 1

Components of Total Cholesterol

Total cholesterol represents the sum of all cholesterol-carrying lipoproteins in the blood, specifically:

• LDL cholesterol - the "bad" cholesterol that deposits lipids in arterial walls and increases cardiovascular risk 1
• HDL cholesterol - the "protective" cholesterol that transports lipids back to the liver for disposal 1
• VLDL cholesterol (very-low-density lipoprotein) - calculated as triglycerides divided by 5 (in mg/dL) 1

The mathematical relationship is expressed through the Friedewald formula: LDL cholesterol = total cholesterol - (HDL cholesterol + [triglycerides/5]) 1

Clinical Limitations of Total Cholesterol Alone

Total cholesterol can be misleading because two patients with identical total cholesterol values may have vastly different cardiovascular risk profiles depending on their HDL and LDL components. 1

For example:

• A patient with total cholesterol of 200 mg/dL, HDL of 60 mg/dL, and LDL of 120 mg/dL has lower risk 1
• A patient with total cholesterol of 200 mg/dL, HDL of 35 mg/dL, and LDL of 145 mg/dL has substantially higher risk 1

Practical Measurement Considerations

Total cholesterol can be measured at any time of day without fasting because levels do not vary appreciably with eating, making it convenient for initial screening 1

However, this convenience comes with trade-offs:

• Nonfasting total cholesterol measurements may miss patients with isolated low HDL cholesterol 1
• A complete fasting lipid profile (12-hour fast) provides total cholesterol, triglycerides, HDL cholesterol, and calculated LDL cholesterol, offering more complete cardiovascular risk assessment 1

Risk Stratification Thresholds

According to the American Heart Association guidelines for children and adolescents (applicable principles extend to adults):

• Acceptable: Total cholesterol <170 mg/dL 1
• Borderline: 170-199 mg/dL 1
• High: ≥200 mg/dL 1

For adults, total cholesterol ≥240 mg/dL is considered high risk and warrants further evaluation with a complete lipid profile 2

Superior Alternative Metrics

The total cholesterol/HDL ratio provides superior risk discrimination compared to total cholesterol alone because it captures the balance between atherogenic and protective lipoproteins 3, 4, 5

Research demonstrates:

• The total cholesterol/HDL ratio was the best predictor of subclinical atherosclerosis (measured by intima-media thickness) with correlation coefficient r=0.23 (p<0.0001) 6
• This ratio added independent risk-discriminating ability beyond total cholesterol or LDL cholesterol alone (p<0.02) in predicting coronary heart disease events 4
• Clinically significant discordance exists in 21-26% of patients where total cholesterol/HDL ratio is elevated despite LDL and non-HDL cholesterol being below median values 5

Critical Clinical Pitfalls

Never initiate lipid-lowering drug therapy based solely on total cholesterol without obtaining a complete fasting lipid profile including HDL cholesterol measurement 7

Additional caveats:

• The Friedewald formula for calculating LDL is invalid when triglycerides exceed 400 mg/dL (4.5 mmol/L), requiring direct LDL measurement or alternative calculation methods 3, 2
• When abnormal values are detected, repeat testing and average two measurements before making definitive treatment decisions 1, 2
• Total cholesterol screening should trigger fasting lipid profile if values are ≥170 mg/dL in children or ≥200 mg/dL in adults 1