Total Cholesterol to HDL Ratio: Clinical Utility and Interpretation
The total cholesterol/HDL ratio is a valuable risk assessment tool but should not be used as a treatment target; instead, focus on absolute LDL cholesterol goals based on cardiovascular risk category. 1
Understanding the Ratio
The total cholesterol/HDL cholesterol ratio combines atherogenic lipoproteins (total cholesterol) with protective HDL cholesterol into a single risk marker, making it clinically useful for cardiovascular risk stratification. 1 While often used interchangeably with the LDL/HDL ratio in practice, the total cholesterol/HDL ratio is specifically recommended when using the SCORE cardiovascular risk model. 2
Key Clinical Principle
European guidelines explicitly state that no specific treatment goals are defined for HDL cholesterol, and the ratio should be used as a marker of increased risk rather than as a therapeutic target. 2, 1 This is a critical distinction—the ratio helps identify high-risk patients but does not guide treatment decisions.
Risk Interpretation Framework
General Population Thresholds
- HDL cholesterol <1.0 mmol/L (40 mg/dL) in men and <1.2 mmol/L (46 mg/dL) in women serve as markers of increased cardiovascular risk. 2
- A total cholesterol/HDL ratio <3.5 indicates low risk, while a ratio <4.5 indicates moderately increased risk. 3
- The ratio is most informative when total cholesterol exceeds 6.5 mmol/L (250 mg/dL), as it can identify patients who may have lower actual risk despite elevated total cholesterol. 3
Special Population: Rheumatoid Arthritis
The total cholesterol/HDL ratio is specifically recommended for cardiovascular risk assessment in patients with rheumatoid arthritis when using the SCORE model, with a 1.5 multiplication factor applied to the calculated risk if certain disease criteria are met. 2
Treatment Approach: Focus on Absolute Targets
Rather than targeting a specific ratio, treatment should focus on absolute LDL cholesterol goals based on cardiovascular risk category:
Primary Prevention (Asymptomatic Individuals)
- General goal: Total cholesterol <5 mmol/L (190 mg/dL) and LDL cholesterol <3 mmol/L (115 mg/dL). 2
- High-risk individuals (10-year cardiovascular death risk ≥5%): Total cholesterol <4.5 mmol/L (175 mg/dL) and LDL cholesterol <2.5 mmol/L (100 mg/dL). 2
Secondary Prevention (Established CVD or Diabetes)
- Total cholesterol <4.5 mmol/L (175 mg/dL) and LDL cholesterol <2.5 mmol/L (100 mg/dL). 2
- More recent guidelines suggest even lower targets: LDL <1.8 mmol/L (70 mg/dL) or at least a 50% reduction in LDL for very high-risk patients. 2
Critical Clinical Pitfalls
Do not rely on the ratio alone when total cholesterol is <6.5 mmol/L (250 mg/dL). In patients with total cholesterol below this threshold, measuring triglycerides and HDL identifies very few additional high-risk patients—only 0.6% of screened individuals had both elevated triglycerides (≥2.3 mmol/L) and low HDL (<0.9 mmol/L). 3
Always obtain a complete fasting lipid profile before initiating lipid-lowering drug therapy. 3 The ratio provides context but cannot replace comprehensive lipoprotein assessment, particularly for characterizing the specific dyslipidemia pattern. 3
The Friedewald formula for calculating LDL cholesterol is invalid when triglycerides exceed 4.5 mmol/L (400 mg/dL). 2, 4 In such cases, use direct LDL measurement or newer calculation methods like the Sampson-NIH2 equation (valid up to triglycerides of 9 mmol/L). 4
Practical Algorithm for Lipid Assessment
Measure total cholesterol first in asymptomatic individuals for initial screening. 2
If total cholesterol <6.5 mmol/L (250 mg/dL): The ratio adds minimal additional risk information; focus on overall cardiovascular risk assessment and lifestyle modification. 3
If total cholesterol ≥6.5 mmol/L (250 mg/dL): Obtain complete fasting lipid profile including HDL and triglycerides. 3 Calculate the ratio to refine risk assessment—a favorable ratio (<4.5) may indicate moderately increased rather than high risk. 3
Base treatment decisions on absolute LDL cholesterol levels and overall cardiovascular risk category, not on achieving a specific ratio target. 2, 1