What are the ideal ratios of total cholesterol to High-Density Lipoprotein (HDL) cholesterol, Low-Density Lipoprotein (LDL) to HDL cholesterol, and triglyceride to HDL cholesterol in a healthy lipid profile?

Lipid Profile Ratios and Their Clinical Interpretation

Primary Recommendation: Focus on Absolute Values, Not Ratio Targets

The TC/HDL-C ratio and LDL-C/HDL-C ratio should be used for cardiovascular risk stratification, but treatment decisions must target absolute LDL-C levels based on risk category—not the ratios themselves. 1, 2

The European Society of Cardiology explicitly states that while ratios are useful for risk estimation, "for diagnosis and as treatment targets the components of the ratio have to be considered separately." 2 This is critical because nearly all lipid-lowering trials have used LDL-C as the indicator of treatment response, with robust evidence that every 1.0 mmol/L (40 mg/dL) reduction in LDL-C produces dose-dependent reductions in cardiovascular disease. 2

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Total Cholesterol/HDL-C Ratio

Risk Stratification Values

• The TC/HDL-C ratio provides additional risk stratification information beyond individual lipid components. 3, 1
• Research demonstrates that TC/HDL-C ratio is a better predictor of subclinical atherosclerosis (measured by intima-media thickness) than LDL-C/HDL-C ratio, with the strongest correlation (r = 0.23, p < 0.0001). 4
• In patients with elevated triglycerides (>168 mg/dL), the TC/HDL-C ratio captures cardiovascular risk more accurately than LDL-C/HDL-C ratio because it accounts for atherogenic remnant particles not reflected in calculated LDL-C. 5

Clinical Application

• Use TC/HDL-C ratio when applying the SCORE cardiovascular risk model, particularly in patients with rheumatoid arthritis or other inflammatory conditions. 1
• The ratio is especially valuable in women (who often have high HDL-C) and patients with diabetes or metabolic syndrome (who often have low HDL-C), where total cholesterol alone may be misleading. 3

Critical Caveat

• No specific treatment goals are defined for the TC/HDL-C ratio—it serves as a marker of increased risk, not a therapeutic target. 1, 2

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LDL-C/HDL-C Ratio

Limitations in Risk Assessment

• The LDL-C/HDL-C ratio may underestimate cardiovascular risk in overweight, hyperinsulinemic patients with high triglyceride-low HDL-C dyslipidemia. 5
• For any given LDL-C/HDL-C ratio, patients in the highest triglyceride tertile (>168 mg/dL) have significantly higher TC/HDL-C ratios and worse metabolic profiles associated with insulin resistance syndrome. 5
• Greater differences in features of insulin resistance (insulinemia, apolipoprotein B, LDL particle size) are noted across tertiles of TC/HDL-C ratio than LDL-C/HDL-C ratio. 5

When to Use

• The LDL-C/HDL-C ratio provides additional risk stratification beyond LDL alone, particularly for identifying patients at higher risk despite seemingly acceptable LDL levels. 2
• The ratio combines an atherogenic lipoprotein (LDL) with a protective one (HDL), making intuitive sense for risk assessment. 2

Treatment Approach

• Focus therapeutic interventions on lowering absolute LDL-C levels, not achieving a specific LDL-C/HDL-C ratio. 2
• Even with a favorable ratio, elevated absolute LDL-C levels still warrant appropriate management according to risk category. 2

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Triglyceride/HDL-C Ratio

Clinical Significance

• The TG/HDL-C ratio is a marker of insulin resistance and metabolic syndrome, but is not established as a primary treatment target. 5, 6
• In COVID-19 patients, TG/HDL-C ratio was significantly related to survival (HR = 3.860,95%CI = 1.289 to 11.558, P < 0.05), though not as strongly as other metabolic markers. 6

Interpretation Context

• Elevated TG/HDL-C ratio indicates increased cardiovascular risk, particularly in the context of metabolic syndrome features. 5
• This ratio helps identify patients who may benefit from lifestyle interventions targeting insulin resistance (weight loss, exercise, dietary modification). 5

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Practical Clinical Algorithm

Step 1: Initial Screening

• Measure total cholesterol first in asymptomatic individuals for initial screening. 1
• If TC ≥6.5 mmol/L (250 mg/dL), obtain complete fasting lipid profile including HDL-C and triglycerides. 1

Step 2: Calculate Ratios for Risk Stratification

• Calculate TC/HDL-C ratio and LDL-C/HDL-C ratio for additional risk stratification. 1, 2
• Use the Friedewald formula for LDL-C calculation: LDL-C = TC - HDL-C - TG/2.2 (mmol/L) or TG/5 (mg/dL). 3
• Critical pitfall: The Friedewald formula is invalid when triglycerides exceed 4.5 mmol/L (400 mg/dL)—use direct LDL measurement or newer calculation methods like the Sampson-NIH2 equation in such cases. 1

Step 3: Identify High-Risk Features

• HDL-C <1.0 mmol/L (40 mg/dL) in men or <1.2 mmol/L (46 mg/dL) in women indicates increased cardiovascular risk. 7, 1
• Triglycerides ≥1.7 mmol/L (150 mg/dL) indicate high triglycerides; ≥2.3 mmol/L (200 mg/dL) indicate very high triglycerides. 7
• In patients with TC <6.5 mmol/L (250 mg/dL), isolated hypertriglyceridemia (≥2.3 mmol/L) combined with low HDL-C (<0.9 mmol/L) identifies only 0.6% of screened patients at increased risk—most are overweight/obese and benefit from lifestyle modification. 8

Step 4: Set Absolute LDL-C Treatment Targets (Not Ratio Targets)

• Primary prevention (asymptomatic): LDL-C <3 mmol/L (115 mg/dL) and TC <5 mmol/L (190 mg/dL). 1
• High-risk individuals (10-year CV death risk ≥5%): LDL-C <2.5 mmol/L (100 mg/dL) and TC <4.5 mmol/L (175 mg/dL). 1
• Very high-risk patients (established CVD or diabetes): LDL-C <1.8 mmol/L (70 mg/dL) or at least 50% reduction in LDL-C. 1

Step 5: Refine Risk Assessment Using Ratios

• Among 790 patients with predominant hypercholesterolemia (TC ≥6.5 mmol/L and TG <2.3 mmol/L), measurement of HDL-C showed that 9% had only moderately increased risk with TC/HDL-C ratio <4.5. 8
• This means TC alone may overestimate risk in a considerable number of patients, and HDL-C measurement allows more precise risk estimation. 8

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Critical Clinical Pitfalls

Measurement Timing

• Triglyceride measurements require a 12-hour fast for accuracy, while total and HDL cholesterol can be measured non-fasting. 7
• During acute myocardial infarction, HDL-C decreases by 31% and TC by 24% within seven days, with the HDL/TC ratio decreasing significantly—therefore, lipid measurements should be performed on admission, not at discharge, to get reliable estimates of baseline cardiovascular risk factors. 9

Treatment Decisions

• A patient should not be started on lipid-lowering drugs without a full lipoprotein assessment including HDL-C measurement. 8
• When abnormal values are detected, repeat testing and averaging two measurements is recommended before making definitive treatment decisions. 7

Ratio Interpretation

• The ratio must be interpreted as part of a complete lipid profile, not in isolation. 2
• Consider other cardiovascular risk factors including hypertension, diabetes, smoking, and family history when making treatment decisions. 2
• Diagnostic thresholds for initiating treatment vary based on the presence of other cardiovascular risk factors. 7