Is the low-density lipoprotein (LDL) to high-density lipoprotein (HDL) ratio more important than the triglyceride (TG) to high-density lipoprotein (HDL) ratio for assessing cardiovascular risk?

LDL/HDL Ratio is More Important for Cardiovascular Risk Assessment

The LDL/HDL cholesterol ratio should be prioritized over the triglyceride/HDL ratio for cardiovascular risk assessment, as LDL cholesterol remains the primary target of lipid-lowering therapy according to all major cardiovascular guidelines 1, 2.

Guideline-Based Rationale

The European Society of Cardiology/European Atherosclerosis Society explicitly states that LDL cholesterol must be of prime concern in the prevention of cardiovascular disease 1. Every 1.0 mmol/L reduction in LDL cholesterol is associated with a 20-25% reduction in cardiovascular mortality and non-fatal myocardial infarction 1. This dose-dependent relationship has been consistently demonstrated across multiple randomized controlled trials.

Primary vs. Secondary Targets

Major guidelines establish a clear hierarchy:

• Primary target: LDL cholesterol with specific treatment goals (<1.8 mmol/L or 70 mg/dL for very high-risk patients) 1
• Secondary targets: Include triglycerides, non-HDL cholesterol, and various ratios—but only after achieving LDL goals 3, 4

The 2012 European guidelines note that while the apoB:apoA1 ratio (which incorporates HDL) is "one of the strongest risk markers," it is "still not established whether this variable should be used as a treatment goal" 1. This same limitation applies to other ratios including TG/HDL.

Evidence Regarding Triglyceride/HDL Ratio

While the TG/HDL ratio has been studied as a marker of insulin resistance and small dense LDL particles 5, 6, the evidence shows important limitations:

• The TG/HDL ratio does not improve discrimination of cardiovascular events beyond triglycerides alone in prospective studies 5
• It does not add predictive value for identifying small dense LDL phenotype compared to triglycerides measured independently 5
• Guidelines consistently note that there are no randomized trials providing sufficient evidence to derive target levels for triglycerides 1

Clinical Application Algorithm

For cardiovascular risk assessment, follow this sequence:

1. Measure fasting lipid panel including LDL-C, HDL-C, triglycerides, and total cholesterol
2. Calculate LDL/HDL ratio (or use absolute LDL-C as primary metric)
3. Initiate statin therapy targeting LDL-C goals based on risk category 3, 1:
   • Very high risk (established ASCVD): LDL-C <70 mg/dL
   • High risk: LDL-C <100 mg/dL
   • Moderate risk: LDL-C <115 mg/dL
4. After achieving LDL goal, consider secondary targets including:
   • Non-HDL cholesterol (if triglycerides >200 mg/dL) 3
   • Triglycerides as a marker (goal <150 mg/dL) 3, 1

Important Caveats

The TG/HDL ratio has specific utility in certain contexts that should not be ignored:

• In patients with metabolic syndrome, diabetes, or hypertriglyceridemia, the combination of elevated triglycerides and low HDL indicates a pattern of atherogenic dyslipidemia 1
• A TG/HDL ratio >3.5 (when TG in mg/dL and HDL in mg/dL) may identify patients with insulin resistance who warrant more aggressive intervention 6
• However, this information should guide intensity of LDL-lowering therapy, not replace LDL as the primary target

Common pitfall: Focusing on ratios while neglecting absolute LDL-C levels. The 2024 practical implementation statement emphasizes that nearly 75% of patients with atherosclerotic cardiovascular disease have LDL-C above guideline-recommended levels, representing a critical treatment gap 7.

The evidence is unequivocal: LDL cholesterol reduction through statin therapy has proven mortality benefit in randomized trials 1, 8, while no intervention trial has demonstrated that targeting the TG/HDL ratio improves outcomes. Therefore, the LDL/HDL relationship (primarily through absolute LDL-C measurement) takes precedence in clinical decision-making 1, 2.