Cardiovascular Risk Assessment Using the Triglyceride-to-HDL Cholesterol Ratio

Clinical Utility and Risk Prediction

The combination of elevated triglycerides and low HDL cholesterol is extremely common in high-risk patients with type 2 diabetes, abdominal obesity, insulin resistance, and physical inactivity, forming part of the atherogenic dyslipidemic triad, as noted by the European Heart Journal 1, 2
Elevated triglycerides are independently associated with cardiovascular disease risk, even after adjustment for HDL cholesterol, according to Circulation Research and Circulation 3, 4

Fasting triglycerides >1.7 mmol/L (150 mg/dL) are considered a marker of increased cardiovascular risk, though this is not an evidence-based treatment target, as stated by the European Heart Journal 1, 2
HDL cholesterol <1.0 mmol/L (40 mg/dL) in men and <1.2 mmol/L (45 mg/dL) in women indicates increased risk, but there is insufficient evidence to use HDL as a therapeutic goal, according to the European Heart Journal 1, 2
Focus on absolute LDL cholesterol targets based on overall cardiovascular risk: <1.8 mmol/L (70 mg/dL) for very high-risk patients, as recommended by the European Heart Journal 2

Nonfasting triglycerides >5 mmol/L (440 mg/dL) versus <1 mmol/L (88 mg/dL) were associated with 17-fold and 5-fold risk of myocardial infarction in women and men, respectively, during 27 years of follow-up, as reported by Circulation Research 3
Meta-analyses show that elevated triglycerides confer a relative risk of 1.14 in men and 1.37 in women for cardiovascular disease after adjustment for HDL cholesterol, according to Circulation 4
Genetic studies provide causal evidence: a 1-mmol/L genetic increase in remnant cholesterol was associated with a 2.8-fold causal risk increase for ischemic heart disease, as found by Circulation Research 5

The TG/HDL ratio is a valuable marker that reflects the relationship between triglyceride-rich lipoproteins and high-density lipoprotein cholesterol, providing insight into cardiovascular risk beyond traditional lipid measurements 6, 7

A TG/HDL ratio of 0.49 suggests lower risk of atherosclerotic cardiovascular disease (ASCVD) 7
Lower remnant cholesterol levels are associated with reduced cardiovascular risk independent of LDL cholesterol levels 7

Comprehensive cardiovascular risk assessment should include evaluation of absolute LDL cholesterol levels (target depends on overall risk) 6, 8
Assessment of non-HDL cholesterol (total cholesterol minus HDL cholesterol) should be considered 9
Consideration of other cardiovascular risk factors (hypertension, diabetes, smoking, family history) is necessary 6

Standard lipid monitoring according to age and risk factors is appropriate for a favorable TG/HDL ratio of 0.49 6
No specific intervention is needed to improve this particular ratio 6, 8

The TG/HDL ratio should be interpreted as part of a complete lipid profile, not in isolation 6, 9
Even with a favorable TG/HDL ratio, elevated absolute LDL cholesterol levels would still warrant appropriate management 8
Fasting status can affect triglyceride levels and thus the ratio; confirm whether the measurement was taken in a fasting state 6

The American Heart Association emphasizes that triglyceride measurement provides no additional information about vascular risk given knowledge of HDL-C and total cholesterol levels for population-wide assessment, highlighting the importance of considering multiple factors in cardiovascular risk evaluation 10, 11

The relationship between TG/HDL-C ratio and insulin resistance varies by ethnicity and sex, emphasizing the need for personalized interpretation of this ratio in clinical practice 10, 11

The predictive value of the TG/HDL ratio varies significantly by ethnicity, with black patients with metabolic syndrome or type 2 diabetes may not exhibit high triglyceride levels as commonly as other ethnic groups 12
Always obtain fasting lipid measurements (12-hour fast) for accurate triglyceride assessment, as recommended by the American Heart Association 12

Focus therapeutic interventions on lowering LDL cholesterol to evidence-based targets based on cardiovascular risk category, as recommended by the American Diabetes Association 13
When triglycerides are elevated (≥150 mg/dL), prioritize glycemic control first, then consider pharmacotherapy, according to the European Society of Cardiology 13
The treatment algorithm for elevated triglycerides includes optimizing glycemic control, implementing lifestyle interventions, and considering pharmacological treatment with fibric acid derivatives, as suggested by the American College of Cardiology 13

First-line treatment for high LDL is HMG-CoA reductase inhibitors (statins), as recommended by the American Heart Association 13
For high triglycerides with high LDL, the first choice is improved glycemic control plus high-dose statin, according to the American Diabetes Association 13

Interpret TG/HDL ratios cautiously in pregnant women, as physiologic changes may elevate the ratio without indicating pathology, as noted by the American College of Obstetricians and Gynecologists 12
Delay lipid assessment until acute conditions resolve to avoid misdiagnosis, as recommended by the American Heart Association 14

Nonfasting triglycerides >5 mmol/L (440 mg/dL) versus <1 mmol/L (88 mg/dL) were associated with 17-fold and 5-fold increased risk of myocardial infarction in women and men respectively during 27 years of follow-up, according to the American College of Cardiology 15
A 1-mmol/L genetic increase in remnant cholesterol (triglyceride-rich lipoproteins) was associated with a 2.8-fold causal risk increase for ischemic heart disease, compared to only 1.4-fold observational risk, as stated by the American Heart Association 16
Genetic studies using 185 single nucleotide polymorphisms showed that genetically determined elevated triglyceride levels were strongly associated with ischemic heart disease, even after adjusting for both LDL and HDL cholesterol levels, as reported by the National Lipid Association 17
Genetic studies demonstrate that elevated triglyceride-rich lipoproteins are causally associated with atherosclerotic cardiovascular disease, whereas low HDL cholesterol per se is not, according to the American College of Cardiology 16, 17
Higher cardiovascular risks in women than men have been observed with elevated triglycerides, partly explained by confounding from higher alcohol intake in men, as noted by the American Heart Association 15
The strong inverse association between triglycerides and HDL cholesterol suggests an intricate biological relationship that may not be most suitably represented by simple multivariate analysis, as stated by the American College of Cardiology 18

The American Heart Association recommends optimal fasting triglycerides of <100 mg/dL (1.1 mmol/L) for optimal metabolic health 19, 20

The American College of Cardiology suggests that optimal HDL cholesterol targets are ≥40 mg/dL (1.0 mmol/L) in men and ≥46 mg/dL (1.2 mmol/L) in women, although the exact citation is not provided, the general guideline is supported by 19, 20