Does The Triglyceride to HDL Ratio Matter For Heart Disease?

There are a number of Medfluencers telling people that high LDL cholesterol is acceptable as long as your triglyceride to HDL cholesterol ratio is low. They also cite other ratios like total cholesterol to HDL cholesterol or various other ratios.

Unfortunately, these generalizations are neither true nor accurate. Relying on ratios can be dangerous. There are significant gender, racial, and ethnic differences in HDL-C and triglyceride levels.

Using HDL in any ratio is inaccurate because African Americans, women, and other ethnicities or races have different patterns, levels, and subclasses.

Sure, sometimes people with higher triglycerides will always be worse off in terms of health. This is mainly driven by concurrent elevations in apoB.

They may have higher triglycerides due to consuming more calories, higher BMI, insulin resistance, and diabetes. They are absolutely higher risk. You really don’t need a study to tell you that. But using any studies to derive any conclusion about TG/HDL-C ratio is just bad science and bad analysis. Especially, when you don’t correct for apoB. In many of these studies, the group with the “better ratios” actually had far fewer risk factors (BMI, smoking, IR, diabetes, heart failure, etc).

Correcting For LDL-C and apoB

Ultimately, nearly every study or databank that has ever been analyzed has shown that when you correct for apoB or LDL-C, no ratios or risk factors matter.

Want to know which smokers have the highest rates of heart disease? It’s the ones with the highest apoB.

Want to know which diabetics have the highest rates of heart disease? It’s the ones with the highest apoB.

Want to know which hypertensives have the highest rates of heart disease? It’s the ones with the highest apoB.

Want to know which obese individuals have the highest rates of heart disease? It’s the ones with the highest apoB.

Want to know which females have the highest rates of heart disease? It’s the ones with the highest apoB.

Want to know which Hispanics have the highest rates of heart disease? It’s the ones with the highest apoB.

Want to know which African Americans have the highest rates of heart disease? It’s the ones with the highest apoB.

Want to know which short people have the highest rates of heart disease? It’s the ones with the highest apoB.

Want to know which football players have the highest rates of heart disease? It’s the ones with the highest apoB.

It’s that simple. We don’t need to make this more complicated. Since LDL-C (apoB) is causative of atherosclerosis, we don’t need to massage the data or look for non-existent correlations. Read the next chapter.

Triglycerides and HDL Mostly Genetic

In another large study, “The association of genetically predicted TG with CAD persisted but it was no longer associated with mortality outcomes after controlling for apoB”.

Study:
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2814089

Again, HDL-C can vary widely between races, genders, and ethnicities. Here are a few great articles to read on this topic.

Ethnic and Racial Differences:
https://www.jacc.org/doi/10.1016/j.jacc.2022.09.027
https://pubmed.ncbi.nlm.nih.gov/2403106/
https://pubmed.ncbi.nlm.nih.gov/9517868/
https://pubmed.ncbi.nlm.nih.gov/1576221/

Differences between the sexes:
https://pubmed.ncbi.nlm.nih.gov/1547192/
https://pubmed.ncbi.nlm.nih.gov/8218107/
https://pubmed.ncbi.nlm.nih.gov/1139779/

Ratios Don’t Matter When You Correct For ApoB

When you take into account apolipoprotein B levels, no other markers or ratios matter.

What does this mean?

Let’s say you have a “healthy” ratio of triglycerides to HDL cholesterol. However, you have an extremely high apoB level. You are at increased risk regardless of what the ratio says.

Similarly, let’s say you have a “bad” ratio of triglycerides to HDL-C (insert any other ratio you want), but your apoB level is very low. You are protected from atherosclerosis.

One exception to this rule: You are protected against ASCVD if you have very low apoB, unless the person has one of the rare genetic hypoalphalipoproteinemia (HDL-C usually < 15 mg/dL).

Improving Ratios Doesn't Improve Outcomes

We also have several trials where drugs that raised HDL-C (niacin, fibrates, estrogen, CETP inhibitors) did not reduce CV events which means neither HDL-C nor any ratio containing it can be used as a goal of therapy.

The ratios make no difference when you look at the actual cause of atherosclerosis, which is LDL cholesterol or apoB particles.

A study that looked at 347,797 participants with genetically higher or lower apoB and triglycerides, they found that, while TG did associate with CV outcomes, that association was no longer associated with CV outcomes after you control for apoB.

Study:
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2814089

Articles that elaborate:
https://www.lipidjournal.com/article/S1933-2874(10)00044-9/fulltext
https://www.jacc.org/doi/10.1016/j.jacc.2022.09.027
https://pubmed.ncbi.nlm.nih.gov/21122647/
https://pubmed.ncbi.nlm.nih.gov/23068583/
https://pubmed.ncbi.nlm.nih.gov/15492304/
https://pubmed.ncbi.nlm.nih.gov/14581403/
https://pubmed.ncbi.nlm.nih.gov/19450572/