Why Your Total Cholesterol Number Doesn’t Tell the Whole Story

A normal total cholesterol number can feel like good news, but it doesn’t always tell the full story. Marschall Runge, M.D., Ph.D., the Frank D. and Agnes C. McKay Professor of Medicinal Science and former dean of the University of Michigan Medical School, says a person can land in a “normal” total cholesterol range while actually carrying a combination of high LDL and low HDL, both independently linked to a higher risk of heart attack and cardiac death.

We spoke with Runge about why LDL targets vary so much from patient to patient, why raising HDL with medication hasn’t been shown to lower cardiac risk the way lowering LDL does, and what changed in the newly updated 2026 American College of Cardiology/American Heart Association dyslipidemia guidelines.

A lot of patients fixate on their total cholesterol number. Why isn’t that the most useful number to focus on?

Marschall Runge, M.D., Ph.D.: “Total” cholesterol is typically reported and, for many years, was considered an important measure to target therapies. However, it is a sum of several different, more specific measurements, including LDL “bad” cholesterol, HDL “good” cholesterol, and other lipid components, as impacted by triglycerides. A person may have a total cholesterol that falls into the normal range but actually represents a sum of high LDL and low HDL measures, both of which are associated with increased risk of heart attack and cardiac death.

Why isn’t there one universal “normal” LDL target?

MR: LDL levels are very important but, like all “target” results, are important to take in context, which is why the thinking on desired LDL levels has changed over time. The general “target” for LDL cholesterol has decreased over the past 25 years based on results from large studies correlating LDL levels with cardiac risk, which have led to changes in guidelines (see the most recent information on guidelines below). The context is this: If a person is healthy and has no other cardiac risk factors (important factors include diabetes, hypertension, history of cigarette smoking, family history), their recommended LDL cholesterol target is not as low as for someone with multiple risk factors. And there are extreme cases (not listed in guidelines) for a person of very high risk and prior cardiac events where an even lower LDL level is recommended and requires newer genetic therapies that result in LDL cholesterol levels below 25 mg/dL.

What do you wish more patients understood about HDL, since it’s often misunderstood as a number to maximize?

MR: HDL cholesterol also has a strong association with cardiovascular disease based on large epidemiologic studies. HDL cholesterol levels that fall below the normal range, in general, are associated with higher cardiac risk, and HDL cholesterol levels that are well above the normal range are associated with lower cardiac risk. There are some healthy lifestyle factors that can move your HDL cholesterol higher, such as diet and exercise. That said, there are not data that using medications to increase HDL levels results in lower cardiac risk. This is quite different than with LDL cholesterol, where the use of medications (such as statins) to lower LDL cholesterol lowers cardiac risk.

While not what you asked, I also want to point out a recent study involving a drug that effectively reduces high triglyceride levels. This seemed to make all kinds of sense from a biological perspective — there is a correlation of high triglycerides with increased cardiac risk. However, although the study participants saw a dramatic reduction in triglyceride levels, there was no reduction in cardiac risk.

What changed with the 2026 ACC/AHA dyslipidemia guideline update that patients should know about?

MR: The 2026 guidelines focus more on early intervention and aggressive targets for LDL cholesterol based on data that long-term reduction of LDL cholesterol will reduce lifetime cardiovascular risk. The new guidelines also integrated the updated PREVENT-ASCVD risk calculator. It integrates many cardiac risk factors and provides a better and more comprehensive assessment of cardiovascular risk than previous models.

What’s one thing patients can do before their next appointment to get more out of a cholesterol conversation with their doctor?

MR: Ask for information on what your individual risk is, based on the PREVENT-ASCVD risk calculator or other cardiac risk factor predictors. This is valuable to you as it provides the critical “measure-treat-remeasure” cycle that is so important in reducing your cardiac risk. It also will enable conversations with your doctor on what the most appropriate approaches to you as an individual are and the choices you may face.