For over a century, heart disease has reigned as the leading cause of death in the U.S., with recent estimates from the American Heart Association now showing that nearly half of all Americans have at least one of three key risk factors for developing the condition: smoking, high blood pressure and high cholesterol.

But unlike quitting smoking and maintaining a good blood pressure, lowering your cholesterol isn't as straightforward as previously thought, according to Dr. Joshua Septimus, a primary care physician at Houston Methodist.

A typical cholesterol panel will consist of the following tests: triglycerides, LDL cholesterol, HDL cholesterol, non-HDL cholesterol, total cholesterol, and the ratio of cholesterol to HDL.

"I don't really look at ratios, and I don't really look at total cholesterol, which I would almost consider irrelevant in 2024," says Dr. Septimus. "I would also encourage people to stop looking at their HDL. If you're getting a traditional lipid profile today, I would ultimately encourage patients to pay attention to their non-HDL cholesterol."

People often refer to "bad" and "good" cholesterol, but Dr. Septimus says those terms need to be thrown out because the same cholesterol is found in both LDL and HDL. It's a matter of which lipoprotein is carrying the cholesterol that determines its behavior, he notes.

Lipoproteins aren't something most people have heard of, he says. But it's these particles — particularly apoB and a variant called Lp(a) — that are most determinant when it comes to heart disease and stroke risk, according to Dr. Septimus.

Here's what you need to know about these two key cholesterol indicators, including who should test for them, how often and what they could mean for your heart health.

What are lipoproteins?

Being a type of fat, cholesterol doesn't dissolve in water, which presents a problem since blood is mostly that. Lipoproteins, Dr. Septimus explains, are complex particles designed, not unlike cars, to transport cholesterol and other fats across the bloodstream without separating.

There are five main types of cholesterol-carrying particles:

• Chylomicrons
• Very-low-density lipoprotein (VLDL)
• Low-density lipoprotein (LDL)
• Intermediate-density lipoprotein (IDL)
• High-density lipoprotein (HDL)

ApoB — or apolipoprotein B — is a specific protein found on all heart disease-causing cholesterol particles; that includes chylomicrons, VLDL, LDL and IDL. The only type that doesn't involve apoB — and is not involved in the process by which plaque forms in arteries' interior lining — is HDL.

"What really matters [when it comes to checking cholesterol levels] is just how many of the apoB-containing lipoproteins there are, and people who have a high HDL tend to have fewer apoB particles," says Dr. Septimus.

Lp(a) — or lipoprotein(a) — is a unique variant of LDL that's like an "apoB-carrying particle on steroids," meaning it's a much more atherogenic (heart disease-causing) particle compared to others, according to Dr. Septimus. In other words, those with high levels of Lp(a) are more likely to have a heart attack, stroke, or aortic stenosis — a term that means narrowing of the heart's main blood vessel.

The problem is that Lp(a) levels are largely genetically determined, and currently, there are no widely available medications that can lower it. Ultimately, roughly one in three people who have familial high cholesterol will also have high levels of Lp(a), according to the CDC.

(Related: What Causes High Cholesterol?)

Who should test for Lp(a) and apoB?

"While there is a lot of continuity between what's called non-HDL and lipoprotein levels, it's not perfect, and since apoB is the atherogenic lipoprotein, it's just better to measure it directly," says Dr. Septimus. "That test is inexpensive and very well-established, so I order t on every patient annually."

"The other wrinkle in all of this is Lp(a)," he adds. "I order an Lp(a) test once on every patient, and if the patient is pre-menopausal when ordered, I check it again post-menopausal because it changes."

"We do not have a therapy for Lp(a), but the presence of it is another one of those risk factors like age that you just want to know about," he continues.

Both Lp(a) and apoB levels can be measured through a simple blood test that can be incorporated into your routine blood work.

In addition, in patients who are at an intermediate risk for developing heart disease or who may be weary of cholesterol-lowering medications, Dr. Septimus says he may also order a coronary artery calcium (CAC) score — a CT scan of your heart that measures the amount of calcium buildup you have in your coronary arteries, which may also help predict your risk of a future heart attack. This test is typically ordered every three to five years.

Unfortunately, he says, there are a number of potential pitfalls when it comes to this test.

"CAC tests only find calcified plaque, so you have to be old enough to have calcified plaque," says Dr. Septimus. "So I generally will not order it for men under 50 or women under 55 because it can give you a false sense of security unless you're positive at a young age, which is very alarming and extremely useful information."

"The second big caveat is that once you start on statin therapy, your calcium score will go up because it's taking soft, vulnerable plaque and hardening it, making it safer and less likely to rupture," he says. "Therefore you should not interpret an elevated coronary calcium score after starting statin therapy as a bad thing."

What is non-HDL cholesterol?

Dr. Septimus says that not everything on that panel necessarily matters — like total cholesterol, cholesterol ratios and HDL. But what exactly is non-HDL cholesterol, the measures he says matter?

"Non-HDL incorporates not only LDL particles, but also what are called the remnant lipoproteins, IDL and VLDL," Dr. Septimus says. "They are all atherogenic, so when you test for non-HDL cholesterol, you're incorporating all of those into it, and that non-HDL level better correlates with apoB."

Even better, non-HDL does not depend on a patient fasting, which is hugely beneficial, says Dr. Septimus, as the other levels — such as triglycerides — can be artificially elevated if a patient isn't fasting.

How often should you get your cholesterol levels tested?

"There are guidelines for that from the U.S. Preventive Services Task Force," says Dr. Septimus, "But you always have to take those guidelines with a grain of salt."

The U.S. Preventive Services Task Force is an independent, volunteer panel of national experts in disease prevention and evidence-based medicine. Both it and the CDC recommend most healthy adults should have their cholesterol checked every four to six years. Both also recommend that people who have heart disease, diabetes or a family history of high cholesterol get their levels checked more often.

However, whereas the CDC says children and adolescents should get their cholesterol checked at least twice before turning 21 years old, the task force does not, citing insufficient evidence.

"The task force specifically advises using only evidence published in randomized controlled trials," says Dr. Septimus. "That's also why the task force does not recommend annual physicals — you can't study or quantify the benefit of a yearly conversation with a professional."

The problem with a four-to-six-year recommendation, according to Dr. Septimus, is that a lot can happen in between testing, including dietary and lifestyle changes that can significantly impact even otherwise healthy individuals.

"If you go five years between getting your cholesterol checked, that's five years of feedback that you're not getting," he says. "That's why I recommend that patients get their cholesterol checked every year once they are adults."

"For example, there's a subset of people with a particular genetic makeup who, if they follow the keto diet, will get a hyper-absorption of cholesterol, and those patients will look like they have a family history of high cholesterol," says Dr. Septimus. "In these particular individuals, you can get a total cholesterol of over 400 on these types of high-fat diets."

"So, what happens if you're one of these individuals?" he asks. "You go on a keto diet, lose weight, feel good and look good, but inside you're piling cholesterol onto your arteries."

"If you catch it at the year mark instead of the five-year mark, you can make some tweaks and try to do that diet in a safer way," he adds.

(Related: Is the Keto Diet Healthy? Weighing the Risks)

At what point should you consider cholesterol-lowering medication?

If you have high cholesterol, you may be confronted with the question of whether to initiate statin therapy — the mainstay class of medications that treat high cholesterol today. But can implementing lifestyle changes such as eating a heart-healthy diet, being more physically active, losing weight and quitting smoking be enough to keep your cholesterol levels in check?

It depends, says Dr. Septimus.

"Therapeutic lifestyle changes are the bedrock of everything we do, but we know realistically that patients don't often do them and that high cholesterol is heavily genetic and less about diet and lifestyle than people think it is," he says. "You initiate medical therapy in addition to lifestyle therapy when someone's risk for heart disease or stroke warrants it."

That risk is calculated using a variety of factors, including family history, smoking status and high blood pressure, but age tends to carry the most weight, says Dr. Septimus.

"If you have someone who is 35 years old, their 10-year risk is going to be really low," he says. "However, if you have a 75-year-old patient whose cholesterol is otherwise normal, their 10-year risk is going to be really high, so it's kind of a balancing act of these factors."

"Ultimately, statin therapy is recommended as the first-line treatment for high cholesterol because they're cheap, safe and effective," he adds. "They save lives."

(Related: How Does Diet Impact Your Cholesterol Levels?)