This lesser-known cholesterol can quadruple your heart-attack risk

For years, Brett Bond thought he had a relatively low risk for heart disease. He managed his mildly elevated blood sugar and cholesterol with medication, and he was eating healthy, exercising regularly, and shedding stress.

Then three years ago Bond, a 60-year-old investment banker from Charlotte, North Carolina, read a book that mentioned a risk factor for heart attacks and strokes that he’d never heard of—a lesser-known type of cholesterol called lipoprotein(a), or Lp(a). At his next appointment, he asked his doctor to test for the lipid; the doctor was reluctant but ultimately agreed.

Bond was stunned to learn that Lp(a) levels in his blood far exceeded healthy norms. Based on this result, his doctor checked for calcium deposits in his arteries—known precursors to cardiac events—and found some. “It was devastating,” he says, “because I felt like I was in the best health of my life.”

While this form of cholesterol isn’t as abundant in our blood as others, more patients may soon learn they’re in the same boat as Bond. In March, the American Heart Association, the American College of Cardiologists (ACC), and other medical groups released new cholesterol guidelines that for the first time recommend that everyone get a one-time test to determine their level of Lp(a)—pronounced “L, P, little A.”

No drugs are currently available that directly target this lipid compound, although several pharmaceutical companies are developing them. Yet even without these medicines, there’s been a growing recognition that testing is important.

That’s a shift from previous practices; most doctors—even some cardiologists—used to dismiss checking for Lp(a) because of the lack of medicines. “They’d say there’s nothing we can do about it. But that’s not true, there’s actually a lot we can do. And hopefully in the future there will be even more,” says Ron Blankstein, a preventive cardiologist at Brigham and Women’s Hospital, who helped write the guidelines on behalf of the ACC.

An independent risk factor for heart disease

Most cholesterol testing and treatment focuses on low-density lipoprotein or LDL, because it accumulates inside the arteries and eventually leads to calcium buildup, which can rupture and block the blood vessel, leading to a heart attack or stroke. But Lp(a) turns out to be even more harmful. Though LDL particles tend to outnumber Lp(a) particles in the blood, the latter tend to be stickier and amass more readily in arteries. Lp(a) particles additionally have properties that increase inflammation and trigger blood clots, Blankstein notes.

Scientists actually began documenting Lp(a)'s role in heart disease as early as the 1980s. Subsequent research confirmed its cardiac risk in 2009, when a large study in Copenhagen found people with high levels had almost four times more heart attacks. The study was observational, meaning it can’t definitively prove that the Lp(a) causes hearted attacks just that there’s a correlation. In another observational study published in 2024, Blankstein’s team found it increases risk even in people without prior heart disease symptoms.

Lp(a) is primarily influenced by genetics, where variations in the aptly named LPA gene influence levels. Quantities are set in early childhood and tend not to vary much after. 

Someone who has a family history of early heart disease, who had a heart attack in their thirties or forties, or whose LDL cholesterol has not gone down despite taking cholesterol-lowering drugs like statins is likely to have high Lp(a), Blankstein says.

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A simple blood test

You can generally get your blood tested for Lp(a) alongside other routine blood work. Testing only once is sufficient for most people, the guidelines state, because levels tend not to change much over the years.

Normal ranges are below 125 nanomoles per liter (nmol/L). Because of Lp(a)’s genetic ties, people who test above the cutoff are also urged to alert family members. In the United States, Black people and Asian Americans are more prone to higher readings than Hispanic or white people.

Even when people have Lp(a) numbers slightly above 125 nmol/L, heart-disease risk increases 40 percent, the guidelines state. But doctors are most concerned are when levels pass 200, when risk doubles. That’s why Bond’s results were so concerning; his level was close to 300 (nmol/L).

“There is a dose-dependent effect: the higher Lp(a) is, the worse,” says Jennifer Kwan, a cardiologist who treats high-risk patients at Yale Medicine. For example, risk quadruples at 430 nmol/L.

Very high levels are even more dangerous than better-known risks for heart-attack and stroke. “In individuals who don’t have heart disease, it seems it is equivalent to having two other modifiable risk factors combined,” Blankstein says, such as high LDL cholesterol and diabetes, or hypertension and a family history of heart disease.

Still, even very high numbers “don’t necessarily mean you’re going to have a heart attack,” Kwan says. The next step is a computed tomography test to check for coronary artery calcium. If that score nears zero, even when Lp(a) is high, heart attack and stroke odds are low, researchers reported in March. But when both are elevated, the risk jumps sixfold.

Targeted medicines are on the horizon

At present, the only treatment available for high Lp(a), especially when someone has calcium plaques, involves intensifying drug interventions for other cardiac risks. The aim is to drive down the overall danger.

This can include increasing the dosage or type of medicine prescribed for elevated blood pressure, LDL cholesterol, or diabetes, or, for someone overweight or a smoker, adding GLP-1 agonists or anti-craving medicines.

That’s been the case for Bond, who now takes stronger medications, including a potent drug called a PCSK9 inhibitor that’s exceptionally good at lowering LDL levels. He also wears a blood-sugar monitor to track daily levels and checks his blood pressure every morning.

Medication options could expand soon. Several large clinical trials are underway for drugs specifically targeting Lp(a). Most are injections aimed at suppressing production of the compound in the liver. Small, early studies show this effectively lowers it.

Preliminary results from a large-scale, multi-hospital study where people who already have cardiovascular disease were given a monthly injection of a trial medicine or a placebo is expected later this year. Researchers are also testing drug candidates in people without a known cardiac history, to assess whether reducing Lp(a) levels keeps them healthy.

Lifestyle still matters most

Because Lp(a) risk is mainly driven by genetics, lifestyle changes, like diet and exercise, don’t tend to make a significant difference, but doctors still recommend it because research has shown that maintaining a healthy lifestyle can drive down everyone’s cardiac risk, as much as 80 percent.

This includes a heart-healthy diet like the Mediterranean diet which, while not specifically reducing Lp(a), diminishes the overall odds of cardiovascular disease, Kwan says. Other important heart-friendly activities are exercise, stress reduction, consistent sleep, and socializing enough to avoid loneliness.

(Forget 10,000 steps a day—science now has a more accurate number.)

As for Bond, he’d already adopted many of these habits eight years ago, when his blood sugar first crept up. But he laments all the years before he made these changes, when he was over-stressed by his investment banking career, barely exercising, and eating so much junk food he was 30 pounds heavier.

“I wish I had known about my Lp(a) level earlier, because it would have been a strong motivator back then,” Bond says. “It might have made a big difference for my health.”