LDL cholesterol still drives treatment decisions in assessing heart disease risk, but a new study suggests apolipoprotein B (apoB), which measures artery-clogging particles, could do a better job.

In a computer simulation involving 250,000 statin-eligible individuals, published in JAMA, study authors found that apoB-guided treatment improved outcomes and remained highly cost-effective. However, it also led to more intensive therapy, raising questions about whether better apoB is a better target or simply more treatment driving the benefit.

Investigators created a cohort using participants without atherosclerotic cardiovascular disease (ASCVD) from the 2005-2016 US National Health and Nutrition Examination Survey (NHANES). Participants had no prior history of CVD, were on average 66 years old, and were eligible for statin therapy. They also had an average 10-year risk score for ASCVD of about 21%. 

The researchers then compared three treatment strategies based on different targets: an LDL-C goal < 100 mg/dL, a non-HDL goal of < 118 mg/dL, and an apoB goal of < 78.7 mg/dL. Participants who didn’t meet these goals underwent uptitration of statin therapy; if goals were still not met, ezetimibe was added.

Benefits of Targeting ApoB

Over a lifetime, heart attack, stroke, healthcare costs, and life expectancy measured by quality-adjusted life years (QALY) were tracked. Researchers concluded that treatment-based apoB, compared with non-HDL-C and LDL-C, offered optimal outcomes. It outperformed other lipid targets, preventing roughly 1000 additional events per 250,000 patients.

ApoB-guided care was also associated with higher lifetime healthcare costs, largely because patients lived longer and remained on preventive therapy for more years. The cost of ApoB testing itself, however, contributed minimally. Despite these higher overall costs, the strategy was considered highly cost-effective, with an incremental cost-effectiveness ratio of about $30,000 per QALY gained. That was well below the willingness-to-pay threshold of $120,000. 

Perhaps most striking, the model found that intensifying therapy for all statin-eligible patients — regardless of lipid targets — would deliver the greatest health benefit at a favorable cost, raising questions about the need for strict treatment thresholds.

 

Nishant Shah, MD, an associate professor of medicine at the Duke Clinical Research Institute in Durham, North Carolina, believes that apoB, which is already a strong marker of residual risk, can be an excellent determinant of how much lipid-lowering treatment is needed. 

“[ApoB] can also help clinicians understand if a patient's LDL-C is low enough for them, especially if apoB remains elevated when the LDL-C appears to be at goal. Therefore, lipid-lowering therapy may need to be adjusted based on apoB level if there is discordance with the LDL-C value,” said Shah, who was not involved in the study.

He noted the new 2026 dyslipidemia guideline also has goals for apoB to modify risk. 

“Based on the estimates in this study, there may also be other benefits from reducing apoB as well,” Shah said.

Will Prescribing Habits Change?

Despite these results, study author Ciaran N. Kohli-Lynch, PhD, MSc, is skeptical about whether clinicians will start recommending apoB screening, but he remains optimistic that with time, this may change.

“There are a couple of barriers to incorporating apoB testing for treatment intensification,” said Kohli-Lynch, who is a health economist in the Department of Preventive Medicine at Northwestern University Feinberg School of Medicine in Chicago. 

“First, LDL-C has long been the standard for risk assessment and treatment, and changing established practice takes time — even when strong evidence supports alternatives. Second, apoB is not included in standard lipid panels, so ordering it requires an additional step and may add cost,” he said.

However, these barriers may decrease as guidelines evolve, according to Kohli-Lynch. 

“We hope our study provides the population-level cost-effectiveness evidence needed to inform future updates and make adoption of apoB more straightforward for clinicians and health systems,” he said.

More Data Needed

In an accompanying editorial, health policy experts Ankur Pandya, PhD, of the Harvard T.H. Chan School of Public Health in Boston, and Jinyi Zhu, PhD, of Vanderbilt University School of Medicine in Nashville, praised the findings but noted the clinical implications remain uncertain.

“The analysis supports using an apoB target over LDL-C and non-HDL-C,” Pandya said in an interview. “The remaining questions are whether apoB should be used upfront rather than after LDL goals are met, and how broadly it should be applied.

“In the study, apoB strategies intensified treatment in about 51% to 64% of patients, but treating all eligible patients performed even better — raising the possibility that a more aggressive approach may be optimal.”

Shah reports no relevant financial relationships. Kohli-Lynch reports consultancy fees from Boehringer Ingelheim. The study was supported by American Heart Association Career Development Award 24CDA1274989 (Kohli-Lynch). Pandya reports no relevant financial relationships.

Lois Anzelowitz Levine is a medical and lifestyle writer in Dallas.