New findings from more than 20,000 patients across three major NIH studies suggest that elevated Lipoprotein(a) [Lp(a)] may contribute to cardiovascular risk that remains even after standard treatment. The results indicate that people with high Lp(a) may benefit from more aggressive efforts to reduce other heart disease risk factors.
The late-breaking findings were presented at the Society for Cardiovascular Angiography & Interventions (SCAI) 2026 Scientific Sessions and Canadian Association of Interventional Cardiology/Association Canadienne de cardiologie d’intervention (CAIC-ACCI) Summit in Montreal.
What Is Lipoprotein(a)?
Lp(a) is a cholesterol-carrying particle found in the blood. It resembles LDL, often called “bad” cholesterol, but includes an additional protein that may make it more likely to contribute to cardiovascular disease.
High Lp(a) levels are largely determined by genetics. They can increase cardiovascular risk even when more familiar cholesterol measurements fall within normal ranges. Approximately one in five people has high Lp(a), yet most people with elevated levels do not know it because the condition typically causes no symptoms.
Scientists have long recognized a connection between elevated Lp(a) and cardiovascular disease. However, researchers are still working to understand how well Lp(a) predicts future risk in people who already have heart disease compared with those who do not.
More Than 20,000 Patients Analyzed
For the new analysis, researchers examined previously collected plasma samples from 20,070 participants aged 40 years and older who had taken part in the ACCORD, PEACE, and SPRINT NIH randomized trials.
The samples were tested in a dedicated translational laboratory with a standardized assay, with results reported using the current standard of nmo/L. Participants were divided into groups according to their Lp(a) levels (<75, 75-125, 125-175, or ≥ 175 nmo/L) and according to whether they already had heart disease.
Researchers then used Cox models that accounted for demographics, comorbidities, lipids, and therapies.
Participants had a mean age of 65.2±8.5 years, and 64.9% of patients were male. Researchers focused primarily on major adverse cardiovascular events (MACE), which included myocardial infarction, stroke, coronary revascularization, or cardiac death.
Very High Lp(a) Linked to Greater Risk
During a median follow-up period of 3.98 years, 1,461 (7.3%) MACE events occurred.
An Lp(a) level greater than or equal to 175 nmo/L was independently associated with an increased risk of MACE (HR 1.31, 95% CI: 1.10-1.55), cardiovascular death (HR 1.49, 95% CI: 1.07-2.06), and stroke (HR 1.64, 95% CI: 1.14-2.37).
However, having Lp(a) at this level was not associated with a higher risk of heart attack.
The association was also stronger among participants who already had heart disease (HR 1.30, 95%CI: 1.07-1.57) than among those without existing heart disease (HR 1.18, 95% CI: 0.91-1.54).
A Simple Blood Test Could Reveal Hidden Risk
“For the first time, we can quantify the specific level of Lp(a) that puts patients at a significantly higher risk of major cardiovascular events, especially stroke and death,” said Subhash Banerjee, MD, FSCAI, interventional cardiologist at Baylor Scott & White in Dallas, Texas. “Regardless of age, patients can take a simple, low-cost blood test to determine whether they have this genetic condition. If elevated Lp(a) levels are detected, they should work closely with their healthcare provider to aggressively lower LDL cholesterol and manage other cardiovascular risk factors as much as possible. This knowledge is especially valuable as new targeted treatment options are on the horizon.”
The researchers also emphasized that stored biospecimens can reveal new information from clinical trials that have already been completed. They plan to examine additional patient groups in future analyses, including people with chronic kidney disease and peripheral artery disease.