More than 20,000 patients from three major National Institutes of Health (NIH) studies were included in a new analysis showing that elevated Lipoprotein(a) [Lp(a)] is tied to ongoing cardiovascular risk, even in people receiving standard treatment. The findings suggest patients with high Lp(a) levels may need more aggressive management of heart disease risk factors. Researchers presented the late-breaking results at the Society for Cardiovascular Angiography & Interventions (SCAI) 2026 Scientific Sessions and the Canadian Association of Interventional Cardiology/Association Canadienne de cardiologie d’intervention (CAIC-ACCI) Summit in Montreal.
Lp(a) is a cholesterol-carrying particle found in the bloodstream. It resembles LDL cholesterol, often called “bad” cholesterol, but includes an extra protein that may make it more harmful to the cardiovascular system. High Lp(a) levels are usually inherited and can increase the risk of heart disease even when standard cholesterol numbers appear normal.
Experts estimate that roughly 20% of people have elevated Lp(a), though most do not realize it because the condition typically causes no symptoms. While researchers have long known that high Lp(a) is connected to cardiovascular disease, questions have remained about how strongly it predicts future risk in people both with and without existing heart disease.
NIH Trials Reveal Elevated Stroke and Death Risk
To investigate further, researchers examined stored plasma samples from 20,070 adults age 40 and older who participated in the ACCORD, PEACE, and SPRINT NIH randomized trials. All samples were analyzed in a specialized translational laboratory using a standardized assay and measured using the current reporting standard of nmo/L.
Participants were divided into groups based on their Lp(a) levels (<75, 75-125, 125-175, or ≥ 175 nmo/L) as well as whether they already had cardiovascular disease. Statistical models accounted for factors such as age, medical conditions, lipid levels, and treatment history.
The average participant age was 65.2±8.5 years, and 64.9% were men. Researchers tracked major adverse cardiovascular events (MACE), including myocardial infarction, stroke, coronary revascularization, and cardiac death.
During a median follow-up period of 3.98 years, 1,461 (7.3%) major cardiovascular events occurred. Patients with Lp(a) levels greater than or equal to 175 nmo/L faced a significantly higher 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, elevated Lp(a) at this threshold was not linked to a higher risk of heart attack.
The association was stronger among participants who already had heart disease (HR 1.30, 95%CI: 1.07-1.57) compared to those without established disease (HR 1.18, 95% CI: 0.91-1.54).
Simple Blood Test Could Identify High-Risk Patients
“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.”
Researchers added that studying stored biospecimens from completed clinical trials may continue to uncover valuable insights. Future analyses are expected to focus on additional patient groups, including people with chronic kidney disease and peripheral artery disease.