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 associated with ongoing cardiovascular risk, even in people receiving standard treatment. The findings suggest that patients with elevated Lp(a) levels may need to manage their heart disease risk factors more aggressively. The researchers presented their latest results at the Society of Cardiovascular Angiography and Interventions (SCAI) 2026 Scientific Sessions and the Canadian Society of Interventional Cardiology/Consortium on Cardiac Interventions (CAIC-ACCI) Summit in Montreal.
Lp(a) is a cholesterol-carrying particle present in the bloodstream. It is similar to LDL cholesterol, often referred to as “bad” cholesterol, but contains extra proteins that can be more harmful to the cardiovascular system. High Lp(a) levels are usually inherited and can increase your risk of heart disease even if your standard cholesterol levels appear normal.
Experts estimate that around 20% of people have elevated Lp(a), but most people don’t realize it because the condition usually doesn’t cause symptoms. Researchers have long known that high Lp(a) is associated with cardiovascular disease, but questions remain about how strongly Lp(a) predicts future risk, both in people with and without pre-existing heart disease.
NIH trial reveals increased risk of stroke and death
To investigate further, researchers tested archived plasma samples taken from 20,070 adults aged 40 and older who participated in the ACCORD, PEACE, and SPRINT NIH randomized trials. All samples were analyzed using standardized assays in specialized translational laboratories and measured using current reporting standards of nmo/L.
Participants were divided into groups based on Lp(a) levels (<75, 75-125, 125-175, or ≥175 nmo/L) and whether they already had cardiovascular disease. The statistical model took into account factors such as age, medical conditions, lipid levels, and treatment history.
The mean age of participants was 65.2 ± 8.5 years, and 64.9% were male. Researchers tracked major adverse cardiovascular events (MACE), including myocardial infarction, stroke, coronary revascularization, and cardiac death.
During a median follow-up of 3.98 years, 1,461 (7.3%) major cardiovascular events occurred. Patients with Lp(a) levels ≥175 nmo/L were more likely to have 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 associated with increased risk of heart attack.
This association was stronger in participants with pre-existing heart disease (HR 1.30, 95% CI: 1.07-1.57) compared to participants without pre-existing heart disease (HR 1.18, 95% CI: 0.91-1.54).
A simple blood test could identify high-risk patients
“For the first time, we have been able to quantify the specific levels of Lp(a) that put patients at significantly higher risk for serious cardiovascular events, particularly stroke and death,” said Subhash Banerjee, MD, FSCAI, an interventional cardiologist at Baylor Scott & White in Dallas, Texas.
“Patients of any age can take a simple, low-cost blood test to determine whether they have this genetic disease. 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 best as possible. This knowledge is especially valuable as new targeted treatment options are on the horizon.”
The researchers added that studying archived biological specimens from completed clinical trials may continue to provide valuable insights. Future analyzes are expected to focus on additional patient groups, such as patients with chronic kidney disease and peripheral artery disease.
