A cholesterol-related risk factor may be hiding in plain sight for millions of people. Lipoprotein(a), or Lp(a), is an inherited blood particle that can raise the risk of cardiovascular problems even when standard cholesterol results look acceptable.
New research involving more than 20,000 patients adds detail to how very high Lp(a) levels may affect people with and without existing heart disease.
The findings were presented 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.
What Is Lp(a)?
Lp(a) is a cholesterol-carrying particle in the bloodstream. It resembles LDL, commonly known as “bad” cholesterol, but contains an additional protein called apolipoprotein(a). High Lp(a) levels are mainly controlled by genetics, rather than lifestyle.
About one in five people is estimated to have elevated Lp(a). Most do not know they have it because high levels usually produce no noticeable symptoms. As a result, the risk can remain hidden until cardiovascular disease develops.
Researchers have known for years that elevated Lp(a) is linked with cardiovascular disease. However, questions remain about how strongly it predicts future events in people who already have heart disease compared with those who have not been diagnosed with it.
Study Included 20,070 Adults
Researchers analyzed stored plasma samples from 20,070 participants aged 40 and older. The participants had previously taken part in three NIH randomized clinical trials: ACCORD, PEACE, and SPRINT.
The samples were tested at a dedicated translational laboratory using a standardized assay. Results were reported in nmol/L, the current standard measurement for Lp(a).
Participants were grouped by Lp(a) levels of less than 75, 75-125, 125-175, or at least 175 nmol/L. Researchers also separated participants based on whether they already had heart disease.
The study population had an average age of 65.2 years, with a standard deviation of 8.5 years. Men accounted for 64.9% of participants. Researchers adjusted their analysis for demographics, other medical conditions, lipid levels, and treatments.
The main outcome was major adverse cardiovascular events (MACE), including heart attack, stroke, coronary revascularization, and cardiovascular death.
Very High Levels Raised Risk
During a median follow-up of 3.98 years, researchers recorded 1,461 MACE events, representing 7.3% of participants.
Lp(a) levels of at least 175 nmol/L were independently associated with a higher risk of MACE. The hazard ratio was 1.31, with a 95% confidence interval of 1.10-1.55. The same level was linked to cardiovascular death, with a hazard ratio of 1.49, and stroke, with a hazard ratio of 1.64.
However, very high Lp(a) was not associated with a higher risk of heart attack in this analysis.
The relationship appeared stronger among participants who already had heart disease. Their hazard ratio was 1.30, compared with 1.18 among those without established heart disease.
A Blood Test Can Detect It
Subhash Banerjee, MD, FSCAI, an interventional cardiologist at Baylor Scott & White in Dallas, Texas, said the findings help identify a specific Lp(a) level linked with higher cardiovascular 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,” Banerjee said.
He added that a simple, low-cost blood test can identify the genetic condition regardless of age. When Lp(a) is elevated, Banerjee said patients should work with healthcare providers to lower LDL cholesterol and address other cardiovascular risk factors. He also noted that new targeted treatments for Lp(a) are being developed.
The research also shows the value of stored blood samples from completed clinical trials. Researchers plan to study additional groups, including people with chronic kidney disease and peripheral artery disease.
High Lp(a) can exist without symptoms and may add cardiovascular risk beyond standard cholesterol measurements. The new findings suggest that very high levels, particularly 175 nmol/L or higher, are associated with greater risks of major cardiovascular events, stroke, and cardiovascular death. Because genetics largely determine Lp(a), testing can provide information that routine cholesterol checks may not reveal.
