A study of more than 20,000 people has found that very high levels of lipoprotein(a), an inherited cholesterol-related particle rarely tested for in routine checkups, are linked to a significantly greater risk of major cardiovascular events, particularly stroke and cardiovascular death — even in patients whose other heart-disease treatments were on track.
Researchers analyzed blood samples from 20,070 adults age 40 and older who had taken part in three earlier National Institutes of Health-funded trials, grouping participants by their lipoprotein(a), or Lp(a), levels and tracking major adverse cardiovascular events over a median follow-up of nearly four years. Among participants with Lp(a) at or above 175 nanomoles per liter, the risk of a major cardiovascular event was 31% higher, the risk of cardiovascular death was 49% higher and the risk of stroke was 64% higher than among those with lower levels, after adjusting for standard treatments such as statins. The elevated risk held even though the highest Lp(a) group was not significantly more likely to suffer a heart attack, a pattern the researchers said points to a particular link with strokes. The findings were presented at the Society for Cardiovascular Angiography and Interventions' 2026 scientific sessions in Montreal.
Why Lp(a) is different
Unlike LDL, the "bad" cholesterol most heart-health advice targets, Lp(a) levels are almost entirely determined by genetics and change little with diet, exercise or weight loss. Roughly one in five people carries elevated Lp(a), and because it is not part of a standard lipid panel, most never find out. Current cholesterol-lowering drugs such as statins and ezetimibe do little to move it, which has left doctors with few tools to act on the number even when it is measured.
That gap is part of why cardiologists have pushed for broader testing. Newly updated American Heart Association and American College of Cardiology guidance calls for every adult to have their Lp(a) checked at least once in their lifetime, reasoning that a single test can flag a lifelong risk that standard cholesterol screening misses entirely, particularly in people with a family history of early heart disease or stroke that isn't otherwise explained.
Testing alone would mean little without something to do with the result, and several Lp(a)-lowering drugs are now in late-stage development. Pelacarsen, an antisense therapy from Novartis, and olpasiran, an siRNA drug that silences the gene behind Lp(a) production, are both in phase 3 trials and have each been shown to cut Lp(a) levels by large margins in earlier testing. Neither is yet approved, and outcomes data proving that lowering Lp(a) actually reduces heart attacks and strokes — rather than just the lab number — are still pending.
For now, the practical takeaway from the new analysis is about identifying risk rather than treating it. Researchers say patients found to have high Lp(a) should be considered for more aggressive management of the cardiovascular risk factors that can be controlled, such as blood pressure and LDL cholesterol, while the field awaits trial results on the new drugs aimed directly at Lp(a) itself.
