Data continue to show that an elevated level of lipoprotein(a) (Lp[a]) is a risk factor for cardiovascular disease (CVD). Researchers at the American College of Cardiology 75th Annual Scientific Session & Expo (ACC.26) presented new data building on this research.

Following these presentations, featured expert Nihar Desai, MD, MPH, was interviewed by Conference Reporter Associate Editor-in-Chief Mona Shah, PharmD. Clinical perspectives from Dr Desai on these findings are presented here.

Dyslipidemia has long been recognized as being among the most important causal risk factors for CVD, with low-density lipoprotein (LDL) being a very important target for identifying patients who are at risk and for mitigating that risk with evidence-based therapies. The American College of Cardiology/American Heart Association (ACC/AHA) Joint Committee on Clinical Practice Guidelines recently released updated guidelines on the management of dyslipidemia, and they continue to focus on LDL.

Lp(a) has a very close structural homology with LDL. This has raised interest in the role of Lp(a) as a potential CVD risk factor, with a pathobiology that includes prothrombotic, proatherosclerotic, and proinflammatory effects. This, coupled with its epidemiology, where there appears to be a relationship between higher Lp(a) levels and an increased risk for all kinds of CVD events, highlights the potential importance of Lp(a).

The new dyslipidemia guidelines include some important statements about Lp(a), including our strongest endorsement of Lp(a) screening and an emerging consensus that 50 mg/dL does seem to represent where the CVD risk starts to increase. However, in terms of what we should be doing about elevated Lp(a) levels now, I think that this is still an area of transition. If you follow the guidelines, do the screening, and really integrate Lp(a) into your CVD risk assessment—in the absence of dedicated Lp(a)-lowering therapies—elevated Lp(a) is currently best positioned to help inform how aggressively to treat all the other CVD risk factors. It is exciting to be looking forward to the emergence of dedicated therapies to lower Lp(a) levels, and we are all eagerly awaiting the results of ongoing phase 3 clinical trials and how those results might inform clinical decision making.

In the interim, we can assess a patient’s individual CVD risk and create personalized care plans to mitigate that risk, while informing them that we now—consistent with the guidelines—recommend measuring Lp(a) for everyone at least once. Further, if Lp(a) comes back elevated, we want to do everything we can for all the other CVD risk factors, including smoking cessation, blood pressure control, obesity management, and lowering LDL cholesterol and hemoglobin A_1c. Additionally, there is some evidence suggesting that you can use Lp(a) to guide clinical decision making regarding the role of aspirin and whether to integrate it into a CVD prevention program for a particular patient. However, the pendulum has probably swung away from this for most patients.

There was a lot of interest in elevated Lp(a) at ACC.2026, including its relationship with coronary artery calcium (CAC) scoring. For example, Stacey Knight, PhD, and colleagues reported that, in a large cohort, elevated Lp(a) and CAC scoring were found to be independent predictors of atherosclerotic CVD and major adverse CV events risk, with the risk increasing progressively with higher CAC scores and/or higher Lp(a) levels. Additionally, Harpreet Bhatia, MD, MAS, FACC, et al found in their even larger pooled cohort that patients who have a CAC score above 0 and an Lp(a) level above 50 mg/dL seem to have the highest atherosclerotic CVD risk (ie, almost 3-fold higher relative to those who have a CAC score of 0 and an Lp(a) level <50 mg/dL).

In a large data analysis by Osman Yousafzai, MD, and colleagues presented at ACC.26, the TriNetX database (TriNetX, LLC) was used to determine the relationship between elevated Lp(a) at more granular strata above 50 mg/dL and patient outcomes, including all-cause mortality, atrial fibrillation, and major adverse CV events. With these more granular strata of Lp(a) (ie, 51-75 mg/dL, 76-99 mg/dL, 100-124 mg/dL, 125-149 mg/dL, and 150-174 mg/dL), there was found to be a stepwise increase in risk across all these outcomes. I think this study helps highlight that Lp(a) is not a binary risk predictor, but there is, in fact, a stepwise relationship such that the higher the Lp(a), the higher the risks for adverse CV outcomes and all-cause mortality across multiple Lp(a) ranges.