Elevated Lp(a) Levels Linked to Cardiovascular Event Risk, Regardless of ASCVD History

Ron Blankstein, MD
Credit: Brigham and Women's Hospital

Data from an analysis of the Mass General Brigham Lp(a) Registry is providing clinicians with further insight into the associations of lipoprotein(a) [Lp(a)] and major adverse cardiovascular events based on patient history of atherosclerotic cardiovascular disease.

Leveraging data from more than 16,000 patients, results of the study suggest elevated Lp(a) was independently associated with long-term risk of major adverse cardiovascular events regardless of baseline atherosclerotic cardiovascular disease among patients in the registry, with this increase in risk most apparent among patients without baseline atherosclerotic cardiovascular disease.¹

“This study provides meaningful insights as to the optimal thresholds for risk assessment and how such thresholds may be different for primary and secondary prevention cohorts,” wrote investigators.¹ “These insights can guide both current clinical risk assessment as well as future trials for Lp(a)-lowering therapies as we have identified populations of patients (both primary and secondary prevention) who would not be included in current Lp(a) trials but have significant residual Lp(a) attributable risk.”

Built from electronic health record data from Brigham and Women's Hospital and Massachusetts General Hospital, the Mass General Brigham Lp(a) Registry was created to provide meaningful observational data related to the differential risk associated with Lp(a). Containing data related to patients screened 2000 through 2019, the registry contained data from more than 21,000 patients who underwent Lp(a) testing.^1,2

From the registry, a team of investigators led by identified a cohort of 21,410 patients who underwent Lp(a) testing with a mass- or particle-based assay during the study period. After the exclusion of those with severe renal disease, those with a malignant neoplasm, and individuals who died during the covariate assessment window, 16,419 individuals were deemed eligible for inclusion.¹

Using data from these patients, investigators designed their analysis to compare risk of incident major adverse cardiovascular events based on Lp(a) percentile groups and baseline atherosclerotic cardiovascular disease. Investigators noted Cox proportional hazards modeling was used to estimate associations of percentile group with major adverse cardiovascular events. For the purpose of analysis, incident major adverse cardiovascular events included nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or cardiovascular mortality.¹

The 16,419-patient cohort identified for inclusion was 41% women, had a median age 60 years (Interquartile Range [IQR], 49-72 years), and had a median follow-up of 11.9 (IQR, 6.2-14.4) years. Among this cohort, 10,181 individuals had a historic of atherosclerotic cardiovascular disease at baseline. Overall, 1067 (6.5%) individuals experienced a nonfatal myocardial infraction, 1373 (8.4%) individuals experienced a nonfatal ischemic stroke, 1362 (8.3%) individuals underwent coronary revascularization, and 2416 (14.7%) individuals died of cardiovascular causes.¹

Upon analysis, an increased risk of incident major adverse cardiovascular events was observed among those with baseline atherosclerotic cardiovascular disease in the 71st to 90th percentile group (adjusted Hazard Ratio [aHR], 1.21; 95% Confidence Interval [CI], 1.11-1.32; P < .001) as well as the 91st to 100th percentile group (aHR, 1.26; 95% CI, 1.12-1.41; P < .001). Investigators highlighted a linear trend of elevated risk for incident major adverse cardiovascular events was observed with increasing Lp(a) among those without baseline atherosclerotic cardiovascular disease, with individuals in the 91st to 100th percentile group at the greatest relative risk (aHR, 1.93; 95% CI, 1.54-2.42; P < .001).¹

In an Editorial Comment, Nathan Wong, PhD, MPH, of the Heart Disease Prevention Program in the Division of Cardiology at theUniversity of California Irvine, underlines the growing acknowledgement of Lp(a)’s associations with cardiovascular risk and notes, if ongoing outcomes trials prove successful, screening for Lp(a) will need to be a point of emphasis both in the clinic and also within major guidelines.³

“The current report by Berman et alextends our understanding that Lp(a) and ASCVD risk thresholds can differ between individuals with and without prior ASCVD,” Wong wrote.³ “The failure to screen and identify those with Lp(a)-associated risks represents a missed opportunity to address this risk, not only with our existing repertoire of treatments but hopefully in the future with the development of promising therapies targeting Lp(a).”

References:

1. _{^{Berman AN, Biery DW, Besser SA, et al. Lipoprotein(a) and Major Adverse Cardiovascular Events in Patients With or Without Baseline Atherosclerotic Cardiovascular Disease. J Am Coll Cardiol. 2024;83(9):873-886. doi:10.1016/j.jacc.2023.12.031}}
2. _{^{Berman AN, Biery DW, Ginder C, et al. Study of lipoprotein(a) and its impact on atherosclerotic cardiovascular disease: Design and rationale of the Mass General Brigham Lp(a) Registry. Clin Cardiol. 2020;43(11):1209-1215. doi:10.1002/clc.23456}}
3. _{^{Wong ND. Lipoprotein(a): Ready for Prime Time?. J Am Coll Cardiol. 2024;83(9):887-889. doi:10.1016/j.jacc.2024.01.004}}