Epidemiology
Adding Lp(a) to an EHR-based ASCVD risk score reclassifies 21.3% of borderline-risk patients (Circ Genom Precis Med 2025)
Original title: Lipoprotein(a) Atherosclerotic Cardiovascular Disease Risk Score Development and Prediction in Primary Prevention From Real-World Data
Using a large electronic health record database, the authors built a 10-year ASCVD risk model incorporating Lp(a) cut points at 25, 50 and 75 mg/dL in 5,902 adults (mean age 48.7 years, 51.2% women, 7.7% Black), with external validation in a pooled cohort of 21,864 participants from four US prospective studies. Each 25 mg/dL increment in Lp(a) carried an adjusted hazard ratio of 1.23 (95% CI 1.10-1.37) for composite ASCVD, and patients with Lp(a) at or above 75 mg/dL had 88% higher ASCVD risk (hazard ratio 1.88, 95% CI 1.30-2.70) and more than double the stroke risk (hazard ratio 2.55, 95% CI 1.54-4.23). Adding Lp(a) improved the model's C-statistic from 0.7475 to 0.7556 in the training set and from 0.7350 to 0.7368 externally, and reclassified 21.3% of borderline-intermediate risk patients. A real-world demonstration that Lp(a) meaningfully sharpens ASCVD risk prediction beyond standard EHR variables.
Original abstract
Background: Lipoprotein(a) [Lp(a)] is a predictor of atherosclerotic cardiovascular disease (ASCVD); however, there are few algorithms incorporating Lp(a), especially from real-world settings. We developed an electronic health record (EHR)-based risk prediction algorithm including Lp(a).
Methods: Utilizing a large EHR database, we categorized Lp(a) cut points at 25, 50, and 75 mg/dL and constructed 10-year ASCVD risk prediction models incorporating Lp(a), with external validation in a pooled cohort of 4 US prospective studies. Net reclassification improvement was determined among borderline-intermediate risk patients.
Results: We included 5902 patients aged ≥18 years (mean age 48.7±16.7 years, 51.2% women, and 7.7% Black). Our EHR model included Lp(a), age, sex, Black race/ethnicity, systolic blood pressure, total and high-density lipoprotein cholesterol, diabetes, smoking, and hypertension medication. Over a mean follow-up of 6.8 years, ASCVD event rates (per 1000 person-years) ranged from 8.7 to 16.7 across Lp(a) groups. A 25 mg/dL increment in Lp(a) was associated with an adjusted hazard ratio of 1.23 (95% CI, 1.10-1.37) for composite ASCVD. Those with Lp(a) ≥75 mg/dL had an 88% higher risk of ASCVD (hazard ratio, 1.88 [95% CI, 1.30-2.70]) and more than double the risk of incident stroke (hazard ratio, 2.55 [95% CI, 1.54-4.23]). C-statistics for our EHR and EHR+Lp(a) models in our EHR training data set were 0.7475 and 0.7556, respectively, with external validation in our pooled cohort (n=21 864) of 0.7350 and 0.7368, respectively. Among those at borderline/intermediate risk, the net reclassification improvement was 21.3%.
Conclusions: We show the feasibility of developing an improved ASCVD risk prediction model incorporating Lp(a) based on a real-world adult clinic population. The inclusion of Lp(a) in ASCVD prediction models can reclassify risk in patients who may benefit from more intensified ASCVD prevention efforts.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.