cvMOBIUS-2 Registry in over 1.9 million people highlights suboptimal lipoprotein(a) testing in real-world practice

November 2026

Despite guidelines recommending lipoprotein(a) testing in all adults at least once during the lifetime, implementation in routine clinical practice lags behind. Moreover, among people identified with elevated lipoprotein(a) and elevated cholesterol, over half did not undergo lipid-lowering therapy intensification.

Shah NP, Shrader P, Freeman N, et al. Lipoprotein(a) testing and changes in lipid-lowering therapy in patients with ASCVD: findings from the cvMOBIUS-2 Registry. Circ Popul Health Outcomes 2026;19:e013883.

STUDY SUMMARY.

Objective

To evaluate patterns of lipoprotein(a) [Lp(a)] testing and the impact of testing on LDL-C (low-density lipoprotein cholesterol) management in real-world clinical practice.

 

 

Study design

cvMOBIUS-2 registry (Cardiovascular Multicenter Observational Investigation of Lipid Care in the United States-2) using electronic health record patient data

 

 

Study population

The registry evaluated data from 1,948, 540 adults (≥18 years) with established atherosclerotic cardiovascular disease (ASCVD) with at least one outpatient visit at a participating health system between January 1, 2021, to January 1, 2025. ASCVD was defined as coronary heart disease, ischaemic cerebrovascular disease, atherosclerotic peripheral artery disease, or prior coronary or peripheral revascularization or carotid revascularization based on procedure codes from an inpatient or outpatient visit.

 

 

Main study variables

 

Number of patients who underwent Lp(a) testing; lipid management of patients identified with elevated Lp(a) levels, defined as Lp(a) ≥125 nmol/L or ≥50 mg/dL.

 

 

Methods

The proportion of individuals with ASCVD who underwent Lp(a) testing and the diagnostic yield, defined as the proportion of individuals with an elevated Lp(a), were evaluated over time. Electronic health record data relating to the use of  guideline-based lipid-lowering therapy (including any statin, high intensity statin, ezetimibe, bempedoic acid, and proprotein convertase subtilisin kexin type 9 inhibitors), at the time of the Lp(a) test and for up to 1 year thereafter was evaluated to investigate changes in lipid-lowering therapy.  

 

Results

Overall, 36, 410 patients (1.9%) had a documented Lp(a) test, and this proportion increased only slightly over time (from 0.2% in 2021, 0.4% in 2022, 0.6% in 2023, and 0.8% in 2024). Lp(a) testing was higher among younger than older adults (3.9% of those aged 18–40 years and 3.7% of those aged 41–60 years versus 1.8% of those aged 61–80 and 0.4% of those >80 years). Among tested patients, 31.1% had elevated Lp(a), defined as ≥125 nmol/L or ≥50 mg/dL.  Among those tested, female patients were less likely to undergo Lp(a) testing (odds ratio 0.95, 95% confidence interval 0.93–0.98]) but were more likely to have an elevated Lp(a) (odds ratio ≥1.19, 1.14–1.25). Overall, 34.3% of female patients vs. 29.1% of male patients had an elevated Lp(a).

 

At the time of the Lp(a) test, 65.4% of patients were prescribed a statin; patients with high Lp(a) were more likely to be on any statin, a high-intensity statin, ezetimibe, or a PCSK9 inhibitor before testing. While elevated Lp(a) was associated with greater lipid-lowering therapy intensification, more than half of patients with a concomitant LDL-C level ≥55 mg/dL, did not have intensification of lipid treatment: 35.1% of those with Lp(a) 125–<200 nmol/L or 50–<80 mg/dL, and 40% with an Lp(a) ≥200 nmol/L or ≥80 mg/dL.

 

Author conclusions

Lp(a) testing remains low despite guideline recommendations. Although those with elevated Lp(a) were more likely to undergo lipid-lowering therapy intensification, over half of those with Lp(a) ≥200 nmol/L or ≥80 mg/dL had no change in therapy. These results highlight a significant gap in clinical care and an opportunity to improve the use of Lp(a) testing to guide LDL-C management.

 

Comment

A wealth of evidence supports Lp(a) as a strong, independent, causal risk factor for ASCVD, which is predominantly inherited (1). As elevated Lp(a) is common, affecting about one in five individuals (2), this means that about 1.4 billion individuals worldwide are exposed to elevated Lp(a) and are therefore at elevated cardiovascular risk (3). Thus, implementation of guideline recommendations that all adults should undergo Lp(a) testing at least once during their lifetime is essential to reduce preventable ASCVD in these vulnerable individuals (4-6).

 

The clinical reality, however, is that implementation of Lp(a) testing in routine clinical practice is far from ideal, as shown by the cvMOBIUS-2 registry in patients with ASCVD. According to electronic health record data, fewer than 2% of patients underwent Lp(a) testing, with only marginal improvement over the last 4 years. Although a US registry, the results also align with evidence from Europe (7). The authors recognize that when registry data were collected (January 1, 2021–January 1, 2025) was a transitional era with evolving guideline recommendations regarding Lp(a) testing. Despite this limitation, it is evident that innovative strategies are needed to improve guideline implementation and uptake of Lp(a) testing in routine clinical practice.

 

The 2025 Brussels International Declaration on Lp(a) Testing and Management (8) has called for urgent action to ensure systematic testing of Lp(a) as early as possible in adult life as key to cardiovascular disease prevention. Central to this is increased awareness of Lp(a) and its impact on cardiovascular health. With education one of the pillars underpinning the mission of the R3i, the Foundation has an important role in working with academic partners to achieve this.

 

References

  1. Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J 2022;43:3925–46.
  2. Langsted A, Kamstrup PR, Nordestgaard BG. High lipoprotein(a) and high risk of mortality. Eur Heart J 2019;40:2760–70.
  3. Tsimikas S, Stroes ESG. The dedicated “Lp(a) clinic”: a concept whose time has arrived? Atherosclerosis 2020;300:1–9.
  4. Blumenthal RS, Morris PB, Gaudino M, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2026;87:2624-757.
  5. Mach F, Koskinas KC, Roeters van Lennep JE, et al. Focused update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J 2025;46:4359-78.
  6. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111-88.
  7. Sturzebecher PE, Schorr JJ, Klebs SHG, et al. Trends and consequences of lipoprotein(a) testing: cross-Sectional and longitudinal health insurance claims database analyses. Atherosclerosis 2023;367:24–33.
  8. Kronenberg F, Bedlington N, Ademi Z, et al. The Brussels International Declaration on Lipoprotein(a) Testing and Management. Atherosclerosis 2025; https://doi.org/10.1016/j.atherosclerosis.2025.119218

Key words: Lipoprotein(a) testing; atherosclerotic cardiovascular disease; genetic risk factor; registry