Front Cardiovasc Med. 2026 Sep 16;13:1949855. doi: 10.3389/fcvm.2026.1949855. eCollection 2026.
ABSTRACT
INTRODUCTION: Lipoprotein(a) (Lp(a)) is an independent, genetically-determined cardiovascular risk factor not currently incorporated into standard cardiovascular risk prediction models such as QRISK3. Understanding the relationship between Lp(a) and estimated cardiovascular risk may identify individuals whose risk is not identified by conventional risk calculators.
METHODS: Analysis was performed on n = 14,848 participants from the Randox Health 2025 dataset. QRISK3 scores were estimated as 10-year cardiovascular risk using demographic, clinical, lifestyle, and medical-history, mapped to QRISK3 definitions. Participants were classified with low (<10%) or elevated (≥10%) estimated 10-year cardiovascular risk. Lp(a) concentrations were categorised into three-group-classification: low risk ≤75 nmol/L, grey zone 76-125 nmol/L, and high risk >125 nmol/L. Associations between Lp(a) and QRISK3 groups were assessed using non-parametric tests.
RESULTS AND DISCUSSION: Among n = 14,848 participants, n = 1,426 (9.6%) had estimated QRISK3 score ≥10%, while n = 2,670 (18.0%) had Lp(a) >125 nmol/L. Participants with QRISK3 ≥10% were older (64 vs. 40-years; p < 0.001), commonly male (77% vs. 23%; p < 0.001), higher systolic blood-pressure (140 vs. 124mmHg; p < 0.001), higher BMI (27.3 vs. 25.0 kg/m2; p < 0.001), and a higher prevalence of diabetes and established cardiovascular risk factors (p < 0.001). Elevated Lp(a) concentrations (>125 nmol/L) were more common in individuals with QRISK3 scores ≥10% than those individuals with QRISK3 scores <10% (21% vs. 18%; p = 0.002). Among individuals with elevated Lp(a), 89% remained below the treatment threshold of QRISK3 <10%. A total of n = 2,371 participants (16%) exhibited elevated Lp(a) levels while remaining within low QRISK3 risk.Median estimated QRISK3 scores increased incrementally across Lp(a) groups (1.4%, 1.4%, and 1.8%, for low-, intermediate-, and high-Lp(a) groups, respectively; p < 0.001), although absolute differences were small.Elevated Lp(a) levels were common within the Randox Health 2025 cohort and demonstrated limited concordance with estimated QRISK3. Most individuals with high Lp(a) had QRISK3 scores below conventional treatment thresholds, indicating discordance between Lp(a)-based risk and QRISK3-derived 10-year risk classification. These findings suggest elevated Lp(a) identifies a cardiovascular risk not incorporated into QRISK3 supporting consideration of Lp(a) measurement alongside conventional cardiovascular risk assessment. Participants were not excluded based on established cardiovascular disease; therefore, the findings should be interpreted as applying to a real-world health-screening population rather than a strictly defined primary-prevention cohort.
PMID:42819403 | PMC:PMC13624064 | DOI:10.3389/fcvm.2026.1949855