Abstract Introduction Lipoprotein(a) Lp(a) is a poorly modifiable cardiovascular risk factor, primarily determined by genetics. While Lp(a) levels may vary under certain conditions or treatments(1), it is generally considered a stable marker in adults. Current guidelines recommend measuring it at least once in a lifetime to evaluate cardiovascular risk(1). Purpose This study aims to verify the variation (∆) in Lp(a) measurements, both in absolute terms (nmol/L) and percentage (%), through two serial determinations over time. Methods This retrospective study included 7717 patients from a familial dyslipidemia unit. Among them, 284 patients (3.6%) had at least two Lp(a) measurements over 5.5 years (June 2019-December 2024), with a average interval of 1.36±0.9 years. Serum Lp(a) quantification (nmol/L) was measured using a Cobas c701 autoanalyzer through a particle-enhanced immunoturbidimetric assay(2). This method is comparable to a monoclonal antibody-based ELISA assay, detecting a specific epitope on Kringle IV type 9 and unaffected by isoform size variability(3,4). No serum sample showed interference from hemolysis, jaundice or lipemia(5), and high levels of rheumatoid factors or Apo B were excluded. The variables studied did not exhibit a normal distribution, so non-parametric tests (U-Mann-Whitney) were utilized to compare the groups. Results The patients mean age was 56 years old (ranged beween 18-65). The median (P25, percentile 25 – P75 percentile 75) baseline Lp(a) serum levels was 59 (24-201) nmol/L. The variation (∆) between measurements was 13.2 (5.2-29.0) nmol/L, with a percentage variation of 22.9 (10.0-45.7) %. Women had a less favorable lipid profile (Table 1) with higher Lp(a) levels in both measurements. While absolute variations were similar between sexes, the percentage variation was higher in men (Table 1). One hundred and thirty two patients (46.5%) showed a variation of ≥25%, with 54.5% demonstrating decreases in the second Lp(a) measurement. This variation was higher in men (53.8% vs. 46.2%, p=0.012). For the Lp(a) cut-off points 24, 72, and 120 nmol/L, this variation was 22.7%, 72%, and 82.6%, respectively (Figure 1). No significant differences in ≥25% variation was observed between sex and age groups 50 and 50 years old (46.4% vs. 46.5% p=0.9). Conclusions Detecting ≥25% variation in nearly half of the patients questions the stability of Lp(a) as a stable marker over time. However, this variability is mainly seen at lower Lp(a) concentrations, while levels above 120 nmol/L remain more stable over time. All these findings indicate that, although Lp(a) levels are mainly due to genetics, there is significant biological variability that must be considered, especially in patients with levels close to clinical risk thresholds.
Quiroga et al. (Sat,) studied this question.