Dynamic lipoprotein(a) changes in acute coronary syndromes: implications for accurate cardiovascular risk assessment

Abstract Background Lipoprotein(a) Lp(a) is an independent risk factor for atherosclerotic cardiovascular (CV) disease. Recent clinical trials have been documenting some changes up to 25% in the placebo groups and in the context of acute coronary syndromes (ACS) mild transient increases up to 10–20% were described. Purpose The aim of this study was to evaluate Lp(a) levels variability in patients admitted due to ACS and to explore possible factors associated with relevant differences in the measurements. Methods A retrospective single-center analysis of patients with more than one measurement of Lp(a) levels and at least one of them collect in the admission due to ACS (85 of 221 patients) was conducted. Demographics, cardiovascular risk factors, comorbidities and medication use were registered. Context of measurement, time intervals and laboratory parameters with lipid profile were collected. Relevant Lp(a) variability was defined as an absolute change ≥ 50 nmol/L or a relative change ≥ 25%, calculated as (highest value – lowest value) / lowest value * 100. Patients who had relevant variability were compared with patients without. Statistical analysis was done using Chi-square and Mann-Whitney tests. Results A total of 85 patients were analyzed (67 males, 78.8%). Absolute Lp(a) values range from 1.2 to 818.5 nmol/L in the first measurement (90.6% in the context of ACS) and 2.8 to 878.7 nmol/L in the second measurement (71.8% in the context of ACS). Lp(a) variability ranged from – 141.0 to + 221.8 nmol/L, with a median absolute variation of 15.0 51.8 nmol/L and 29.6 63.0 %. Relevant variation was verified in 53 (62.4%) patients, as disposed on Graph 1, also representing Lp(a) levels on the first and second measurement by patient and the time interval between both measurements. This factor was the only one that was significantly different between patients with and without relevant Lp(a) variation (155 332 days versus 32 197 days, respectively; p = 0.009). On a sub-analysis excluding patients that collected both measurements on the same ACS admission (n = 13), Lp(a) decreased from a median value of 71.4 135.9 nmol/L on the first analysis to 67.8 179.5 nmol/L in the second analysis. Conclusion This single-center retrospective analysis elicits that Lp(a) levels had substantial variability in patients with ACS, with relevant changes observed in over 60% of cases, confirming previous data that Lp(a) levels may fluctuate over time, particularly in the context of acute events. However, the variability identified was higher than previously described. Longer intervals between measurements were significantly associated with greater variability, while other demographic or clinical factors were not. These findings underscore that a single Lp(a) measurement may not fully capture a patient’s risk profile in the context of acute settings and further studies should clarify how many and at what times should we repeat Lp(a) levels.