Intra-Individual Variability of Lipoprotein(a) After Acute Coronary Syndrome: A Long-Term Cohort Study

<b>Background:</b> Lipoprotein(a) [Lp(a)] is a causal and independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and is largely genetically determined. However, recent studies indicate significant intra-individual variability, particularly among patients with intermediate Lp(a) levels (30-50 mg/dL). Yet, data on long-term variability are limited, and acute coronary syndrome (ACS) may further influence Lp(a) levels, raising questions regarding the optimal timing of assessment after ACS. <b>Methods:</b> We studied 235 ACS patients across two follow-up cohorts. Baseline Lp(a) was measured 24 h before hospital discharge. Cohort A had follow-up measurements at 4 months and 8 months; Cohort B had them at 5 years. Clinically meaningful intra-individual variability was defined as ≥20 mg/dL or ≥25% change. <b>Results:</b> 57.9% of patients exhibited clinically significant Lp(a) variability. Changes in risk category occurred in 15.3% of patients in the baseline high-risk group, 60.6% of patients in the intermediate-risk group, and 5.5% of patients in the baseline low-risk group. In the multivariable analysis, incomplete revascularization was an independent predictor of high Lp(a) variability (odds ratio (OR) 2.22; 95% confidence interval (CI) 1.14-4.31; <i>p</i> = 0.02) while female sex and age-adjusted menopause showed a trend (OR 1.92; 95% CI 0.93-4.00; <i>p</i> = 0.08 and OR 11.18; 95% CI 0.79-157.58; <i>p</i> = 0.07, respectively) without reaching statistical significance. The median absolute changes from baseline to 4-month and from baseline to 5-year follow-up were 7.9 mg/dL (interquartile range (IQR) 3.0-18.9) and 10.7 mg/dL (IQR 3.0-21.7), respectively. Concordance between 4- and 8-month Lp(a) measurements was excellent. <b>Conclusions:</b> Early post-ACS intra-individual variability in Lp(a) is common, mainly affecting risk reclassification in intermediate-risk patients. In those patients, early, targeted, repeat Lp(a) measurement may improve cardiovascular risk stratification, whereas mid- to long-term reassessment appears unnecessary.