The impact of cumulative lipoprotein(a) exposure on stroke recurrence: a population-based prospective study

Background The risk of stroke recurrence is driven not only by contemporary lipid concentration but also by the cumulative duration of exposure. Most research focused on cumulative low-density lipoprotein cholesterol exposure; however, cumulative lipoprotein(a) (Lp(a)) exposure received less attention. This study aimed to explore the association of cumulative Lp(a) exposure with stroke recurrence in patients with acute ischaemic stroke or transient ischaemic attack.Methods This prospective cohort study recruited eligible patients from the China National Stroke Registry-III between 2015 and 2018. Cumulative Lp(a) exposure was estimated by multiplying the participant’s age by Lp(a) concentration. Participants were categorised into four groups based on the quartiles of cumulative Lp(a) exposure. Cox proportional hazards regression and spline regression were adopted to explore the associations between cumulative Lp(a) exposure and stroke outcomes. Scatter plot was used to illustrate the distribution of cumulative exposure in high-risk populations.Results A total of 10 678 patients were enrolled in this study. Within 1-year follow-up, 1048 (9.81%) patients developed stroke recurrence. To identify patients at high risk of stroke recurrence, we predefined a protocol that combines Q1–Q3 into a single reference group, given the left skew of cumulative Lp(a) exposure. After multivariable adjustment, the Q4 of cumulative Lp(a) exposure (≥2229 mg/dL years) was associated with increased risk of stroke recurrence (adjusted hazard ratio, 1.15; 95% CI 1.00 to 1.33; p=0.0442). Results also suggested important non-linearity in the association with stroke recurrence ( P for non-linearity=0.0438).Conclusion The exploratory findings suggest that cumulative Lp(a) exposure is associated with recurrent stroke, though whether this metric provides incremental prognostic value beyond age and baseline Lp(a) requires further validation.