Serum Lipoprotein(a) and Hemorrhagic Stroke Risk: A Systematic Review and Meta-Analysis

Lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular disease and ischemic stroke, but its relationship with hemorrhagic stroke remains uncertain. We performed a systematic review and meta-analysis evaluating circulating Lp(a) levels and hemorrhagic stroke risk.

MEDLINE and Scopus were searched from inception to May 10, 2026, for observational studies reporting circulating Lp(a) in adults with hemorrhagic stroke. Continuous Lp(a) outcomes were pooled as standardized mean differences (SMDs); odds ratios (ORs) from case-control studies and hazard ratios (HRs) from prospective cohort studies were analyzed separately using inverse-variance random-effects models. A combined log-ratio model was included as exploratory analysis.

Eight studies (526,909 participants; 2,895 hemorrhagic stroke cases) were included in the systematic review; individual analyses drew on subsets. Three studies showed higher Lp(a) levels in hemorrhagic stroke than in healthy controls (SMD, 0.32; 95% CI, 0.18-0.47; I²=0%). Two case-control studies showed greater odds of hemorrhagic stroke (pooled OR, 1.72; 95% CI, 1.31-2.27), whereas four prospective cohort studies showed no association (pooled HR, 0.88; 95% CI, 0.67-1.14; I²=71.8%); the subgroup difference was significant (p=0.0005). An exploratory model combining OR- and HR-based estimates showed no statistically significant association (1.06; 95% CI, 0.80-1.40). Lp(a) did not differ significantly between hemorrhagic and ischemic stroke (SMD, -0.13; 95% CI, -0.40 to 0.15).

Post-event studies reported higher circulating Lp(a) levels in hemorrhagic stroke, but this evidence was at serious risk of bias and should be regarded as hypothesis-generating. Prospective cohort studies showed no significant association with incident hemorrhagic stroke.