Lipoprotein(a) -Related Cognitive Vulnerability After Stroke Beyond High-Sensitivity C-Reactive Protein

Area of Science:

• Neurology
• Cardiology
• Biochemistry

Background:

• Post-stroke cognitive impairment (PSCI) is a common consequence of ischemic stroke.
• Lipoprotein(a) (Lp(a)) is a genetically determined vascular risk factor implicated in cardiovascular disease.
• The relationship between Lp(a) and cognitive decline after stroke, particularly the role of systemic inflammation, remains unclear.

Purpose of the Study:

• To investigate whether systemic inflammation mediates or modifies the association between Lp(a) and PSCI.
• To analyze the independent and combined effects of Lp(a) and high-sensitivity C-reactive protein (hs-CRP) on cognitive outcomes post-stroke.

Main Methods:

• Analysis of data from 954 patients with acute ischemic stroke from the Third China National Stroke Registry.
• Measurement of baseline serum Lp(a) and hs-CRP levels.
• Assessment of PSCI using the Montreal Cognitive Assessment (MoCA) at 1 year.
• Application of multivariable logistic regression, interaction, joint exposure, and causal mediation analyses.

Main Results:

• Higher baseline Lp(a) levels were significantly associated with an increased risk of PSCI (OR, 1.479; 95% CI, 1.007-2.170).
• Hs-CRP was not independently associated with PSCI after multivariable adjustment.
• No significant interaction was found between Lp(a) and hs-CRP regarding PSCI risk.
• Mediation analysis indicated that hs-CRP did not significantly mediate the Lp(a)-PSCI association (proportion mediated = 1.46%).

Conclusions:

• Elevated Lp(a) is independently associated with an increased risk of PSCI, irrespective of baseline cognitive function.
• The association between Lp(a) and PSCI is not substantially mediated or modified by hs-CRP-indexed systemic inflammation.
• Lp(a)-related cognitive vulnerability post-stroke may stem from vascular mechanisms not fully captured by hs-CRP, with inflammation contributing to cumulative risk.