High-Density Lipoprotein Carries Markers that Track with Recovery from Stroke.

Rationale: Prospective cohort studies question the value of HDL-C for stroke risk prediction. Objective: Investigate the relationship between long-term functional recovery and HDL proteome and function. Methods and Results: Changes in HDL protein composition and function (cholesterol efflux capacity, or CEC) in patients after acute ischemic stroke at two time points (24 h, 35 patients; 96 h, 20 patients) and in 35 control subjects were measured. The recovery from stroke was assessed by 3 month The National Institute of Health Stroke Scale (NIHSS) and Modified Rankin scale (mRS) scores. When compared to control subject after adjustments for sex and HDL-C levels, twelve proteins some of which participate in acute phase response and platelet activation (APMAP, GPLD1, APOE, IHH, ITIH4, SAA2, APOA4, CLU, ANTRX2, PON1, SERPINA1, and APOF) were significantly (adj. p<0.05) altered in stroke HDL at 96h. The first eight of these proteins were also significantly altered at 24h. Consistent with inflammatory remodeling, CEC was reduced by 32% (P<0.001) at both time points. Baseline stroke severity adjusted regression model showed that changes within 96 hours post stroke in APOF, APOL1, APMAP, APOC4, APOM, PCYOX1, PON1, and APOE correlate with stroke recovery scores (R2=0.38-0.73, adjusted p<0.05). APOF (R2=0.73), and APOL1 (R2=0.60) continued to significantly correlate with recovery scores after accounting for tPA treatment.Conclusions: Changes in HDL proteins during early acute phase of stroke associate with recovery. Monitoring HDL proteins may provide clinical biomarkers that inform on stroke recuperation .