Genetically-Determined Low-density Lipoprotein in Ischemic Stroke Survivors

Area of Science:

• Genetics
• Cardiovascular Medicine
• Neurology

Background:

• Polygenic susceptibility to hypertension and diabetes impacts ischemic stroke survivors.
• Polygenic susceptibility to hyperlipidemia (PSH) may negatively affect cholesterol control in these patients.

Purpose of the Study:

• To investigate the association between PSH and cholesterol control in ischemic stroke survivors.
• To determine if PSH predicts adverse clinical outcomes, including recurrent stroke and acute coronary events.

Main Methods:

• A genetic association study using data from the Vitamin Intervention Stroke Prevention (VISP) study.
• Polygenic risk score developed using 38 LDL-c genetic variants, categorized into low, intermediate, and high PSH.
• Multivariable regression models tested associations with hyperlipidemia and clinical outcomes, replicated in the UK Biobank.

Main Results:

• High PSH was linked to a 66% higher risk of uncontrolled hyperlipidemia and an 83% higher risk of resistant hyperlipidemia in VISP.
• High PSH increased the risk of recurrent stroke (2x) and acute coronary events (80%) in VISP.
• Findings were replicated in the UK Biobank, showing a >2x higher risk for uncontrolled and resistant hyperlipidemia with high PSH.

Conclusions:

• Higher PSH is associated with poorer lipid control and increased risk of recurrent vascular events in acute ischemic stroke survivors.
• These findings support evaluating polygenic profiles for identifying stroke survivors with failed risk factor control.
• Comprehensive genetic profiling may aid in personalized risk management strategies for stroke survivors.