Neutrophil counts and cardiovascular disease

Area of Science:

• Cardiovascular Medicine
• Inflammation Biology
• Genetics and Epidemiology

Background:

• Neutrophils are key inflammatory cells.
• High neutrophil counts are associated with atherosclerosis.
• Previous anti-inflammatory trials show cardiovascular benefits.

Purpose of the Study:

• To investigate associations between neutrophil counts and nine cardiovascular endpoints.
• To utilize both observational and genetic (Mendelian randomization) approaches.
• To determine if high neutrophil counts are a causal risk factor for atherosclerotic cardiovascular disease.

Main Methods:

• Observational study in Copenhagen General Population Study (n=101,730).
• One-sample Mendelian randomization (MR) in UK Biobank (n=365,913).
• Two-sample MR using Blood Cell Consortium data (n=563,085).
• Assessed nine cardiovascular endpoints including ischaemic heart disease, myocardial infarction, and stroke.

Main Results:

• Observational analyses revealed high neutrophil counts associated with increased risk for all studied cardiovascular outcomes.
• Genetically predicted higher neutrophil counts showed increased risk for ischaemic heart disease (OR 1.15), myocardial infarction (OR 1.22), and peripheral arterial disease (OR 1.19).
• Two-sample MR confirmed associations for ischaemic heart disease and myocardial infarction, with consistent results across sensitivity analyses.

Conclusions:

• Both observational and genetic evidence support a causal link between high neutrophil counts and atherosclerotic cardiovascular disease.
• High blood neutrophil count is identified as a causal risk factor for atherosclerotic cardiovascular disease.
• Findings reinforce the role of inflammation in cardiovascular pathology.