Plasma proteome and incident myocardial infarction: sex-specific differences

Area of Science:

• Cardiovascular Disease Research
• Proteomics
• Genetics

Background:

• Limited population-based studies exist on circulating proteins and myocardial infarction (MI) risk in both sexes.
• Understanding protein biomarkers for MI is crucial for risk prediction and prevention.

Purpose of the Study:

• To investigate associations between circulating cardiometabolic proteins and incident MI risk.
• To explore potential sex-specific differences in these protein-MI relationships.
• To validate findings using cohort and Mendelian randomization (MR) analyses.

Main Methods:

• Utilized a discovery cohort (n=11,751) with 259 protein measurements and followed up for incident MI.
• Performed replication analyses in the UK Biobank (n=51,613).
• Employed MR analyses using genetic variants as instrumental variables for proteins and MI genetic association data.

Main Results:

• Identified 45 proteins associated with incident MI in discovery and replication cohorts.
• Observed 13 sex-specific associations, predominantly in women.
• MR analysis linked higher renin, follistatin, and RARRES2 to increased MI risk; TFPI, TNFRSF1A, TNFRSF1B, and PGF showed inverse associations.

Conclusions:

• Established novel and confirmed existing circulating protein associations with incident MI.
• Provided the first evidence of sex-specific patterns in multiple protein-MI associations.
• Highlighted specific proteins (renin, follistatin, RARRES2) as potential risk factors for MI.