Protein biomarkers associated with risk of myocardial infarction in women: the HUNT study

Background Emerging evidence indicates that circulating proteins associated with myocardial infarction (MI) are sex-specific, suggesting distinct sex-related patterns in MI incidence. This study aimed to identify circulating protein biomarkers associated with the 10-year risk of incident Type-1 MI in women.Methods This retrospective nested case-control study included women (mean age, SD: 62.2, 7.5 years) from the Trøndelag Health Study (Norway) with no history of cardiovascular disease (CVD) at baseline. Using registry data, 75 cases experiencing MI during 10-year follow-up and 140 CVD-free controls were selected. Circulating proteins were measured using the SomaScan assay. The primary analysis consisted of a per-protein age-adjusted logistic regression within the 5K assay, with effects expressed per SD and false-discovery-rate control. Candidate proteins were defined a priori as those with q<0.20. Consistency of the candidates was examined in an independently assayed sample (7K assay; 15 cases, 140 controls).Results No protein reached q<0.05; 10 proteins met the candidate threshold (6 with an estimated OR for incident MI>1, 4<1). In the independent sample, 9 of 10 candidates showed concordant effect direction, and effect sizes in the main and independent sample were positively correlated (r=0.73). Several candidates had cardiovascular or inflammatory relevance. Lower circulating brain-derived neurotrophic factor receptor BDNF/NT-3 growth factors receptor showed an inverse association with incident MI (OR per SD 0.56; 95% CI 0.40 to 0.77; q<0.18).Conclusions Untargeted proteomics in women identified candidate proteins for incident MI that may provide insights into underlying predisposing mechanisms. These hypothesis-generating findings require replication in larger cohorts.