Background: Limited information is available regarding risk factors for the near-term (4 years) onset of myocardial infarction (MI). We evaluated established cardiovascular risk factors and putative circulating biomarkers as predictors for MI within 4 years of measurement.
Methods: We conducted a matched, nested case-control study (252 cases and 499 controls) drawing on 45 735 men and women participating in the Copenhagen City Heart Study and the Copenhagen General Population Study. Established risk factors and 17 putative biomarkers, including inflammation-sensitive plasma proteins (C-reactive protein, fibrinogen, alpha(l)-antitrypsin, complement 3), apolipoproteins (A1, B, E, B/A1 ratio), markers of iron overload (iron, transferrin, transferrin saturation), creatinine, alkaline phosphatase, gamma-glutamyl transpeptidase, and leukocytes (lymphocyte count, neutrophil count, neutrophil/lymphocyte ratio) were assessed.
Results: Among women and men, only 13% and 50%, respectively, of those with near-term MI were classified as high risk by Framingham risk score at baseline. After adjustment for established risk factors, odds ratios for near-term MI, which compared highest to lowest quintiles, were 2.87(95% CI 1.51-5.48; P = 0.001) for alpha(l)-antitrypsin, 2.84(1.42-5.67; P = 0.003) for C-reactive protein, 1.97(1.09-3.57; P = 0.03) for creatinine, 1.99(1.09-3.65; P = 0.03) for fibrinogen, and 0.37(0.19-0.73; P = 0.004) for iron. The corresponding odds ratio for all biomarkers combined was 7.24 (3.28-16.0; P < 0.001).
Conclusions: We identified 5 biomarkers associated with increased near-term risk of MI independently of established risk factors. All putative biomarkers combined explained a 7-fold increase in the odds of near-term MI.