Contribution of novel biomarkers to incident stable angina and acute coronary syndrome: the PRIME Study

To compare whether novel inflammatory and haemostatic biomarkers are more predictive of well-characterized incident acute coronary syndrome (ACS) than stable angina (SA). We used data from the PRIME Study, a prospective cohort of 9758 asymptomatic middle- aged men recruited in Northern Ireland and France between 1991 and 1993. A nested case - control study was established with the baseline plasma sample of 269 incident cases and 538 matched controls. Odds ratios ( ORs) for SA and ACS were estimated by conditional logistic regression analysis. After 5 years of follow- up, 107 incident SA and 162 ACS cases were validated. After adjustment for traditional risk factors, higher circulating levels of hs- CRP, ICAM1, interleukin 6 and interleukin 18 were equally predictive of SA and ACS ( all P- values of OR comparison > 0.05). In contrast, elevated levels of fibrinogen, von Willebrand factor, and possibly higher level of D- dimers and lower level of tissue factor pathway inhibitor were associated with ACS only. The comparison of the ORs showed a statistically significant difference for von Willebrand factor only [ OR(4th vs. 1st quartile) = 2.99 ( 1.49 - 6.02) for ACS vs. 0.80 ( 0.33 - 1.94) for SA; P(z test) = 0.02]. This is the first population-based study suggesting that higher levels of circulating haemostatic markers and of von Willebrand factor, in particular, are significantly more predictive of incident ACS than SA.