Abstract 4147562: Traditional modifiable cardiovascular risk factors and the risk of future CHD in the general population: an attempt towards better understanding residual risk.

Background: Up to 20% of patients presenting with an acute coronary heart disease (CHD) event do not report any traditional modifiable cardiovascular risk factors (CVRFs) on admission. However, major predictors of CHD events in the absence of CVRFs are still unknown. Aims: To establish whether increased concentrations of emerging circulating biomarkers at baseline (hsCRP, cystatin C, fibrinogen, NT-proBNP and troponin I), might be associated with future CHD events in subjects from the general population, who demonstrated no traditional CVRFs (hypertension, diabetes mellitus, dyslipidemia, smoking) at time of enrollment. Methods: Overall 213,310 subjects (median age 50.6 yrs.; 57.0% males) from 21 European prospective population-based cohorts were included. All participants were free of CHD at baseline and were followed-up prospectively for incident CHD events. Subjects were characterized in accordance to CVRF burden into2not present" or having 1 or ≥2 CVRFs at baseline. Fine and Gray competing risk-adjusted models were performed for the association between biomarkers and future CHD events in an interaction with the CVRF groups. Results: Overall, 18.6% of subjects revealed no traditional CVRF at baseline (n=39,722). During a median follow-up of 13.95 years, 17,544 subjects developed an incident CHD event (event rate 20.0%). Of those, 532 events were among subjects, who were free of four traditional CVRFs at baseline (event rate 6.7%). Among all studied biomarkers, only fibrinogen was not associated with incident CHD among those without CVRFs, whereas the association between all remaining biomarkers and future events was found to be even more prominent in subjects without than in those with CVRFs. The corresponding sub-distribution Hazard Ratios (sHRs) with 95% CI were for hsCRP (<2 vs. ≥2 mg/L) 1.64 (1.22-2.19) in those without CVRFs vs. 1.37 (1.21-1.55)/1.24 (1.14-1.35) in those with 1 or ≥2 CVRFs, respectively; for cystatin C (<median vs. ≥median) the sHRs were 1.79 (1.29-2.47) vs 1.30 (1.13-1.50)/1.10 (0.98-1.22), for NT-proBNP (<90 th pctl vs ≥90 th pctl) 2.23 (1.40-3.56) vs. 1.42 (1.13-1.79)/1.50 (1.31-1.73) and for troponin I (<6 vs. ≥6 ng/L) 2.03 (1.40-2.95) vs. 1.24 (1.07-1.45)/1.24 (1.12-1.36), respectively. Conclusion: In the general population low event rates for incident CHD were found among CVRF-free subjects at baseline. Moreover, circulating biomarkers might substantially improve the prediction of future CHD events in this low-risk population.