P4155Multiple modality biomarkers predict ischemic heart disease in middle-aged men from the general population during a 21-year follow-up

Background Ischemic heart disease (IHD) often develops after decades of preceding subclinical coronary atherosclerosis. An early prediction of risk for IHD in a general population would be helpful for preventive decision-making. It is well known that biomarkers including troponine, natriuretic peptides and inflammatory biomarkers are useful prognostic predictors for IHD, their long-term predictive values in a general population for incident IHD have not been studied. Purpose The aim of the study was to investigate the predictive value of multi-modality biomarkers on the incident IHD in a random male sample from the general population followed from the age of 50 to 71 years. Method “The study of Men Born in 1943” is a longitudinal cohort study of men living in the city of Gothenburg in Sweden. All patients underwent a baseline examination in 1993, which included physical examination, questionnaires and blood samples. Because of multifactorial nature of atherosclerosis, a panel of biomarkers representing multiple mechanisms such as high-sensitivity troponine (hs-TNT), interleukin-6 (IL-6), cystatin C, high-sensitivity C-reactive protein (hs-CRP), urat, ferritin, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were analyzed from blood samples collected at 50 years of age. Incident IHD was defined as new-onset one of following (myocardial infarction, hospitalized unstable angina and intervention with either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) during 1993–2014. The impact of biomarkers on incident IHD was studied using univariable, followed by stepwise and multivariable Cox proportional hazards models. Results Among the, 753 patients in the study, 105 patients (13,9%) developed IHD during 21 years of follow up with an event rate per 1000 person years 7.49 and a 95% confidence interval (CI) of 6.19 - 9.07. In Cox proportional hazards model for time to first occurrence of IHD, univariable analyses showed that multi-modality biomarker (CRP >1 mg/ml, NT-proBNP >100 pg/mL, troponin >10 ng/L, IL-6 >8 ng/L) provide most powerful prediction, followed by total cholesterol and fasting plasma glucose. In multivariable Cox proportional hazards model for time to first of IHD, above four-biomarker combination modality remains a most powerful predictor with risk increased by one additional biomarker [Hazard Ratio (95% CI): 1.69 (1.26 - 2.26), p=0.0004], followed by total cholesterol (mmol/L) with risk increased by one [Hazard Ratio (95% CI: 1.31 (1.09 - 1.56), p=0.0031], and fasting plasma glucose (mmol/L) with risk increased by one unit [Hazard Ratio (95% CI): 1.11 (1.01 - 1.22), p=0.038]. Conclusion A multi-modality biomarker strategy can be used to predict increased risk of developing IHD during the following two decades after 50 years, enabling us to identify individuals who might benefit from early intensive risk modification to prevent the development of IHD.