Serum nitric oxide metabolites (NOx) for prognosis of cardiovascular death and acute myocardial infarction in an ESSE-RF case-control cohort with 6.5 year follow up

Aims. The goal of the present case-control study was to assess associations of a panel of routine and experimental biomarkers with the risk for cardiovascular death and acute myocardial infarction (AMI) in a cohort recruited from the multicenter study “Cardiovascular Epidemiology in Russian Federation” (ESSE-RF).Methods and Results. A total of 222 subjects included cardiovascular death (N=48) and AMI cases (N=63) detected during 6.5-year follow up with corresponding numbers of matched healthy controls. The levels of 15 routine and experimental biochemical markers were assayed to analyze associations with the outcomes using logistic and Cox proportional hazard regressions validated by comparison between various groups to assess the estimated hazard ratio (eHR). Elevated levels of cardiac troponin I (cTnI), C-reactive protein (CRP), and metabolites of nitric oxide (NOx) were independently associated (P<0.001) with a higher risk of cardiovascular death in various models with adjusted eHRs ranging from 1.83 to 3.74. Elevated levels of NOx and cTnI were significantly (P<0.001) and independently associated with a higher risk of nonfatal AMI with eHR ranging from 1.78 to 2.67. Elevated levels of angiopoietin-like protein 3 (ANGPTL3) were significantly (P<0.001) and independently associated with a lower risk of cardiovascular death in certain models (eHRs from 0.09 to 0.16) and a higher risk of nonfatal AMI (eHR 2.07; P=0.01).Conclusion. Subsequent large scale validation studies should focus on the investigation of predictive impact of cTnI, NOx, CRP, and ANGPTL3 for the development of nationwide recommendations for individual baseline stratification of patients with potential cardiovascular risks.