Inflammation and hemostasis in older octogenarians: implication in 5-year survival

Social changes and medical advances have increased longevity, but the conditions governing healthy vs unhealthy cardiovascular (CV) aging are not fully known. Factors beyond classical CV risk factors may have an important unrecognized value. We sought to identify proteins differentially expressed in healthy octogenarians (HOs) without a history of cardiovascular disease (CVD) and preserved functional and cognitive state compared with octogenarians with a history of CVD and cognitive decline (UHOs) using a systems biology approach, and investigated how these proteins relate to CV mortality at 5-year follow-up. Plasmas obtained from older octogenarians (87 ± 0 years) were analyzed by 2-DE + MS and bioinformatic pathway analysis in HOs (N = 38) and UHOs with cognitive (MEC<25) and functional (Barthel<90) decline and a previous ischemic event (acute myocardial infarction and/or stroke; N = 27). Results were validated by ELISA in HOs and UHOs and in an additional group of older octogenarians without cognitive impairment but with a previous CVD manifestation (HO-CVD; N = 35). UHOs showed a coordinated change in several inflammation-related proteins (AMBP, RBP4, and ITIH4; P < 0.05), together with a significant increase in the major inducer of the acute-phase reaction, interleukin-6 (P = 0.03). UHOs also showed a coordinated increase in hemostatic proteins that was associated with an impairment of fibrinolysis and an increased 5-year CV mortality (P = 0.003). The combination of inflammation (ITIH4 and interleukin-6) and hemostatic markers (D-dimer, A2AP, and coagulation factor XIII) was able to discriminate the presence of an unhealthy phenotype in the elderly (AUC = 0.750; P = 0.001). Unhealthy older octogenarians show increased levels of several plasma proteins of inflammation and coagulation. In older octogenarians, the increase in hemostatic markers indicated an increase in 5-year CV mortality at follow-up.