Abstract 14288: α1-Antichymotrypsin Complex (SERPINA3) is an Independent Predictor of Long-Term All-Cause Mortality, but Did Not Predict CVD Events

Abstract

Introduction: SERPINA3 is an acute phase protein triggered by inflammation. It inhibits neutrophil cathepsin which cleaves protease-activated receptor 4 (PAR-4) via a thrombin-independent pathway, and mast cell chymase which mediates the production of angiotensin-II via an ACE-independent pathway. SERPINA3 is upregulated after an acute myocardial infarction (MI), but data on its long-term prognostic value in MI patients are scarce. Aim: To assess the utility of SERPINA3 as a prognostic marker in patients hospitalized for chest pain of suspected coronary origin. Methods: A total of 871 consecutive patients were included (ClinicalTrials.gov Identifier: NCT00521976). Stepwise Cox regression models, applying continuous log e -transformed values, were fitted for each of the biomarkers with all-cause mortality and cardiac death within median 24-months (mo) and all-cause mortality within median 7 years (y) as the dependent variables, adding an analysis of 1) all-cause mortality or MI, and 2) all-cause mortality or MI or stroke at 7 y follow up (FU). The hazard ratio (HR) (95% CI) was assessed in a univariate and multivariable model, adjusting for traditional clinical cardiovascular risk factors, adding BNP, hsCRP, TnT. Results: Plasma samples from 847 patients were available. At 24 mo FU, 138 (15.8%) patients had died, of which 86 were cardiac deaths. The univariate analysis showed a positive, significant association between SERPINA3 and total death [HR 1.42 (95% 1.19-1.68), p =0.000], but was not significant for cardiac death. Associations after multivariable adjustment were statistically non-significant. At 7 y FU, 332 (38.1%) patients had died. After adjustment, SERPINA3 was independently associated with all-cause mortality [HR 1.14 (95% CI, 1.02-1.28), p=0.022], but not for MI (n=203), and stroke (n=55), respectively, and remained essentially unaffected for all-cause mortality or MI combined (n=404) [HR 1.12 (95% CI, 1.01-1.24), p=0.031], slightly weakened when stroke also was added (n=422) [HR 1.10 (95% CI, 1.00-1.22), p=0.060]. Conclusions: SERPINA3 predicts long-term all-cause mortality, but had no prognostic bearing on short-term cardiac death. Introducing non-fatal CVD events during long-term FU did not improve its prognostic value.