Oxygen-regulated protein 150 and prognosis following myocardial infarction

Leong L Ng (1) , Russell J O'Brien , Paulene A Quinn , Iain B Squire , Joan E Davies

1 Department of Cardiovascular Sciences [Leicester]

Oxygen regulated protein (ORP150) is a chaperonin expressed in tissues undergoing hypoxic or endoplasmic reticulum stress. We investigated plasma levels of ORP150 in acute myocardial infarction (AMI) patients and its relationship to prognosis together with a known risk marker N-terminal pro-B-type natriuretic peptide(N-BNP). Plasma from 396 consecutive AMI patients was obtained for measurement of ORP150 and N-BNP. Mortality and cardiovascular morbidity (acute coronary syndromes/heart failure) was determined during follow-up. A specific ORP150 assay detected the 150kD protein in plasma extracts, including 3 and 7kD fragments. During follow-up (median 455 days) 43(10.9%) patients died. Both N-BNP and ORP150 levels were higher in those who died compared to survivors (median[range] N-BNP 724[14.5-28840] vs 6167[154.9-33884] pmol/L P<0.0005; ORP150 257[5.9-870.9] vs 331[93.3-831.8] pmol/L P<0.001). In a Cox regression model for mortality prediction, both N-BNP(odds ratio 5.06, P<0.001) and ORP150(odds ratio 2.39, P<0.01) added prognostic information beyond creatinine and use of thrombolytics. Kaplan-Meier survival analysis revealed ORP150 added prognostic information to N-BNP, especially in those with supramedian N-BNP levels. A simplified dual-marker approach with both markers below, either above or both above their respective medians effectively stratified mortality risk(log rank statistic for trend 32.7, P<0.00005). ORP150 levels were not predictive of other cardiovascular morbidity (acute coronary syndromes, heart failure). ORP150 and peptide fragments derived from it are secreted following AMI and provides independent prognostic information on mortality. High levels associated with endoplasmic reticulum/hypoxic stress predict a poor outcome.

Mots clés: Medicine

Leong L Ng, Russell J O'Brien, Paulene A Quinn, Iain B Squire, Joan E Davies. Oxygen-regulated protein 150 and prognosis following myocardial infarction. Clinical Science, 2006, 112 (9), pp.477-484. ⟨10.1042/CS20060304⟩. ⟨hal-00479352⟩