Oxygen-regulated protein 150 and prognosis following myocardial infarction.
ORP150 (oxygen-regulated protein 150) is a chaperonin expressed in tissues undergoing hypoxic or endoplasmic reticulum stress. In the present study, we investigated plasma levels of ORP150 in patients with AMI (acute myocardial infarction) and its relationship with prognosis, together with a known risk marker N-BNP (N-terminal pro-B-type natriuretic peptide). Plasma from 396 consecutive patients with AMI 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 150 kDa protein in plasma extracts, including 3 and 7 kDa 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 with the survivors [N-BNP, 724 (14.5-28840) compared with 6167 (154.9-33884) pmol/l (P<0.0005); ORP150, 257 (5.9-870.9) compared with 331 (93.3-831.8) pmol/l (P<0.001); values are medians (range)]. 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 the use of thrombolytics. A Kaplan-Meier survival analysis revealed that ORP150 added prognostic information to N-BNP, especially in those with supra-median N-BNP levels. A simplified dual-marker approach with both markers below and 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 or heart failure). In conclusion, ORP150 and peptide fragments derived from it are secreted following AMI and provide independent prognostic information on mortality. High levels associated with endoplasmic reticulum/hypoxic stress predict a poor outcome.
Ng
Leong L
LL
Pharmacology and Therapeutics Group, Department of Cardiovascular Sciences, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, UK. lln1@le.ac.uk
O'Brien
Russell J
RJ
Quinn
Paulene A
PA
Squire
Iain B
IB
Davies
Joan E
JE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D005260:Female; D018840:HSP70 Heat-Shock Proteins; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000401:mortality*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011379:Prognosis; D011506:Proteins / Q000378:metabolism*; D012044:Regression Analysis; D016019:Survival Analysis
D018840:HSP70 Heat-Shock Proteins; D010446:Peptide Fragments; D011506:Proteins; C050087:oxygen-regulated proteins; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain