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A multimarker approach may be useful for risk stratification in AMI (acute myocardial infarction) patients, particularly utilizing pathways that are pathophysiologically distinct. Our aim was to assess the prognostic value of PR3 (proteinase 3) in patients post-AMI. We compared the prognostic value of PR3, an inflammatory marker, with an established marker NT-proBNP (N-terminal pro-B-type natriuretic peptide) post-AMI. We recruited 900 consecutive post-AMI patients (700 men; age, 64.6±12.4 years) in a prospective study with follow-up over 347 (0–764) days. Plasma PR3 was significantly higher in patients who died [666.2 (226.8–4035.5) ng/ml; P<0.001] or were readmitted with heart failure [598 (231.6–1803.9) ng/ml, P<0.004] compared with event-free survivors [486.9 (29.3–3118.2) ng/ml]. Using Cox modelling, log10 PR3 [HR (hazard ratio), 3.80] and log10 NT-proBNP (HR, 2.51) were significant independent predictors of death or heart failure. When patients were stratified by plasma NT-proBNP (median, 1023 pmol/l), PR3 gave additional predictive value for death or heart failure, in both the patients in whom NT-proBNP level was above the median (log rank for trend, 12.54; P<0.0004) and those with NT-proBNP level below the median (log rank for trend, 3.83; P<0.05). Neither marker predicted recurrent AMI. In conclusion, this is the first report showing a potential role for the serine protease PR3 in determining mortality and incidence of heart failure following AMI, independent of established conventional risk factors. PR3 may represent a clinically useful marker of prognosis after an AMI as part of a multimarker strategy. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the predictive value of MMP (matrix metalloproteinase)-2, MMP-3 and MMP-9 levels in patients with acute coronary syndrome for death, readmission with HF (heart failure) or recurrent MI (myocardial infarction) and to compare them with established markers, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the GRACE (Global Registry of Acute Coronary Events) score. A single blood test was taken 4 days after admission in 1024 consecutive patients with acute MI with end points observed over 519 (134–1059) days [value is median (range)]. MMP-2 and MMP-3 were increased in patients who died (n=111) compared with survivors (P<0.006 and P=0.01 respectively), but were similar in patients with HF (n=106) or MI (n=138). MMP-9 levels were similar across study end points. Using Cox proportional hazards modelling, MMP-2 demonstrated an independent prediction of death [HR (hazard ratio) 6.60, P=0.001], along with NT-proBNP (HR 4.62, P<0.001) and the GRACE score (HR 1.03, P<0.001), but MMP-3, MMP-9 or log10-troponin I did not. For 1 year mortality, the areas under the receiver operating characteristic curves were 0.60 and 0.58 for MMP-2 and MMP-3 respectively, compared with 0.82 for NT-proBNP and 0.84 for the GRACE score (all P<0.001). Kaplan–Meier analysis revealed that MMP-2 levels in the top quartile were associated with higher mortality rates (log rank 12.49, P=0.006). On univariate analysis, MMP-2 and MMP-3 had a weak association with HF readmission, which was lost after adjustment for clinical factors. None of the MMPs tested predicted MI. In conclusion, this is the first single centre study that identifies MMP2 as an independent predictor of all-cause mortality post-ACS (acute coronary syndrome); however, NT-proBNP and the GRACE score are superior for risk stratification in this cohort. [ABSTRACT FROM AUTHOR]

The GRACE (Global Registry of Acute Coronary Events) risk score has been shown to offer predictive power with regard to death and AMI (acute myocardial infarction) in patients with ACS (acute coronary syndromes). NT-proBNP (N-terminal pro-B-type natriuretic peptide) has also been found to be useful in predicting mortality following ACS. In the present study, we sought to investigate the use of the GRACE score and NT-proBNP levels at predicting risk of early and late deaths following ACS. We studied 1033 patients (740 men, mean age 66.5±12.7 years) with AMI. Blood was drawn once within 24 h following the onset of chest pain. The plasma concentration of NT-proBNP was determined using an in-house non-competitive immunoassay. Patients were GRACE risk scored. The 30-day mortality was 3.7% and the 6-month mortality was 7.8%, and all were related to higher GRACE risk scores (P=0.001 for trend). Higher NT-proBNP levels were also related to increased mortality (P<0.0001). In a Cox proportional hazards model, independent predictors of 30-day and 6-month mortality included NT-proBNP levels and the GRACE risk score. The receiver-operating curve for the GRACE risk score was complemented by NT-proBNP levels for prediction of 30-day mortality [AUC (area under the curve), 0.85] and 6-month mortality (AUC, 0.81). NT-proBNP gives complementary information to the GRACE risk score for predicting early and late mortality. The inclusion of the NT-proBNP blood test is useful in risk-stratifying patients after ACS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]