title: Underestimated and under-recognized: the late consequences of acute coronary syndrome (GRACE UK-Belgian Study).
abstract: OBJECTIVE
  To define the long-term outcome of patients presenting with acute coronary syndrome [ST-segment elevation myocardial infarction (STEMI), and non-STEMI and unstable angina acute coronary syndrome (ACS) without biomarker elevation] and to test the hypothesis that the GRACE (Global Registry of Acute Coronary Events) risk score predicts mortality and death/MI at 5 years.
  
  
  RESULTS
  In the GRACE long-term study, UK and Belgian centres prospectively recruited and followed ACS patients for a median of 5 years (1797 days). Primary outcome events: deaths, cardiovascular deaths (CVDs) and MIs. Secondary events: stroke and re-hospitalization for ACS. There were 736 deaths, 19.8% (482 CVDs, 13%) and 347 (9.3%) MIs (>24 h), 261 strokes (7.7%), and 452 (17%) subsequent revascularizations. Rehospitalization was common: average 1.6 per patient; 31.2% had >1 admission, 9.2% had 5+ admissions. These events were despite high rates of guideline indicated therapies. The GRACE score was highly predictive of all-cause death, CVD, and CVD/MI at 5 years (death: χ(2) likelihood ratio 632; Wald 709.9, P< 0.0001, C-statistic 0.77; for CVD C-statistic 0.75, P < 0.0001; CVD/MI C-statistic 0.70, P < 0.0001). Compared with the low-risk GRACE stratum (ESC Guideline criteria), those with intermediate [hazard ratio (HR) 2.14, 95% CI 1.63, 2.81] and those with high-risk (HR 6.36, 95% CI 4.95, 8.16) had two- and six-fold higher risk of later death (Cox proportional hazard). A landmark analysis after 6 months confirmed that the GRACE score predicted long-term death (χ(2) likelihood ratio 265.4; Wald 289.5, P < 0.0001). Although in-hospital rates of death and MI are higher following STEMI, the cumulative rates of death (and CVD) were not different, by class of ACS, over the duration of follow-up (Wilcoxon = 1.5597, df = 1, P = 0.21). At 5 years after STEMI 269/1403 (19%) died; after non-STEMI 262/1170 (22%) after unstable angina (UA) 149/850 (17%). Two-thirds (68%) of STEMI deaths occurred after initial hospital discharge, but this was 86% for non-STEMI and 97% for UA.
  
  
  CONCLUSIONS
  The GRACE risk score predicts early and 5 year death and CVD/MI. Five year morbidity and mortality are as high in patients following non-ST MI and UA as seen following STEMI. Their morbidity burden is high (MI, stroke, readmissions) and the substantial late mortality in non-STE ACS is under-recognized. The findings highlight the importance of pursuing novel approaches to diminish long-term risk.
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK. K.A.A.Fox@ed.ac.uk
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.forename: Kathryn F
authors.initials: KF
authors.lastname: Carruthers
authors.forename: Donald R
authors.initials: DR
authors.lastname: Dunbar
authors.forename: Catriona
authors.initials: C
authors.lastname: Graham
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Manning
authors.forename: Herbert
authors.initials: H
authors.lastname: De Raedt
authors.forename: Ian
authors.initials: I
authors.lastname: Buysschaert
authors.forename: Diether
authors.initials: D
authors.lastname: Lambrechts
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
mesh_terms: D054058:Acute Coronary Syndrome / Q000401:mortality* / Q000628:therapy; D000368:Aged; D000789:Angina, Unstable / Q000401:mortality*; D015906:Angioplasty, Balloon, Coronary / Q000401:mortality; D001530:Belgium / Q000453:epidemiology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009203:Myocardial Infarction / Q000401:mortality*; D009204:Myocardial Revascularization / Q000401:mortality; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D020521:Stroke / Q000401:mortality*; D006113:United Kingdom / Q000453:epidemiology