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Relation Between Blood Pressure at Hospital Discharge After an Acute Coronary Syndrome and Long-Term Survival
Relation Between Blood Pressure at Hospital Discharge After an Acute Coronary Syndrome and Long-Term Survival Cheuk-Kit Wong, MDa,*, Peter Herbison, MScb, and Eng Wei Tang, MMeda There are limited data on the relation between blood pressure (BP) at hospital discharge and long-term outcomes after acute coronary syndromes. In this study, of 1,053 consecutive survivors of acute coronary syndromes (mean age 64.9 ⴞ 12.6 years, 63% men), patients with lower diastolic BP were older, had higher Global Registry of Acute Coronary Events (GRACE) discharge risk scores, and had higher 2-year mortality. When modeled with GRACE score in predicting survival, only diastolic BP but not pulse pressure or systolic BP was significant in predicting survival up to 5 years. When cardioprotective medications and in-hospital revascularization were incorporated in the model, the independent predictors for survival included lower GRACE score, higher diastolic BP, and the use of  blockers and statins. The square term of diastolic BP was also significant, indicating a J-shaped relation. Adding diastolic BP to GRACE score tended to improve the C index for predicting 6-, 12-, and 24-month survival (p ⴝ 0.14, 0.07, and 0.09, respectively). In conclusion, this study established the independent prognostic relation between diastolic BP and survival after acute coronary syndromes. © 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;101:1239 –1241) For subjects aged ⬎50 years, systolic blood pressure (BP) can be more important than diastolic BP in predicting cardiovascular risk.1 In the Framingham study, at ages ⬎60 years, lower diastolic BP actually predicted higher coronary risk,2 a finding supported by the International VerapamilTrandolapril Study (INVEST) of 22,576 patients (mean age 66 years) with stable coronary disease.3 There are limited data on the relation between BP at the time of hospital discharge and outcomes after acute coronary syndromes (ACS). The PREVENIR study of 1,247 patients found that suboptimally controlled systolic BP (⬎140 mm Hg) after ACS independently predicted higher 6-month cardiovascular events.4 However, cardioprotective medications such as  blockers and angiotensin-converting enzyme inhibitors reduce BP, and high systolic BP may actually reflect their underuse.5 Recent guidelines recommend BP ⬍130/80 mm Hg with coronary disease6,7 and caution in lowering diastolic BP to ⬍60 mm Hg.6 In the present study, we evaluated in survivors of ACS the relation between the last in-hospital measurement of BP and survival up to 5 years, adjusting for baseline risk measured by Global Registry of Acute Coronary Events (GRACE) discharge risk score8 and the use of cardioprotective medications.9 Methods and Results This study retrospectively included consecutive patients with ACS admitted into 2 related centers in New Zealand (Dunedin Hospital and Invercargill Hospital) from 2000 to 2002.8,10 Patients with ACS precipitated by significant nonDepartments of aCardiology and bPreventive and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin Public Hospital, Dunedin, New Zealand. Manuscript received October 12, 2007; revised manuscript received and accepted December 11, 2007. *Corresponding author: Tel: 643-4747980; fax: 643-4747655. E-mail address: [email protected] (C.-K. Wong). 0002-9149/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2007.12.022
cardiac co-morbidities, trauma, or surgery were excluded. This study protocol was in accordance with the local hospital research guidelines.8,10 All clinical data were collected by a research physician, including the use of cardioprotective medications (aspirin,  blockers, statins, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) at hospital discharge and details of the hospitalization.8,10 The latter included age, gender, cardiac risk factors, history of ischemic heart disease, history of stroke, peripheral vascular disease, smoking, presenting heart rate, BP, Killip class, episodes of cardiac arrest on arrival and cardiogenic shock, initial electrocardiographic characteristics (degree of ST deviation and T-wave changes), troponin I level, creatinine level, left ventricular function, and in-hospital therapy, including revascularization. Patients were classified into 3 categories: those with ST elevation myocardial infarctions, non–ST elevation myocardial infarctions, or unstable angina pectoris.8,10 The last recorded BP before discharge was collected. All-cause mortality was used as the study end point, over a follow-up period of up to 5 years. Information on deaths (until April 1, 2005) was obtained from medical records and the New Zealand national death registry. GRACE hospital discharge risk score11 was calculated for the present cohort as described previously.8 Parameters in the GRACE score are age, history of heart failure, history of myocardial infarction, elevated heart rate and low systolic BP on arrival, ST-segment depression, elevated initial serum creatinine, elevated cardiac enzymes, and not having in-hospital percutaneous coronary intervention.8,11 The GRACE score discriminated survivors from nonsurvivors with a C index of 0.80 to 0.82 at multiple time points from 6 months to 4 years.8 The C index is a measure of model discrimination (equivalent to the area under the receiver-operating characteristic curve) used to determine how well an algorithm discriminates survivors from nonsurvivors. www.AJConline.org
1240
The American Journal of Cardiology (www.AJConline.org)
Table 1 Patient characteristics, Global Registry of Acute Coronary Events hospital discharge risk score, in-hospital revascularization, and use of medications on discharge Variable
Age (yrs) GRACE score In-hospital revascularization Discharge medications Aspirin  blockers ACE inhibitors/ARBs Statins 2-year mortality
Diastolic blood pressure (mmHg) ⱖ80 (n ⫽ 200)
70 to ⬍80 (n ⫽ 336)
60 to ⬍70 (n ⫽ 326)
⬍60 (n ⫽ 191)
p Value*
62.8 ⫾ 12.3 108 ⫾ 34 46%
64.7 ⫾ 12.5 117 ⫾ 38 45%
65.6 ⫾ 12.7 122 ⫾ 39 44%
66.3 ⫾ 13.0 123 ⫾ 39 49%
0.004 ⬍0.0005 0.622
98% 81% 56% 59% 8.5%
96% 74% 50% 60% 8.7%
98% 79% 51% 58% 13.0%
97% 74% 54% 60% 19.5%
0.843 0.388 0.910 0.972 ⬍0.0005
Data are expressed as mean ⫾ SD or as percentages. * Trend p values. ACE ⫽ angiotensin-converting enzyme inhibitors; ARB ⫽ angiotensin receptor blockers.
Baseline characteristics are summarized using frequencies and percentages for categorical variables and means and SDs (or medians and interquartile ranges [IQRs]) for continuous variables. A multivariate Cox proportional-hazards analysis was performed to test if systolic BP, diastolic BP, and pulse pressure (systolic BP ⫺ diastolic BP) were associated with mortality. This was done after confirming the proportionality of the hazards (death) along the 5-year follow-up period. Systolic and diastolic BP were entered into the models as continuous variables by themselves and after squaring. This was done to explore for a J-shaped relation. In all models, adjustments were made for GRACE hospital discharge risk score. Interactions between BP and in-hospital revascularization were explored. Because discharge medications, including aspirin,  blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins, would have prognostic effects,12 they were also entered into the model. Survival curves according to diastolic BP and adjusted for all significant predictors were generated. C indexes were calculated in all logistic regression models on 6-month, 12-month, and 2-year survival.8 Of 1,143 consecutive patients with ACS, including 446 with ST elevation myocardial infarctions, 450 with non–ST elevation myocardial infarctions, and 247 with unstable angina pectoris, the 1,057 hospital survivors (mean age 64.9 ⫾ 12.6 years, 63% men) formed the study cohort. Survival status was available for all at 2 years, for 82% at 3 years, and for 54% at 4 years of follow-up (median follow-up time 43 months, IQR 32 to 53). Four patients had missing data on diastolic BP. The mean last recorded systolic BP before discharge was 122.1 ⫾ 18.6 mm Hg (median 120, IQR 110 to 132), the mean last recorded diastolic BP was 67.5 ⫾ 11.6 mm Hg (median 70, IQR 60 to 75), and the mean pulse pressure was 54.9 ⫾ 15.4 mm Hg (median 52, IQR 44 to 64). Table 1 shows the characteristics of the 1,053 patients and 2-year mortality according to diastolic BP at discharge (⬎80, 70 to ⬍80, 60 to ⬍70, and ⬍60 mm Hg). Patients with lower diastolic BPs had higher GRACE scores and higher 2-year mortality (8.5%, 8.7%, 13.0%, and 19.5%, respectively, p ⬍0.0005).
Figure 1. Adjusted survival curves according to diastolic BP at discharge.
When BP parameters were modeled with GRACE score in predicting survival, only diastolic BP was significant. Neither pulse pressure nor systolic BP was a predictor in any model (p ⬎0.2). When cardioprotective medications and revascularization were incorporated into the model, the independent predictors of survival included lower GRACE score, higher diastolic BP, and the use of  blockers and statins. The square term for diastolic BP was also significant in the mortality model. There was no interaction between diastolic BP and in-hospital revascularization in the mortality model. The survival curve showing the effect of different diastolic BP on mortality adjusted to other prognostic factors is shown in Figure 1. Adding diastolic BP to GRACE score tended to improve the C index for predicting 6-, 12-, and 24-month survival (p ⫽ 0.14, 0.07, and 0.09, respectively). Discussion The present study provides information on the link between diastolic BP and survival up to 5 years after ACS. The poorer prognosis from lower diastolic BP was consistent
Coronary Artery Disease/BP After ACS and Survival
with the Framingham data2 in patients of similar age range and the INVEST data in patients of similar age range and with concomitant stable coronary disease.3 Lower diastolic BP can reflect more advanced arteriosclerosis2 or a lower left ventricular ejection fraction, although this was not analyzed in INVEST or the present study. The significance of the square term for diastolic BP indicated a reverse-J-shaped effect: although higher diastolic BP was associated with better outcomes, no further benefit was seen when diastolic BP was ⬎90 mm Hg, as shown in Figure 1. The present cohort was undersized to determine the exact diastolic BP value at which the relation with survival changed. In patients with stable coronary disease, an exploratory analysis3 of INVEST, a 22,576patient study, found that the risk for death and for myocardial infarction progressively increased with lower diastolic BP beyond 84 mm Hg. In INVEST, an interaction between diastolic BP and revascularization was observed. Low diastolic BP was associated with a relatively lower risk for the primary outcome (death, nonfatal stroke, and nonfatal myocardial infarction) in patients with revascularization than in those without revascularization.3 This may reflect poorer myocardial perfusion from lower diastolic BP in patients with coronary stenoses. The present study of 1,053 patients with ACS did not find any interaction. It is possible that patients with lower diastolic BP were in poorer general health, including anemia, malnutrition, and other factors not captured by our data. Also, the GRACE discharge risk score is a simple bedside algorithm that does not incorporate results from imaging, including ejection fraction measurements. Its simplicity, however, underpins its clinical utility. Future prospective studies should evaluate the additional contribution from BP parameters to the GRACE score. In conclusion, the present study established the prognostic relation between diastolic BP and survival after ACS independent of the use of cardioprotective medications.12 and the GRACE discharge risk score.8 1. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Rocella EJ. The
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3.
4.
5. 6.
7.
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12.
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seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. The JNC 7 report. JAMA 2003;289:2560 –2572. Franklin SS, Larson MG, Khan SA, Wong ND, Leip EP, Kanel WB, Levy D. Does the relation of blood pressure to coronary heart disease risk changes with aging? The Framingham heart study. Circulation 2001;103:1245–1249. Messerli FH, Mancia G, Conti CR, Hewkin AC, Kupfer S, Champion A, Kolloch R, Benetos A, Pepine CJ. Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med 2006;144:884 – 893. Amar J, Chamontin B, Ferrieres J, Danchin N, Grenier O, Cantet C, Cambou JP. Hypertension control at hospital discharge after acute coronary event: influence on cardiovascular prognosis—the PREVENIR study. Heart 2002;88:587–591. Wong CK, White HD. Relationship between blood pressure after an acute coronary event and subsequent cardiovascular risk. Heart 2002; 88:555–558. Rosendorff C, Black HR, Cannon CP, Gersh BJ, Gore J, Izzo JL, Kaplan NM, O’Connor CM, O’Gara PT, Opail S. Treatment of hypertension in the prevention and management of ischemic heart disease: a scientific statement from the American Heart Association Council for High Blood Pressure Research and the Council on Clinical Cardiology and Epidemiology and Prevention. Circulation 2007;115: 2761–2788. The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension and European Society of Cardiology. 2007 guidelines for the management of arterial hypertension. J Hypertens 2007;25:1105–1187. Tang EW, Wong CK, Herbison P. GRACE hospital discharge risk score accurately predicts long-term mortality post acute coronary syndrome [published correction appears in Am Heart J 2007;154:851]. Am Heart J 2007;153:29 –35. Smith SC, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, Grundy SM, Hiratzka L, Jones D, Krumholz HM, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update. J Am Coll Cardiol 2006;47:2130 –2139. Tang EW, Wong CK, Herbison P. Community hospital versus tertiary hospital comparison in the treatment and outcome of patients with acute coronary syndrome: a New Zealand experience. N Z Med J 2006;119:U2078. Eagle KA, Lim MJ, Dabbous OH, Pieper KS, Goldberg RJ, Van de Werf F, Goodman SG, Granger CB, Steg PG, Gore JM, et al. A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month post-discharge death in an international registry. JAMA 2004;291:2727–2733. Wong CK, Tang EW, Herbison P. The use of different evidence-based medications and 5-year survival after an acute coronary syndrome: an observational study. Int J Cardiol. Epub 2008. DOI: 10.1016/j. ijcard.2007.11.05.
cardiac co-morbidities, trauma, or surgery were excluded. This study protocol was in accordance with the local hospital research guidelines.8,10 All clinical data were collected by a research physician, including the use of cardioprotective medications (aspirin,  blockers, statins, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) at hospital discharge and details of the hospitalization.8,10 The latter included age, gender, cardiac risk factors, history of ischemic heart disease, history of stroke, peripheral vascular disease, smoking, presenting heart rate, BP, Killip class, episodes of cardiac arrest on arrival and cardiogenic shock, initial electrocardiographic characteristics (degree of ST deviation and T-wave changes), troponin I level, creatinine level, left ventricular function, and in-hospital therapy, including revascularization. Patients were classified into 3 categories: those with ST elevation myocardial infarctions, non–ST elevation myocardial infarctions, or unstable angina pectoris.8,10 The last recorded BP before discharge was collected. All-cause mortality was used as the study end point, over a follow-up period of up to 5 years. Information on deaths (until April 1, 2005) was obtained from medical records and the New Zealand national death registry. GRACE hospital discharge risk score11 was calculated for the present cohort as described previously.8 Parameters in the GRACE score are age, history of heart failure, history of myocardial infarction, elevated heart rate and low systolic BP on arrival, ST-segment depression, elevated initial serum creatinine, elevated cardiac enzymes, and not having in-hospital percutaneous coronary intervention.8,11 The GRACE score discriminated survivors from nonsurvivors with a C index of 0.80 to 0.82 at multiple time points from 6 months to 4 years.8 The C index is a measure of model discrimination (equivalent to the area under the receiver-operating characteristic curve) used to determine how well an algorithm discriminates survivors from nonsurvivors. www.AJConline.org
1240
The American Journal of Cardiology (www.AJConline.org)
Table 1 Patient characteristics, Global Registry of Acute Coronary Events hospital discharge risk score, in-hospital revascularization, and use of medications on discharge Variable
Age (yrs) GRACE score In-hospital revascularization Discharge medications Aspirin  blockers ACE inhibitors/ARBs Statins 2-year mortality
Diastolic blood pressure (mmHg) ⱖ80 (n ⫽ 200)
70 to ⬍80 (n ⫽ 336)
60 to ⬍70 (n ⫽ 326)
⬍60 (n ⫽ 191)
p Value*
62.8 ⫾ 12.3 108 ⫾ 34 46%
64.7 ⫾ 12.5 117 ⫾ 38 45%
65.6 ⫾ 12.7 122 ⫾ 39 44%
66.3 ⫾ 13.0 123 ⫾ 39 49%
0.004 ⬍0.0005 0.622
98% 81% 56% 59% 8.5%
96% 74% 50% 60% 8.7%
98% 79% 51% 58% 13.0%
97% 74% 54% 60% 19.5%
0.843 0.388 0.910 0.972 ⬍0.0005
Data are expressed as mean ⫾ SD or as percentages. * Trend p values. ACE ⫽ angiotensin-converting enzyme inhibitors; ARB ⫽ angiotensin receptor blockers.
Baseline characteristics are summarized using frequencies and percentages for categorical variables and means and SDs (or medians and interquartile ranges [IQRs]) for continuous variables. A multivariate Cox proportional-hazards analysis was performed to test if systolic BP, diastolic BP, and pulse pressure (systolic BP ⫺ diastolic BP) were associated with mortality. This was done after confirming the proportionality of the hazards (death) along the 5-year follow-up period. Systolic and diastolic BP were entered into the models as continuous variables by themselves and after squaring. This was done to explore for a J-shaped relation. In all models, adjustments were made for GRACE hospital discharge risk score. Interactions between BP and in-hospital revascularization were explored. Because discharge medications, including aspirin,  blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins, would have prognostic effects,12 they were also entered into the model. Survival curves according to diastolic BP and adjusted for all significant predictors were generated. C indexes were calculated in all logistic regression models on 6-month, 12-month, and 2-year survival.8 Of 1,143 consecutive patients with ACS, including 446 with ST elevation myocardial infarctions, 450 with non–ST elevation myocardial infarctions, and 247 with unstable angina pectoris, the 1,057 hospital survivors (mean age 64.9 ⫾ 12.6 years, 63% men) formed the study cohort. Survival status was available for all at 2 years, for 82% at 3 years, and for 54% at 4 years of follow-up (median follow-up time 43 months, IQR 32 to 53). Four patients had missing data on diastolic BP. The mean last recorded systolic BP before discharge was 122.1 ⫾ 18.6 mm Hg (median 120, IQR 110 to 132), the mean last recorded diastolic BP was 67.5 ⫾ 11.6 mm Hg (median 70, IQR 60 to 75), and the mean pulse pressure was 54.9 ⫾ 15.4 mm Hg (median 52, IQR 44 to 64). Table 1 shows the characteristics of the 1,053 patients and 2-year mortality according to diastolic BP at discharge (⬎80, 70 to ⬍80, 60 to ⬍70, and ⬍60 mm Hg). Patients with lower diastolic BPs had higher GRACE scores and higher 2-year mortality (8.5%, 8.7%, 13.0%, and 19.5%, respectively, p ⬍0.0005).
Figure 1. Adjusted survival curves according to diastolic BP at discharge.
When BP parameters were modeled with GRACE score in predicting survival, only diastolic BP was significant. Neither pulse pressure nor systolic BP was a predictor in any model (p ⬎0.2). When cardioprotective medications and revascularization were incorporated into the model, the independent predictors of survival included lower GRACE score, higher diastolic BP, and the use of  blockers and statins. The square term for diastolic BP was also significant in the mortality model. There was no interaction between diastolic BP and in-hospital revascularization in the mortality model. The survival curve showing the effect of different diastolic BP on mortality adjusted to other prognostic factors is shown in Figure 1. Adding diastolic BP to GRACE score tended to improve the C index for predicting 6-, 12-, and 24-month survival (p ⫽ 0.14, 0.07, and 0.09, respectively). Discussion The present study provides information on the link between diastolic BP and survival up to 5 years after ACS. The poorer prognosis from lower diastolic BP was consistent
Coronary Artery Disease/BP After ACS and Survival
with the Framingham data2 in patients of similar age range and the INVEST data in patients of similar age range and with concomitant stable coronary disease.3 Lower diastolic BP can reflect more advanced arteriosclerosis2 or a lower left ventricular ejection fraction, although this was not analyzed in INVEST or the present study. The significance of the square term for diastolic BP indicated a reverse-J-shaped effect: although higher diastolic BP was associated with better outcomes, no further benefit was seen when diastolic BP was ⬎90 mm Hg, as shown in Figure 1. The present cohort was undersized to determine the exact diastolic BP value at which the relation with survival changed. In patients with stable coronary disease, an exploratory analysis3 of INVEST, a 22,576patient study, found that the risk for death and for myocardial infarction progressively increased with lower diastolic BP beyond 84 mm Hg. In INVEST, an interaction between diastolic BP and revascularization was observed. Low diastolic BP was associated with a relatively lower risk for the primary outcome (death, nonfatal stroke, and nonfatal myocardial infarction) in patients with revascularization than in those without revascularization.3 This may reflect poorer myocardial perfusion from lower diastolic BP in patients with coronary stenoses. The present study of 1,053 patients with ACS did not find any interaction. It is possible that patients with lower diastolic BP were in poorer general health, including anemia, malnutrition, and other factors not captured by our data. Also, the GRACE discharge risk score is a simple bedside algorithm that does not incorporate results from imaging, including ejection fraction measurements. Its simplicity, however, underpins its clinical utility. Future prospective studies should evaluate the additional contribution from BP parameters to the GRACE score. In conclusion, the present study established the prognostic relation between diastolic BP and survival after ACS independent of the use of cardioprotective medications.12 and the GRACE discharge risk score.8 1. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Rocella EJ. The
2.
3.
4.
5. 6.
7.
8.
9.
10.
11.
12.
1241
seventh report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. The JNC 7 report. JAMA 2003;289:2560 –2572. Franklin SS, Larson MG, Khan SA, Wong ND, Leip EP, Kanel WB, Levy D. Does the relation of blood pressure to coronary heart disease risk changes with aging? The Framingham heart study. Circulation 2001;103:1245–1249. Messerli FH, Mancia G, Conti CR, Hewkin AC, Kupfer S, Champion A, Kolloch R, Benetos A, Pepine CJ. Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med 2006;144:884 – 893. Amar J, Chamontin B, Ferrieres J, Danchin N, Grenier O, Cantet C, Cambou JP. Hypertension control at hospital discharge after acute coronary event: influence on cardiovascular prognosis—the PREVENIR study. Heart 2002;88:587–591. Wong CK, White HD. Relationship between blood pressure after an acute coronary event and subsequent cardiovascular risk. Heart 2002; 88:555–558. Rosendorff C, Black HR, Cannon CP, Gersh BJ, Gore J, Izzo JL, Kaplan NM, O’Connor CM, O’Gara PT, Opail S. Treatment of hypertension in the prevention and management of ischemic heart disease: a scientific statement from the American Heart Association Council for High Blood Pressure Research and the Council on Clinical Cardiology and Epidemiology and Prevention. Circulation 2007;115: 2761–2788. The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension and European Society of Cardiology. 2007 guidelines for the management of arterial hypertension. J Hypertens 2007;25:1105–1187. Tang EW, Wong CK, Herbison P. GRACE hospital discharge risk score accurately predicts long-term mortality post acute coronary syndrome [published correction appears in Am Heart J 2007;154:851]. Am Heart J 2007;153:29 –35. Smith SC, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, Grundy SM, Hiratzka L, Jones D, Krumholz HM, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update. J Am Coll Cardiol 2006;47:2130 –2139. Tang EW, Wong CK, Herbison P. Community hospital versus tertiary hospital comparison in the treatment and outcome of patients with acute coronary syndrome: a New Zealand experience. N Z Med J 2006;119:U2078. Eagle KA, Lim MJ, Dabbous OH, Pieper KS, Goldberg RJ, Van de Werf F, Goodman SG, Granger CB, Steg PG, Gore JM, et al. A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month post-discharge death in an international registry. JAMA 2004;291:2727–2733. Wong CK, Tang EW, Herbison P. The use of different evidence-based medications and 5-year survival after an acute coronary syndrome: an observational study. Int J Cardiol. Epub 2008. DOI: 10.1016/j. ijcard.2007.11.05.