278 Plasma PCSK9 Levels Do Not Predict Angiographic Coronary Artery Disease But Associate With The Risk Of Myocardial Infarction In Women Independent Of LDL Cholesterol

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Abstracts

rescue PCI procedures into the CCN cardiac registry. In addition, CCN concurrently implemented quality assurance and follow up processes to ensure accuracy and completeness of the submitted data. Preliminary results would be used to define baseline performance and benchmark for quality improvement initiatives. RESULTS: For the baseline reporting time period (June 2010 March 2012), the CCN registry had a total of 8,343 patient records: 6,558 pPCI; 674 Rescue PCI and 1,111 Pharmacoinvasive PCI. The median provincial door-to-balloon time for pPCI field transfers, walk-ins and non-PCI hospitals transfers was 86 minutes (IQR: 54-118). In total, 78% of field transfers and walk-ins to a PCI centre achieved 90 minute benchmark and 60% of transfers from non-PCI hospital achieved the 120 minute benchmark. For pharmacoinvasive and rescue patients (treated with fibrinolysis as their initial reperfusion therapy) the median door-to-needle time was 29 minutes (IQR: 18-50). In February, 2012 CCN launched a comprehensive baseline pPCI report distributed to each PCI hospital to share hospital and provincial results, and provide performance feedback and benchmarking to inform ongoing quality improvement processes. CONCLUSION: Through this initiative, CCN has developed a foundation for the provision of pPCI performance feedback to support ongoing quality improvement. We identified early targets to enhance quality, including improving door-to-balloon times for transfers from non-PCI hospitals, and field transfers and walk ins. Formalized data collection and provincial reporting processes contributes to enhanced quality of care through the adoption of standard key performance metrics, data definitions and benchmarking between programs. This allows for ongoing monitoring, reporting and feedback to identify trends from baseline and support ongoing quality improvement. Canadian Cardiovascular Society (CCS) CCS147 Poster CAD ACS & AMI MONDAY POSTERS II Monday, October 29, 2012 277 DILTIAZEM ATTENUATES CARDIOVASCULAR TOXICITIES AND REDUCES MORTALITY INDUCED BY ISOPROTERENOL IN A FREELY MOVING RAT MODEL IN VIVO PK Yeung, D Seeto Halifax, Nova Scotia BACKGROUND: Diltiazem (DTZ) is proven effective for hypertension and angina and has potential also for management of ischemic heart disease. We investigated in this study its cardiovascular protective effect against injury induced by isoproterenol using a freely moving rat model in vivo. METHODS: Sprague Dawley (SD) rats weighing between 250 and 300g were each injected subcutaneously (sc) with either 5 or 10 mg/kg of DTZ (n ⫽ 6 in each group), or saline as control (n ⫽ 10) twice daily for 4 doses. One hour after the last injec-

tion, a single dose of isoproterenol (30 mg/kg) was injected sc to each rat. Blood samples were collected at 0, 0.05, 0.25, 1, 1.2, 1.5, 2, 3, 4, 5 and 6 hours for measurement of adenine nucleotides (ATP, ADP and AMP) by a validated HPLC. Hemodynamic recording (SBP, DBP, and HR) were collected for the duration of the experiment. Differences between groups were considered significant at p ⬍ 0.05 (t-test). RESULTS: Isoproterenol induced 50% mortality within 5 hours after injection in the control rats (p ⬍ 0.05). It decreased SBP and DBP immediately after the injection (⬍ 15 min) by ⫺64 ⫾ 20 and ⫺61 ⫾ 19 mmHg, respectively, but increased HR by ⫹70 ⫾ 53 bpm which was further increased to ⫹157 ⫾ 56 bpm by the end of the experiment (p ⬍ 0.05). Both SBP and DBP were rebounded to pre-treatment level after 1-2 hours after injection (p ⬍ 0.05), and then continued to fall for the remaining of the experiment. Isoproterenol also increased RBC concentrations of AMP from 0.04 ⫾ 0.02 to 0.29 ⫾ 0.21 mM at the end of the experiment (p ⬍ 0.05). The rats that died had greater increase of the AMP concentration than the surviving ones. Treatment with 10 mg/kg of DTZ reduced mortality from 50% to ⬍20%, and the immediate fall of SBP from ⫺64 to ⫺40 mmHg and DBP from ⫺61 to ⫺37 mmHg (p ⬍ 0.05). RBC concentrations of AMP were also reduced after DTZ from ⫹0.25 to ⫹0.08 mM (68% reduction) (p ⬍ 0.05). There was no protection after the 5 mg/kg DTZ dose. CONCLUSION: DTZ (10 mg/kg) significantly reduces mortality, RBC concentrations of AMP and cardiovascular toxicity induced by isoproterenol. CIHR, NSHRF, DPEF

278 PLASMA PCSK9 LEVELS DO NOT PREDICT ANGIOGRAPHIC CORONARY ARTERY DISEASE BUT ASSOCIATE WITH THE RISK OF MYOCARDIAL INFARCTION IN WOMEN INDEPENDENT OF LDL CHOLESTEROL NA Almontashiri, M Fan, H Chen, GA Wells, R Roberts, AF Stewart Ottawa, Ontario BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the LDL-receptor (LDL-R) and causes it to be degraded, leading to elevation in plasma low density lipoprotein cholesterol (LDL-C). Statins, while lowering LDL-C, increase plasma PCSK9 levels. Current clinical trials are targeting PCSK9 interaction with the LDL-R to further lower LDL-C in patients taking a statin. Mutations that prevent secretion of PCSK9 are associated with a 30-40% reduction in LDL-C but a surprising 88% reduction in events associated with coronary artery disease (CAD), suggesting that plasma PCSK9 may have additional risk effects beyond LDL-C. METHODS: Plasma PCSK9 levels were measured by ELISA in 652 angiographically defined controls (less than 30% coronary stenosis) age and sex matched to 1297 cases of CAD (more than 50% stenosis in a major coronary artery) selected from 5,211 subjects of the Ottawa Heart Genomics Study.

S196 RESULTS: Multivariate analysis revealed higher PCSK9 levels in

women, in CAD cases and with statin use. Among individuals taking a statin, PCSK9 levels were higher in CAD cases than controls, likely due to higher statin dose or compliance among CAD cases. Surprisingly, for individuals not taking a statin (405 CAD cases and 285 controls), plasma PCSK9 levels were not associated with angiographically defined CAD. Importantly, in women not taking a statin, elevated plasma PCSK9 levels were associated with increased incidence of myocardial infarction (MI) without elevating LDL-C. CONCLUSION: Our study is the first to document a direct association between increased plasma PCSK9 levels and the risk of MI in women independent of the known effect of PCSK9 on LDL-C. Our study cautions against the use of antibodies to block PCSK9 interaction with the LDL-R to further lower LDL-C, currently in clinical trials. Since degradation with the LDL-R is one of the main PCSK9 clearance mechanisms, this approach would elevate plasma PCSK9 and potentially increase the risk of MI, particularly in women. CIHR

279 MANAGEMENT AND OUTCOMES OF NON-ST ELEVATION ACUTE CORONARY SYNDROMES IN RELATION TO PRIOR USE OF ANTI-ANGINAL THERAPIES JS Kang, SG Goodman, RT Yan, J Lopez-Sendon, Y Pesant, JJ Graham, D Fitchett, GC Wong, BF Rose, FA Spencer, AT Yan Toronto, Ontario

Randomized trials have established the efficacy of anti-anginal medications in the treatment of chronic stable coronary disease. The objective of this study was to examine the relationships between chronic treatment with these agents and the clinical presentation, in-hospital management and shortterm outcomes of patients across the spectrum of non-ST-elevation acute coronary syndromes (NSTE-ACS). METHODS: Using data from the Global Registry of Acute Coronary Events (GRACE) and Canadian Registry of Acute Coronary Events (CANRACE), we stratified patients with NSTE-ACS according to the use of anti-anginal therapies (beta-blockers [BB], calcium channel blockers [CCB], and nitrates) prior to presentation, compared their clinical characteristics on presentation, in-hospital management and outcomes. We performed multivariable analysis to examine the independent association between prior use of anti-anginal therapies and coronary angiography during index hospitalization. RESULTS: Of the 10,019 patients with NSTE-ACS, 45.9%, 28.3% and 25.8% were on no, 1, and ⱖ 2 anti-anginal therapies, respectively, prior to ACS presentation. The most commonly used anti-anginal agents were BB, used in 39.3% of patients, followed by nitrates in 24.4% and CCB in 23.6%. Compared to patients not on any anti-anginal therapy prior to presentation, those on treatment were more likely to be older, female, and to have hypertension, diabetes, previous angina,

Canadian Journal of Cardiology Volume 28 2012

stroke, myocardial infarction, PCI and CABG (all p⬍ 0.001); and were less likely to present with positive biomarker (p ⬍ 0.001). In-hospital management and outcomes are summarized in the Table.

In multivariable analysis, prior use of anti-anginal therapies was independently associated with a lower use of coronary angiography in hospital (adjusted OR⫽0.84, 95% CI 0.71-0.99, p⫽0.034). CONCLUSIONS: Patients receiving anti-anginal therapy prior to presentation of NSTE-ACS were older and more frequently had pre-existing cardiovascular disease and previous revascularization. They had higher unadjusted rates of heart failure and recurrent angina, but a lower rate of myocardial (re-)infarction during index hospitalization, compared to their counterparts who were not on prior anti-anginal therapy. Prior treatment with anti-anginal agents is independently associated with a lower use of coronary angiography in hospital.

BACKGROUND:

280 REAL-WORLD MANAGEMENT AND OUTCOMES OF PATIENTS WITH SUSPECTED ACUTE CORONARY SYNDROMES IN RELATION TO INITIAL DIAGNOSTIC IMPRESSIONS: INSIGHTS FROM THE CANADIAN GRACE AND CANRACE STUDIES R Bajaj, SG Goodman, RT Yan, AJ Bagnall, G Gyenes, RC Welsh, KA Eagle, D Brieger, K Ramanathan, FR Grondin, AT Yan Toronto, Ontario BACKGROUND: Despite detailed history, ECG, and sensitive biomarkers, early diagnosis of acute coronary syndrome (ACS) remains challenging and a considerable proportion of patients are diagnosed with “possible” ACS on admission. We sought to examine the clinical characteristics, management patterns, predictive accuracy of the GRACE risk score, and outcomes in relation to “definite” versus “possible” ACS diagnosis at hospital admission. METHODS: The Global Registry of Acute Coronary Events (GRACE/ GRACE2) and Canadian Registry of Acute Coronary Events (CANRACE) enrolled 16,618 patients with suspected ACS from 1999 to 2008. Patients were classified into two groups: “possible” versus “definite” ACS according to the treating physician. We compared demographic and clinical characteristics, use of cardiac procedures, prognostic accuracy