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Carotid Intima-media Thickness can Predict Coronary Artery Plaque Severity and Composition in Asymptomatic Patients at Intermediate Risk for Coronary Artery Disease
CSANZ 2012 Abstracts
S31
72
73
Cardiac Troponin Levels in the Elderly—Time to Re-think Threshold Levels?
Cardioprotection from Ischaemia and Reperfusion Injury by a Novel Synthetic Flavonol is Prevented by Treatment with PD98059, but not with LY294002
I. Webb 1,2,∗ , S. Yam 1 , R. Cooke 3 , A. Aitkin 1,2 , P. Larsen 1,4 , S. Harding 1,2 1 Wellington Cardiovascular Research Group, Wellington, New
Zealand 2 Cardiology Department, Wellington Hospital, Wellington, New Zealand 3 Laboratory Sciences, Wellington Hospital, Wellington, New Zealand 4 Department of Surgery and Anaesthesia, University of Otago, Wellington, New Zealand Background: High-sensitivity troponin T (hs-TnT) is commonly used in the diagnosis of myocardial infarction (MI). However, factors other than ischaemia are increasingly recognised to influence baseline hs-TNT and this is of particular importance in avoiding inappropriate “rule in” or delayed “rule out” of MI. We sought to determine the impact of increasing age on baseline hs-TnT levels. Methods: Data on all patients with hs-TnT measurements in our Emergency Department over an eight-month period between 2010 and 2011 were reviewed. Those with a clinical suspicion of ACS, a significant rise or fall in hs-TnT or those other acute illnesses known to elevate hs-TnT were excluded. Demographics, clinical details and laboratory investigations were obtained from the medical records. Results: Of 3219 patients with hs-TnT measurements taken, 615 were excluded because of suspected ACS and 1287 for other reasons, including impaired renal function (eGFR <45 ml/h/m2 ), arrhythmia, sepsis and acute heart failure. Of the remaining 1317 patients, 39.6% were male and the median age was 63 years (16–101). Multivariate analysis identified increasing age (p < 0.001) as the strongest independent predictor of elevated hs-TnT. Other independent predictors included prior myocardial infarction (p = 0.01), atrial fibrillation (p < 0.001), gender (p < 0.0001), smoking (p = 0.04), renal dysfunction (p < 0.0001) and hypertension (p < 0.005). Conclusion: Our data suggest increasing age is independently associated with elevated levels of hs-TnT. Elderly patients without myocardial infarction commonly have hsTnT levels above the currently recommended upper limit of normal. It may therefore be necessary to define age specific upper limits of normal for hs-TnT. http://dx.doi.org/10.1016/j.hlc.2012.05.082
C. Thomas 1,∗ , D. Ng 2 , A. Kedikaetswe 3 , C. May 3 1 La
Trobe University, Australia of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Australia 3 Florey Neuroscience Institutes, Parkville, Australia 2 Department
We examined the roles of the MEK/ERK1/2 and PI3K/Akt arms of the reperfusion injury survival kinases (RISK) pathway in mediating the cardioprotective actions of NP202, a novel water soluble pro-drug of 3 ,4 dihydroxyflavonol, against ischaemia-reperfusion injury. In anesthetised sheep, the left anterior descending coronary artery was occluded for 1 h, followed by 3 h of reperfusion. At 10 min before reperfusion, sheep were treated with a MEK inhibitor, PD98059 (4 mg bolus then 8 mg over 1 h, IV), or a PI3K inhibitor, LY294002 (4 mg bolus then 10 mg over 1 h, IV), followed 5 min before reperfusion by vehicle or NP202 (6.6 mg/kg, IV). At the end of reperfusion infarct size was measured, and tissue from the normal left ventricle, non-infarcted area-at-risk (NAR), and infarcted myocardium were collected to assess activation of mitogen-activated protein kinase pathways by Western blot analysis. Infarct area was 78 ± 6% of the area at risk with vehicle treatment, and was reduced by NP202 (46 ± 4%, P < 0.05). PD98059, but not LY294002, abolished this cardioprotective effect of NP202. After reperfusion, expression of phosphorylated ERK1/2 (normalised to total ERK), compared with normal left ventricle (0.95 ± 0.32), was increased in the NAR (11.7 ± 2.1) and infarct area (10.4 ± 3.5), and was increased further in the NAR by NP202 (25.6 ± 6.9, P < 0.05). NP202 did not increase levels of phosphorylated Akt. In isolated myocytes, treatment with NP202 activated ERK1/2. In conclusion, these findings indicate that selective inhibition of the ERK1/2 arm, but not the PI3K/AKT arm, of the RISK pathway, by NP202, leads to cardioprotection against reperfusion injury. http://dx.doi.org/10.1016/j.hlc.2012.05.083 74 Carotid Intima-media Thickness can Predict Coronary Artery Plaque Severity and Composition in Asymptomatic Patients at Intermediate Risk for Coronary Artery Disease A. Ellims 1,2,∗ , P. Lew 1,2 , A. Taylor 1,2 1 The
Alfred Hospital, Melbourne, Australia IDI Heart and Diabetes Research Institute, Melbourne, Australia
2 Baker
Background: The optimal management of asymptomatic patients at intermediate risk for coronary artery disease (CAD) is not clearly established. Furthermore, many of these patients have no discernible coronary atherosclerosis. We utilised coronary CT angiography (CCTA) to evaluate coronary artery atheroma in this risk
ABSTRACTS
Heart, Lung and Circulation 2012;21:S1–S142
S32
Heart, Lung and Circulation 2012;21:S1–S142
CSANZ 2012 Abstracts
ABSTRACTS
group and determined whether surrogate markers of CAD can predict plaque severity and composition. Methods: We performed 64-slice CCTA on 100 asymptomatic subjects (86% male, mean age 61 ± 6 years) at intermediate CAD risk according to the Framingham cardiovascular risk score. CAD severity was graded as normal, non-obstructive (i.e. <50% stenosis), one-, two- or three-vessel disease. Plaque composition was classified as non-calcified, mixed or calcified. Surrogate markers of CAD risk included: brachial-ankle pulse wave velocity; ankle-brachial index; carotid intima-media thickness (CIMT); lipoprotein(a); and high-sensitivity CRP. Results: Coronary artery plaque was identified by CCTA in 83 patients – 24 patients had at least one obstructive plaque and non-calcified plaque was detected in 64 patients. CIMT correlated with CAD severity (r = 0.24, p = 0.02) and was also higher in patients with noncalcified plaque compared to those without (0.74 ± 0.15 vs. 0.68 ± 0.14 mm, p = 0.03). There were no associations observed between Framingham risk score or other surrogate markers of CAD and subclinical coronary atherosclerosis. Conclusions: Most patients at intermediate risk of CAD have coronary atherosclerosis, although the pattern of disease varies greatly. CIMT may improve the risk stratification of these patients be predicting both the severity and composition of coronary plaque. http://dx.doi.org/10.1016/j.hlc.2012.05.084 75 Characteristics of Aortic Wall Extracellular Matrix in Patients with Acute Myocardial Infarction: Tissue Microarray Detection of Collagen I, Collagen III and Elastin Levels C. Kong ∗ , X. Lin, C. Woo, C. Lee, M. Richards, H. Wong, V. Sorokin National University Health System, Australia Extracellular matrix (ECM) remodelling of the vessel wall is hypothesised to be an important step in atherosclerosis. Changes of ECM are associated with the gradual progression of atherosclerotic lesion from lipid streak to complicated unstable plaque, leading to a complete vessel occlusion and eventually myocardial infarction (MI). Understanding of this process is critical in the treatment and prevention of ischaemic heart disease (IHD). We investigated the histopathological characteristics of aortic wall ECM in IHD patients. Collagen I, collagen III and elastin were assessed immunohistochemically in patients with acute MI and patients with stable angina, using aortic punch tissues obtained from coronary artery bypass graft surgery. Fluorescence tissue images were analysed using tissue microarray technique. The results showed that collagen III expression was found to be significantly lower in acute MI group (p < 0.001). As a result of this change, patients with MI also revealed significant reduction in collagen III/collagen I ratio. The elastin/collagen III ratio was significantly higher in the MI group (p < 0.001). Our study
provided evidence of decrease in collagen III content in patients with MI, which could possibly explain the mechanism of plaque vulnerability and weakening of plaque cap. A reduction in collagen III content, especially away from the atherosclerotic lesions, might be explained by the systemic vascular changes in patients with MI and inflammation and immune responses could be a potential cause of these systemic transformation. The biochemical mechanisms and factors regulating collagen III production might be potential markers to predict possible cardiovascular events. http://dx.doi.org/10.1016/j.hlc.2012.05.085 76 Clinical Outcomes in the First Year after Small versus Large Heart Attacks R. Lane 2 , D. Smyth 1 , J. Elliott 1,2,∗ 1 Dept
Cardiology, Christchurch Hospital, New Zealand Medicine, University of Otago Christchurch, Christchurch, New Zealand
2 Dept
Background: We have documented improving one year outcomes after treatment of acute myocardial infarction (AMI) over the last 15 years at our hospital. It is not known if this is due to changes in the diagnosis of AMI, and inclusion of patients with minor biomarker elevations. Methods: Retrospective audit of consecutive AMI patients admitted to the Cardiology Dept from October 1 to December 31 2010. Baseline characteristics, in-hospital investigations, discharge medications and one year outcomes were recorded. Patients were grouped according to peak TnI and CK levels and one year outcomes were assessed. Results: Both TnI and CK were measured in 168 of 182 consecutive patients admitted to cardiology with AMI. One hundred percent of 26 patients with a TnI < 0.3 had a NSTEMI, compared to 88% of 53 with a TnI > 0.3 and CK < 300/350, and 37% of 89 with a CK > 300/350 (twice upper limit of normal in women and men, respectively). Mean age was 69 years in those with TNI < 0.03, 66 years in those with TNI > 0.3, and 61 years in those with CK > 300/350, an echocardiogram was performed in 54%, 82% and 89%, angiography was performed in 74%, 87% and 97%, and revascularisation in 44%, 76% and 92%, respectively. Discharge medications were very similar between groups. At one year, cumulative death rates were 19%, 2% and 9% (p = 0.036) and death or AMI had occurred in 26%, 9% and 10%, respectively (p = 0.067). Conclusion: Small elevations in TNI are associated with higher rather than lower risks of death and death or reinfarction at one year compared with patients with larger rises in biomarkers. http://dx.doi.org/10.1016/j.hlc.2012.05.086
S31
72
73
Cardiac Troponin Levels in the Elderly—Time to Re-think Threshold Levels?
Cardioprotection from Ischaemia and Reperfusion Injury by a Novel Synthetic Flavonol is Prevented by Treatment with PD98059, but not with LY294002
I. Webb 1,2,∗ , S. Yam 1 , R. Cooke 3 , A. Aitkin 1,2 , P. Larsen 1,4 , S. Harding 1,2 1 Wellington Cardiovascular Research Group, Wellington, New
Zealand 2 Cardiology Department, Wellington Hospital, Wellington, New Zealand 3 Laboratory Sciences, Wellington Hospital, Wellington, New Zealand 4 Department of Surgery and Anaesthesia, University of Otago, Wellington, New Zealand Background: High-sensitivity troponin T (hs-TnT) is commonly used in the diagnosis of myocardial infarction (MI). However, factors other than ischaemia are increasingly recognised to influence baseline hs-TNT and this is of particular importance in avoiding inappropriate “rule in” or delayed “rule out” of MI. We sought to determine the impact of increasing age on baseline hs-TnT levels. Methods: Data on all patients with hs-TnT measurements in our Emergency Department over an eight-month period between 2010 and 2011 were reviewed. Those with a clinical suspicion of ACS, a significant rise or fall in hs-TnT or those other acute illnesses known to elevate hs-TnT were excluded. Demographics, clinical details and laboratory investigations were obtained from the medical records. Results: Of 3219 patients with hs-TnT measurements taken, 615 were excluded because of suspected ACS and 1287 for other reasons, including impaired renal function (eGFR <45 ml/h/m2 ), arrhythmia, sepsis and acute heart failure. Of the remaining 1317 patients, 39.6% were male and the median age was 63 years (16–101). Multivariate analysis identified increasing age (p < 0.001) as the strongest independent predictor of elevated hs-TnT. Other independent predictors included prior myocardial infarction (p = 0.01), atrial fibrillation (p < 0.001), gender (p < 0.0001), smoking (p = 0.04), renal dysfunction (p < 0.0001) and hypertension (p < 0.005). Conclusion: Our data suggest increasing age is independently associated with elevated levels of hs-TnT. Elderly patients without myocardial infarction commonly have hsTnT levels above the currently recommended upper limit of normal. It may therefore be necessary to define age specific upper limits of normal for hs-TnT. http://dx.doi.org/10.1016/j.hlc.2012.05.082
C. Thomas 1,∗ , D. Ng 2 , A. Kedikaetswe 3 , C. May 3 1 La
Trobe University, Australia of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Australia 3 Florey Neuroscience Institutes, Parkville, Australia 2 Department
We examined the roles of the MEK/ERK1/2 and PI3K/Akt arms of the reperfusion injury survival kinases (RISK) pathway in mediating the cardioprotective actions of NP202, a novel water soluble pro-drug of 3 ,4 dihydroxyflavonol, against ischaemia-reperfusion injury. In anesthetised sheep, the left anterior descending coronary artery was occluded for 1 h, followed by 3 h of reperfusion. At 10 min before reperfusion, sheep were treated with a MEK inhibitor, PD98059 (4 mg bolus then 8 mg over 1 h, IV), or a PI3K inhibitor, LY294002 (4 mg bolus then 10 mg over 1 h, IV), followed 5 min before reperfusion by vehicle or NP202 (6.6 mg/kg, IV). At the end of reperfusion infarct size was measured, and tissue from the normal left ventricle, non-infarcted area-at-risk (NAR), and infarcted myocardium were collected to assess activation of mitogen-activated protein kinase pathways by Western blot analysis. Infarct area was 78 ± 6% of the area at risk with vehicle treatment, and was reduced by NP202 (46 ± 4%, P < 0.05). PD98059, but not LY294002, abolished this cardioprotective effect of NP202. After reperfusion, expression of phosphorylated ERK1/2 (normalised to total ERK), compared with normal left ventricle (0.95 ± 0.32), was increased in the NAR (11.7 ± 2.1) and infarct area (10.4 ± 3.5), and was increased further in the NAR by NP202 (25.6 ± 6.9, P < 0.05). NP202 did not increase levels of phosphorylated Akt. In isolated myocytes, treatment with NP202 activated ERK1/2. In conclusion, these findings indicate that selective inhibition of the ERK1/2 arm, but not the PI3K/AKT arm, of the RISK pathway, by NP202, leads to cardioprotection against reperfusion injury. http://dx.doi.org/10.1016/j.hlc.2012.05.083 74 Carotid Intima-media Thickness can Predict Coronary Artery Plaque Severity and Composition in Asymptomatic Patients at Intermediate Risk for Coronary Artery Disease A. Ellims 1,2,∗ , P. Lew 1,2 , A. Taylor 1,2 1 The
Alfred Hospital, Melbourne, Australia IDI Heart and Diabetes Research Institute, Melbourne, Australia
2 Baker
Background: The optimal management of asymptomatic patients at intermediate risk for coronary artery disease (CAD) is not clearly established. Furthermore, many of these patients have no discernible coronary atherosclerosis. We utilised coronary CT angiography (CCTA) to evaluate coronary artery atheroma in this risk
ABSTRACTS
Heart, Lung and Circulation 2012;21:S1–S142
S32
Heart, Lung and Circulation 2012;21:S1–S142
CSANZ 2012 Abstracts
ABSTRACTS
group and determined whether surrogate markers of CAD can predict plaque severity and composition. Methods: We performed 64-slice CCTA on 100 asymptomatic subjects (86% male, mean age 61 ± 6 years) at intermediate CAD risk according to the Framingham cardiovascular risk score. CAD severity was graded as normal, non-obstructive (i.e. <50% stenosis), one-, two- or three-vessel disease. Plaque composition was classified as non-calcified, mixed or calcified. Surrogate markers of CAD risk included: brachial-ankle pulse wave velocity; ankle-brachial index; carotid intima-media thickness (CIMT); lipoprotein(a); and high-sensitivity CRP. Results: Coronary artery plaque was identified by CCTA in 83 patients – 24 patients had at least one obstructive plaque and non-calcified plaque was detected in 64 patients. CIMT correlated with CAD severity (r = 0.24, p = 0.02) and was also higher in patients with noncalcified plaque compared to those without (0.74 ± 0.15 vs. 0.68 ± 0.14 mm, p = 0.03). There were no associations observed between Framingham risk score or other surrogate markers of CAD and subclinical coronary atherosclerosis. Conclusions: Most patients at intermediate risk of CAD have coronary atherosclerosis, although the pattern of disease varies greatly. CIMT may improve the risk stratification of these patients be predicting both the severity and composition of coronary plaque. http://dx.doi.org/10.1016/j.hlc.2012.05.084 75 Characteristics of Aortic Wall Extracellular Matrix in Patients with Acute Myocardial Infarction: Tissue Microarray Detection of Collagen I, Collagen III and Elastin Levels C. Kong ∗ , X. Lin, C. Woo, C. Lee, M. Richards, H. Wong, V. Sorokin National University Health System, Australia Extracellular matrix (ECM) remodelling of the vessel wall is hypothesised to be an important step in atherosclerosis. Changes of ECM are associated with the gradual progression of atherosclerotic lesion from lipid streak to complicated unstable plaque, leading to a complete vessel occlusion and eventually myocardial infarction (MI). Understanding of this process is critical in the treatment and prevention of ischaemic heart disease (IHD). We investigated the histopathological characteristics of aortic wall ECM in IHD patients. Collagen I, collagen III and elastin were assessed immunohistochemically in patients with acute MI and patients with stable angina, using aortic punch tissues obtained from coronary artery bypass graft surgery. Fluorescence tissue images were analysed using tissue microarray technique. The results showed that collagen III expression was found to be significantly lower in acute MI group (p < 0.001). As a result of this change, patients with MI also revealed significant reduction in collagen III/collagen I ratio. The elastin/collagen III ratio was significantly higher in the MI group (p < 0.001). Our study
provided evidence of decrease in collagen III content in patients with MI, which could possibly explain the mechanism of plaque vulnerability and weakening of plaque cap. A reduction in collagen III content, especially away from the atherosclerotic lesions, might be explained by the systemic vascular changes in patients with MI and inflammation and immune responses could be a potential cause of these systemic transformation. The biochemical mechanisms and factors regulating collagen III production might be potential markers to predict possible cardiovascular events. http://dx.doi.org/10.1016/j.hlc.2012.05.085 76 Clinical Outcomes in the First Year after Small versus Large Heart Attacks R. Lane 2 , D. Smyth 1 , J. Elliott 1,2,∗ 1 Dept
Cardiology, Christchurch Hospital, New Zealand Medicine, University of Otago Christchurch, Christchurch, New Zealand
2 Dept
Background: We have documented improving one year outcomes after treatment of acute myocardial infarction (AMI) over the last 15 years at our hospital. It is not known if this is due to changes in the diagnosis of AMI, and inclusion of patients with minor biomarker elevations. Methods: Retrospective audit of consecutive AMI patients admitted to the Cardiology Dept from October 1 to December 31 2010. Baseline characteristics, in-hospital investigations, discharge medications and one year outcomes were recorded. Patients were grouped according to peak TnI and CK levels and one year outcomes were assessed. Results: Both TnI and CK were measured in 168 of 182 consecutive patients admitted to cardiology with AMI. One hundred percent of 26 patients with a TnI < 0.3 had a NSTEMI, compared to 88% of 53 with a TnI > 0.3 and CK < 300/350, and 37% of 89 with a CK > 300/350 (twice upper limit of normal in women and men, respectively). Mean age was 69 years in those with TNI < 0.03, 66 years in those with TNI > 0.3, and 61 years in those with CK > 300/350, an echocardiogram was performed in 54%, 82% and 89%, angiography was performed in 74%, 87% and 97%, and revascularisation in 44%, 76% and 92%, respectively. Discharge medications were very similar between groups. At one year, cumulative death rates were 19%, 2% and 9% (p = 0.036) and death or AMI had occurred in 26%, 9% and 10%, respectively (p = 0.067). Conclusion: Small elevations in TNI are associated with higher rather than lower risks of death and death or reinfarction at one year compared with patients with larger rises in biomarkers. http://dx.doi.org/10.1016/j.hlc.2012.05.086