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Cardiac autonomic dysfunction is associated with altered exercise haemodynamics in patients with type 2 diabetes
Abstracts
S271
620 ATRIAL FIBRILLATION IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION WHICH DOES NOT IMPROVE WITH CARDIOVERSION
621 CALCITONIN RECEPTOR-IMMUNOREACTIVITY ASSOCIATED WITH SPECIFIC CELLS IN DISEASED ARTERIES
Scott R. Willoughby, Christopher X. Wong, Sean Jolly, Anisha Prabhu, Han Sung Lim, Adam J. Nelson, Stephen Worthley, Matthew I. Worthley, Prashanthan Sanders
P.J. Wookey 1,2, , A. Zulli 1,2 , D.L. Hare 1,2
Cardiovascular Research Centre, Department of Cardiology, Royal Adelaide Hospital and the Disciplines of Medicine and Physiology, University of Adelaide, Adelaide, Australia Background: How and why patients with atrial fibrillation (AF) develop atrial thrombus remains to be fully determined. Considerable evidence exists to implicate in part the effect of atrial mechanical remodelling due to arrhythmia. Whether endothelial dysfunction contributes to the heightened risk of thrombus in patients with AF or after cardioversion (CV) is not known. Methods: We studied 14 patients with “lone” persistent AF (mean age 60 ± 4 years: 12 M) undergoing CV and compared them to 14 age and gender matched subjects in sinus rhythm. Endothelial function was assessed using finger peripheral arterial tonometry (PAT) under controlled conditions. Endothelial function, expressed as the reactive hyperaemia response (RHI), was assessed by calculating the ratio of post-occlusion to baseline PAT using the validated EndoPAT 2000 system. This system compensates for systemic changes using simultaneous recordings from the un-occluded contra-lateral finger. Endothelial function was evaluated at baseline in both groups and immediately (2 h) after electrical CV in patients with AF. Results: Compared to the control group patients with AF had significant endothelial dysfunction at baseline as indicated by a lower PAT ratio (1.6 ± 0.1 PAT ratio in AF vs 2.0 ± 0.1 in controls, p < 0.04). There was no difference in endothelial-independent responses between groups. Following successful CV to sinus rhythm AF patients did not show improvement in PAT ratio (1.6 ± 0.1 PAT ratio at baseline vs 1.8 ± 0.2 PAT ratio post-CV, p = 0.12). Conclusion: Patients with “lone” AF demonstrate evidence of endothelial dysfunction with impaired reactive hyperaemia responses compared to controls. There was no immediate improvement in endothelial function with successful CV to sinus rhythm. These findings suggest that endothelial dysfunction may play a role in the risk for thromboembolic complications in AF and after CV. doi:10.1016/j.hlc.2009.05.666
1 Department of Cardiology, Austin Health, University of Melbourne, Melbourne, Australia 2 Department of Medicine, Austin Health, University of Melbourne, Melbourne, Australia
Calcitonin receptor-immunoreactivity (CTR-ir) was investigated in two different contexts of cardiovascular disease, namely, in diseased human arteries and in atherosclerotic arteries from rabbits fed atherogenic diets that included in one group, a regression period for healing. These immunohistochemical studies used anti-CTR antibodies directed against separate epitopes of human CTR. CTR-ir cells have been identified in the pro-monocyte subpopulation in peripheral blood and are derived from bone marrow. In nascent atherosclerotic plaque of rabbits fed an atherogenic diet (0.5% cholesterol/1% methionine for 4 weeks) CTR-ir cells were concentrated in and around the endothelial layer. In more mature plaque, CTR-ir cells integrated into the endothelial layer and formed into foam cells in the neo-intima. In the regression model in which animals were returned to a normal diet for 8 weeks (cholesterol normal), plaque was stabilised and CTR-ir was reduced considerably. In the vasa vasorum of diseased human radial arteries CTR-ir was found in cells located in the endothelial layer and within the surrounding parenchyma, in fibroblast-like cells and smaller round cells. Within the media CTR-ir was found in structures that resembled vessels and were aligned with smooth muscle cells. CTR-ir cells in diseased arteries may play a role in the healing processes of atherosclerotic plaque as expression is found amongst the first recruited cell types which are lost with plaque stabilisation and healing. In more advanced disease in studies with human radial arteries, CTR-ir micro-vessel-like structures course through the media and may represent more irreversible events. Promonocytes may play an important role in these events. doi:10.1016/j.hlc.2009.05.667 622 CARDIAC AUTONOMIC DYSFUNCTION IS ASSOCIATED WITH ALTERED EXERCISE HAEMODYNAMICS IN PATIENTS WITH TYPE 2 DIABETES J.W. Sacre, J.S. Coombes, J.E. Sharman University of Queensland, Brisbane, Australia Purpose: Pts with type 2 diabetes (T2DM) demonstrate a paradoxical reduction in augmentation index (AIx) and an exaggerated central BP response during exercise, which is related to adverse cardiac remodelling. Cardiac autonomic neuropathy (CAN) is a common complication of T2DM, and this study aimed to determine the association of CAN with abnormal exercise haemodynamics in these pts.
ABSTRACTS
Heart, Lung and Circulation 2009;18S:S1–S286
S272
Heart, Lung and Circulation 2009;18S:S1–S286
Abstracts
ABSTRACTS
Table 1. Variable
NORM
ABN
P-value
Resting AIx (%) Exercise AIx (%)
29.0 ± 9.4 21.5 ± 10
25.3 ± 9.0 10.9 ± 9.9
0.37 0.025
Methods: CAN was assessed using heart rate variability (coefficient of variation of RR intervals—CV). Brachial BP was measured using cuff sphygmomanometry, and pulse wave analysis from radial tonometry was used to measure AIx and central BP. All measures were performed at rest and during steady state cycling exercise at 30% HR reserve in 21 apparently healthy pts with T2DM. Pts were separated into normal (NORM, n = 11, 63 ± 8y, 73% male) and impaired (ABN, n = 10, 58 ± 9y, 80% male) autonomic function groups, classified by resting CV. Results: There were no significant group differences in age, gender, HbA1c, resting HR, brachial and central BP, or resting AIx (p > 0.05 for all). Pts in the ABN group had significantly reduced resting CV (2.7 ± 0.6% vs 6.4 ± 2.3%; p < 0.001). Despite no difference between groups in exercise brachial and central BP, exercise AIx was lower in the ABN patients (Table 1). There was also a lower rest to exercise change in CV (−0.9 ± 1.2% vs −3.9 ± 2.5%; p = 0.002) and HR corrected AIx (−3.3 ± 9.8 vs 6.5 ± 6.5%; p = 0.02) in the ABN group. Moreover, exercise AIx was significantly associated with exercise CV (r = 0.47; p = 0.03). Conclusion: Exercise AIx is related to cardiac autonomic function, which may explain the paradoxical reduction of this variable in T2DM pts. doi:10.1016/j.hlc.2009.05.668 623 CARDIOVASCULAR RISK MANAGEMENT AMONG FEMALE AND MALE PATIENTS IN AUSTRALIAN GENERAL PRACTICE: THE AUSHEART STUDY F. Turnbull 1 , H. Arima 1 , E. Heeley 1 , D. Peiris 1 , A. Weekes 2 , C. Morgan 2 , A. Cass 1 , C. Anderson 1 , A. Patel 1 , J. Chalmers 1 1 The George Institute for International Health, Sydney, Australia 2 Servier laboratories, Melbourne, Australia
Objective: To determine whether there are differences in the management of cardiovascular risk between men and women attending Australian General Practices. Methods: The Australian HypErtension and Absolute Risk sTudy (AusHEART) was a nationally representative, cluster-stratified, cross-sectional survey among 322 general practitioners (GPs). Each GP was asked to collect data on cardiovascular risk factors and their management in 15–20 consecutive patients (age ≥55 years) who presented between May and June, 2008. Five-year absolute cardiovascular risk was centrally calculated based on submitted data using an adjusted Framingham risk equation recommended by Australian guidelines.
Results: Of the 5283 patients, 2968 (56%) were female. The proportions of patients classified as being at ‘low’ (<10%), ‘medium’ (10–15%) or ‘high’ (≥15%) absolute risk were 28%, 8% and 41%, respectively for women and 9%, 10%, 43%, respectively for men. Established cardiovascular disease was less frequent among female (23%) compared with male patients (37%; p < 0.0001). Among patients with ‘low’, ‘medium’ and ‘high’ estimated risk of cardiovascular disease, the use of blood pressure lowering therapy, statin therapy and anti-platelet therapy was broadly comparable by sex. However, among patients with established cardiovascular disease, treatment rates were consistently lower for women compared with men; statin therapy (64% vs 74%), antiplatelet therapy (64% vs 74%), combination therapy with blood pressure-lowering and statin (53% vs 64%) and combination of all three therapies (44% vs 56%) (all p < 0.001). Conclusions: Despite similar indications for preventive therapy, there exists greater treatment gaps for women than men among primary care patients in Australia. doi:10.1016/j.hlc.2009.05.669 624 COMPARISON OF DIGITAL SUBTRACTION ANGIOGRAPHY (DSA), CT ANGIOGRAPHY (CTA) AND MR ANGIOGRAPHY (MRA) FOR ANATOMIC RISK ASSESSMENT PRIOR TO CAROTID ARTERY STENTING J. Morton, S. McCormack, J.P. Harris, G.H. White, M.K.C. Ng Royal Prince Alfred Hospital, Sydney, Australia Introduction: Cerebral embolisation is the most feared complication of carotid artery stenting (CAS). Previous research has attempted to risk-stratify patients based on several factors, however this assessment is usually based solely on DSA. We compared DSA, CTA and MRA for diagnosing high-risk anatomic factors and the effect on outcome. Methods: 24 consecutive patients undergoing CAS had 28 stenting procedures. Patients were assessed with CTA, MRA and DSA pre-procedure. Patients were assigned a risk-score from 0 to 6 for DSA, CTA and MRA based on: arch type, arch/lesion calcification, common-carotid (CCA) ostial stenosis, CCA and internal-carotid tortuosity (measured angles 30–60◦ and >60◦ ), and lesion-length. Patients had a follow-up brain MRI 58 ± 32 days after stenting. Results: There was a significant difference between risk-scores: DSA = 2.83 ± 1.15, CTA = 4.06 ± 1.16, MRA = 3.50 ± 0.89 (p = 0.005). The most disparity was between DSA and CTA (44% had ≥2 risk-points difference), mostly due to increased CTA detection of unfavourable calcification in the aortic arch and lesion. There was significantly higher rate of diagnosis of 30–60◦ angulations on DSA (2.44 ± 0.98/patient) compared to CTA (1.67 ± 1.28) and MRA (1.61 ± 0.85) (p = 0.037); however, diagnosis of >90◦ angulation was similar in all
S271
620 ATRIAL FIBRILLATION IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION WHICH DOES NOT IMPROVE WITH CARDIOVERSION
621 CALCITONIN RECEPTOR-IMMUNOREACTIVITY ASSOCIATED WITH SPECIFIC CELLS IN DISEASED ARTERIES
Scott R. Willoughby, Christopher X. Wong, Sean Jolly, Anisha Prabhu, Han Sung Lim, Adam J. Nelson, Stephen Worthley, Matthew I. Worthley, Prashanthan Sanders
P.J. Wookey 1,2, , A. Zulli 1,2 , D.L. Hare 1,2
Cardiovascular Research Centre, Department of Cardiology, Royal Adelaide Hospital and the Disciplines of Medicine and Physiology, University of Adelaide, Adelaide, Australia Background: How and why patients with atrial fibrillation (AF) develop atrial thrombus remains to be fully determined. Considerable evidence exists to implicate in part the effect of atrial mechanical remodelling due to arrhythmia. Whether endothelial dysfunction contributes to the heightened risk of thrombus in patients with AF or after cardioversion (CV) is not known. Methods: We studied 14 patients with “lone” persistent AF (mean age 60 ± 4 years: 12 M) undergoing CV and compared them to 14 age and gender matched subjects in sinus rhythm. Endothelial function was assessed using finger peripheral arterial tonometry (PAT) under controlled conditions. Endothelial function, expressed as the reactive hyperaemia response (RHI), was assessed by calculating the ratio of post-occlusion to baseline PAT using the validated EndoPAT 2000 system. This system compensates for systemic changes using simultaneous recordings from the un-occluded contra-lateral finger. Endothelial function was evaluated at baseline in both groups and immediately (2 h) after electrical CV in patients with AF. Results: Compared to the control group patients with AF had significant endothelial dysfunction at baseline as indicated by a lower PAT ratio (1.6 ± 0.1 PAT ratio in AF vs 2.0 ± 0.1 in controls, p < 0.04). There was no difference in endothelial-independent responses between groups. Following successful CV to sinus rhythm AF patients did not show improvement in PAT ratio (1.6 ± 0.1 PAT ratio at baseline vs 1.8 ± 0.2 PAT ratio post-CV, p = 0.12). Conclusion: Patients with “lone” AF demonstrate evidence of endothelial dysfunction with impaired reactive hyperaemia responses compared to controls. There was no immediate improvement in endothelial function with successful CV to sinus rhythm. These findings suggest that endothelial dysfunction may play a role in the risk for thromboembolic complications in AF and after CV. doi:10.1016/j.hlc.2009.05.666
1 Department of Cardiology, Austin Health, University of Melbourne, Melbourne, Australia 2 Department of Medicine, Austin Health, University of Melbourne, Melbourne, Australia
Calcitonin receptor-immunoreactivity (CTR-ir) was investigated in two different contexts of cardiovascular disease, namely, in diseased human arteries and in atherosclerotic arteries from rabbits fed atherogenic diets that included in one group, a regression period for healing. These immunohistochemical studies used anti-CTR antibodies directed against separate epitopes of human CTR. CTR-ir cells have been identified in the pro-monocyte subpopulation in peripheral blood and are derived from bone marrow. In nascent atherosclerotic plaque of rabbits fed an atherogenic diet (0.5% cholesterol/1% methionine for 4 weeks) CTR-ir cells were concentrated in and around the endothelial layer. In more mature plaque, CTR-ir cells integrated into the endothelial layer and formed into foam cells in the neo-intima. In the regression model in which animals were returned to a normal diet for 8 weeks (cholesterol normal), plaque was stabilised and CTR-ir was reduced considerably. In the vasa vasorum of diseased human radial arteries CTR-ir was found in cells located in the endothelial layer and within the surrounding parenchyma, in fibroblast-like cells and smaller round cells. Within the media CTR-ir was found in structures that resembled vessels and were aligned with smooth muscle cells. CTR-ir cells in diseased arteries may play a role in the healing processes of atherosclerotic plaque as expression is found amongst the first recruited cell types which are lost with plaque stabilisation and healing. In more advanced disease in studies with human radial arteries, CTR-ir micro-vessel-like structures course through the media and may represent more irreversible events. Promonocytes may play an important role in these events. doi:10.1016/j.hlc.2009.05.667 622 CARDIAC AUTONOMIC DYSFUNCTION IS ASSOCIATED WITH ALTERED EXERCISE HAEMODYNAMICS IN PATIENTS WITH TYPE 2 DIABETES J.W. Sacre, J.S. Coombes, J.E. Sharman University of Queensland, Brisbane, Australia Purpose: Pts with type 2 diabetes (T2DM) demonstrate a paradoxical reduction in augmentation index (AIx) and an exaggerated central BP response during exercise, which is related to adverse cardiac remodelling. Cardiac autonomic neuropathy (CAN) is a common complication of T2DM, and this study aimed to determine the association of CAN with abnormal exercise haemodynamics in these pts.
ABSTRACTS
Heart, Lung and Circulation 2009;18S:S1–S286
S272
Heart, Lung and Circulation 2009;18S:S1–S286
Abstracts
ABSTRACTS
Table 1. Variable
NORM
ABN
P-value
Resting AIx (%) Exercise AIx (%)
29.0 ± 9.4 21.5 ± 10
25.3 ± 9.0 10.9 ± 9.9
0.37 0.025
Methods: CAN was assessed using heart rate variability (coefficient of variation of RR intervals—CV). Brachial BP was measured using cuff sphygmomanometry, and pulse wave analysis from radial tonometry was used to measure AIx and central BP. All measures were performed at rest and during steady state cycling exercise at 30% HR reserve in 21 apparently healthy pts with T2DM. Pts were separated into normal (NORM, n = 11, 63 ± 8y, 73% male) and impaired (ABN, n = 10, 58 ± 9y, 80% male) autonomic function groups, classified by resting CV. Results: There were no significant group differences in age, gender, HbA1c, resting HR, brachial and central BP, or resting AIx (p > 0.05 for all). Pts in the ABN group had significantly reduced resting CV (2.7 ± 0.6% vs 6.4 ± 2.3%; p < 0.001). Despite no difference between groups in exercise brachial and central BP, exercise AIx was lower in the ABN patients (Table 1). There was also a lower rest to exercise change in CV (−0.9 ± 1.2% vs −3.9 ± 2.5%; p = 0.002) and HR corrected AIx (−3.3 ± 9.8 vs 6.5 ± 6.5%; p = 0.02) in the ABN group. Moreover, exercise AIx was significantly associated with exercise CV (r = 0.47; p = 0.03). Conclusion: Exercise AIx is related to cardiac autonomic function, which may explain the paradoxical reduction of this variable in T2DM pts. doi:10.1016/j.hlc.2009.05.668 623 CARDIOVASCULAR RISK MANAGEMENT AMONG FEMALE AND MALE PATIENTS IN AUSTRALIAN GENERAL PRACTICE: THE AUSHEART STUDY F. Turnbull 1 , H. Arima 1 , E. Heeley 1 , D. Peiris 1 , A. Weekes 2 , C. Morgan 2 , A. Cass 1 , C. Anderson 1 , A. Patel 1 , J. Chalmers 1 1 The George Institute for International Health, Sydney, Australia 2 Servier laboratories, Melbourne, Australia
Objective: To determine whether there are differences in the management of cardiovascular risk between men and women attending Australian General Practices. Methods: The Australian HypErtension and Absolute Risk sTudy (AusHEART) was a nationally representative, cluster-stratified, cross-sectional survey among 322 general practitioners (GPs). Each GP was asked to collect data on cardiovascular risk factors and their management in 15–20 consecutive patients (age ≥55 years) who presented between May and June, 2008. Five-year absolute cardiovascular risk was centrally calculated based on submitted data using an adjusted Framingham risk equation recommended by Australian guidelines.
Results: Of the 5283 patients, 2968 (56%) were female. The proportions of patients classified as being at ‘low’ (<10%), ‘medium’ (10–15%) or ‘high’ (≥15%) absolute risk were 28%, 8% and 41%, respectively for women and 9%, 10%, 43%, respectively for men. Established cardiovascular disease was less frequent among female (23%) compared with male patients (37%; p < 0.0001). Among patients with ‘low’, ‘medium’ and ‘high’ estimated risk of cardiovascular disease, the use of blood pressure lowering therapy, statin therapy and anti-platelet therapy was broadly comparable by sex. However, among patients with established cardiovascular disease, treatment rates were consistently lower for women compared with men; statin therapy (64% vs 74%), antiplatelet therapy (64% vs 74%), combination therapy with blood pressure-lowering and statin (53% vs 64%) and combination of all three therapies (44% vs 56%) (all p < 0.001). Conclusions: Despite similar indications for preventive therapy, there exists greater treatment gaps for women than men among primary care patients in Australia. doi:10.1016/j.hlc.2009.05.669 624 COMPARISON OF DIGITAL SUBTRACTION ANGIOGRAPHY (DSA), CT ANGIOGRAPHY (CTA) AND MR ANGIOGRAPHY (MRA) FOR ANATOMIC RISK ASSESSMENT PRIOR TO CAROTID ARTERY STENTING J. Morton, S. McCormack, J.P. Harris, G.H. White, M.K.C. Ng Royal Prince Alfred Hospital, Sydney, Australia Introduction: Cerebral embolisation is the most feared complication of carotid artery stenting (CAS). Previous research has attempted to risk-stratify patients based on several factors, however this assessment is usually based solely on DSA. We compared DSA, CTA and MRA for diagnosing high-risk anatomic factors and the effect on outcome. Methods: 24 consecutive patients undergoing CAS had 28 stenting procedures. Patients were assessed with CTA, MRA and DSA pre-procedure. Patients were assigned a risk-score from 0 to 6 for DSA, CTA and MRA based on: arch type, arch/lesion calcification, common-carotid (CCA) ostial stenosis, CCA and internal-carotid tortuosity (measured angles 30–60◦ and >60◦ ), and lesion-length. Patients had a follow-up brain MRI 58 ± 32 days after stenting. Results: There was a significant difference between risk-scores: DSA = 2.83 ± 1.15, CTA = 4.06 ± 1.16, MRA = 3.50 ± 0.89 (p = 0.005). The most disparity was between DSA and CTA (44% had ≥2 risk-points difference), mostly due to increased CTA detection of unfavourable calcification in the aortic arch and lesion. There was significantly higher rate of diagnosis of 30–60◦ angulations on DSA (2.44 ± 0.98/patient) compared to CTA (1.67 ± 1.28) and MRA (1.61 ± 0.85) (p = 0.037); however, diagnosis of >90◦ angulation was similar in all