- Email: [email protected]
The Association of Obesity with Arterial Function and Structure - A Systematic Review and Meta-Analysis
Abstracts
45 Sore Throat: A Harbinger of a Lethal Diagnosis K. Rajakariar 1,∗ , A. Koshy 1 , S. Tsui 1,2 , G. Proimos 1,3 1 Department
of Cardiology, Box Hill Hospital, Australia 2 Department of Radiology, Box Hill Hospital, Australia 3 Department of Cardiology, The Austin Hospital, Australia Background: Initial clinical diagnosis of aortic dissection can be challenging. Classical symptoms are often absent, and atypical presentations are associated with delayed diagnosis and increased mortality rates. We describe two cases of isolated throat discomfort as the only symptom of a Stanford type A aortic dissection. Case Presentation: In the first case, a previously healthy 77 year old man presented in significant distress with isolated throat discomfort. Electrocardiogram (ECG) showed transient high grade atrioventricular block with normal troponins. Transthoracic echocardiogram later demonstrated a 5.9 cm ascending aorta. A computed tomography (CT) aortogram confirmed type A aortic dissection extending into the great vessels. He suffered a cardiac arrest shortly after and died. The second case involved a 57 year old man who initially described chest pain, with an ECG demonstrating ST elevation in aVR with reciprocal infero-lateral ST depression and normal troponins. Coronary angiogram was unremarkable. Post-procedure, he complained of isolated throat discomfort raising suspicion of possible aortic dissection. Urgent CT aortogram was performed, and demonstrated a type A dissection extending into the great vessels. He subsequently underwent successful graft replacement. Conclusion: A sore throat may be the sole feature to prompt consideration of aortic dissection in a patient where symptoms are disproportionate to the overall clinical state. The throat discomfort is attributable to propagation of the dissection plane to the great vessels, as was the case in both patients. The contrasting case series illustrates the importance of considering this atypical symptom as an early manifestation of aortic dissection. http://dx.doi.org/10.1016/j.hlc.2016.06.046 46 The 3 Adrenergic Receptor Agonist, CL 216, 343, Promotes Angiogenesis
K. Bubb, O. Tang ∗ , T. Hansen, T. Huang, G. Figtree Kolling Institute, University of Sydney, Australia Background: 3 adrenergic receptor (3AR) agonists activate endothelial nitric oxide synthase (eNOS). We have demonstrated that this is at least partially due to decreased
S21
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. ..
glutathionylation-mediated uncoupling of eNOS, restoring NO production, and decreasing superoxide generation. Given NO is a key regulator of angiogenesis, we have now examined the effect of 3AR on endothelial cell migration and tubule formation. Methods and Results: Angiogenesis was measured in vitro in human umbilical vein endothelial cells using migration and tubule formation assays; both recorded using timelapse video-microscopy. For migration assays, a scratch wound was produced in the cell monolayer. 12 hours post-scratch, wound closure was 57.8±4.6% in controls. Cells treated with the 3AR agonist, CL 216,343 (CL) exhibited a concentrationdependent increase in migration which was ∼20% greater at the higher concentrations (P<0.001, Two-way ANOVA). For tubule formation experiments, 1 x 104 cells were added to wells coated with matrigel and tubules formed over 4-12 hours. The formation of tubules was augmented by CL, with the maximal increase 70% higher than control (P<0.05, Student’s t-test). In both of these experiments, the NOS inhibitor, L-NAME (300 mol/L) abolished the CLdependent increase. Studies are ongoing to determine the effect of CL on in vivo angiogenesis and to elucidate the mechanisms. Conclusion: The 3 adrenergic agonist, CL 216, 343, increases angiogenesis in vitro by an NO-dependent mechanism. As 3AR agonists are clinically available for management of non-cardiac conditions, these findings may be imminently translatable as a new therapy for chronic myocardial or peripheral artery ischaemia. http://dx.doi.org/10.1016/j.hlc.2016.06.047 47 The Association of Obesity with Arterial Function and Structure - A Systematic Review and Meta-Analysis J. Ne 1,2,∗ , T. Cai 1,2 , D. Celermajer 1 , I. Caterson 2 , T. Gill 2 , C. Lee 2 , M. Skilton 2 1 The
University of Sydney, Sydney Medical School, Australia 2 Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, Australia Background: Obesity is an established risk factor for cardiovascular events. Although the mechanisms by which obesity affects cardiovascular risk have not been fully elucidated, atherosclerosis is likely to be involved. We undertook a comprehensive systematic review and meta-analysis to study how obesity (measured with BMI) is associated with brachial flow-mediated dilatation and carotid intima-media thickness, key non-invasive measures of arterial function and structure respectively. Methods: Electronic searches for “Obesity and flowmediated dilatation” and “Obesity and intima-media thickness” were performed using Ovid Medline and Embase databases. No language limits were applied. Meta-analysis was undertaken to obtain pooled estimates for the obese and healthy weight adults. Results: Of the 4822 articles retrieved, 19 studies on flowmediated dilatation and 19 studies on intima-media thickness
Abstracts
S22
were included. Obesity was associated with lower flowmediated dilatation (-1.92% [95% CI -2.92, -0.92], P=0.0002) and greater carotid intima-media thickness (0.07 mm [95% CI 0.05, 0.08], P<0.00001). These associations did not differ by age or sex. There was some evidence that the association of obesity with lower flow-mediated dilatation was more marked in studies using distal (forearm) occlusion than in studies which used proximal (upper arm) occlusion (P=0.10). The magnitudes of these effect sizes for brachial flow-mediated dilatation and carotid intima-media thickness are consistent with obese adults having a 12 to 33% higher risk of cardiovascular events and a 7 to 12% higher risk of myocardial infarction respectively. Conclusion: Arterial function is lower and intimamedia thickness is greater in obese adults, suggesting that atherosclerosis contributes to obesity-related cardiovascular events. http://dx.doi.org/10.1016/j.hlc.2016.06.048 48 The Hypoplastic Aortic Arch - Recognition and Management T. Goh 1,∗ , K. Goh 2 , E. Goh 2 , T. Goh 2 , Y. Willis 3 , C. Chan 3 , J. Au 2 , A. Yang 2 1 Mercy
Hospital Heidelberg, Australia Clinic, Australia 3 Heartwise Clinic, Australia 2 Wholeheart
Introduction: Follow up of post coarctation repair reveals a significant proportion of hypertension despite good outcomes. This study examines the recognition/role of hypoplastic arch[HA][primary/secondary] in causing persisting hypertension[hbp] and the management thereof. Materials and Methods: select cohort of 90 pts. 70 coarctation repair,15 CHD, 5 “normal” followed from infancy/early childhood duration 2 - 39 yrs mean 22.6yrs median 22 yrs male 59 female 31 Pts regularly reviewed 6-12mthly with 1. Clinical bp 2. Home bp readings 3. Amb. Bp where indicated 4. TTE with emphasis on aortic arch size and doppler. 5. Exercise bp 6. CTA/MRI imaging [indexed z score] 6. Social health counselling. Poiseuille Law is applied. Z score normogram of pts. plotted from Kaiser et el Jour CVMR 2008, 10:56 Z < - 2 or less is diagnostic of HA Results: 1. HA 36 coa pts 15 CHD pts, 5 “normals”, total 56 pts. Noted mostly at puberty/early adulthood with hbp. TTE findings of small arch and vel 2m/s were investigative pointers. Distorted growth affects outcomes and necessitates serial reviews. Management: 33 adult pts stented[normalised Z] had good outcomes [may take 12-24mths] fu 3 – 11 yr 3 had partial stent responses. 3 on medication. Conclusion: Hypoplasia recognition requires indexed serial studies. Hypoplasia plays important role in persistent hypertension post “good”coa repair Primary hypoplasia has been recognised recently.
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. ..
Stents normalise arch dimensions with normotension outcomes and no medication. Continuous Medication can also treat hbp. Further studies and discussions needed for formulating management strategies. http://dx.doi.org/10.1016/j.hlc.2016.06.049 49 The Role of ePLAR in Determining Patient Suitability and Response to Vasodilator Therapy in Pulmonary Hypertension D. Sidhom 1,∗ , G. Scalia 2,3 1 James
Cook University, Australia Partners, Auchenflower, Australia 3 University of Queensland, Australia 2 HeartCare
Background: While right heart catheterisation is the gold standard for both diagnosis and monitoring response to therapy in pulmonary hypertension (PHT), the echocardiographic pulmonary to left atrial ratio (ePLAR) offers a novel and non-invasive echo parameter to differentiate patients with pre- and post-capillary PHT. The population normal for ePLAR is 0.30 ±0.09m/s, with a cut-off of >0.26m/s for pre capillary PHT. The effect of specific pulmonary vasodilator therapy on ePLAR remains to be documented. Methods: Nineteen PHT patients treated with pulmonary vasodilator therapy (13 female, 75.2±12.2 yrs) were retrospectively grouped into pre-capillary (n=11) and post capillary (n=8) PHT groups based on their ePLAR values at baseline. Response to vasodilator therapy (fall in ePLAR) was monitored at intermediate follow-up.
Results: At 260+/-236 days, patients in the pre-capillary group had a mean delta ePLAR (change in ePLAR from baseline) improvement of -0.12±0.16m/s, compared to +0.08±0.08m/s from patients in the post capillary group (p=0.003). At 496+/-279 days, the delta ePLAR in precapillary PHT patients was -0.08+/-0.16 m/s, vs +0.11+/-0.11 m/s in post-capillary cases (p=0.018). Conclusion: Patients with pre-capillary PHT (high baseline ePLAR) demonstrate an impressive response therapy. However, post-capillary PHT patients (low baseline ePLAR) have a poor response to therapy. Given the expense of pulmonary vasodilator therapy, ePLAR may provide a triage indicator of patients’ suitability for, and response to, treatment. http://dx.doi.org/10.1016/j.hlc.2016.06.050
45 Sore Throat: A Harbinger of a Lethal Diagnosis K. Rajakariar 1,∗ , A. Koshy 1 , S. Tsui 1,2 , G. Proimos 1,3 1 Department
of Cardiology, Box Hill Hospital, Australia 2 Department of Radiology, Box Hill Hospital, Australia 3 Department of Cardiology, The Austin Hospital, Australia Background: Initial clinical diagnosis of aortic dissection can be challenging. Classical symptoms are often absent, and atypical presentations are associated with delayed diagnosis and increased mortality rates. We describe two cases of isolated throat discomfort as the only symptom of a Stanford type A aortic dissection. Case Presentation: In the first case, a previously healthy 77 year old man presented in significant distress with isolated throat discomfort. Electrocardiogram (ECG) showed transient high grade atrioventricular block with normal troponins. Transthoracic echocardiogram later demonstrated a 5.9 cm ascending aorta. A computed tomography (CT) aortogram confirmed type A aortic dissection extending into the great vessels. He suffered a cardiac arrest shortly after and died. The second case involved a 57 year old man who initially described chest pain, with an ECG demonstrating ST elevation in aVR with reciprocal infero-lateral ST depression and normal troponins. Coronary angiogram was unremarkable. Post-procedure, he complained of isolated throat discomfort raising suspicion of possible aortic dissection. Urgent CT aortogram was performed, and demonstrated a type A dissection extending into the great vessels. He subsequently underwent successful graft replacement. Conclusion: A sore throat may be the sole feature to prompt consideration of aortic dissection in a patient where symptoms are disproportionate to the overall clinical state. The throat discomfort is attributable to propagation of the dissection plane to the great vessels, as was the case in both patients. The contrasting case series illustrates the importance of considering this atypical symptom as an early manifestation of aortic dissection. http://dx.doi.org/10.1016/j.hlc.2016.06.046 46 The 3 Adrenergic Receptor Agonist, CL 216, 343, Promotes Angiogenesis
K. Bubb, O. Tang ∗ , T. Hansen, T. Huang, G. Figtree Kolling Institute, University of Sydney, Australia Background: 3 adrenergic receptor (3AR) agonists activate endothelial nitric oxide synthase (eNOS). We have demonstrated that this is at least partially due to decreased
S21
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. ..
glutathionylation-mediated uncoupling of eNOS, restoring NO production, and decreasing superoxide generation. Given NO is a key regulator of angiogenesis, we have now examined the effect of 3AR on endothelial cell migration and tubule formation. Methods and Results: Angiogenesis was measured in vitro in human umbilical vein endothelial cells using migration and tubule formation assays; both recorded using timelapse video-microscopy. For migration assays, a scratch wound was produced in the cell monolayer. 12 hours post-scratch, wound closure was 57.8±4.6% in controls. Cells treated with the 3AR agonist, CL 216,343 (CL) exhibited a concentrationdependent increase in migration which was ∼20% greater at the higher concentrations (P<0.001, Two-way ANOVA). For tubule formation experiments, 1 x 104 cells were added to wells coated with matrigel and tubules formed over 4-12 hours. The formation of tubules was augmented by CL, with the maximal increase 70% higher than control (P<0.05, Student’s t-test). In both of these experiments, the NOS inhibitor, L-NAME (300 mol/L) abolished the CLdependent increase. Studies are ongoing to determine the effect of CL on in vivo angiogenesis and to elucidate the mechanisms. Conclusion: The 3 adrenergic agonist, CL 216, 343, increases angiogenesis in vitro by an NO-dependent mechanism. As 3AR agonists are clinically available for management of non-cardiac conditions, these findings may be imminently translatable as a new therapy for chronic myocardial or peripheral artery ischaemia. http://dx.doi.org/10.1016/j.hlc.2016.06.047 47 The Association of Obesity with Arterial Function and Structure - A Systematic Review and Meta-Analysis J. Ne 1,2,∗ , T. Cai 1,2 , D. Celermajer 1 , I. Caterson 2 , T. Gill 2 , C. Lee 2 , M. Skilton 2 1 The
University of Sydney, Sydney Medical School, Australia 2 Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, Australia Background: Obesity is an established risk factor for cardiovascular events. Although the mechanisms by which obesity affects cardiovascular risk have not been fully elucidated, atherosclerosis is likely to be involved. We undertook a comprehensive systematic review and meta-analysis to study how obesity (measured with BMI) is associated with brachial flow-mediated dilatation and carotid intima-media thickness, key non-invasive measures of arterial function and structure respectively. Methods: Electronic searches for “Obesity and flowmediated dilatation” and “Obesity and intima-media thickness” were performed using Ovid Medline and Embase databases. No language limits were applied. Meta-analysis was undertaken to obtain pooled estimates for the obese and healthy weight adults. Results: Of the 4822 articles retrieved, 19 studies on flowmediated dilatation and 19 studies on intima-media thickness
Abstracts
S22
were included. Obesity was associated with lower flowmediated dilatation (-1.92% [95% CI -2.92, -0.92], P=0.0002) and greater carotid intima-media thickness (0.07 mm [95% CI 0.05, 0.08], P<0.00001). These associations did not differ by age or sex. There was some evidence that the association of obesity with lower flow-mediated dilatation was more marked in studies using distal (forearm) occlusion than in studies which used proximal (upper arm) occlusion (P=0.10). The magnitudes of these effect sizes for brachial flow-mediated dilatation and carotid intima-media thickness are consistent with obese adults having a 12 to 33% higher risk of cardiovascular events and a 7 to 12% higher risk of myocardial infarction respectively. Conclusion: Arterial function is lower and intimamedia thickness is greater in obese adults, suggesting that atherosclerosis contributes to obesity-related cardiovascular events. http://dx.doi.org/10.1016/j.hlc.2016.06.048 48 The Hypoplastic Aortic Arch - Recognition and Management T. Goh 1,∗ , K. Goh 2 , E. Goh 2 , T. Goh 2 , Y. Willis 3 , C. Chan 3 , J. Au 2 , A. Yang 2 1 Mercy
Hospital Heidelberg, Australia Clinic, Australia 3 Heartwise Clinic, Australia 2 Wholeheart
Introduction: Follow up of post coarctation repair reveals a significant proportion of hypertension despite good outcomes. This study examines the recognition/role of hypoplastic arch[HA][primary/secondary] in causing persisting hypertension[hbp] and the management thereof. Materials and Methods: select cohort of 90 pts. 70 coarctation repair,15 CHD, 5 “normal” followed from infancy/early childhood duration 2 - 39 yrs mean 22.6yrs median 22 yrs male 59 female 31 Pts regularly reviewed 6-12mthly with 1. Clinical bp 2. Home bp readings 3. Amb. Bp where indicated 4. TTE with emphasis on aortic arch size and doppler. 5. Exercise bp 6. CTA/MRI imaging [indexed z score] 6. Social health counselling. Poiseuille Law is applied. Z score normogram of pts. plotted from Kaiser et el Jour CVMR 2008, 10:56 Z < - 2 or less is diagnostic of HA Results: 1. HA 36 coa pts 15 CHD pts, 5 “normals”, total 56 pts. Noted mostly at puberty/early adulthood with hbp. TTE findings of small arch and vel 2m/s were investigative pointers. Distorted growth affects outcomes and necessitates serial reviews. Management: 33 adult pts stented[normalised Z] had good outcomes [may take 12-24mths] fu 3 – 11 yr 3 had partial stent responses. 3 on medication. Conclusion: Hypoplasia recognition requires indexed serial studies. Hypoplasia plays important role in persistent hypertension post “good”coa repair Primary hypoplasia has been recognised recently.
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. ..
Stents normalise arch dimensions with normotension outcomes and no medication. Continuous Medication can also treat hbp. Further studies and discussions needed for formulating management strategies. http://dx.doi.org/10.1016/j.hlc.2016.06.049 49 The Role of ePLAR in Determining Patient Suitability and Response to Vasodilator Therapy in Pulmonary Hypertension D. Sidhom 1,∗ , G. Scalia 2,3 1 James
Cook University, Australia Partners, Auchenflower, Australia 3 University of Queensland, Australia 2 HeartCare
Background: While right heart catheterisation is the gold standard for both diagnosis and monitoring response to therapy in pulmonary hypertension (PHT), the echocardiographic pulmonary to left atrial ratio (ePLAR) offers a novel and non-invasive echo parameter to differentiate patients with pre- and post-capillary PHT. The population normal for ePLAR is 0.30 ±0.09m/s, with a cut-off of >0.26m/s for pre capillary PHT. The effect of specific pulmonary vasodilator therapy on ePLAR remains to be documented. Methods: Nineteen PHT patients treated with pulmonary vasodilator therapy (13 female, 75.2±12.2 yrs) were retrospectively grouped into pre-capillary (n=11) and post capillary (n=8) PHT groups based on their ePLAR values at baseline. Response to vasodilator therapy (fall in ePLAR) was monitored at intermediate follow-up.
Results: At 260+/-236 days, patients in the pre-capillary group had a mean delta ePLAR (change in ePLAR from baseline) improvement of -0.12±0.16m/s, compared to +0.08±0.08m/s from patients in the post capillary group (p=0.003). At 496+/-279 days, the delta ePLAR in precapillary PHT patients was -0.08+/-0.16 m/s, vs +0.11+/-0.11 m/s in post-capillary cases (p=0.018). Conclusion: Patients with pre-capillary PHT (high baseline ePLAR) demonstrate an impressive response therapy. However, post-capillary PHT patients (low baseline ePLAR) have a poor response to therapy. Given the expense of pulmonary vasodilator therapy, ePLAR may provide a triage indicator of patients’ suitability for, and response to, treatment. http://dx.doi.org/10.1016/j.hlc.2016.06.050